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People with long COVID have specific blood biomarkers, study says
The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.
“This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.
Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.
Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.
People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.
“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.
The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.
The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said.
“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.
The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.
A version of this article appeared on WebMD.com.
The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.
“This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.
Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.
Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.
People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.
“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.
The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.
The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said.
“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.
The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.
A version of this article appeared on WebMD.com.
The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.
“This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.
Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.
Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.
People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.
“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.
The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.
The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said.
“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.
The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.
A version of this article appeared on WebMD.com.
Thyroid ablation safety addressed by expert consensus
“There are no documents to date in the United States focusing primarily on the safe adoption and implementation of ablation techniques, including learning curve considerations and necessary pre-procedural skillsets,” reports the ATA task force in the consensus statement, which was published in Thyroid.
“Although these emerging technologies hold great promise, they are not without risk and require development of a unique skill set and environment for optimal, safe performance and consistent outcomes,” task force co-author Catherine F. Sinclair, MD, an associate professor at the Icahn School of Medicine at Mount Sinai, New York, said in an interview.
Chemical ablation has long been utilized as a nonsurgical option for benign thyroid nodule ablation. However, the current array of treatment options has expanded with thermal ablation. Techniques such as radiofrequency ablation (RFA), laser ablation, microwave ablation, and high-intensity focused ultrasound have gained favor as minimally invasive alternatives to surgery.
Much has been published on indications and outcomes with the use of the techniques. The multidisciplinary global task force was convened to address key issues regarding safety and utilization. The report is directed toward specialists, including surgeons, endocrinologists, and interventional radiologists.
The recommendations cover three broad categories: safety considerations spanning preprocedural to postprocedural periods; necessary skill sets for optimal, safe performance with the approaches; and the expectations for success in the context of risks and benefits.
Ablation methods can depend on nodule type
Among key issues addressed are which ablation methods are most appropriate for which types of nodules. Recommendations include chemical ablation, typically involving the injection of dehydrated ethanol in a target nodule. In solid nodules, diffusion with chemical ablation can be unpredictable, which makes it more appropriate for cystic nodules.
Thermal ablation is considered best suited for patients with compressive and/or cosmetic complaints that clearly involve a single or dominant nodule, as well as for autonomously functioning thyroid nodules that cause subclinical or overt hyperthyroidism.
While ethanol ablation is recommended as a first-line treatment for benign cystic thyroid nodules, its efficacy decreases when there is an increase of more than 20% of the solid component. In such cases, RFA or a combination of ethanol ablation and RFA may be considered, the task force recommends.
Patient counseling – managing expectations
Another key consideration in treatment with thyroid nodule ablation is managing patients’ expectations.
Patients should be advised of benefits, such as the avoidance of surgery and general anesthesia and less recovery time. Risks can include thermal or chemical injury to the recurrent laryngeal nerve and other vital structures. The task force underscores discussion of alternative options with patients.
Alternative management options to ablation, including observation, radioactive iodine for functioning nodules, and surgery should also be discussed, and “their relative advantages and disadvantages should be presented without bias such that the patient can make an informed, individual treatment decision,” the task force recommends.
Patients should be informed that, in contrast to surgical management, the benefits of ablation are not immediate; rather, they accrue over the course of months. Reduction in nodule size within the first month is often limited.
Pain, soreness, and some swelling of the nodule and surrounding tissues are common in the first week. These symptoms usually peak in the first 3-5 days after the procedure. Importantly, patients rarely require opioid medications, and their use should be avoided, the task force recommends.
Patients should also be informed about the possibilities of nodule regrowth following ablation and the possible need for more than one ablation procedure.
“Although regrowth definitions in the literature vary, risk of regrowth after thermal ablation is 5%-40% and increases the larger the baseline nodule volume,” the task force notes.
Of note, most studies on ablation to date have shown that thermal ablation complication rates are low. Twelve months post procedure, volume reductions are typically greater than 50%.
Follow-up
For long-term monitoring following ablation, follow-up neck ultrasound is typically recommended at 1-3 months and at 6 and 12 months post ablation to assess volume reduction, nodule appearance, nodule vascularity, and areas at risk for regrowth, the authors note.
Prolonged serial biochemical evaluation of thyroid function is only recommended in cases of hyperfunctioning thyroid nodules.
Key considerations for additional ablative sessions for nodules greater than 20-30 mL in volume should include a failure to achieve adequate reduction in volume, nodule regrowth in previously untreated peripheral areas, and/or persistent or new compressive symptoms.
Learning curve
Dr. Sinclair underscored that successful thyroid nodule ablation requires skill – and experience.
“Probably the greatest concern shared by the writing group on this statement was the potential for clinicians to start ablation practices without having an appropriate prior skill set,” she said.
“Ablation is an advanced, ultrasound-guided procedure, and clinicians need to be experienced in performing neck ultrasounds and biopsies,” she added. “To consider performing ablations without this skill set is both unrealistic and dangerous.”
RFA, currently the most commonly used thermal ablation method for benign thyroid nodule ablation in the U.S., “has a good safety profile but can have a steep learning curve initially,” she said.
Among the most important recommendations is that for their first 20-60 ablation procedures, clinicians should consider limiting treatment to small- to medium-sized benign nodules rather than large-volume disease, Dr. Sinclair added.
“In addition, prior to starting thyroid ablation practices, clinicians should be proficient in ultrasound imaging and fine-needle biopsies and can gain valuable experience by practicing on phantoms and having expert proctoring for the first few cases,” she said.
For initial ablative cases, the task force recommends that clinicians select moderate-size (< 20-30 mL), nonvascular nodules with favorable characteristics and location. The final volume reduction should be based not only on baseline nodule characteristics, such as volume and vascularity, but also on the practitioner’s skill.
Clinicians furthermore should be board certified or eligible in an appropriate medical specialty, have extensive background knowledge, and “should have clinical experience in the clinical diagnosis and treatment of thyroid nodules; neck imaging anatomy; thyroid ultrasound imaging and fine needle aspiration biopsy procedures; and ultrasound risk stratification for benign and malignant thyroid tumors,” the group recommends.
Importantly, the statement is designed to reflect a consensus opinion of the panel of experts but is not meant to serve as a formal guideline or a standard of care for the clinical practice of thermal ablation, Dr. Sinclair added.
“It is not the intent of the statement to replace individual decision-making, the wishes of the patient or family, or clinical judgment.”
The authors’ disclosures are detailed in the published report.
A version of this article first appeared on Medscape.com.
“There are no documents to date in the United States focusing primarily on the safe adoption and implementation of ablation techniques, including learning curve considerations and necessary pre-procedural skillsets,” reports the ATA task force in the consensus statement, which was published in Thyroid.
“Although these emerging technologies hold great promise, they are not without risk and require development of a unique skill set and environment for optimal, safe performance and consistent outcomes,” task force co-author Catherine F. Sinclair, MD, an associate professor at the Icahn School of Medicine at Mount Sinai, New York, said in an interview.
Chemical ablation has long been utilized as a nonsurgical option for benign thyroid nodule ablation. However, the current array of treatment options has expanded with thermal ablation. Techniques such as radiofrequency ablation (RFA), laser ablation, microwave ablation, and high-intensity focused ultrasound have gained favor as minimally invasive alternatives to surgery.
Much has been published on indications and outcomes with the use of the techniques. The multidisciplinary global task force was convened to address key issues regarding safety and utilization. The report is directed toward specialists, including surgeons, endocrinologists, and interventional radiologists.
The recommendations cover three broad categories: safety considerations spanning preprocedural to postprocedural periods; necessary skill sets for optimal, safe performance with the approaches; and the expectations for success in the context of risks and benefits.
Ablation methods can depend on nodule type
Among key issues addressed are which ablation methods are most appropriate for which types of nodules. Recommendations include chemical ablation, typically involving the injection of dehydrated ethanol in a target nodule. In solid nodules, diffusion with chemical ablation can be unpredictable, which makes it more appropriate for cystic nodules.
Thermal ablation is considered best suited for patients with compressive and/or cosmetic complaints that clearly involve a single or dominant nodule, as well as for autonomously functioning thyroid nodules that cause subclinical or overt hyperthyroidism.
While ethanol ablation is recommended as a first-line treatment for benign cystic thyroid nodules, its efficacy decreases when there is an increase of more than 20% of the solid component. In such cases, RFA or a combination of ethanol ablation and RFA may be considered, the task force recommends.
Patient counseling – managing expectations
Another key consideration in treatment with thyroid nodule ablation is managing patients’ expectations.
Patients should be advised of benefits, such as the avoidance of surgery and general anesthesia and less recovery time. Risks can include thermal or chemical injury to the recurrent laryngeal nerve and other vital structures. The task force underscores discussion of alternative options with patients.
Alternative management options to ablation, including observation, radioactive iodine for functioning nodules, and surgery should also be discussed, and “their relative advantages and disadvantages should be presented without bias such that the patient can make an informed, individual treatment decision,” the task force recommends.
Patients should be informed that, in contrast to surgical management, the benefits of ablation are not immediate; rather, they accrue over the course of months. Reduction in nodule size within the first month is often limited.
Pain, soreness, and some swelling of the nodule and surrounding tissues are common in the first week. These symptoms usually peak in the first 3-5 days after the procedure. Importantly, patients rarely require opioid medications, and their use should be avoided, the task force recommends.
Patients should also be informed about the possibilities of nodule regrowth following ablation and the possible need for more than one ablation procedure.
“Although regrowth definitions in the literature vary, risk of regrowth after thermal ablation is 5%-40% and increases the larger the baseline nodule volume,” the task force notes.
Of note, most studies on ablation to date have shown that thermal ablation complication rates are low. Twelve months post procedure, volume reductions are typically greater than 50%.
Follow-up
For long-term monitoring following ablation, follow-up neck ultrasound is typically recommended at 1-3 months and at 6 and 12 months post ablation to assess volume reduction, nodule appearance, nodule vascularity, and areas at risk for regrowth, the authors note.
Prolonged serial biochemical evaluation of thyroid function is only recommended in cases of hyperfunctioning thyroid nodules.
Key considerations for additional ablative sessions for nodules greater than 20-30 mL in volume should include a failure to achieve adequate reduction in volume, nodule regrowth in previously untreated peripheral areas, and/or persistent or new compressive symptoms.
Learning curve
Dr. Sinclair underscored that successful thyroid nodule ablation requires skill – and experience.
“Probably the greatest concern shared by the writing group on this statement was the potential for clinicians to start ablation practices without having an appropriate prior skill set,” she said.
“Ablation is an advanced, ultrasound-guided procedure, and clinicians need to be experienced in performing neck ultrasounds and biopsies,” she added. “To consider performing ablations without this skill set is both unrealistic and dangerous.”
RFA, currently the most commonly used thermal ablation method for benign thyroid nodule ablation in the U.S., “has a good safety profile but can have a steep learning curve initially,” she said.
Among the most important recommendations is that for their first 20-60 ablation procedures, clinicians should consider limiting treatment to small- to medium-sized benign nodules rather than large-volume disease, Dr. Sinclair added.
“In addition, prior to starting thyroid ablation practices, clinicians should be proficient in ultrasound imaging and fine-needle biopsies and can gain valuable experience by practicing on phantoms and having expert proctoring for the first few cases,” she said.
For initial ablative cases, the task force recommends that clinicians select moderate-size (< 20-30 mL), nonvascular nodules with favorable characteristics and location. The final volume reduction should be based not only on baseline nodule characteristics, such as volume and vascularity, but also on the practitioner’s skill.
Clinicians furthermore should be board certified or eligible in an appropriate medical specialty, have extensive background knowledge, and “should have clinical experience in the clinical diagnosis and treatment of thyroid nodules; neck imaging anatomy; thyroid ultrasound imaging and fine needle aspiration biopsy procedures; and ultrasound risk stratification for benign and malignant thyroid tumors,” the group recommends.
Importantly, the statement is designed to reflect a consensus opinion of the panel of experts but is not meant to serve as a formal guideline or a standard of care for the clinical practice of thermal ablation, Dr. Sinclair added.
“It is not the intent of the statement to replace individual decision-making, the wishes of the patient or family, or clinical judgment.”
The authors’ disclosures are detailed in the published report.
A version of this article first appeared on Medscape.com.
“There are no documents to date in the United States focusing primarily on the safe adoption and implementation of ablation techniques, including learning curve considerations and necessary pre-procedural skillsets,” reports the ATA task force in the consensus statement, which was published in Thyroid.
“Although these emerging technologies hold great promise, they are not without risk and require development of a unique skill set and environment for optimal, safe performance and consistent outcomes,” task force co-author Catherine F. Sinclair, MD, an associate professor at the Icahn School of Medicine at Mount Sinai, New York, said in an interview.
Chemical ablation has long been utilized as a nonsurgical option for benign thyroid nodule ablation. However, the current array of treatment options has expanded with thermal ablation. Techniques such as radiofrequency ablation (RFA), laser ablation, microwave ablation, and high-intensity focused ultrasound have gained favor as minimally invasive alternatives to surgery.
Much has been published on indications and outcomes with the use of the techniques. The multidisciplinary global task force was convened to address key issues regarding safety and utilization. The report is directed toward specialists, including surgeons, endocrinologists, and interventional radiologists.
The recommendations cover three broad categories: safety considerations spanning preprocedural to postprocedural periods; necessary skill sets for optimal, safe performance with the approaches; and the expectations for success in the context of risks and benefits.
Ablation methods can depend on nodule type
Among key issues addressed are which ablation methods are most appropriate for which types of nodules. Recommendations include chemical ablation, typically involving the injection of dehydrated ethanol in a target nodule. In solid nodules, diffusion with chemical ablation can be unpredictable, which makes it more appropriate for cystic nodules.
Thermal ablation is considered best suited for patients with compressive and/or cosmetic complaints that clearly involve a single or dominant nodule, as well as for autonomously functioning thyroid nodules that cause subclinical or overt hyperthyroidism.
While ethanol ablation is recommended as a first-line treatment for benign cystic thyroid nodules, its efficacy decreases when there is an increase of more than 20% of the solid component. In such cases, RFA or a combination of ethanol ablation and RFA may be considered, the task force recommends.
Patient counseling – managing expectations
Another key consideration in treatment with thyroid nodule ablation is managing patients’ expectations.
Patients should be advised of benefits, such as the avoidance of surgery and general anesthesia and less recovery time. Risks can include thermal or chemical injury to the recurrent laryngeal nerve and other vital structures. The task force underscores discussion of alternative options with patients.
Alternative management options to ablation, including observation, radioactive iodine for functioning nodules, and surgery should also be discussed, and “their relative advantages and disadvantages should be presented without bias such that the patient can make an informed, individual treatment decision,” the task force recommends.
Patients should be informed that, in contrast to surgical management, the benefits of ablation are not immediate; rather, they accrue over the course of months. Reduction in nodule size within the first month is often limited.
Pain, soreness, and some swelling of the nodule and surrounding tissues are common in the first week. These symptoms usually peak in the first 3-5 days after the procedure. Importantly, patients rarely require opioid medications, and their use should be avoided, the task force recommends.
Patients should also be informed about the possibilities of nodule regrowth following ablation and the possible need for more than one ablation procedure.
“Although regrowth definitions in the literature vary, risk of regrowth after thermal ablation is 5%-40% and increases the larger the baseline nodule volume,” the task force notes.
Of note, most studies on ablation to date have shown that thermal ablation complication rates are low. Twelve months post procedure, volume reductions are typically greater than 50%.
Follow-up
For long-term monitoring following ablation, follow-up neck ultrasound is typically recommended at 1-3 months and at 6 and 12 months post ablation to assess volume reduction, nodule appearance, nodule vascularity, and areas at risk for regrowth, the authors note.
Prolonged serial biochemical evaluation of thyroid function is only recommended in cases of hyperfunctioning thyroid nodules.
Key considerations for additional ablative sessions for nodules greater than 20-30 mL in volume should include a failure to achieve adequate reduction in volume, nodule regrowth in previously untreated peripheral areas, and/or persistent or new compressive symptoms.
Learning curve
Dr. Sinclair underscored that successful thyroid nodule ablation requires skill – and experience.
“Probably the greatest concern shared by the writing group on this statement was the potential for clinicians to start ablation practices without having an appropriate prior skill set,” she said.
“Ablation is an advanced, ultrasound-guided procedure, and clinicians need to be experienced in performing neck ultrasounds and biopsies,” she added. “To consider performing ablations without this skill set is both unrealistic and dangerous.”
RFA, currently the most commonly used thermal ablation method for benign thyroid nodule ablation in the U.S., “has a good safety profile but can have a steep learning curve initially,” she said.
Among the most important recommendations is that for their first 20-60 ablation procedures, clinicians should consider limiting treatment to small- to medium-sized benign nodules rather than large-volume disease, Dr. Sinclair added.
“In addition, prior to starting thyroid ablation practices, clinicians should be proficient in ultrasound imaging and fine-needle biopsies and can gain valuable experience by practicing on phantoms and having expert proctoring for the first few cases,” she said.
For initial ablative cases, the task force recommends that clinicians select moderate-size (< 20-30 mL), nonvascular nodules with favorable characteristics and location. The final volume reduction should be based not only on baseline nodule characteristics, such as volume and vascularity, but also on the practitioner’s skill.
Clinicians furthermore should be board certified or eligible in an appropriate medical specialty, have extensive background knowledge, and “should have clinical experience in the clinical diagnosis and treatment of thyroid nodules; neck imaging anatomy; thyroid ultrasound imaging and fine needle aspiration biopsy procedures; and ultrasound risk stratification for benign and malignant thyroid tumors,” the group recommends.
Importantly, the statement is designed to reflect a consensus opinion of the panel of experts but is not meant to serve as a formal guideline or a standard of care for the clinical practice of thermal ablation, Dr. Sinclair added.
“It is not the intent of the statement to replace individual decision-making, the wishes of the patient or family, or clinical judgment.”
The authors’ disclosures are detailed in the published report.
A version of this article first appeared on Medscape.com.
FROM THYROID
Weight loss linked to mortality risk in older women
Weight loss of at least 5% over a 3-year period was associated with significantly increased mortality in women at age 90, 95, and 100 years compared with those whose weight remained stable, based on data from more than 50,000 individuals.
Previous studies of later-life weight changes and mortality have yielded inconsistent results driven by considerations of weight loss intentionality, and data on older adults in particular are limited, wrote Aladdin H. Shadyab, PhD, of the University of California, San Diego, and colleagues.
In a study published in the Journals of Gerontology: Medical Sciences, the researchers reviewed data from the Women’s Health Initiative, a prospective study of factors affecting chronic disease development in postmenopausal women. The study population included 54,437 women who entered the WHI between 1993 and 1998 at ages 50-79 years. The mean baseline age was 69.8 years; 89.5% of the participants were White, 5.7% were Black, 2.7% were Asian, 2.5% were Hispanic/Latino, and the remaining 1.0% were multiracial, American Indian/Alaskan Native, Native Hawaiian/Other Pacific Islander, or unknown.
The primary outcomes were the associations of short-term (3-year) and long-term (10-year) weight changes with survival to ages 90, 95, and 100 years.
A total of 30,647 women survived to at least 90 years (56.3%).
Overall, women with a short-term weight loss of 5% or more of body weight were 33% less likely to survive to age 90 years, 35% less likely to survive to age 95 years, and 38% less likely to survive to age 100 years than were those whose weight remained stable (odds ratios, 0.67, 0.65, and 0.62, respectively).
The associations were stronger in cases of unintentional short-term weight loss. Intentional weight loss from baseline to year 3 was associated with 17% lower odds of survival to age 90 compared to stable weight (OR, 0.83), but unintentional weight loss was associated with 51% lower odds of survival to age 90 (OR, 0.49).
Similarly, women with 10-year weight loss of at least 5% were 40% less likely to survive to 90 years and 49% less likely to survive to 95 years (OR, 0.60 and OR, 0.51, respectively). The sample size was too small to assess the relation of 10-year weight loss with survival to 100 years, and intentionality was not assessed for 10-year weight changes.
By contrast, weight gain of at least 5% had no significant effect on survival to ages 90, 95, or 100 years, but stable weight over time increased the odds of living to ages 90 to 100 years by 1.2-fold to 2-fold compared to either intentional or unintentional weight loss of at least 5%.
The trends in results were similar across body weight categories (normal weight, overweight, and obese as defined by body mass index). Baseline age and smoking status had no significant effect on the results.
Some of the proportion of self-reported intentional weight loss in the study population may have been unintentional, the researchers wrote in their discussion.
“It is important to note that perceived intentionality of weight loss may be influenced by the many societal pressures to lose weight, especially among women, and therefore overestimate the behavioral changes underlying experienced weight loss in older adults,” they said.
The findings were limited by several factors including the potential for inaccurate self-reported weight loss intention, and the likelihood that the mean older age of the population at baseline (older than 60 years) meant that they were more likely to live longer regardless of weight changes, the researchers noted. Other limitations included the primarily White study population, and other residual confounding factors such as ill health that might drive weight loss, the researchers noted.
However, the results were strengthened by the large sample size and long follow-up period, and suggest that “blanket recommendations for weight loss in older women are unlikely to lead to better survival at advanced ages,” they concluded.
Data support weight monitoring
The investigators acknowledged that their data do not affect clinical recommendations for moderate weight loss in older women to improve health outcomes, especially in those with overweight or obesity, but instead “support close monitoring of the amount and speed of weight loss, particularly when unintentional, as an indicator of underlying poor health and predictor of decreased lifespan in older women.”
Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, agreed with this conclusion. The current study suggests that when older women lose a significant amount of weight unintentionally, it could be a sign of failing health, he said.
Weight gain or loss in old age is very different from weight issues in younger people, where clinicians may be encouraging weight loss to improve health outcomes, Dr. Skolnik said in an interview.
A key take-home message for clinicians, in addition to monitoring weight in older patients, is to emphasize nutrition for individuals in their 80s, 90s, and beyond, he said.
The study was supported by the National Heart, Lung, and Blood Institute. Dr. Shadyab had no financial conflicts to disclose. Dr. Skolnik had no financial conflicts to disclose and serves on the editorial advisory board of Family Practice News.
Weight loss of at least 5% over a 3-year period was associated with significantly increased mortality in women at age 90, 95, and 100 years compared with those whose weight remained stable, based on data from more than 50,000 individuals.
Previous studies of later-life weight changes and mortality have yielded inconsistent results driven by considerations of weight loss intentionality, and data on older adults in particular are limited, wrote Aladdin H. Shadyab, PhD, of the University of California, San Diego, and colleagues.
In a study published in the Journals of Gerontology: Medical Sciences, the researchers reviewed data from the Women’s Health Initiative, a prospective study of factors affecting chronic disease development in postmenopausal women. The study population included 54,437 women who entered the WHI between 1993 and 1998 at ages 50-79 years. The mean baseline age was 69.8 years; 89.5% of the participants were White, 5.7% were Black, 2.7% were Asian, 2.5% were Hispanic/Latino, and the remaining 1.0% were multiracial, American Indian/Alaskan Native, Native Hawaiian/Other Pacific Islander, or unknown.
The primary outcomes were the associations of short-term (3-year) and long-term (10-year) weight changes with survival to ages 90, 95, and 100 years.
A total of 30,647 women survived to at least 90 years (56.3%).
Overall, women with a short-term weight loss of 5% or more of body weight were 33% less likely to survive to age 90 years, 35% less likely to survive to age 95 years, and 38% less likely to survive to age 100 years than were those whose weight remained stable (odds ratios, 0.67, 0.65, and 0.62, respectively).
The associations were stronger in cases of unintentional short-term weight loss. Intentional weight loss from baseline to year 3 was associated with 17% lower odds of survival to age 90 compared to stable weight (OR, 0.83), but unintentional weight loss was associated with 51% lower odds of survival to age 90 (OR, 0.49).
Similarly, women with 10-year weight loss of at least 5% were 40% less likely to survive to 90 years and 49% less likely to survive to 95 years (OR, 0.60 and OR, 0.51, respectively). The sample size was too small to assess the relation of 10-year weight loss with survival to 100 years, and intentionality was not assessed for 10-year weight changes.
By contrast, weight gain of at least 5% had no significant effect on survival to ages 90, 95, or 100 years, but stable weight over time increased the odds of living to ages 90 to 100 years by 1.2-fold to 2-fold compared to either intentional or unintentional weight loss of at least 5%.
The trends in results were similar across body weight categories (normal weight, overweight, and obese as defined by body mass index). Baseline age and smoking status had no significant effect on the results.
Some of the proportion of self-reported intentional weight loss in the study population may have been unintentional, the researchers wrote in their discussion.
“It is important to note that perceived intentionality of weight loss may be influenced by the many societal pressures to lose weight, especially among women, and therefore overestimate the behavioral changes underlying experienced weight loss in older adults,” they said.
The findings were limited by several factors including the potential for inaccurate self-reported weight loss intention, and the likelihood that the mean older age of the population at baseline (older than 60 years) meant that they were more likely to live longer regardless of weight changes, the researchers noted. Other limitations included the primarily White study population, and other residual confounding factors such as ill health that might drive weight loss, the researchers noted.
However, the results were strengthened by the large sample size and long follow-up period, and suggest that “blanket recommendations for weight loss in older women are unlikely to lead to better survival at advanced ages,” they concluded.
Data support weight monitoring
The investigators acknowledged that their data do not affect clinical recommendations for moderate weight loss in older women to improve health outcomes, especially in those with overweight or obesity, but instead “support close monitoring of the amount and speed of weight loss, particularly when unintentional, as an indicator of underlying poor health and predictor of decreased lifespan in older women.”
Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, agreed with this conclusion. The current study suggests that when older women lose a significant amount of weight unintentionally, it could be a sign of failing health, he said.
Weight gain or loss in old age is very different from weight issues in younger people, where clinicians may be encouraging weight loss to improve health outcomes, Dr. Skolnik said in an interview.
A key take-home message for clinicians, in addition to monitoring weight in older patients, is to emphasize nutrition for individuals in their 80s, 90s, and beyond, he said.
The study was supported by the National Heart, Lung, and Blood Institute. Dr. Shadyab had no financial conflicts to disclose. Dr. Skolnik had no financial conflicts to disclose and serves on the editorial advisory board of Family Practice News.
Weight loss of at least 5% over a 3-year period was associated with significantly increased mortality in women at age 90, 95, and 100 years compared with those whose weight remained stable, based on data from more than 50,000 individuals.
Previous studies of later-life weight changes and mortality have yielded inconsistent results driven by considerations of weight loss intentionality, and data on older adults in particular are limited, wrote Aladdin H. Shadyab, PhD, of the University of California, San Diego, and colleagues.
In a study published in the Journals of Gerontology: Medical Sciences, the researchers reviewed data from the Women’s Health Initiative, a prospective study of factors affecting chronic disease development in postmenopausal women. The study population included 54,437 women who entered the WHI between 1993 and 1998 at ages 50-79 years. The mean baseline age was 69.8 years; 89.5% of the participants were White, 5.7% were Black, 2.7% were Asian, 2.5% were Hispanic/Latino, and the remaining 1.0% were multiracial, American Indian/Alaskan Native, Native Hawaiian/Other Pacific Islander, or unknown.
The primary outcomes were the associations of short-term (3-year) and long-term (10-year) weight changes with survival to ages 90, 95, and 100 years.
A total of 30,647 women survived to at least 90 years (56.3%).
Overall, women with a short-term weight loss of 5% or more of body weight were 33% less likely to survive to age 90 years, 35% less likely to survive to age 95 years, and 38% less likely to survive to age 100 years than were those whose weight remained stable (odds ratios, 0.67, 0.65, and 0.62, respectively).
The associations were stronger in cases of unintentional short-term weight loss. Intentional weight loss from baseline to year 3 was associated with 17% lower odds of survival to age 90 compared to stable weight (OR, 0.83), but unintentional weight loss was associated with 51% lower odds of survival to age 90 (OR, 0.49).
Similarly, women with 10-year weight loss of at least 5% were 40% less likely to survive to 90 years and 49% less likely to survive to 95 years (OR, 0.60 and OR, 0.51, respectively). The sample size was too small to assess the relation of 10-year weight loss with survival to 100 years, and intentionality was not assessed for 10-year weight changes.
By contrast, weight gain of at least 5% had no significant effect on survival to ages 90, 95, or 100 years, but stable weight over time increased the odds of living to ages 90 to 100 years by 1.2-fold to 2-fold compared to either intentional or unintentional weight loss of at least 5%.
The trends in results were similar across body weight categories (normal weight, overweight, and obese as defined by body mass index). Baseline age and smoking status had no significant effect on the results.
Some of the proportion of self-reported intentional weight loss in the study population may have been unintentional, the researchers wrote in their discussion.
“It is important to note that perceived intentionality of weight loss may be influenced by the many societal pressures to lose weight, especially among women, and therefore overestimate the behavioral changes underlying experienced weight loss in older adults,” they said.
The findings were limited by several factors including the potential for inaccurate self-reported weight loss intention, and the likelihood that the mean older age of the population at baseline (older than 60 years) meant that they were more likely to live longer regardless of weight changes, the researchers noted. Other limitations included the primarily White study population, and other residual confounding factors such as ill health that might drive weight loss, the researchers noted.
However, the results were strengthened by the large sample size and long follow-up period, and suggest that “blanket recommendations for weight loss in older women are unlikely to lead to better survival at advanced ages,” they concluded.
Data support weight monitoring
The investigators acknowledged that their data do not affect clinical recommendations for moderate weight loss in older women to improve health outcomes, especially in those with overweight or obesity, but instead “support close monitoring of the amount and speed of weight loss, particularly when unintentional, as an indicator of underlying poor health and predictor of decreased lifespan in older women.”
Neil Skolnik, MD, professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, agreed with this conclusion. The current study suggests that when older women lose a significant amount of weight unintentionally, it could be a sign of failing health, he said.
Weight gain or loss in old age is very different from weight issues in younger people, where clinicians may be encouraging weight loss to improve health outcomes, Dr. Skolnik said in an interview.
A key take-home message for clinicians, in addition to monitoring weight in older patients, is to emphasize nutrition for individuals in their 80s, 90s, and beyond, he said.
The study was supported by the National Heart, Lung, and Blood Institute. Dr. Shadyab had no financial conflicts to disclose. Dr. Skolnik had no financial conflicts to disclose and serves on the editorial advisory board of Family Practice News.
FROM THE JOURNALS OF GERONTOLOGY: MEDICAL SCIENCES
Can caffeine improve thyroid function?
“Although the causal relationship between caffeine intake and thyroid function requires further verification, as an easily obtainable and widely consumed dietary ingredient, caffeine is a potential candidate for improving thyroid health in people with metabolic disorders,” reported the authors in the study, published in Nutritional Journal.
Caffeine intake, within established healthy ranges, showed a nonlinear association with thyroid levels.
Moderate caffeine intake has been associated with reducing the risk of metabolic disorders in addition to showing some mental health benefits. However, research on its effects on thyroid hormone, which importantly plays a key role in systemic metabolism and neurologic development, is lacking.
To investigate the effects, Yu Zhou, of the Department of Rehabilitation Medicine, School of Health, Fujian Medical University, Fuzhou, China, and colleagues evaluated data from the National Health and Nutrition Examination Survey (NHANES) III 2007-2012 study involving 2,582 participants for whom data were available regarding medical conditions, dietary intake, thyroid function, and demographic background.
The participants were divided into three subgroups based on sex, age, body mass index, hyperglycemia, hypertension, and cardio-cerebral vascular disease (CVD).
Group 1 (n = 208) was the most metabolically unhealthy. Patients in that group had the highest BMI and were of oldest age. In addition, that group had higher rates of hypertension, hyperglycemia, and CVD, but, notably, it had the lowest level of caffeine consumption.
In group 2 (n = 543), all participants were current smokers, and 90.4% had a habit of drinking alcohol. That group also had the highest percentage of men.
Group 3 (n = 1,183) was the most metabolically healthy, with more women, younger age, and lowest BMI. No participants in that group had hyperglycemia, hypertension, or CVD.
Group 1, the most metabolically unhealthy, had the highest serum thyroid-stimulating hormone (TSH) levels. Of note, while participants with thyroid diseases were initially excluded from the analysis, higher TSH levels are predictive of subclinical hypothyroidism or progression to overt hypothyroidism.
Overall, there was no association between caffeine and TSH levels.
However, a subgroup analysis of the groups showed that in group 1, caffeine intake correlated with TSH nonlinearly (P = .0019), with minimal average consumption of caffeine (< 9.97 mg/d). There was an association with slightly higher TSH levels (P = .035) after adjustment for age, sex, race, drink, disease state, micronutrients, and macronutrients.
However, in higher, moderate amounts of caffeine consumption (9.97 – 264.97 mg/d), there was an inverse association, with lower TSH (P = .001).
There was no association between daily caffeine consumption of more than 264.97 mg and TSH levels.
For context, a typical 8-ounce cup of coffee generally contains 80-100 mg of caffeine, and the Food and Drug Administration indicates that 400 mg/d of caffeine is safe for healthy adults.
Group 2 consumed the highest amount of caffeine. Notably, that group had the lowest serum TSH levels of the three groups. There were no significant associations between caffeine consumption and TSH levels in group 2 or group 3.
There were no significant associations between caffeine consumption and levels of serum FT4 or FT3, also linked to thyroid dysfunction, in any of the groups.
The findings show that “caffeine consumption was correlated with serum TSH nonlinearly, and when taken in moderate amounts (9.97-264.97 mg/d), caffeine demonstrated a positive correlation with serum TSH levels in patients with metabolic disorders,” the authors concluded.
Mechanisms?
Caffeine is believed to modulate pituitary hormone secretion, which has been shown to influence the hypothalamic-pituitary-adrenal axis. The authors speculated that caffeine could potentially affect thyroid activity by affecting pituitary function.
“However, the effects of transient and chronic caffeine administration on human thyroid function need to be verified further, and the related mechanisms remain unclear,” they noted.
Commenting on the study, Maik Pietzner, PhD, of the Berlin Institute of Health, noted that an important limitation of the study is that various patient groups were excluded, including those with abnormal TSH levels.
“What makes me wonder is the high number of exclusions and the focus on very specific groups of people. This almost certainly introduces bias, e.g., what is specific to people not reporting coffee consumption,” Dr. Pietzner said.
Furthermore, “we already know that patients with poor metabolic health do also have slight variations in thyroid hormone levels and also have different dietary patterns,” he explained.
“So reverse confounding might occur in which the poor metabolic health is associated with both poor thyroid hormone levels and coffee consumption,” Dr. Pietzner said.
He also noted the “somewhat odd” finding that the group with the highest metabolic disorders had the lowest coffee consumption, yet the highest TSH levels.
“My guess would be that this might also be a chance finding, given that the distribution of TSH values is very skewed, which can have a strong effect in linear regression models,” Dr. Pietzner said.
In general, “the evidence generated by the study is rather weak, but there is good evidence that higher coffee consumption is linked to better metabolic health, although the exact mechanisms is not known, if indeed causal,” Dr. Pietzner added. “Prospective studies are needed to evaluate whether higher coffee consumption indeed lowers the risk for thyroid disease.”
A version of this article first appeared on Medscape.com.
“Although the causal relationship between caffeine intake and thyroid function requires further verification, as an easily obtainable and widely consumed dietary ingredient, caffeine is a potential candidate for improving thyroid health in people with metabolic disorders,” reported the authors in the study, published in Nutritional Journal.
Caffeine intake, within established healthy ranges, showed a nonlinear association with thyroid levels.
Moderate caffeine intake has been associated with reducing the risk of metabolic disorders in addition to showing some mental health benefits. However, research on its effects on thyroid hormone, which importantly plays a key role in systemic metabolism and neurologic development, is lacking.
To investigate the effects, Yu Zhou, of the Department of Rehabilitation Medicine, School of Health, Fujian Medical University, Fuzhou, China, and colleagues evaluated data from the National Health and Nutrition Examination Survey (NHANES) III 2007-2012 study involving 2,582 participants for whom data were available regarding medical conditions, dietary intake, thyroid function, and demographic background.
The participants were divided into three subgroups based on sex, age, body mass index, hyperglycemia, hypertension, and cardio-cerebral vascular disease (CVD).
Group 1 (n = 208) was the most metabolically unhealthy. Patients in that group had the highest BMI and were of oldest age. In addition, that group had higher rates of hypertension, hyperglycemia, and CVD, but, notably, it had the lowest level of caffeine consumption.
In group 2 (n = 543), all participants were current smokers, and 90.4% had a habit of drinking alcohol. That group also had the highest percentage of men.
Group 3 (n = 1,183) was the most metabolically healthy, with more women, younger age, and lowest BMI. No participants in that group had hyperglycemia, hypertension, or CVD.
Group 1, the most metabolically unhealthy, had the highest serum thyroid-stimulating hormone (TSH) levels. Of note, while participants with thyroid diseases were initially excluded from the analysis, higher TSH levels are predictive of subclinical hypothyroidism or progression to overt hypothyroidism.
Overall, there was no association between caffeine and TSH levels.
However, a subgroup analysis of the groups showed that in group 1, caffeine intake correlated with TSH nonlinearly (P = .0019), with minimal average consumption of caffeine (< 9.97 mg/d). There was an association with slightly higher TSH levels (P = .035) after adjustment for age, sex, race, drink, disease state, micronutrients, and macronutrients.
However, in higher, moderate amounts of caffeine consumption (9.97 – 264.97 mg/d), there was an inverse association, with lower TSH (P = .001).
There was no association between daily caffeine consumption of more than 264.97 mg and TSH levels.
For context, a typical 8-ounce cup of coffee generally contains 80-100 mg of caffeine, and the Food and Drug Administration indicates that 400 mg/d of caffeine is safe for healthy adults.
Group 2 consumed the highest amount of caffeine. Notably, that group had the lowest serum TSH levels of the three groups. There were no significant associations between caffeine consumption and TSH levels in group 2 or group 3.
There were no significant associations between caffeine consumption and levels of serum FT4 or FT3, also linked to thyroid dysfunction, in any of the groups.
The findings show that “caffeine consumption was correlated with serum TSH nonlinearly, and when taken in moderate amounts (9.97-264.97 mg/d), caffeine demonstrated a positive correlation with serum TSH levels in patients with metabolic disorders,” the authors concluded.
Mechanisms?
Caffeine is believed to modulate pituitary hormone secretion, which has been shown to influence the hypothalamic-pituitary-adrenal axis. The authors speculated that caffeine could potentially affect thyroid activity by affecting pituitary function.
“However, the effects of transient and chronic caffeine administration on human thyroid function need to be verified further, and the related mechanisms remain unclear,” they noted.
Commenting on the study, Maik Pietzner, PhD, of the Berlin Institute of Health, noted that an important limitation of the study is that various patient groups were excluded, including those with abnormal TSH levels.
“What makes me wonder is the high number of exclusions and the focus on very specific groups of people. This almost certainly introduces bias, e.g., what is specific to people not reporting coffee consumption,” Dr. Pietzner said.
Furthermore, “we already know that patients with poor metabolic health do also have slight variations in thyroid hormone levels and also have different dietary patterns,” he explained.
“So reverse confounding might occur in which the poor metabolic health is associated with both poor thyroid hormone levels and coffee consumption,” Dr. Pietzner said.
He also noted the “somewhat odd” finding that the group with the highest metabolic disorders had the lowest coffee consumption, yet the highest TSH levels.
“My guess would be that this might also be a chance finding, given that the distribution of TSH values is very skewed, which can have a strong effect in linear regression models,” Dr. Pietzner said.
In general, “the evidence generated by the study is rather weak, but there is good evidence that higher coffee consumption is linked to better metabolic health, although the exact mechanisms is not known, if indeed causal,” Dr. Pietzner added. “Prospective studies are needed to evaluate whether higher coffee consumption indeed lowers the risk for thyroid disease.”
A version of this article first appeared on Medscape.com.
“Although the causal relationship between caffeine intake and thyroid function requires further verification, as an easily obtainable and widely consumed dietary ingredient, caffeine is a potential candidate for improving thyroid health in people with metabolic disorders,” reported the authors in the study, published in Nutritional Journal.
Caffeine intake, within established healthy ranges, showed a nonlinear association with thyroid levels.
Moderate caffeine intake has been associated with reducing the risk of metabolic disorders in addition to showing some mental health benefits. However, research on its effects on thyroid hormone, which importantly plays a key role in systemic metabolism and neurologic development, is lacking.
To investigate the effects, Yu Zhou, of the Department of Rehabilitation Medicine, School of Health, Fujian Medical University, Fuzhou, China, and colleagues evaluated data from the National Health and Nutrition Examination Survey (NHANES) III 2007-2012 study involving 2,582 participants for whom data were available regarding medical conditions, dietary intake, thyroid function, and demographic background.
The participants were divided into three subgroups based on sex, age, body mass index, hyperglycemia, hypertension, and cardio-cerebral vascular disease (CVD).
Group 1 (n = 208) was the most metabolically unhealthy. Patients in that group had the highest BMI and were of oldest age. In addition, that group had higher rates of hypertension, hyperglycemia, and CVD, but, notably, it had the lowest level of caffeine consumption.
In group 2 (n = 543), all participants were current smokers, and 90.4% had a habit of drinking alcohol. That group also had the highest percentage of men.
Group 3 (n = 1,183) was the most metabolically healthy, with more women, younger age, and lowest BMI. No participants in that group had hyperglycemia, hypertension, or CVD.
Group 1, the most metabolically unhealthy, had the highest serum thyroid-stimulating hormone (TSH) levels. Of note, while participants with thyroid diseases were initially excluded from the analysis, higher TSH levels are predictive of subclinical hypothyroidism or progression to overt hypothyroidism.
Overall, there was no association between caffeine and TSH levels.
However, a subgroup analysis of the groups showed that in group 1, caffeine intake correlated with TSH nonlinearly (P = .0019), with minimal average consumption of caffeine (< 9.97 mg/d). There was an association with slightly higher TSH levels (P = .035) after adjustment for age, sex, race, drink, disease state, micronutrients, and macronutrients.
However, in higher, moderate amounts of caffeine consumption (9.97 – 264.97 mg/d), there was an inverse association, with lower TSH (P = .001).
There was no association between daily caffeine consumption of more than 264.97 mg and TSH levels.
For context, a typical 8-ounce cup of coffee generally contains 80-100 mg of caffeine, and the Food and Drug Administration indicates that 400 mg/d of caffeine is safe for healthy adults.
Group 2 consumed the highest amount of caffeine. Notably, that group had the lowest serum TSH levels of the three groups. There were no significant associations between caffeine consumption and TSH levels in group 2 or group 3.
There were no significant associations between caffeine consumption and levels of serum FT4 or FT3, also linked to thyroid dysfunction, in any of the groups.
The findings show that “caffeine consumption was correlated with serum TSH nonlinearly, and when taken in moderate amounts (9.97-264.97 mg/d), caffeine demonstrated a positive correlation with serum TSH levels in patients with metabolic disorders,” the authors concluded.
Mechanisms?
Caffeine is believed to modulate pituitary hormone secretion, which has been shown to influence the hypothalamic-pituitary-adrenal axis. The authors speculated that caffeine could potentially affect thyroid activity by affecting pituitary function.
“However, the effects of transient and chronic caffeine administration on human thyroid function need to be verified further, and the related mechanisms remain unclear,” they noted.
Commenting on the study, Maik Pietzner, PhD, of the Berlin Institute of Health, noted that an important limitation of the study is that various patient groups were excluded, including those with abnormal TSH levels.
“What makes me wonder is the high number of exclusions and the focus on very specific groups of people. This almost certainly introduces bias, e.g., what is specific to people not reporting coffee consumption,” Dr. Pietzner said.
Furthermore, “we already know that patients with poor metabolic health do also have slight variations in thyroid hormone levels and also have different dietary patterns,” he explained.
“So reverse confounding might occur in which the poor metabolic health is associated with both poor thyroid hormone levels and coffee consumption,” Dr. Pietzner said.
He also noted the “somewhat odd” finding that the group with the highest metabolic disorders had the lowest coffee consumption, yet the highest TSH levels.
“My guess would be that this might also be a chance finding, given that the distribution of TSH values is very skewed, which can have a strong effect in linear regression models,” Dr. Pietzner said.
In general, “the evidence generated by the study is rather weak, but there is good evidence that higher coffee consumption is linked to better metabolic health, although the exact mechanisms is not known, if indeed causal,” Dr. Pietzner added. “Prospective studies are needed to evaluate whether higher coffee consumption indeed lowers the risk for thyroid disease.”
A version of this article first appeared on Medscape.com.
FROM NUTRITIONAL JOURNAL
T3 in hypothyroidism gets extra recommendation: British medical groups
New recommendations from the Joint British Thyroid Association/Society add to the increasingly general consensus that liothyronine (LT3) may be useful in combination with standard levothyroxine (LT4) in the treatment of hypothyroidism in some patients whose symptoms persist after standard treatment, despite a lack of evidence of benefit in clinical trials.
“Most patients with primary hypothyroidism respond well to levothyroxine replacement therapy,” recommends the joint association in the consensus statement, by Rupa Ahluwalia, MBBS, MD, of Norfolk and Norwich University Hospitals NHS Trust, United Kingdom, and colleagues, recently published in Clinical Endocrinology.
they wrote.
The ongoing debate over the use of LT3/LT4 combination therapy has persisted for more than 2 decades, with at least 16 randomized controlled trials and four meta-analyses failing to show any significant benefit of the combined regimen in key quality of life and cognitive function outcomes compared with LT4 monotherapy. However, many patients continue to report benefits with combination therapy, so the issue has not been laid to rest.
Wilmar M. Wiersinga, MD, PhD, emeritus professor of endocrinology at the University of Amsterdam, said in an interview: “The scientific community is divided as to whether or not the LT4/LT3 combination therapy has any value whatsoever, whereas the pressure from individual patients and patient associations on physicians – both general practitioners and specialists/endocrinologists – can be very high [in terms of] demanding prescriptions for the combination therapy.
“I welcome this joint statement very much because it provides guidance, especially for clinicians, on a hotly debated issue,” he said.
Persistent symptoms drive pursuit of alternatives
T4 refers to the hormone thyroxine made in the body, and LT4 to the pharmaceutical replacement product for that hormone, levothyroxine. Similarly, T3 refers to the hormone triiodothyronine, made in the body and a precursor to thyroxine, and LT3 refers to its pharmaceutical replacement, liothyronine.
Driving the continued demand from some patients with hypothyroidism and interest among clinicians is the relatively high proportion of patients who continue to experience symptoms even after the normalization of biochemical levels after treatment with LT4, which resolves symptoms in most patients within weeks of therapy.
Those who don’t improve report common ongoing symptoms: fatigue, sleepiness, memory problems, cognitive difficulties (brain fog), and weight gain.
However, with 60% of people commonly having one or more of the same symptoms even when their thyroid levels are normal, pinpointing the actual causes is a challenge, the societies report.
In the absence of other diagnoses, clinicians often turn to alternative treatment strategies, which, as well as addition of LT3 to LT4, also include the use of desiccated thyroid extract (DTE).
DTE was the medication first used to treat hypothyroidism years ago, originally made from pig glands. There are now several prescription medications made from the desiccated (dried) thyroid glands of animals, including brands such as Armour Thyroid, NP Thyroid, and WP Thyroid.
The practice of prescribing combination therapy has already been deemed acceptable by both the European Thyroid Association (ETA) and American Thyroid Association (ATA). The latter recommended in its 2014 guidelines that the combination of LT3/LT4 therapy may be trialed in exceptional circumstances or among patients who fail to improve with LT4 alone.
In following suit, the new Joint British Thyroid Association/Society consensus statement cautions that, first and foremost, “most patients with hypothyroidism should be treated with levothyroxine alone.”
However, combination LT3/LT4 therapy may be considered an option under key important conditions, including:
- When a diagnosis of overt hypothyroidism (documented TSH ≥ 10 mU/L and/or low FT4 pretreatment with thyroid replacement hormones) is established. If overt hypothyroidism cannot be confirmed, patients are recommended to first have a trial without LT4 and a repeat serum TSH after 6 weeks.
- For patients with overt hypothyroidism, prior to consideration of LT3, the dose of LT4 should be optimized to a TSH in the target range of 0.3-2.0 mU/L for 3 to 6 months. In some patients, it may be acceptable to have serum TSH below reference range (e.g., 0.1-0.3 mU/L), but not fully suppressed in the long term, instead of starting LT3.
- A trial of combination therapy may be warranted with confirmed overt hypothyroidism and persistent symptoms despite LT4 treatment and the exclusion of other comorbidities.
- Clinicians should not feel obliged to start LT3 or continue LT3 medication provided by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest.
- When opting for LT3, a minimum of 3 to 6 months on the combination therapy should be considered before determining response to the trial, and for assessment, monitoring with serum TSH only is recommended.
- Patients should be counseled regarding the risk of arrhythmias, accelerated bone loss, and stroke associated with iatrogenic hyperthyroidism and the need for long-term monitoring.
- Given the short half-life of LT3, splitting doses across 24 hours is recommended for many people.
The joint association does not recommend the use of desiccated thyroid extract (which appears to be surprisingly on the rise, as recently reported).
Reasons for persistent symptoms are murky; don’t forget menopause
The key reason for the emphasis on making sure patients have overt hypothyroidism before trying LT3 is that patients are often treated with LT4 despite not even having hypothyroidism to begin with.
“In reality, many patients with subclinical hypothyroidism [TSH 5-10 mU/L] are now treated with levothyroxine, fueling a rise in its use, such that it is now the third most frequently prescribed medication in the United Kingdom,” the authors explained.
“In contrast, few patients are advised to seek lifestyle and exercise changes, despite the fact that there is positive evidence to support their benefits,” they continued.
In a recent podcast, Anthony Bianco, MD, a past president of the ATA, underscored another important factor complicating the ability to make conclusive hypothyroidism diagnoses in women: menopause.
“In my experience, the most confusing factor [in treatment decisions] is menopausal syndrome,” he said.
“The symptoms are very similar. Most patients with hypothyroidism are women. Are we getting close to menopause? Are we dealing with this? Is estrogen replacement therapy an option for this woman? Should we consult a colleague?” Dr. Bianco explained.
And there are other possibilities, including anemia, iron deficiency, other autoimmune diseases, and diabetes, he added.
“Exclude everything that you know,” Dr. Bianco said. “Use your common sense.”
Although the new statement echoes other guidelines, the recommendations are helpful amid the ever-present debate, said Dr. Wiersinga, the endocrinologist from the Netherlands.
Because of the pressure to try combination therapy, from patients and patient associations, the statement’s position that doctors must stand by their clinical judgment is important, he noted.
“I think many doctors would welcome the recommendation that doctors are not obliged to prescribe any medication that they believe is not in the patient’s best interest, and, in particular, that ‘doctors have no obligation to continue to provide prescriptions for LT3 or desiccated thyroid extract that have been started by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest,’” he asserted.
“Also, the recommendation that an endocrinologist should be involved when a trial of T3 is considered is very valuable,” he added, noting the potential scenario of patients going to a general practitioner if turned down by a specialist for LT3.
An international consensus statement published by members of the ATA, ETA, and British Thyroid Association in 2021 further set forth recommendations for the development of future trials of LT3/LT4 combination therapy to establish more conclusive guidance.
Senior author Simon H. Pearce has reported receiving speaker fees from IBSA, Merck, Quidel, Berlin-Chemie, and consulting for Apitope/Worg and Immunovant/Roivant on issues unrelated to T3. The other authors of the consensus statement have reported no relevant financial relationships. Dr. Wiersinga has reporting consulting for Prolevi Bio.
A version of this article first appeared on Medscape.com.
New recommendations from the Joint British Thyroid Association/Society add to the increasingly general consensus that liothyronine (LT3) may be useful in combination with standard levothyroxine (LT4) in the treatment of hypothyroidism in some patients whose symptoms persist after standard treatment, despite a lack of evidence of benefit in clinical trials.
“Most patients with primary hypothyroidism respond well to levothyroxine replacement therapy,” recommends the joint association in the consensus statement, by Rupa Ahluwalia, MBBS, MD, of Norfolk and Norwich University Hospitals NHS Trust, United Kingdom, and colleagues, recently published in Clinical Endocrinology.
they wrote.
The ongoing debate over the use of LT3/LT4 combination therapy has persisted for more than 2 decades, with at least 16 randomized controlled trials and four meta-analyses failing to show any significant benefit of the combined regimen in key quality of life and cognitive function outcomes compared with LT4 monotherapy. However, many patients continue to report benefits with combination therapy, so the issue has not been laid to rest.
Wilmar M. Wiersinga, MD, PhD, emeritus professor of endocrinology at the University of Amsterdam, said in an interview: “The scientific community is divided as to whether or not the LT4/LT3 combination therapy has any value whatsoever, whereas the pressure from individual patients and patient associations on physicians – both general practitioners and specialists/endocrinologists – can be very high [in terms of] demanding prescriptions for the combination therapy.
“I welcome this joint statement very much because it provides guidance, especially for clinicians, on a hotly debated issue,” he said.
Persistent symptoms drive pursuit of alternatives
T4 refers to the hormone thyroxine made in the body, and LT4 to the pharmaceutical replacement product for that hormone, levothyroxine. Similarly, T3 refers to the hormone triiodothyronine, made in the body and a precursor to thyroxine, and LT3 refers to its pharmaceutical replacement, liothyronine.
Driving the continued demand from some patients with hypothyroidism and interest among clinicians is the relatively high proportion of patients who continue to experience symptoms even after the normalization of biochemical levels after treatment with LT4, which resolves symptoms in most patients within weeks of therapy.
Those who don’t improve report common ongoing symptoms: fatigue, sleepiness, memory problems, cognitive difficulties (brain fog), and weight gain.
However, with 60% of people commonly having one or more of the same symptoms even when their thyroid levels are normal, pinpointing the actual causes is a challenge, the societies report.
In the absence of other diagnoses, clinicians often turn to alternative treatment strategies, which, as well as addition of LT3 to LT4, also include the use of desiccated thyroid extract (DTE).
DTE was the medication first used to treat hypothyroidism years ago, originally made from pig glands. There are now several prescription medications made from the desiccated (dried) thyroid glands of animals, including brands such as Armour Thyroid, NP Thyroid, and WP Thyroid.
The practice of prescribing combination therapy has already been deemed acceptable by both the European Thyroid Association (ETA) and American Thyroid Association (ATA). The latter recommended in its 2014 guidelines that the combination of LT3/LT4 therapy may be trialed in exceptional circumstances or among patients who fail to improve with LT4 alone.
In following suit, the new Joint British Thyroid Association/Society consensus statement cautions that, first and foremost, “most patients with hypothyroidism should be treated with levothyroxine alone.”
However, combination LT3/LT4 therapy may be considered an option under key important conditions, including:
- When a diagnosis of overt hypothyroidism (documented TSH ≥ 10 mU/L and/or low FT4 pretreatment with thyroid replacement hormones) is established. If overt hypothyroidism cannot be confirmed, patients are recommended to first have a trial without LT4 and a repeat serum TSH after 6 weeks.
- For patients with overt hypothyroidism, prior to consideration of LT3, the dose of LT4 should be optimized to a TSH in the target range of 0.3-2.0 mU/L for 3 to 6 months. In some patients, it may be acceptable to have serum TSH below reference range (e.g., 0.1-0.3 mU/L), but not fully suppressed in the long term, instead of starting LT3.
- A trial of combination therapy may be warranted with confirmed overt hypothyroidism and persistent symptoms despite LT4 treatment and the exclusion of other comorbidities.
- Clinicians should not feel obliged to start LT3 or continue LT3 medication provided by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest.
- When opting for LT3, a minimum of 3 to 6 months on the combination therapy should be considered before determining response to the trial, and for assessment, monitoring with serum TSH only is recommended.
- Patients should be counseled regarding the risk of arrhythmias, accelerated bone loss, and stroke associated with iatrogenic hyperthyroidism and the need for long-term monitoring.
- Given the short half-life of LT3, splitting doses across 24 hours is recommended for many people.
The joint association does not recommend the use of desiccated thyroid extract (which appears to be surprisingly on the rise, as recently reported).
Reasons for persistent symptoms are murky; don’t forget menopause
The key reason for the emphasis on making sure patients have overt hypothyroidism before trying LT3 is that patients are often treated with LT4 despite not even having hypothyroidism to begin with.
“In reality, many patients with subclinical hypothyroidism [TSH 5-10 mU/L] are now treated with levothyroxine, fueling a rise in its use, such that it is now the third most frequently prescribed medication in the United Kingdom,” the authors explained.
“In contrast, few patients are advised to seek lifestyle and exercise changes, despite the fact that there is positive evidence to support their benefits,” they continued.
In a recent podcast, Anthony Bianco, MD, a past president of the ATA, underscored another important factor complicating the ability to make conclusive hypothyroidism diagnoses in women: menopause.
“In my experience, the most confusing factor [in treatment decisions] is menopausal syndrome,” he said.
“The symptoms are very similar. Most patients with hypothyroidism are women. Are we getting close to menopause? Are we dealing with this? Is estrogen replacement therapy an option for this woman? Should we consult a colleague?” Dr. Bianco explained.
And there are other possibilities, including anemia, iron deficiency, other autoimmune diseases, and diabetes, he added.
“Exclude everything that you know,” Dr. Bianco said. “Use your common sense.”
Although the new statement echoes other guidelines, the recommendations are helpful amid the ever-present debate, said Dr. Wiersinga, the endocrinologist from the Netherlands.
Because of the pressure to try combination therapy, from patients and patient associations, the statement’s position that doctors must stand by their clinical judgment is important, he noted.
“I think many doctors would welcome the recommendation that doctors are not obliged to prescribe any medication that they believe is not in the patient’s best interest, and, in particular, that ‘doctors have no obligation to continue to provide prescriptions for LT3 or desiccated thyroid extract that have been started by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest,’” he asserted.
“Also, the recommendation that an endocrinologist should be involved when a trial of T3 is considered is very valuable,” he added, noting the potential scenario of patients going to a general practitioner if turned down by a specialist for LT3.
An international consensus statement published by members of the ATA, ETA, and British Thyroid Association in 2021 further set forth recommendations for the development of future trials of LT3/LT4 combination therapy to establish more conclusive guidance.
Senior author Simon H. Pearce has reported receiving speaker fees from IBSA, Merck, Quidel, Berlin-Chemie, and consulting for Apitope/Worg and Immunovant/Roivant on issues unrelated to T3. The other authors of the consensus statement have reported no relevant financial relationships. Dr. Wiersinga has reporting consulting for Prolevi Bio.
A version of this article first appeared on Medscape.com.
New recommendations from the Joint British Thyroid Association/Society add to the increasingly general consensus that liothyronine (LT3) may be useful in combination with standard levothyroxine (LT4) in the treatment of hypothyroidism in some patients whose symptoms persist after standard treatment, despite a lack of evidence of benefit in clinical trials.
“Most patients with primary hypothyroidism respond well to levothyroxine replacement therapy,” recommends the joint association in the consensus statement, by Rupa Ahluwalia, MBBS, MD, of Norfolk and Norwich University Hospitals NHS Trust, United Kingdom, and colleagues, recently published in Clinical Endocrinology.
they wrote.
The ongoing debate over the use of LT3/LT4 combination therapy has persisted for more than 2 decades, with at least 16 randomized controlled trials and four meta-analyses failing to show any significant benefit of the combined regimen in key quality of life and cognitive function outcomes compared with LT4 monotherapy. However, many patients continue to report benefits with combination therapy, so the issue has not been laid to rest.
Wilmar M. Wiersinga, MD, PhD, emeritus professor of endocrinology at the University of Amsterdam, said in an interview: “The scientific community is divided as to whether or not the LT4/LT3 combination therapy has any value whatsoever, whereas the pressure from individual patients and patient associations on physicians – both general practitioners and specialists/endocrinologists – can be very high [in terms of] demanding prescriptions for the combination therapy.
“I welcome this joint statement very much because it provides guidance, especially for clinicians, on a hotly debated issue,” he said.
Persistent symptoms drive pursuit of alternatives
T4 refers to the hormone thyroxine made in the body, and LT4 to the pharmaceutical replacement product for that hormone, levothyroxine. Similarly, T3 refers to the hormone triiodothyronine, made in the body and a precursor to thyroxine, and LT3 refers to its pharmaceutical replacement, liothyronine.
Driving the continued demand from some patients with hypothyroidism and interest among clinicians is the relatively high proportion of patients who continue to experience symptoms even after the normalization of biochemical levels after treatment with LT4, which resolves symptoms in most patients within weeks of therapy.
Those who don’t improve report common ongoing symptoms: fatigue, sleepiness, memory problems, cognitive difficulties (brain fog), and weight gain.
However, with 60% of people commonly having one or more of the same symptoms even when their thyroid levels are normal, pinpointing the actual causes is a challenge, the societies report.
In the absence of other diagnoses, clinicians often turn to alternative treatment strategies, which, as well as addition of LT3 to LT4, also include the use of desiccated thyroid extract (DTE).
DTE was the medication first used to treat hypothyroidism years ago, originally made from pig glands. There are now several prescription medications made from the desiccated (dried) thyroid glands of animals, including brands such as Armour Thyroid, NP Thyroid, and WP Thyroid.
The practice of prescribing combination therapy has already been deemed acceptable by both the European Thyroid Association (ETA) and American Thyroid Association (ATA). The latter recommended in its 2014 guidelines that the combination of LT3/LT4 therapy may be trialed in exceptional circumstances or among patients who fail to improve with LT4 alone.
In following suit, the new Joint British Thyroid Association/Society consensus statement cautions that, first and foremost, “most patients with hypothyroidism should be treated with levothyroxine alone.”
However, combination LT3/LT4 therapy may be considered an option under key important conditions, including:
- When a diagnosis of overt hypothyroidism (documented TSH ≥ 10 mU/L and/or low FT4 pretreatment with thyroid replacement hormones) is established. If overt hypothyroidism cannot be confirmed, patients are recommended to first have a trial without LT4 and a repeat serum TSH after 6 weeks.
- For patients with overt hypothyroidism, prior to consideration of LT3, the dose of LT4 should be optimized to a TSH in the target range of 0.3-2.0 mU/L for 3 to 6 months. In some patients, it may be acceptable to have serum TSH below reference range (e.g., 0.1-0.3 mU/L), but not fully suppressed in the long term, instead of starting LT3.
- A trial of combination therapy may be warranted with confirmed overt hypothyroidism and persistent symptoms despite LT4 treatment and the exclusion of other comorbidities.
- Clinicians should not feel obliged to start LT3 or continue LT3 medication provided by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest.
- When opting for LT3, a minimum of 3 to 6 months on the combination therapy should be considered before determining response to the trial, and for assessment, monitoring with serum TSH only is recommended.
- Patients should be counseled regarding the risk of arrhythmias, accelerated bone loss, and stroke associated with iatrogenic hyperthyroidism and the need for long-term monitoring.
- Given the short half-life of LT3, splitting doses across 24 hours is recommended for many people.
The joint association does not recommend the use of desiccated thyroid extract (which appears to be surprisingly on the rise, as recently reported).
Reasons for persistent symptoms are murky; don’t forget menopause
The key reason for the emphasis on making sure patients have overt hypothyroidism before trying LT3 is that patients are often treated with LT4 despite not even having hypothyroidism to begin with.
“In reality, many patients with subclinical hypothyroidism [TSH 5-10 mU/L] are now treated with levothyroxine, fueling a rise in its use, such that it is now the third most frequently prescribed medication in the United Kingdom,” the authors explained.
“In contrast, few patients are advised to seek lifestyle and exercise changes, despite the fact that there is positive evidence to support their benefits,” they continued.
In a recent podcast, Anthony Bianco, MD, a past president of the ATA, underscored another important factor complicating the ability to make conclusive hypothyroidism diagnoses in women: menopause.
“In my experience, the most confusing factor [in treatment decisions] is menopausal syndrome,” he said.
“The symptoms are very similar. Most patients with hypothyroidism are women. Are we getting close to menopause? Are we dealing with this? Is estrogen replacement therapy an option for this woman? Should we consult a colleague?” Dr. Bianco explained.
And there are other possibilities, including anemia, iron deficiency, other autoimmune diseases, and diabetes, he added.
“Exclude everything that you know,” Dr. Bianco said. “Use your common sense.”
Although the new statement echoes other guidelines, the recommendations are helpful amid the ever-present debate, said Dr. Wiersinga, the endocrinologist from the Netherlands.
Because of the pressure to try combination therapy, from patients and patient associations, the statement’s position that doctors must stand by their clinical judgment is important, he noted.
“I think many doctors would welcome the recommendation that doctors are not obliged to prescribe any medication that they believe is not in the patient’s best interest, and, in particular, that ‘doctors have no obligation to continue to provide prescriptions for LT3 or desiccated thyroid extract that have been started by other health care practitioners or accessed without medical advice if they judge this not to be in the patient’s best interest,’” he asserted.
“Also, the recommendation that an endocrinologist should be involved when a trial of T3 is considered is very valuable,” he added, noting the potential scenario of patients going to a general practitioner if turned down by a specialist for LT3.
An international consensus statement published by members of the ATA, ETA, and British Thyroid Association in 2021 further set forth recommendations for the development of future trials of LT3/LT4 combination therapy to establish more conclusive guidance.
Senior author Simon H. Pearce has reported receiving speaker fees from IBSA, Merck, Quidel, Berlin-Chemie, and consulting for Apitope/Worg and Immunovant/Roivant on issues unrelated to T3. The other authors of the consensus statement have reported no relevant financial relationships. Dr. Wiersinga has reporting consulting for Prolevi Bio.
A version of this article first appeared on Medscape.com.
FROM CLINICAL ENDOCRINOLOGY
Surgery, radioactive iodine for hyperthyroidism up survival
CHICAGO – new data from a large cohort study suggest.
“I think this is something we need to take into our discussions with patients because treatment for hyperthyroidism is very much individualized decision-making ... The effects on mortality are not usually one of the factors we discuss there. But now, we have strong data from a very large cohort of patients indicating that this is something that does need to be discussed,” lead author Kristien Boelaert, MD, who is the current president of the British Thyroid Association, said in an interview.
Dr. Boelaert presented the findings of the EGRET (Weight Changes, Cardio-Metabolic Risks and Mortality in Patients With Hyperthyroidism) study at the Annual Meeting of the Endocrine Society.
Other notable findings from EGRET were that the patients on antithyroid medication were thinner than expected, suggesting undertreatment, and that no differences were found for major adverse cardiac events (MACE) across the treatment options, leaving unexplained the reasons for the increased mortality in the medicated group.
Asked to comment, session moderator Spyridoula Maraka, MD, said: “I think this is very important work because so far when we counsel our patients about the different treatment modalities we focus more on risk for recurrence and other short-term outcomes.”
“But these data give us a bigger perspective on mortality and cardiovascular outcomes ... We haven’t had such good quality data to accurately counsel our patients,” added Dr. Maraka, of the University of Arkansas for Medical Sciences, Little Rock.
Mortality higher for medication-treated, but why?
“Hyperthyroidism or an overactive thyroid gland is common, affecting up to 3% of the population, and is associated with long-term adverse cardiac and metabolic consequences. The optimal treatment choice remains unclear,” explained Dr. Boelaert, professor of endocrinology at the University of Birmingham, England, outlining the reasons they conducted the EGRET study.
The study population was 55,318 patients (77% women) with newly diagnosed hyperthyroidism identified from a U.K. population-based primary care electronic health record database. Of those, 77.8% were treated with antithyroid medication, 14.6% with radioactive iodine, and 7.8% with surgery (total or hemithyroidectomy). The health records were linked with national mortality data and Health Survey England data on body mass index (BMI) for comparison.
Dr. Boelaert noted that the trial design “is the best we have” because a randomized clinical trial comparing hyperthyroid treatments would be extremely difficult given the need to individualize therapy and the impossibility of blinding. On the other hand, with the current study, “it’s certainly the largest patient group we’ve looked at.”
Over an average 12.1 years of follow-up, the proportion of patients who died was 14.1% in the medication group, 18.7% of those who had radioiodine therapy, and 9.2% of those who underwent surgery.
Compared with the number who would have been expected to die based on the general background population, the likelihood of reduced life expectancy for the treated groups was increased 2.10-fold for radioiodine, 2.13-fold for surgery, and 2.71-fold for medication. All were significantly higher than the general population (P < .0001).
After further adjustment for multiple confounders, mortality risk was reduced in patients treated with radioiodine (by 13%) or surgery (by 20%), compared with those treated with antithyroid medication, both significant reductions (P < .0001).
After exclusion of the 3.9% with baseline cardiovascular disease, MACE (defined as cardiovascular death or hospitalization for stroke or myocardial infarction) occurred in 9.9%, 13.4%, and 8.0% of the medication, radioiodine, and surgery groups, respectively.
After adjustments, there were no differences in MACE, compared with medications, with hazard ratios of 1.00 (P = .94) for radioactive iodine and 0.97 for surgery (P = .61).
“We were expecting to see a reduction in cardiovascular events, as previous studies suggest that radioactive iodine patients have fewer cardiovascular deaths. We did not see that but our protocol wasn’t set up to get every single specific cause of death. That will require further ongoing analysis,” said Dr. Boelaert.
Weight gain: Worth it for longer life
Compared with the background population, thyroidectomy was associated with an increased likelihood of developing obesity (BMI > 30 kg/m2) in both men (odds ratio, 1.56; P < .001), and women (OR, 1.27; P < .001), while radioiodine increased obesity risk in women (OR, 1.12; P < .001) but not in men (OR, 1.03; P = .55).
Among the women, those treated with antithyroid medications had an average 0.28 kg/m2 lower BMI, compared with the background population, and those treated with surgery had a 0.83 kg/m2 higher BMI. Both differences were significant (P < .001).
The BMI differences were not significant for radioactive iodine in women and for medications and radioactive iodine in men, although the men treated surgically also had a significantly higher BMI (1.09 kg/m2; P < .001).
“The patients on antithyroid drugs were lighter than we would expect. I think that’s ongoing hyperthyroidism. I strongly believe that ... to get rid of hyperthyroidism you have to make patients hypothyroid ... It’s really important that you get good control,” Dr. Boelaert commented.
Dr. Maraka, who is also endocrine section chief of the Arkansas Veteran’s Healthcare System, Little Rock, commented: “[Dr. Boelaert’s] concern is that the patients on antithyroid drugs are not adequately controlled, and we know very well that uncontrolled hyperthyroidism is associated with increased mortality and increased cardiovascular outcomes. This suggests that if patients are on antithyroid medications, they should at least be monitored very well.”
Regarding the possible cause of the increased mortality, if not cardiovascular, Dr. Maraka also pointed out that typically once antithyroid medications are stopped, about half of patients will stay in remission and the other half will return to hyperthyroidism.
“It might be that this kind of ‘yo-yo’ is what’s actually leading to the increased mortality, compared to patients who had definitive treatment and this problem was taken care of. This is speculation but it might be what we’re seeing,” Dr. Maraka observed.
The BMI differences worked out to a weight gain with surgery of approximately 2.1 kg (4.6 lb) for a woman with a height of 160 cm and 2.4 kg for 170 cm. Among men, those differences were 3.2 kg and 3.5 kg for heights of 170 cm and 190 cm, respectively.
Dr. Boelaert said, “I think we should discuss this with patients. They will say they don’t want to get fat, but the absolute weight gain is ... not that much.”
“I personally think that 2 kg is not a big price to pay to live longer. I hope that’s what we’ll be telling our patients in clinic in the next few years after we get this published.”
Dr. Boelaert and Dr. Maraka have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – new data from a large cohort study suggest.
“I think this is something we need to take into our discussions with patients because treatment for hyperthyroidism is very much individualized decision-making ... The effects on mortality are not usually one of the factors we discuss there. But now, we have strong data from a very large cohort of patients indicating that this is something that does need to be discussed,” lead author Kristien Boelaert, MD, who is the current president of the British Thyroid Association, said in an interview.
Dr. Boelaert presented the findings of the EGRET (Weight Changes, Cardio-Metabolic Risks and Mortality in Patients With Hyperthyroidism) study at the Annual Meeting of the Endocrine Society.
Other notable findings from EGRET were that the patients on antithyroid medication were thinner than expected, suggesting undertreatment, and that no differences were found for major adverse cardiac events (MACE) across the treatment options, leaving unexplained the reasons for the increased mortality in the medicated group.
Asked to comment, session moderator Spyridoula Maraka, MD, said: “I think this is very important work because so far when we counsel our patients about the different treatment modalities we focus more on risk for recurrence and other short-term outcomes.”
“But these data give us a bigger perspective on mortality and cardiovascular outcomes ... We haven’t had such good quality data to accurately counsel our patients,” added Dr. Maraka, of the University of Arkansas for Medical Sciences, Little Rock.
Mortality higher for medication-treated, but why?
“Hyperthyroidism or an overactive thyroid gland is common, affecting up to 3% of the population, and is associated with long-term adverse cardiac and metabolic consequences. The optimal treatment choice remains unclear,” explained Dr. Boelaert, professor of endocrinology at the University of Birmingham, England, outlining the reasons they conducted the EGRET study.
The study population was 55,318 patients (77% women) with newly diagnosed hyperthyroidism identified from a U.K. population-based primary care electronic health record database. Of those, 77.8% were treated with antithyroid medication, 14.6% with radioactive iodine, and 7.8% with surgery (total or hemithyroidectomy). The health records were linked with national mortality data and Health Survey England data on body mass index (BMI) for comparison.
Dr. Boelaert noted that the trial design “is the best we have” because a randomized clinical trial comparing hyperthyroid treatments would be extremely difficult given the need to individualize therapy and the impossibility of blinding. On the other hand, with the current study, “it’s certainly the largest patient group we’ve looked at.”
Over an average 12.1 years of follow-up, the proportion of patients who died was 14.1% in the medication group, 18.7% of those who had radioiodine therapy, and 9.2% of those who underwent surgery.
Compared with the number who would have been expected to die based on the general background population, the likelihood of reduced life expectancy for the treated groups was increased 2.10-fold for radioiodine, 2.13-fold for surgery, and 2.71-fold for medication. All were significantly higher than the general population (P < .0001).
After further adjustment for multiple confounders, mortality risk was reduced in patients treated with radioiodine (by 13%) or surgery (by 20%), compared with those treated with antithyroid medication, both significant reductions (P < .0001).
After exclusion of the 3.9% with baseline cardiovascular disease, MACE (defined as cardiovascular death or hospitalization for stroke or myocardial infarction) occurred in 9.9%, 13.4%, and 8.0% of the medication, radioiodine, and surgery groups, respectively.
After adjustments, there were no differences in MACE, compared with medications, with hazard ratios of 1.00 (P = .94) for radioactive iodine and 0.97 for surgery (P = .61).
“We were expecting to see a reduction in cardiovascular events, as previous studies suggest that radioactive iodine patients have fewer cardiovascular deaths. We did not see that but our protocol wasn’t set up to get every single specific cause of death. That will require further ongoing analysis,” said Dr. Boelaert.
Weight gain: Worth it for longer life
Compared with the background population, thyroidectomy was associated with an increased likelihood of developing obesity (BMI > 30 kg/m2) in both men (odds ratio, 1.56; P < .001), and women (OR, 1.27; P < .001), while radioiodine increased obesity risk in women (OR, 1.12; P < .001) but not in men (OR, 1.03; P = .55).
Among the women, those treated with antithyroid medications had an average 0.28 kg/m2 lower BMI, compared with the background population, and those treated with surgery had a 0.83 kg/m2 higher BMI. Both differences were significant (P < .001).
The BMI differences were not significant for radioactive iodine in women and for medications and radioactive iodine in men, although the men treated surgically also had a significantly higher BMI (1.09 kg/m2; P < .001).
“The patients on antithyroid drugs were lighter than we would expect. I think that’s ongoing hyperthyroidism. I strongly believe that ... to get rid of hyperthyroidism you have to make patients hypothyroid ... It’s really important that you get good control,” Dr. Boelaert commented.
Dr. Maraka, who is also endocrine section chief of the Arkansas Veteran’s Healthcare System, Little Rock, commented: “[Dr. Boelaert’s] concern is that the patients on antithyroid drugs are not adequately controlled, and we know very well that uncontrolled hyperthyroidism is associated with increased mortality and increased cardiovascular outcomes. This suggests that if patients are on antithyroid medications, they should at least be monitored very well.”
Regarding the possible cause of the increased mortality, if not cardiovascular, Dr. Maraka also pointed out that typically once antithyroid medications are stopped, about half of patients will stay in remission and the other half will return to hyperthyroidism.
“It might be that this kind of ‘yo-yo’ is what’s actually leading to the increased mortality, compared to patients who had definitive treatment and this problem was taken care of. This is speculation but it might be what we’re seeing,” Dr. Maraka observed.
The BMI differences worked out to a weight gain with surgery of approximately 2.1 kg (4.6 lb) for a woman with a height of 160 cm and 2.4 kg for 170 cm. Among men, those differences were 3.2 kg and 3.5 kg for heights of 170 cm and 190 cm, respectively.
Dr. Boelaert said, “I think we should discuss this with patients. They will say they don’t want to get fat, but the absolute weight gain is ... not that much.”
“I personally think that 2 kg is not a big price to pay to live longer. I hope that’s what we’ll be telling our patients in clinic in the next few years after we get this published.”
Dr. Boelaert and Dr. Maraka have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – new data from a large cohort study suggest.
“I think this is something we need to take into our discussions with patients because treatment for hyperthyroidism is very much individualized decision-making ... The effects on mortality are not usually one of the factors we discuss there. But now, we have strong data from a very large cohort of patients indicating that this is something that does need to be discussed,” lead author Kristien Boelaert, MD, who is the current president of the British Thyroid Association, said in an interview.
Dr. Boelaert presented the findings of the EGRET (Weight Changes, Cardio-Metabolic Risks and Mortality in Patients With Hyperthyroidism) study at the Annual Meeting of the Endocrine Society.
Other notable findings from EGRET were that the patients on antithyroid medication were thinner than expected, suggesting undertreatment, and that no differences were found for major adverse cardiac events (MACE) across the treatment options, leaving unexplained the reasons for the increased mortality in the medicated group.
Asked to comment, session moderator Spyridoula Maraka, MD, said: “I think this is very important work because so far when we counsel our patients about the different treatment modalities we focus more on risk for recurrence and other short-term outcomes.”
“But these data give us a bigger perspective on mortality and cardiovascular outcomes ... We haven’t had such good quality data to accurately counsel our patients,” added Dr. Maraka, of the University of Arkansas for Medical Sciences, Little Rock.
Mortality higher for medication-treated, but why?
“Hyperthyroidism or an overactive thyroid gland is common, affecting up to 3% of the population, and is associated with long-term adverse cardiac and metabolic consequences. The optimal treatment choice remains unclear,” explained Dr. Boelaert, professor of endocrinology at the University of Birmingham, England, outlining the reasons they conducted the EGRET study.
The study population was 55,318 patients (77% women) with newly diagnosed hyperthyroidism identified from a U.K. population-based primary care electronic health record database. Of those, 77.8% were treated with antithyroid medication, 14.6% with radioactive iodine, and 7.8% with surgery (total or hemithyroidectomy). The health records were linked with national mortality data and Health Survey England data on body mass index (BMI) for comparison.
Dr. Boelaert noted that the trial design “is the best we have” because a randomized clinical trial comparing hyperthyroid treatments would be extremely difficult given the need to individualize therapy and the impossibility of blinding. On the other hand, with the current study, “it’s certainly the largest patient group we’ve looked at.”
Over an average 12.1 years of follow-up, the proportion of patients who died was 14.1% in the medication group, 18.7% of those who had radioiodine therapy, and 9.2% of those who underwent surgery.
Compared with the number who would have been expected to die based on the general background population, the likelihood of reduced life expectancy for the treated groups was increased 2.10-fold for radioiodine, 2.13-fold for surgery, and 2.71-fold for medication. All were significantly higher than the general population (P < .0001).
After further adjustment for multiple confounders, mortality risk was reduced in patients treated with radioiodine (by 13%) or surgery (by 20%), compared with those treated with antithyroid medication, both significant reductions (P < .0001).
After exclusion of the 3.9% with baseline cardiovascular disease, MACE (defined as cardiovascular death or hospitalization for stroke or myocardial infarction) occurred in 9.9%, 13.4%, and 8.0% of the medication, radioiodine, and surgery groups, respectively.
After adjustments, there were no differences in MACE, compared with medications, with hazard ratios of 1.00 (P = .94) for radioactive iodine and 0.97 for surgery (P = .61).
“We were expecting to see a reduction in cardiovascular events, as previous studies suggest that radioactive iodine patients have fewer cardiovascular deaths. We did not see that but our protocol wasn’t set up to get every single specific cause of death. That will require further ongoing analysis,” said Dr. Boelaert.
Weight gain: Worth it for longer life
Compared with the background population, thyroidectomy was associated with an increased likelihood of developing obesity (BMI > 30 kg/m2) in both men (odds ratio, 1.56; P < .001), and women (OR, 1.27; P < .001), while radioiodine increased obesity risk in women (OR, 1.12; P < .001) but not in men (OR, 1.03; P = .55).
Among the women, those treated with antithyroid medications had an average 0.28 kg/m2 lower BMI, compared with the background population, and those treated with surgery had a 0.83 kg/m2 higher BMI. Both differences were significant (P < .001).
The BMI differences were not significant for radioactive iodine in women and for medications and radioactive iodine in men, although the men treated surgically also had a significantly higher BMI (1.09 kg/m2; P < .001).
“The patients on antithyroid drugs were lighter than we would expect. I think that’s ongoing hyperthyroidism. I strongly believe that ... to get rid of hyperthyroidism you have to make patients hypothyroid ... It’s really important that you get good control,” Dr. Boelaert commented.
Dr. Maraka, who is also endocrine section chief of the Arkansas Veteran’s Healthcare System, Little Rock, commented: “[Dr. Boelaert’s] concern is that the patients on antithyroid drugs are not adequately controlled, and we know very well that uncontrolled hyperthyroidism is associated with increased mortality and increased cardiovascular outcomes. This suggests that if patients are on antithyroid medications, they should at least be monitored very well.”
Regarding the possible cause of the increased mortality, if not cardiovascular, Dr. Maraka also pointed out that typically once antithyroid medications are stopped, about half of patients will stay in remission and the other half will return to hyperthyroidism.
“It might be that this kind of ‘yo-yo’ is what’s actually leading to the increased mortality, compared to patients who had definitive treatment and this problem was taken care of. This is speculation but it might be what we’re seeing,” Dr. Maraka observed.
The BMI differences worked out to a weight gain with surgery of approximately 2.1 kg (4.6 lb) for a woman with a height of 160 cm and 2.4 kg for 170 cm. Among men, those differences were 3.2 kg and 3.5 kg for heights of 170 cm and 190 cm, respectively.
Dr. Boelaert said, “I think we should discuss this with patients. They will say they don’t want to get fat, but the absolute weight gain is ... not that much.”
“I personally think that 2 kg is not a big price to pay to live longer. I hope that’s what we’ll be telling our patients in clinic in the next few years after we get this published.”
Dr. Boelaert and Dr. Maraka have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ENDO 2023
Scripts surge for desiccated thyroid extract to treat hypothyroidism
new research has found.
Nationwide MarketScan claims data reveal that, among first-time thyroid hormone prescriptions, those for DTE rose from 5.4% in 2010 to 10.2% in 2020. At the same time, prescriptions for first-line levothyroxine dropped from 91.8% to 87.2%. Prescriptions for liothyronine (LT3), primarily in combination with levothyroxine, remained at about 2% throughout the decade.
The nonlevothyroxine therapies were more commonly prescribed in the West and Southwestern United States, while levothyroxine monotherapy was more frequent in the Northwest and upper Midwest, and also in states with higher densities of primary care physicians and endocrinologists.
The magnitude of this shift in first-line treatment was unexpected.
“We were frankly quite surprised to see that difference in just 10 years,” lead author Matthew Ettleson, MD, of the University of Chicago, said in an interview.
Asked to comment, session moderator Elizabeth N. Pearce, MD, professor of medicine at Boston University Medical Center, said she also found the dramatic shift to DTE surprising.
“It’s unclear why since there hasn’t been a shift in the science or in the guidelines over the last decade. ... I think we need to understand better what is driving this, who the patients are who are seeking it out, and which providers are the primary drivers of these prescriptions,” she said.
Dr. Ettleson presented the findings at the annual meeting of the Endocrine Society. The results were simultaneously published in the Journal of Clinical Endocrinology and Metabolism.
Why the increase in desiccated thyroid extract?
Current guidelines by the American Thyroid Association recommend levothyroxine, a synthetic form of thyroxine (T4) monotherapy, as the standard of care for treating hypothyroidism. However, approximately 10%-20% of levothyroxine-treated patients report bothersome symptoms despite normalization of thyroid-stimulating hormone (TSH) levels.
In 2021, the ATA, along with European and British thyroid societies, issued a consensus statement noting that new trials of triiodothyronine (T3)/T4 combination therapy were “justified.”
However, the MarketScan data were gathered before that statement came out, which doesn’t mention desiccated thyroid extract, “so that’s a bit of a head-scratcher,” Ettleson said.
He said one possibility may be the existence of online materials saying negative things about levothyroxine, so that “people who are just learning about hypothyroidism might already be primed to think about alternative treatments.” Moreover, some patients may view DTE as more “natural” than levothyroxine.
Dr. Ettleson also noted that the distinct geographic variation “didn’t seem random. ... So not only was there a doubling overall but there’s a variation in practice patterns across the country. I don’t have an explanation for that, but I think it’s important to recognize in the medical community that there are these big differences.”
Endocrinologists not as keen to prescribe DTE or T3
Residence in a state with higher endocrinologist density (3.0/100,000 population) was associated with a decreased likelihood of receiving T3 (adjusted odds ratio, 0.33; P < .001) or DTE therapy (aOR, 0.18; P < .001).
Residence in large central metro zones was associated with an increased likelihood of receiving T3 (aOR, 1.32; P < .001) or DTE therapy (aOR, 1.05; P < .008, respectively).
Dr. Pearce observed: “I don’t see DTE in Boston. It’s mostly in the South and Southwest.”
She said she doubted that endocrinologists were the primary prescribers of DTE, as many endocrinologists are “wary” of the pig thyroid–derived product because its T4 to T3 ratio is about 4:1, in contrast to the ratio in humans of 13-14:1.
Thus, DTE contains a much higher proportion of the active hormone T3. It is also much shorter acting, with a half-life of a few hours, compared to a few days for T4, she explained.
“We don’t really know what long-term safety effects are but it’s probably a less physiologic way of dosing thyroid hormone than ... either levothyroxine or levothyroxine in combination with a lower T3 proportion,” she said.
Just trying to understand
Dr. Ettleson emphasized that the goal of his research wasn’t to reverse the trend but to better understand it.
Nonetheless, he also noted, “now that we know there are more patients taking DTE, we need to start looking at rates of atrial fibrillation, fracture, heart failure, and other possible outcomes in this population and compare them with levothyroxine and nonthyroid populations to make sure that it is as safe as levothyroxine.”
“There are no data to suggest increased risk, especially if TSH is monitored and stays in the normal range, but there’s very little data for over 5 or 10 years on DTE-treated patients. We need the data,” he emphasized.
Meanwhile, he’s working on a survey of endocrinologists and non-endocrinologists to ask if they’ve prescribed DTE, and if so, why, and whether it’s because patients asked for it. “There’s a lot more work to be done, but I think it’s exciting. It’s important to see how patients are being treated in the real world ... and understand why it’s happening and what the outcomes are.”
Dr. Ettleson and Dr. Pearce have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research has found.
Nationwide MarketScan claims data reveal that, among first-time thyroid hormone prescriptions, those for DTE rose from 5.4% in 2010 to 10.2% in 2020. At the same time, prescriptions for first-line levothyroxine dropped from 91.8% to 87.2%. Prescriptions for liothyronine (LT3), primarily in combination with levothyroxine, remained at about 2% throughout the decade.
The nonlevothyroxine therapies were more commonly prescribed in the West and Southwestern United States, while levothyroxine monotherapy was more frequent in the Northwest and upper Midwest, and also in states with higher densities of primary care physicians and endocrinologists.
The magnitude of this shift in first-line treatment was unexpected.
“We were frankly quite surprised to see that difference in just 10 years,” lead author Matthew Ettleson, MD, of the University of Chicago, said in an interview.
Asked to comment, session moderator Elizabeth N. Pearce, MD, professor of medicine at Boston University Medical Center, said she also found the dramatic shift to DTE surprising.
“It’s unclear why since there hasn’t been a shift in the science or in the guidelines over the last decade. ... I think we need to understand better what is driving this, who the patients are who are seeking it out, and which providers are the primary drivers of these prescriptions,” she said.
Dr. Ettleson presented the findings at the annual meeting of the Endocrine Society. The results were simultaneously published in the Journal of Clinical Endocrinology and Metabolism.
Why the increase in desiccated thyroid extract?
Current guidelines by the American Thyroid Association recommend levothyroxine, a synthetic form of thyroxine (T4) monotherapy, as the standard of care for treating hypothyroidism. However, approximately 10%-20% of levothyroxine-treated patients report bothersome symptoms despite normalization of thyroid-stimulating hormone (TSH) levels.
In 2021, the ATA, along with European and British thyroid societies, issued a consensus statement noting that new trials of triiodothyronine (T3)/T4 combination therapy were “justified.”
However, the MarketScan data were gathered before that statement came out, which doesn’t mention desiccated thyroid extract, “so that’s a bit of a head-scratcher,” Ettleson said.
He said one possibility may be the existence of online materials saying negative things about levothyroxine, so that “people who are just learning about hypothyroidism might already be primed to think about alternative treatments.” Moreover, some patients may view DTE as more “natural” than levothyroxine.
Dr. Ettleson also noted that the distinct geographic variation “didn’t seem random. ... So not only was there a doubling overall but there’s a variation in practice patterns across the country. I don’t have an explanation for that, but I think it’s important to recognize in the medical community that there are these big differences.”
Endocrinologists not as keen to prescribe DTE or T3
Residence in a state with higher endocrinologist density (3.0/100,000 population) was associated with a decreased likelihood of receiving T3 (adjusted odds ratio, 0.33; P < .001) or DTE therapy (aOR, 0.18; P < .001).
Residence in large central metro zones was associated with an increased likelihood of receiving T3 (aOR, 1.32; P < .001) or DTE therapy (aOR, 1.05; P < .008, respectively).
Dr. Pearce observed: “I don’t see DTE in Boston. It’s mostly in the South and Southwest.”
She said she doubted that endocrinologists were the primary prescribers of DTE, as many endocrinologists are “wary” of the pig thyroid–derived product because its T4 to T3 ratio is about 4:1, in contrast to the ratio in humans of 13-14:1.
Thus, DTE contains a much higher proportion of the active hormone T3. It is also much shorter acting, with a half-life of a few hours, compared to a few days for T4, she explained.
“We don’t really know what long-term safety effects are but it’s probably a less physiologic way of dosing thyroid hormone than ... either levothyroxine or levothyroxine in combination with a lower T3 proportion,” she said.
Just trying to understand
Dr. Ettleson emphasized that the goal of his research wasn’t to reverse the trend but to better understand it.
Nonetheless, he also noted, “now that we know there are more patients taking DTE, we need to start looking at rates of atrial fibrillation, fracture, heart failure, and other possible outcomes in this population and compare them with levothyroxine and nonthyroid populations to make sure that it is as safe as levothyroxine.”
“There are no data to suggest increased risk, especially if TSH is monitored and stays in the normal range, but there’s very little data for over 5 or 10 years on DTE-treated patients. We need the data,” he emphasized.
Meanwhile, he’s working on a survey of endocrinologists and non-endocrinologists to ask if they’ve prescribed DTE, and if so, why, and whether it’s because patients asked for it. “There’s a lot more work to be done, but I think it’s exciting. It’s important to see how patients are being treated in the real world ... and understand why it’s happening and what the outcomes are.”
Dr. Ettleson and Dr. Pearce have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research has found.
Nationwide MarketScan claims data reveal that, among first-time thyroid hormone prescriptions, those for DTE rose from 5.4% in 2010 to 10.2% in 2020. At the same time, prescriptions for first-line levothyroxine dropped from 91.8% to 87.2%. Prescriptions for liothyronine (LT3), primarily in combination with levothyroxine, remained at about 2% throughout the decade.
The nonlevothyroxine therapies were more commonly prescribed in the West and Southwestern United States, while levothyroxine monotherapy was more frequent in the Northwest and upper Midwest, and also in states with higher densities of primary care physicians and endocrinologists.
The magnitude of this shift in first-line treatment was unexpected.
“We were frankly quite surprised to see that difference in just 10 years,” lead author Matthew Ettleson, MD, of the University of Chicago, said in an interview.
Asked to comment, session moderator Elizabeth N. Pearce, MD, professor of medicine at Boston University Medical Center, said she also found the dramatic shift to DTE surprising.
“It’s unclear why since there hasn’t been a shift in the science or in the guidelines over the last decade. ... I think we need to understand better what is driving this, who the patients are who are seeking it out, and which providers are the primary drivers of these prescriptions,” she said.
Dr. Ettleson presented the findings at the annual meeting of the Endocrine Society. The results were simultaneously published in the Journal of Clinical Endocrinology and Metabolism.
Why the increase in desiccated thyroid extract?
Current guidelines by the American Thyroid Association recommend levothyroxine, a synthetic form of thyroxine (T4) monotherapy, as the standard of care for treating hypothyroidism. However, approximately 10%-20% of levothyroxine-treated patients report bothersome symptoms despite normalization of thyroid-stimulating hormone (TSH) levels.
In 2021, the ATA, along with European and British thyroid societies, issued a consensus statement noting that new trials of triiodothyronine (T3)/T4 combination therapy were “justified.”
However, the MarketScan data were gathered before that statement came out, which doesn’t mention desiccated thyroid extract, “so that’s a bit of a head-scratcher,” Ettleson said.
He said one possibility may be the existence of online materials saying negative things about levothyroxine, so that “people who are just learning about hypothyroidism might already be primed to think about alternative treatments.” Moreover, some patients may view DTE as more “natural” than levothyroxine.
Dr. Ettleson also noted that the distinct geographic variation “didn’t seem random. ... So not only was there a doubling overall but there’s a variation in practice patterns across the country. I don’t have an explanation for that, but I think it’s important to recognize in the medical community that there are these big differences.”
Endocrinologists not as keen to prescribe DTE or T3
Residence in a state with higher endocrinologist density (3.0/100,000 population) was associated with a decreased likelihood of receiving T3 (adjusted odds ratio, 0.33; P < .001) or DTE therapy (aOR, 0.18; P < .001).
Residence in large central metro zones was associated with an increased likelihood of receiving T3 (aOR, 1.32; P < .001) or DTE therapy (aOR, 1.05; P < .008, respectively).
Dr. Pearce observed: “I don’t see DTE in Boston. It’s mostly in the South and Southwest.”
She said she doubted that endocrinologists were the primary prescribers of DTE, as many endocrinologists are “wary” of the pig thyroid–derived product because its T4 to T3 ratio is about 4:1, in contrast to the ratio in humans of 13-14:1.
Thus, DTE contains a much higher proportion of the active hormone T3. It is also much shorter acting, with a half-life of a few hours, compared to a few days for T4, she explained.
“We don’t really know what long-term safety effects are but it’s probably a less physiologic way of dosing thyroid hormone than ... either levothyroxine or levothyroxine in combination with a lower T3 proportion,” she said.
Just trying to understand
Dr. Ettleson emphasized that the goal of his research wasn’t to reverse the trend but to better understand it.
Nonetheless, he also noted, “now that we know there are more patients taking DTE, we need to start looking at rates of atrial fibrillation, fracture, heart failure, and other possible outcomes in this population and compare them with levothyroxine and nonthyroid populations to make sure that it is as safe as levothyroxine.”
“There are no data to suggest increased risk, especially if TSH is monitored and stays in the normal range, but there’s very little data for over 5 or 10 years on DTE-treated patients. We need the data,” he emphasized.
Meanwhile, he’s working on a survey of endocrinologists and non-endocrinologists to ask if they’ve prescribed DTE, and if so, why, and whether it’s because patients asked for it. “There’s a lot more work to be done, but I think it’s exciting. It’s important to see how patients are being treated in the real world ... and understand why it’s happening and what the outcomes are.”
Dr. Ettleson and Dr. Pearce have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ENDO 2023
Over half of pregnant patients not properly screened for thyroid disease
BALTIMORE – Less than half of the pregnant patients who met the criteria for thyroid screening were actually screened by their clinician, according to a retrospective cohort study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists in Baltimore. Those who met criteria and did receive screening had higher live birth rates and lower miscarriage rates than those who met the criteria but did not undergo screening, the study found.
“These results suggest that improving thyroid screening adherence may lead to improved pregnancy outcomes,” lead author Allan Dong, MD, of Advocate Lutheran General Hospital in Des Plaines, Ill., told attendees. “However, following targeted screening guidelines can be difficult for clinicians. In practice, universal screening for diabetes and pregnancy may provide more comprehensive screening coverage and potentially lead to improved outcomes.”
Instead of universal screening for thyroid disease, ACOG and the American Thyroid Association recommend targeted screening of high-risk patients, though ATA’s criteria are substantially broader than ACOG’s. But, Dr. Dong told attendees, “guidelines are only beneficial if they are followed appropriately,” and Ob.Gyns. have limited time to screen for risk factors in the midst of other clinical priorities. So he aimed to learn whether Ob.Gyns. were following the guidelines of either organization in screening people at higher risk for thyroid disease.
Dr. Dong and his coauthor, Melisa Lott, DO, reviewed the charts of all 1,025 patients who presented at their institution for new obstetrical visits in 2020 to determine which ones had risk factors that would qualify them for screening under ATA or ACOG guidelines. ACOG’s screening criteria included having a personal or family history of thyroid disease or type 1 diabetes, or there being clinical suspicion for thyroid disease. ATA’s screening criteria included the following:
- Personal or family history of thyroid disease.
- History of head or neck radiation.
- History of a prior thyroid surgery.
- Over age 30.
- Any autoimmune disease.
- A body mass index greater than 40 kg/m2.
- History of pregnancy loss, preterm delivery, or infertility.
- Recently used amiodarone lithium or iodine-based contrast.
- Lived in an area of known iodine deficiency.
- Clinical suspicion of thyroid disease.
ATA screening criteria identified four times as many patients requiring screening than did ACOG criteria, Dr. Dong noted. Of the 198 patients who met ACOG’s criteria, 43.9% were screened with thyroid function testing. Meanwhile, 826 patients – including all those who met ACOG’s criteria – met ATA’s criteria for screening, but only 13.1% of them underwent thyroid function testing.
Live birth rates were significantly higher among patients who met ATA criteria and were screened (92.6%) than among patients who met ATA criteria but were not screened (83.3%, P = .006). Similarly, the miscarriage rate was 4.6% in patients who met ATA criteria and were screened, compared to 12.4% in patients who met the criteria but did not undergo thyroid function testing (P = .009).
“A similar difference, although not statistically significant, was noted when comparing patients who were screened appropriately per ACOG criteria with those who met criteria for screening but were not screened,” Dr. Dong told attendees. “However, our study was underpowered to detect this difference due to the lower number of patients who meet criteria for screening under ACOG guidelines.”
The researchers did not find any significant difference in preterm delivery rates.
Anna Whelan, MD, of Women & Infants Hospital of Brown University, Providence, R.I., was not involved in the study but viewed the poster and pointed out that many of the patients, if seen by a primary care provider prior to pregnancy, would likely have been screened by their PCP. The rate of underscreening therefore suggests that patients “are not getting good, consistent primary care because there’s a lack of primary care physicians,” Dr. Whelan said in an interview.
In addition, she added, “maybe not all obstetricians and those providing care, such as midwives and other providers, are aware of the [ATA] guidelines on who should be screened.” She added that additional education about thyroid screening guidelines might be helpful for providers.
Dr. Dong reported being a stock shareholder in 3M, AbbVie, General Electric, Johnson & Johnson, Medtronic, Pfizer, and Viking Therapeutics. Dr. Whelan had no disclosures.
BALTIMORE – Less than half of the pregnant patients who met the criteria for thyroid screening were actually screened by their clinician, according to a retrospective cohort study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists in Baltimore. Those who met criteria and did receive screening had higher live birth rates and lower miscarriage rates than those who met the criteria but did not undergo screening, the study found.
“These results suggest that improving thyroid screening adherence may lead to improved pregnancy outcomes,” lead author Allan Dong, MD, of Advocate Lutheran General Hospital in Des Plaines, Ill., told attendees. “However, following targeted screening guidelines can be difficult for clinicians. In practice, universal screening for diabetes and pregnancy may provide more comprehensive screening coverage and potentially lead to improved outcomes.”
Instead of universal screening for thyroid disease, ACOG and the American Thyroid Association recommend targeted screening of high-risk patients, though ATA’s criteria are substantially broader than ACOG’s. But, Dr. Dong told attendees, “guidelines are only beneficial if they are followed appropriately,” and Ob.Gyns. have limited time to screen for risk factors in the midst of other clinical priorities. So he aimed to learn whether Ob.Gyns. were following the guidelines of either organization in screening people at higher risk for thyroid disease.
Dr. Dong and his coauthor, Melisa Lott, DO, reviewed the charts of all 1,025 patients who presented at their institution for new obstetrical visits in 2020 to determine which ones had risk factors that would qualify them for screening under ATA or ACOG guidelines. ACOG’s screening criteria included having a personal or family history of thyroid disease or type 1 diabetes, or there being clinical suspicion for thyroid disease. ATA’s screening criteria included the following:
- Personal or family history of thyroid disease.
- History of head or neck radiation.
- History of a prior thyroid surgery.
- Over age 30.
- Any autoimmune disease.
- A body mass index greater than 40 kg/m2.
- History of pregnancy loss, preterm delivery, or infertility.
- Recently used amiodarone lithium or iodine-based contrast.
- Lived in an area of known iodine deficiency.
- Clinical suspicion of thyroid disease.
ATA screening criteria identified four times as many patients requiring screening than did ACOG criteria, Dr. Dong noted. Of the 198 patients who met ACOG’s criteria, 43.9% were screened with thyroid function testing. Meanwhile, 826 patients – including all those who met ACOG’s criteria – met ATA’s criteria for screening, but only 13.1% of them underwent thyroid function testing.
Live birth rates were significantly higher among patients who met ATA criteria and were screened (92.6%) than among patients who met ATA criteria but were not screened (83.3%, P = .006). Similarly, the miscarriage rate was 4.6% in patients who met ATA criteria and were screened, compared to 12.4% in patients who met the criteria but did not undergo thyroid function testing (P = .009).
“A similar difference, although not statistically significant, was noted when comparing patients who were screened appropriately per ACOG criteria with those who met criteria for screening but were not screened,” Dr. Dong told attendees. “However, our study was underpowered to detect this difference due to the lower number of patients who meet criteria for screening under ACOG guidelines.”
The researchers did not find any significant difference in preterm delivery rates.
Anna Whelan, MD, of Women & Infants Hospital of Brown University, Providence, R.I., was not involved in the study but viewed the poster and pointed out that many of the patients, if seen by a primary care provider prior to pregnancy, would likely have been screened by their PCP. The rate of underscreening therefore suggests that patients “are not getting good, consistent primary care because there’s a lack of primary care physicians,” Dr. Whelan said in an interview.
In addition, she added, “maybe not all obstetricians and those providing care, such as midwives and other providers, are aware of the [ATA] guidelines on who should be screened.” She added that additional education about thyroid screening guidelines might be helpful for providers.
Dr. Dong reported being a stock shareholder in 3M, AbbVie, General Electric, Johnson & Johnson, Medtronic, Pfizer, and Viking Therapeutics. Dr. Whelan had no disclosures.
BALTIMORE – Less than half of the pregnant patients who met the criteria for thyroid screening were actually screened by their clinician, according to a retrospective cohort study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists in Baltimore. Those who met criteria and did receive screening had higher live birth rates and lower miscarriage rates than those who met the criteria but did not undergo screening, the study found.
“These results suggest that improving thyroid screening adherence may lead to improved pregnancy outcomes,” lead author Allan Dong, MD, of Advocate Lutheran General Hospital in Des Plaines, Ill., told attendees. “However, following targeted screening guidelines can be difficult for clinicians. In practice, universal screening for diabetes and pregnancy may provide more comprehensive screening coverage and potentially lead to improved outcomes.”
Instead of universal screening for thyroid disease, ACOG and the American Thyroid Association recommend targeted screening of high-risk patients, though ATA’s criteria are substantially broader than ACOG’s. But, Dr. Dong told attendees, “guidelines are only beneficial if they are followed appropriately,” and Ob.Gyns. have limited time to screen for risk factors in the midst of other clinical priorities. So he aimed to learn whether Ob.Gyns. were following the guidelines of either organization in screening people at higher risk for thyroid disease.
Dr. Dong and his coauthor, Melisa Lott, DO, reviewed the charts of all 1,025 patients who presented at their institution for new obstetrical visits in 2020 to determine which ones had risk factors that would qualify them for screening under ATA or ACOG guidelines. ACOG’s screening criteria included having a personal or family history of thyroid disease or type 1 diabetes, or there being clinical suspicion for thyroid disease. ATA’s screening criteria included the following:
- Personal or family history of thyroid disease.
- History of head or neck radiation.
- History of a prior thyroid surgery.
- Over age 30.
- Any autoimmune disease.
- A body mass index greater than 40 kg/m2.
- History of pregnancy loss, preterm delivery, or infertility.
- Recently used amiodarone lithium or iodine-based contrast.
- Lived in an area of known iodine deficiency.
- Clinical suspicion of thyroid disease.
ATA screening criteria identified four times as many patients requiring screening than did ACOG criteria, Dr. Dong noted. Of the 198 patients who met ACOG’s criteria, 43.9% were screened with thyroid function testing. Meanwhile, 826 patients – including all those who met ACOG’s criteria – met ATA’s criteria for screening, but only 13.1% of them underwent thyroid function testing.
Live birth rates were significantly higher among patients who met ATA criteria and were screened (92.6%) than among patients who met ATA criteria but were not screened (83.3%, P = .006). Similarly, the miscarriage rate was 4.6% in patients who met ATA criteria and were screened, compared to 12.4% in patients who met the criteria but did not undergo thyroid function testing (P = .009).
“A similar difference, although not statistically significant, was noted when comparing patients who were screened appropriately per ACOG criteria with those who met criteria for screening but were not screened,” Dr. Dong told attendees. “However, our study was underpowered to detect this difference due to the lower number of patients who meet criteria for screening under ACOG guidelines.”
The researchers did not find any significant difference in preterm delivery rates.
Anna Whelan, MD, of Women & Infants Hospital of Brown University, Providence, R.I., was not involved in the study but viewed the poster and pointed out that many of the patients, if seen by a primary care provider prior to pregnancy, would likely have been screened by their PCP. The rate of underscreening therefore suggests that patients “are not getting good, consistent primary care because there’s a lack of primary care physicians,” Dr. Whelan said in an interview.
In addition, she added, “maybe not all obstetricians and those providing care, such as midwives and other providers, are aware of the [ATA] guidelines on who should be screened.” She added that additional education about thyroid screening guidelines might be helpful for providers.
Dr. Dong reported being a stock shareholder in 3M, AbbVie, General Electric, Johnson & Johnson, Medtronic, Pfizer, and Viking Therapeutics. Dr. Whelan had no disclosures.
FROM ACOG 2023
TransCon PTH nears U.S. approval for hypoparathyroidism?
SEATTLE –
Findings from 110-week phase 2 data for the once-daily investigational parathyroid hormone (PTH) replacement drug were recently presented at the annual scientific & clinical congress of the American Association of Clinical Endocrinology.
Overall, the drug was associated with independence from conventional calcium and active vitamin D therapy in most patients at 110 weeks, with no discontinuations due to adverse effects.
“Patients with hypoparathyroidism have low serum calcium levels and struggle with quality of life and biochemical abnormalities. The data from the TransCon PTH studies seem to show that a lot of these abnormalities can be reversed,” presenter Mishaela R. Rubin, MD, said in an interview.
Other PTH replacement therapies such as Nupara (now discontinued) and teriparatide (off-label) have been used in some patients with hypoparathyroidism.
However, “[TransCon PTH] is delivered in such a way as to have a prolonged half-life, so that’s kind of a special benefit that it has,” added Dr. Rubin of the division of endocrinology and metabolic bone disease, department of medicine, Columbia University, New York.
Asked to comment, session moderator Thanh Hoang, DO, of Walter Reed National Military Medical Center, Silver Spring, Md., said: “I think it’s a very promising medication because right now we don’t have a lot of options ... I think it would help a lot of patients.”
Approval denied, company addressing concerns
On May 1, the Food and Drug Administration issued a complete response letter, signaling denial of approval for the TransCon PTH, citing concerns related to manufacturing control of the product’s drug/device combination product, but not about the product’s safety and efficacy, according to an Ascendis statement.
The company is now working with the FDA to address these issues and is awaiting a European Union decision later this year.
The FDA did not request that the company conduct further clinical trials of TransCon PTH, which now include published 26-week phase 2 and phase 3 data along with the current longer-term phase 2 data presented at AACE.
“The company has said that they’re hopeful the issues will be addressable and that the FDA did not have any concerns about safety,” Dr. Rubin said in an interview.
Calcium normalized, bone turnover improved
Dr. Rubin presented long-term efficacy and safety data from the Phase 2 PaTH Forward trial, which involved 57 of the initial 59 participants who completed week 110 of an open-label extension of the trial.
During the first 4 weeks, patients had been randomized to TransCon PTH at fixed doses of 15 µg/day, 18 µg/day, 21 µg/day, or placebo. After week 4, all patients switched to TransCon PTH titrated to doses of 6-60 µg/day along with conventional therapy, with the goal of maintaining normocalcemia.
Participants were a mean age of 50 years, 81% were women, and 92% were White. Causes of hypoparathyroidism were neck surgery in 80%, autoimmune disease in 2%, and idiopathic disease in 19%. Disease duration was 12 years (range 1-39), and all were taking conventional therapy including calcium and active vitamin D (calcitriol or alfacaldiol).
At 110 weeks, all 57 patients were able to stop taking active vitamin D, and 53 of the 57 (93%) patients achieved independence from conventional therapy, defined as taking 0 µg/day of active vitamin D and no more than 600 mg/day of calcium (the dietary supplement dose). A total of 44 (77%) patients were not taking any calcium or active vitamin D.
“This really establishes the durability up to 2 years of keeping people off conventional therapy,” Dr. Rubin said during her presentation.
There was an initial uptick to 9.4 mg/dL in mean serum calcium, as some participants were still taking active vitamin D, but that dropped to 8.9 mg/dL by week 26. Mean 24-hour urine calcium dropped from 428 mg/day at baseline to 173 mg/day by week 26. Both serum calcium and urine calcium remained in the normal range through week 110 in all patients, at 8.6 mg/dL and 167 mg/day, respectively.
“This is a really important outcome because we know that high urine calcium in these patients sets them at risk for going on to develop nephrocalcinosis, nephrolithiasis, and ultimately, chronic kidney disease,” Dr. Rubin said.
Serum levels of two bone formation markers peaked at 12 weeks after initiation of TransCon PTH. Both trended downward thereafter through week 110 to levels approximating those of age- and sex-matched controls.
“Both markers started off low, consistent with hypoparathyroidism, but with initiation of TransCon PTH we see a robust increase in bone turnover markers, almost as if the bone is ‘waking up,’ if you will. And this is consistent with calcium being mobilized from the skeleton and going into the circulation,” Dr. Rubin explained.
Bone mineral density assessed by dual-energy x-ray absorptiometry normalized, primarily in the first 26 weeks. For lumbar spine L1-L4, mean Z-scores dropped from 1.6 to 1.0 at 26 weeks and down to 0.7 by week 100. For total hip, those values were 1.0, 0.6, and 0.4, respectively. The values approached age- and sex-matched norms, Dr. Rubin noted, to “perhaps where their skeleton would be if they hadn’t had hypoparathyroidism.”
Overall 56 of the 57 (94.9%) patients reported treatment-emergent adverse events, of which 25 (42.4%) were treatment related and none were deemed serious. There were no treatment-emergent adverse events related to hypercalcemia or hypocalcemia leading to health care visits or hospitalization, none leading to discontinuation of study drug, and none to death.
“So overall, a reassuring safety profile,” Dr. Rubin said. “We look forward to presenting the next 2 years’ worth of data to the end of the open-label extension study.”
Dr. Rubin is a paid researcher for Ascendis, which funded the study. Dr. Hoang has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SEATTLE –
Findings from 110-week phase 2 data for the once-daily investigational parathyroid hormone (PTH) replacement drug were recently presented at the annual scientific & clinical congress of the American Association of Clinical Endocrinology.
Overall, the drug was associated with independence from conventional calcium and active vitamin D therapy in most patients at 110 weeks, with no discontinuations due to adverse effects.
“Patients with hypoparathyroidism have low serum calcium levels and struggle with quality of life and biochemical abnormalities. The data from the TransCon PTH studies seem to show that a lot of these abnormalities can be reversed,” presenter Mishaela R. Rubin, MD, said in an interview.
Other PTH replacement therapies such as Nupara (now discontinued) and teriparatide (off-label) have been used in some patients with hypoparathyroidism.
However, “[TransCon PTH] is delivered in such a way as to have a prolonged half-life, so that’s kind of a special benefit that it has,” added Dr. Rubin of the division of endocrinology and metabolic bone disease, department of medicine, Columbia University, New York.
Asked to comment, session moderator Thanh Hoang, DO, of Walter Reed National Military Medical Center, Silver Spring, Md., said: “I think it’s a very promising medication because right now we don’t have a lot of options ... I think it would help a lot of patients.”
Approval denied, company addressing concerns
On May 1, the Food and Drug Administration issued a complete response letter, signaling denial of approval for the TransCon PTH, citing concerns related to manufacturing control of the product’s drug/device combination product, but not about the product’s safety and efficacy, according to an Ascendis statement.
The company is now working with the FDA to address these issues and is awaiting a European Union decision later this year.
The FDA did not request that the company conduct further clinical trials of TransCon PTH, which now include published 26-week phase 2 and phase 3 data along with the current longer-term phase 2 data presented at AACE.
“The company has said that they’re hopeful the issues will be addressable and that the FDA did not have any concerns about safety,” Dr. Rubin said in an interview.
Calcium normalized, bone turnover improved
Dr. Rubin presented long-term efficacy and safety data from the Phase 2 PaTH Forward trial, which involved 57 of the initial 59 participants who completed week 110 of an open-label extension of the trial.
During the first 4 weeks, patients had been randomized to TransCon PTH at fixed doses of 15 µg/day, 18 µg/day, 21 µg/day, or placebo. After week 4, all patients switched to TransCon PTH titrated to doses of 6-60 µg/day along with conventional therapy, with the goal of maintaining normocalcemia.
Participants were a mean age of 50 years, 81% were women, and 92% were White. Causes of hypoparathyroidism were neck surgery in 80%, autoimmune disease in 2%, and idiopathic disease in 19%. Disease duration was 12 years (range 1-39), and all were taking conventional therapy including calcium and active vitamin D (calcitriol or alfacaldiol).
At 110 weeks, all 57 patients were able to stop taking active vitamin D, and 53 of the 57 (93%) patients achieved independence from conventional therapy, defined as taking 0 µg/day of active vitamin D and no more than 600 mg/day of calcium (the dietary supplement dose). A total of 44 (77%) patients were not taking any calcium or active vitamin D.
“This really establishes the durability up to 2 years of keeping people off conventional therapy,” Dr. Rubin said during her presentation.
There was an initial uptick to 9.4 mg/dL in mean serum calcium, as some participants were still taking active vitamin D, but that dropped to 8.9 mg/dL by week 26. Mean 24-hour urine calcium dropped from 428 mg/day at baseline to 173 mg/day by week 26. Both serum calcium and urine calcium remained in the normal range through week 110 in all patients, at 8.6 mg/dL and 167 mg/day, respectively.
“This is a really important outcome because we know that high urine calcium in these patients sets them at risk for going on to develop nephrocalcinosis, nephrolithiasis, and ultimately, chronic kidney disease,” Dr. Rubin said.
Serum levels of two bone formation markers peaked at 12 weeks after initiation of TransCon PTH. Both trended downward thereafter through week 110 to levels approximating those of age- and sex-matched controls.
“Both markers started off low, consistent with hypoparathyroidism, but with initiation of TransCon PTH we see a robust increase in bone turnover markers, almost as if the bone is ‘waking up,’ if you will. And this is consistent with calcium being mobilized from the skeleton and going into the circulation,” Dr. Rubin explained.
Bone mineral density assessed by dual-energy x-ray absorptiometry normalized, primarily in the first 26 weeks. For lumbar spine L1-L4, mean Z-scores dropped from 1.6 to 1.0 at 26 weeks and down to 0.7 by week 100. For total hip, those values were 1.0, 0.6, and 0.4, respectively. The values approached age- and sex-matched norms, Dr. Rubin noted, to “perhaps where their skeleton would be if they hadn’t had hypoparathyroidism.”
Overall 56 of the 57 (94.9%) patients reported treatment-emergent adverse events, of which 25 (42.4%) were treatment related and none were deemed serious. There were no treatment-emergent adverse events related to hypercalcemia or hypocalcemia leading to health care visits or hospitalization, none leading to discontinuation of study drug, and none to death.
“So overall, a reassuring safety profile,” Dr. Rubin said. “We look forward to presenting the next 2 years’ worth of data to the end of the open-label extension study.”
Dr. Rubin is a paid researcher for Ascendis, which funded the study. Dr. Hoang has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SEATTLE –
Findings from 110-week phase 2 data for the once-daily investigational parathyroid hormone (PTH) replacement drug were recently presented at the annual scientific & clinical congress of the American Association of Clinical Endocrinology.
Overall, the drug was associated with independence from conventional calcium and active vitamin D therapy in most patients at 110 weeks, with no discontinuations due to adverse effects.
“Patients with hypoparathyroidism have low serum calcium levels and struggle with quality of life and biochemical abnormalities. The data from the TransCon PTH studies seem to show that a lot of these abnormalities can be reversed,” presenter Mishaela R. Rubin, MD, said in an interview.
Other PTH replacement therapies such as Nupara (now discontinued) and teriparatide (off-label) have been used in some patients with hypoparathyroidism.
However, “[TransCon PTH] is delivered in such a way as to have a prolonged half-life, so that’s kind of a special benefit that it has,” added Dr. Rubin of the division of endocrinology and metabolic bone disease, department of medicine, Columbia University, New York.
Asked to comment, session moderator Thanh Hoang, DO, of Walter Reed National Military Medical Center, Silver Spring, Md., said: “I think it’s a very promising medication because right now we don’t have a lot of options ... I think it would help a lot of patients.”
Approval denied, company addressing concerns
On May 1, the Food and Drug Administration issued a complete response letter, signaling denial of approval for the TransCon PTH, citing concerns related to manufacturing control of the product’s drug/device combination product, but not about the product’s safety and efficacy, according to an Ascendis statement.
The company is now working with the FDA to address these issues and is awaiting a European Union decision later this year.
The FDA did not request that the company conduct further clinical trials of TransCon PTH, which now include published 26-week phase 2 and phase 3 data along with the current longer-term phase 2 data presented at AACE.
“The company has said that they’re hopeful the issues will be addressable and that the FDA did not have any concerns about safety,” Dr. Rubin said in an interview.
Calcium normalized, bone turnover improved
Dr. Rubin presented long-term efficacy and safety data from the Phase 2 PaTH Forward trial, which involved 57 of the initial 59 participants who completed week 110 of an open-label extension of the trial.
During the first 4 weeks, patients had been randomized to TransCon PTH at fixed doses of 15 µg/day, 18 µg/day, 21 µg/day, or placebo. After week 4, all patients switched to TransCon PTH titrated to doses of 6-60 µg/day along with conventional therapy, with the goal of maintaining normocalcemia.
Participants were a mean age of 50 years, 81% were women, and 92% were White. Causes of hypoparathyroidism were neck surgery in 80%, autoimmune disease in 2%, and idiopathic disease in 19%. Disease duration was 12 years (range 1-39), and all were taking conventional therapy including calcium and active vitamin D (calcitriol or alfacaldiol).
At 110 weeks, all 57 patients were able to stop taking active vitamin D, and 53 of the 57 (93%) patients achieved independence from conventional therapy, defined as taking 0 µg/day of active vitamin D and no more than 600 mg/day of calcium (the dietary supplement dose). A total of 44 (77%) patients were not taking any calcium or active vitamin D.
“This really establishes the durability up to 2 years of keeping people off conventional therapy,” Dr. Rubin said during her presentation.
There was an initial uptick to 9.4 mg/dL in mean serum calcium, as some participants were still taking active vitamin D, but that dropped to 8.9 mg/dL by week 26. Mean 24-hour urine calcium dropped from 428 mg/day at baseline to 173 mg/day by week 26. Both serum calcium and urine calcium remained in the normal range through week 110 in all patients, at 8.6 mg/dL and 167 mg/day, respectively.
“This is a really important outcome because we know that high urine calcium in these patients sets them at risk for going on to develop nephrocalcinosis, nephrolithiasis, and ultimately, chronic kidney disease,” Dr. Rubin said.
Serum levels of two bone formation markers peaked at 12 weeks after initiation of TransCon PTH. Both trended downward thereafter through week 110 to levels approximating those of age- and sex-matched controls.
“Both markers started off low, consistent with hypoparathyroidism, but with initiation of TransCon PTH we see a robust increase in bone turnover markers, almost as if the bone is ‘waking up,’ if you will. And this is consistent with calcium being mobilized from the skeleton and going into the circulation,” Dr. Rubin explained.
Bone mineral density assessed by dual-energy x-ray absorptiometry normalized, primarily in the first 26 weeks. For lumbar spine L1-L4, mean Z-scores dropped from 1.6 to 1.0 at 26 weeks and down to 0.7 by week 100. For total hip, those values were 1.0, 0.6, and 0.4, respectively. The values approached age- and sex-matched norms, Dr. Rubin noted, to “perhaps where their skeleton would be if they hadn’t had hypoparathyroidism.”
Overall 56 of the 57 (94.9%) patients reported treatment-emergent adverse events, of which 25 (42.4%) were treatment related and none were deemed serious. There were no treatment-emergent adverse events related to hypercalcemia or hypocalcemia leading to health care visits or hospitalization, none leading to discontinuation of study drug, and none to death.
“So overall, a reassuring safety profile,” Dr. Rubin said. “We look forward to presenting the next 2 years’ worth of data to the end of the open-label extension study.”
Dr. Rubin is a paid researcher for Ascendis, which funded the study. Dr. Hoang has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT AACE 2023
Noninvasive skin test may aid in Cushing diagnosis
SEATTLE – new research suggests.
Tissue accumulation of AGEs – harmful compounds formed by glycation of macromolecules – has been implicated in aging, diabetes, and cardiovascular disease. Now, in a new single-center prospective study, a group of 208 patients with endogenous hypercortisolism was found to have significantly higher median tissue AGE levels than 103 reference subjects without hypercortisolism.
The findings were presented at the annual meeting of the American Association of Clinical Endocrinology by Rashi Sandooja, MD, an endocrinology fellow at the Mayo Clinic, Rochester, Minn.
“Diagnosis of endogenous hypercortisolism can be quite challenging. Often patients can have nonspecific symptoms with biochemical testing being equivocal. In these situations, new biomarkers of hypercortisolism such as AGE measurement could potentially be useful,” Dr. Sandooja said in an interview.
“After proper validation, it could help clinicians in cases which may not be straightforward and could serve as an additional” instrument in the toolkit to reach a conclusive diagnosis, she added.
Asked to comment, session moderator Anupam Kotwal, MD, said in an interview: “I think it’s very exciting data. ... I envision its use in mild autonomous cortisol secretion, where there are not a lot of overt Cushing features but they may have a small adrenal mass. ... It might be used to guide care when there’s not a clear-cut answer.”
However, he cautioned that more validation is needed to determine the correlates of AGEs by different etiologies and magnitudes of cortisol excess.
Moreover, “skin can become thin in hypercortisolism, so is [the reader device] just detecting it more with skin testing? I think a blood test for validation would be a very good next step,” added Dr. Kotwal, who is an assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha.
More work will be needed
Future directions for research should include adding a longitudinal arm and looking at the impact on AGE after patients undergo curative surgery and achieve remission, Dr. Sandooja explained.
“It will be interesting to see if AGE levels continue to be persistently high or decrease after patients achieve sustained remission of hypercortisolism. We are also interested in whether AGE measurement at baseline, prior to surgery may be associated with glucocorticoid withdrawal, myopathy, and metabolic outcomes following the surgery.”
Dr. Kotwal observed: “If the answer is clear for Cushing disease, I don’t know what extra information this would give. Maybe they would monitor people more closely afterward. It would be useful to see, but I think the first low-hanging fruit is use it in a way to guide the care of patients where we’re unclear as to whether initial treatment of this [mild autonomous cortisol secretion] is going to improve their outcomes.”
But, he added, “keeping in mind issues of skin ... we don’t want to distract clinicians and patients from using the tried and tested methods of characterizing Cushing syndrome. I’m always hesitant to bring something into practice before there is a little more information on how it can be used.”
Dr. Sandooja and Dr. Kotwal reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SEATTLE – new research suggests.
Tissue accumulation of AGEs – harmful compounds formed by glycation of macromolecules – has been implicated in aging, diabetes, and cardiovascular disease. Now, in a new single-center prospective study, a group of 208 patients with endogenous hypercortisolism was found to have significantly higher median tissue AGE levels than 103 reference subjects without hypercortisolism.
The findings were presented at the annual meeting of the American Association of Clinical Endocrinology by Rashi Sandooja, MD, an endocrinology fellow at the Mayo Clinic, Rochester, Minn.
“Diagnosis of endogenous hypercortisolism can be quite challenging. Often patients can have nonspecific symptoms with biochemical testing being equivocal. In these situations, new biomarkers of hypercortisolism such as AGE measurement could potentially be useful,” Dr. Sandooja said in an interview.
“After proper validation, it could help clinicians in cases which may not be straightforward and could serve as an additional” instrument in the toolkit to reach a conclusive diagnosis, she added.
Asked to comment, session moderator Anupam Kotwal, MD, said in an interview: “I think it’s very exciting data. ... I envision its use in mild autonomous cortisol secretion, where there are not a lot of overt Cushing features but they may have a small adrenal mass. ... It might be used to guide care when there’s not a clear-cut answer.”
However, he cautioned that more validation is needed to determine the correlates of AGEs by different etiologies and magnitudes of cortisol excess.
Moreover, “skin can become thin in hypercortisolism, so is [the reader device] just detecting it more with skin testing? I think a blood test for validation would be a very good next step,” added Dr. Kotwal, who is an assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha.
More work will be needed
Future directions for research should include adding a longitudinal arm and looking at the impact on AGE after patients undergo curative surgery and achieve remission, Dr. Sandooja explained.
“It will be interesting to see if AGE levels continue to be persistently high or decrease after patients achieve sustained remission of hypercortisolism. We are also interested in whether AGE measurement at baseline, prior to surgery may be associated with glucocorticoid withdrawal, myopathy, and metabolic outcomes following the surgery.”
Dr. Kotwal observed: “If the answer is clear for Cushing disease, I don’t know what extra information this would give. Maybe they would monitor people more closely afterward. It would be useful to see, but I think the first low-hanging fruit is use it in a way to guide the care of patients where we’re unclear as to whether initial treatment of this [mild autonomous cortisol secretion] is going to improve their outcomes.”
But, he added, “keeping in mind issues of skin ... we don’t want to distract clinicians and patients from using the tried and tested methods of characterizing Cushing syndrome. I’m always hesitant to bring something into practice before there is a little more information on how it can be used.”
Dr. Sandooja and Dr. Kotwal reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SEATTLE – new research suggests.
Tissue accumulation of AGEs – harmful compounds formed by glycation of macromolecules – has been implicated in aging, diabetes, and cardiovascular disease. Now, in a new single-center prospective study, a group of 208 patients with endogenous hypercortisolism was found to have significantly higher median tissue AGE levels than 103 reference subjects without hypercortisolism.
The findings were presented at the annual meeting of the American Association of Clinical Endocrinology by Rashi Sandooja, MD, an endocrinology fellow at the Mayo Clinic, Rochester, Minn.
“Diagnosis of endogenous hypercortisolism can be quite challenging. Often patients can have nonspecific symptoms with biochemical testing being equivocal. In these situations, new biomarkers of hypercortisolism such as AGE measurement could potentially be useful,” Dr. Sandooja said in an interview.
“After proper validation, it could help clinicians in cases which may not be straightforward and could serve as an additional” instrument in the toolkit to reach a conclusive diagnosis, she added.
Asked to comment, session moderator Anupam Kotwal, MD, said in an interview: “I think it’s very exciting data. ... I envision its use in mild autonomous cortisol secretion, where there are not a lot of overt Cushing features but they may have a small adrenal mass. ... It might be used to guide care when there’s not a clear-cut answer.”
However, he cautioned that more validation is needed to determine the correlates of AGEs by different etiologies and magnitudes of cortisol excess.
Moreover, “skin can become thin in hypercortisolism, so is [the reader device] just detecting it more with skin testing? I think a blood test for validation would be a very good next step,” added Dr. Kotwal, who is an assistant professor in the division of diabetes, endocrinology and metabolism at the University of Nebraska, Omaha.
More work will be needed
Future directions for research should include adding a longitudinal arm and looking at the impact on AGE after patients undergo curative surgery and achieve remission, Dr. Sandooja explained.
“It will be interesting to see if AGE levels continue to be persistently high or decrease after patients achieve sustained remission of hypercortisolism. We are also interested in whether AGE measurement at baseline, prior to surgery may be associated with glucocorticoid withdrawal, myopathy, and metabolic outcomes following the surgery.”
Dr. Kotwal observed: “If the answer is clear for Cushing disease, I don’t know what extra information this would give. Maybe they would monitor people more closely afterward. It would be useful to see, but I think the first low-hanging fruit is use it in a way to guide the care of patients where we’re unclear as to whether initial treatment of this [mild autonomous cortisol secretion] is going to improve their outcomes.”
But, he added, “keeping in mind issues of skin ... we don’t want to distract clinicians and patients from using the tried and tested methods of characterizing Cushing syndrome. I’m always hesitant to bring something into practice before there is a little more information on how it can be used.”
Dr. Sandooja and Dr. Kotwal reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT AACE 2023