VIDEO: Location of thyroid nodules may predict malignancy

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Nodules located in the upper pole of the thyroid are more likely to be malignant, according to the results of a retrospective, single-center study presented at the annual meeting of the American Association of Clinical Endocrinologists.

When nodules were located in the upper pole of the gland, the risk of malignancy was about 4 times higher than it was for nodules at other locations in the gland. Researchers confirmed the association using a multiple logistic regression model with adjustment for age, gender, body mass index, laterality, and number of nodules (odds ratio, 4.6; P = 0.03). The findings are believed to be the first to show an association between location of thyroid nodules on ultrasound and malignancy risk.

The results appear to elevate the value of ultrasound for predicting thyroid malignancy and should affect guidelines for ultrasound classification of thyroid nodules, researcher Fan Zhang, MD, PhD, a fellow at State University of New York, Brooklyn, said in a video interview. “In the future, I would recommend maybe we could consider including the location of thyroid nodules in the guidelines for better predictive value of malignancies,” she said.

Other ultrasound characteristics known to be associated with malignancy include findings of microcalcifications, increased vascularity, and nodules that are taller than they are wide, according to Dr. Zhang.

The retrospective review included data on 219 clinic patients with thyroid nodules who underwent fine-needle aspiration biopsy between July 2016 and June 2017. Nearly 80% of the nodules in the review were located in the lower pole of the gland, about 10% were in the upper pole, 7% were in the middle pole, and about 2% were found in the isthmus.

Fourteen nodules, or 7.4%, were found to be malignant, Dr. Zhang and her coauthors said in their presentation. Of those 14 malignancies, 7 were among the 149 nodules in the lower pole, 4 were among the 18 in the upper pole, and 3 were among the 21 in the middle pole.

The anatomy of the thyroid gland may be a factor in why upper pole nodules would be more likely to be associated with malignancy, according to Dr. Zhang. “The veins in the upper lobe are more tortuous compared to in the lower lobe,” she said, noting that slow venous drainage may increase the possibility of developing malignancy.

Dr. Zhang had no relevant disclosures to report.

SOURCE: Zhang F et al. AACE 2018, Abstract 1204.

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Nodules located in the upper pole of the thyroid are more likely to be malignant, according to the results of a retrospective, single-center study presented at the annual meeting of the American Association of Clinical Endocrinologists.

When nodules were located in the upper pole of the gland, the risk of malignancy was about 4 times higher than it was for nodules at other locations in the gland. Researchers confirmed the association using a multiple logistic regression model with adjustment for age, gender, body mass index, laterality, and number of nodules (odds ratio, 4.6; P = 0.03). The findings are believed to be the first to show an association between location of thyroid nodules on ultrasound and malignancy risk.

The results appear to elevate the value of ultrasound for predicting thyroid malignancy and should affect guidelines for ultrasound classification of thyroid nodules, researcher Fan Zhang, MD, PhD, a fellow at State University of New York, Brooklyn, said in a video interview. “In the future, I would recommend maybe we could consider including the location of thyroid nodules in the guidelines for better predictive value of malignancies,” she said.

Other ultrasound characteristics known to be associated with malignancy include findings of microcalcifications, increased vascularity, and nodules that are taller than they are wide, according to Dr. Zhang.

The retrospective review included data on 219 clinic patients with thyroid nodules who underwent fine-needle aspiration biopsy between July 2016 and June 2017. Nearly 80% of the nodules in the review were located in the lower pole of the gland, about 10% were in the upper pole, 7% were in the middle pole, and about 2% were found in the isthmus.

Fourteen nodules, or 7.4%, were found to be malignant, Dr. Zhang and her coauthors said in their presentation. Of those 14 malignancies, 7 were among the 149 nodules in the lower pole, 4 were among the 18 in the upper pole, and 3 were among the 21 in the middle pole.

The anatomy of the thyroid gland may be a factor in why upper pole nodules would be more likely to be associated with malignancy, according to Dr. Zhang. “The veins in the upper lobe are more tortuous compared to in the lower lobe,” she said, noting that slow venous drainage may increase the possibility of developing malignancy.

Dr. Zhang had no relevant disclosures to report.

SOURCE: Zhang F et al. AACE 2018, Abstract 1204.

Nodules located in the upper pole of the thyroid are more likely to be malignant, according to the results of a retrospective, single-center study presented at the annual meeting of the American Association of Clinical Endocrinologists.

When nodules were located in the upper pole of the gland, the risk of malignancy was about 4 times higher than it was for nodules at other locations in the gland. Researchers confirmed the association using a multiple logistic regression model with adjustment for age, gender, body mass index, laterality, and number of nodules (odds ratio, 4.6; P = 0.03). The findings are believed to be the first to show an association between location of thyroid nodules on ultrasound and malignancy risk.

The results appear to elevate the value of ultrasound for predicting thyroid malignancy and should affect guidelines for ultrasound classification of thyroid nodules, researcher Fan Zhang, MD, PhD, a fellow at State University of New York, Brooklyn, said in a video interview. “In the future, I would recommend maybe we could consider including the location of thyroid nodules in the guidelines for better predictive value of malignancies,” she said.

Other ultrasound characteristics known to be associated with malignancy include findings of microcalcifications, increased vascularity, and nodules that are taller than they are wide, according to Dr. Zhang.

The retrospective review included data on 219 clinic patients with thyroid nodules who underwent fine-needle aspiration biopsy between July 2016 and June 2017. Nearly 80% of the nodules in the review were located in the lower pole of the gland, about 10% were in the upper pole, 7% were in the middle pole, and about 2% were found in the isthmus.

Fourteen nodules, or 7.4%, were found to be malignant, Dr. Zhang and her coauthors said in their presentation. Of those 14 malignancies, 7 were among the 149 nodules in the lower pole, 4 were among the 18 in the upper pole, and 3 were among the 21 in the middle pole.

The anatomy of the thyroid gland may be a factor in why upper pole nodules would be more likely to be associated with malignancy, according to Dr. Zhang. “The veins in the upper lobe are more tortuous compared to in the lower lobe,” she said, noting that slow venous drainage may increase the possibility of developing malignancy.

Dr. Zhang had no relevant disclosures to report.

SOURCE: Zhang F et al. AACE 2018, Abstract 1204.

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Key clinical point: Thyroid nodules located in the upper pole may be considered a risk factor for malignancy.

Major finding: Assessment by location showed that 28.6% of nodules found in the upper pole were malignant, compared with 4.9% in the lower pole, 18.2% in the middle pole, and 14.3% in the isthmus (odds ratio, 5.8; P = 0.01).

Study details: A retrospective review including data on 219 clinic patients with thyroid nodules who underwent fine-needle aspiration biopsy between July 2016 and June 2017.

Disclosures: Dr. Zhang had no relevant disclosures to report.

Source: Zhang F et al. AACE 2018, Abstract 1204.

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VIDEO: Move beyond BMI to see obesity as a disease

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BOSTON – It’s time to move beyond body mass index and think about obesity as a chronic disease with complications that may need medical therapy, W. Timothy Garvey, MD, said.

“The term ‘obesity’ means so many things to different people,” Dr. Garvey explained in a video interview at the annual meeting of the American Association of Clinical Endocrinologists. “It doesn’t tell you what the impact is of excess adiposity on health.”

In fact, obesity meets the criteria needed to be defined as a disease, said Dr. Garvey, who coauthored a 2017 AACE position statement recommending a new diagnostic term for obesity: adiposity-based chronic disease, or ABCD.

“It’s not going to replace the general use of the term ‘obesity,’ of course; but for medical diagnosis, this term does tell you what we’re treating, and why we’re treating it,” noted Dr. Garvey, of the University of Alabama at Birmingham.

Instead of relying on BMI [body mass index], the ABCD model emphasizes a “complications-centric” approach that drives therapeutic decisions, which may include medication.

“A structured lifestyle intervention is the key to therapy, but if we add medications on to any lifestyle intervention, we’re going to get more bang for the buck,” Dr. Garvey explained.

“We’re going to get more weight loss and be able to keep it off for a longer period of time,” he added. “We want that in situations in particular where the patient really has complications. This could be diabetes, it could be prediabetes, it could be obstructive sleep apnea, symptomatic osteoarthritis in the knees, stress incontinence, hypertension – any one of a number of weight-related complications that are really impairing health.”

 

 

The five medications approved for chronic management of obesity all have been shown to be safe and effective in clinical trials. But they have different mechanisms of action, different side effect profiles, and different warnings and precautions, Dr. Garvey noted.

Understanding the pharmacology of all five drugs is important to help a specific patient achieve the best outcomes.

“There’s no drug that can be recommended, in a hierarchical sense, as being better than any others across the board in all patients,” Dr. Garvey explained. “We really need to individualize therapy based on their side effect profile and their types of complications that present with the patient.”
 

 

Endocrinologists can be particularly helpful in incorporating weight loss therapy into the overall therapeutic plan for refractory cases, he said, or in patients significantly burdened with metabolic complications, including dysglycemia, diabetes, hypertriglyceridemia, and nonalcoholic fatty liver disease.

Primary care physicians, advanced practice clinicians, dietitians, and others are needed on the team to engineer a successful lifestyle intervention for the obese patient. However, Dr. Garvey emphasized that the endocrinology subspecialty encompasses not only endocrinology and diabetes, but also metabolism.

“We need to take the lead here,” Dr. Garvey said. “Obesity is the most common metabolic disease on the planet.”

Dr. Garvey reported disclosures related to Janssen, Novo Nordisk, and Sanofi.
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BOSTON – It’s time to move beyond body mass index and think about obesity as a chronic disease with complications that may need medical therapy, W. Timothy Garvey, MD, said.

“The term ‘obesity’ means so many things to different people,” Dr. Garvey explained in a video interview at the annual meeting of the American Association of Clinical Endocrinologists. “It doesn’t tell you what the impact is of excess adiposity on health.”

In fact, obesity meets the criteria needed to be defined as a disease, said Dr. Garvey, who coauthored a 2017 AACE position statement recommending a new diagnostic term for obesity: adiposity-based chronic disease, or ABCD.

“It’s not going to replace the general use of the term ‘obesity,’ of course; but for medical diagnosis, this term does tell you what we’re treating, and why we’re treating it,” noted Dr. Garvey, of the University of Alabama at Birmingham.

Instead of relying on BMI [body mass index], the ABCD model emphasizes a “complications-centric” approach that drives therapeutic decisions, which may include medication.

“A structured lifestyle intervention is the key to therapy, but if we add medications on to any lifestyle intervention, we’re going to get more bang for the buck,” Dr. Garvey explained.

“We’re going to get more weight loss and be able to keep it off for a longer period of time,” he added. “We want that in situations in particular where the patient really has complications. This could be diabetes, it could be prediabetes, it could be obstructive sleep apnea, symptomatic osteoarthritis in the knees, stress incontinence, hypertension – any one of a number of weight-related complications that are really impairing health.”

 

 

The five medications approved for chronic management of obesity all have been shown to be safe and effective in clinical trials. But they have different mechanisms of action, different side effect profiles, and different warnings and precautions, Dr. Garvey noted.

Understanding the pharmacology of all five drugs is important to help a specific patient achieve the best outcomes.

“There’s no drug that can be recommended, in a hierarchical sense, as being better than any others across the board in all patients,” Dr. Garvey explained. “We really need to individualize therapy based on their side effect profile and their types of complications that present with the patient.”
 

 

Endocrinologists can be particularly helpful in incorporating weight loss therapy into the overall therapeutic plan for refractory cases, he said, or in patients significantly burdened with metabolic complications, including dysglycemia, diabetes, hypertriglyceridemia, and nonalcoholic fatty liver disease.

Primary care physicians, advanced practice clinicians, dietitians, and others are needed on the team to engineer a successful lifestyle intervention for the obese patient. However, Dr. Garvey emphasized that the endocrinology subspecialty encompasses not only endocrinology and diabetes, but also metabolism.

“We need to take the lead here,” Dr. Garvey said. “Obesity is the most common metabolic disease on the planet.”

Dr. Garvey reported disclosures related to Janssen, Novo Nordisk, and Sanofi.

BOSTON – It’s time to move beyond body mass index and think about obesity as a chronic disease with complications that may need medical therapy, W. Timothy Garvey, MD, said.

“The term ‘obesity’ means so many things to different people,” Dr. Garvey explained in a video interview at the annual meeting of the American Association of Clinical Endocrinologists. “It doesn’t tell you what the impact is of excess adiposity on health.”

In fact, obesity meets the criteria needed to be defined as a disease, said Dr. Garvey, who coauthored a 2017 AACE position statement recommending a new diagnostic term for obesity: adiposity-based chronic disease, or ABCD.

“It’s not going to replace the general use of the term ‘obesity,’ of course; but for medical diagnosis, this term does tell you what we’re treating, and why we’re treating it,” noted Dr. Garvey, of the University of Alabama at Birmingham.

Instead of relying on BMI [body mass index], the ABCD model emphasizes a “complications-centric” approach that drives therapeutic decisions, which may include medication.

“A structured lifestyle intervention is the key to therapy, but if we add medications on to any lifestyle intervention, we’re going to get more bang for the buck,” Dr. Garvey explained.

“We’re going to get more weight loss and be able to keep it off for a longer period of time,” he added. “We want that in situations in particular where the patient really has complications. This could be diabetes, it could be prediabetes, it could be obstructive sleep apnea, symptomatic osteoarthritis in the knees, stress incontinence, hypertension – any one of a number of weight-related complications that are really impairing health.”

 

 

The five medications approved for chronic management of obesity all have been shown to be safe and effective in clinical trials. But they have different mechanisms of action, different side effect profiles, and different warnings and precautions, Dr. Garvey noted.

Understanding the pharmacology of all five drugs is important to help a specific patient achieve the best outcomes.

“There’s no drug that can be recommended, in a hierarchical sense, as being better than any others across the board in all patients,” Dr. Garvey explained. “We really need to individualize therapy based on their side effect profile and their types of complications that present with the patient.”
 

 

Endocrinologists can be particularly helpful in incorporating weight loss therapy into the overall therapeutic plan for refractory cases, he said, or in patients significantly burdened with metabolic complications, including dysglycemia, diabetes, hypertriglyceridemia, and nonalcoholic fatty liver disease.

Primary care physicians, advanced practice clinicians, dietitians, and others are needed on the team to engineer a successful lifestyle intervention for the obese patient. However, Dr. Garvey emphasized that the endocrinology subspecialty encompasses not only endocrinology and diabetes, but also metabolism.

“We need to take the lead here,” Dr. Garvey said. “Obesity is the most common metabolic disease on the planet.”

Dr. Garvey reported disclosures related to Janssen, Novo Nordisk, and Sanofi.
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VIDEO: Diabetes patients achieve lipid goals on alirocumab

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BOSTON – The PCSK9 inhibitor alirocumab was superior to ezetimibe in meeting multiple lipid goals In patients with type 2 diabetes, according to results from a pooled analysis of randomized clinical trials.

“Alirocumab is an efficient therapy to get patients at target, which is our clinical daily business and the reason to treat patients,” said investigator Dirk Müller-Wieland, MD, an internist at University Hospital Aachen, Germany.

Dr. Müller-Wieland and his colleagues conducted a pooled analysis of 407 individuals with type 2 diabetes enrolled in one of three randomized trials who had hypercholesterolemia despite background lipid-lowering treatments. They found a total of 241 patients with diabetes who had received alirocumab in the trials, and 166 who had received ezetimibe.

With alirocumab on top of statins, 75.0% of patients met a combined LDL cholesterol, non–HDL cholesterol, and apolipoprotein B threshold after 24 weeks of treatment, compared with 56.7% of patients receiving ezetimibe along with their statins, a significant difference, it was reported at the annual meeting of the American Association of Clinical Endocrinologists.

The proportion of patients achieving LDL levels of less than 70 or 100 mg/dL (depending on cardiovascular risk) was significantly larger in the alirocumab group than in the ezetimibe group, at 80.8% versus 64.3%, Dr. Müller-Wieland reported.

In patients with extreme cardiovascular risk, the proportion of patients achieving LDL levels of less than 55 mg/dL was 66.0% in the alirocumab group, compared with 36.6% in the ezetimibe group, suggesting the PCSK9 inhibitor was “much more efficient than ezetimibe” in reaching that goal, Dr. Müller-Wieland said in a video interview.

For patients in the extreme cardiovascular risk category, as defined in recent guidelines, the AACE recommends a new LDL treatment goal of less than 55 mg/dL, Dr. Müller-Wieland noted.

Significant differences in favor of alirocumab were also reported for the proportion of patients achieving non-HDL and ApoB goals, the report showed.

Adverse events related to treatment occurred in a similar proportion of patients in the alirocumab and ezetimibe groups, according to the investigators.

SOURCE: Müller-Wieland D et al. AACE 2018. Abstract #402.

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BOSTON – The PCSK9 inhibitor alirocumab was superior to ezetimibe in meeting multiple lipid goals In patients with type 2 diabetes, according to results from a pooled analysis of randomized clinical trials.

“Alirocumab is an efficient therapy to get patients at target, which is our clinical daily business and the reason to treat patients,” said investigator Dirk Müller-Wieland, MD, an internist at University Hospital Aachen, Germany.

Dr. Müller-Wieland and his colleagues conducted a pooled analysis of 407 individuals with type 2 diabetes enrolled in one of three randomized trials who had hypercholesterolemia despite background lipid-lowering treatments. They found a total of 241 patients with diabetes who had received alirocumab in the trials, and 166 who had received ezetimibe.

With alirocumab on top of statins, 75.0% of patients met a combined LDL cholesterol, non–HDL cholesterol, and apolipoprotein B threshold after 24 weeks of treatment, compared with 56.7% of patients receiving ezetimibe along with their statins, a significant difference, it was reported at the annual meeting of the American Association of Clinical Endocrinologists.

The proportion of patients achieving LDL levels of less than 70 or 100 mg/dL (depending on cardiovascular risk) was significantly larger in the alirocumab group than in the ezetimibe group, at 80.8% versus 64.3%, Dr. Müller-Wieland reported.

In patients with extreme cardiovascular risk, the proportion of patients achieving LDL levels of less than 55 mg/dL was 66.0% in the alirocumab group, compared with 36.6% in the ezetimibe group, suggesting the PCSK9 inhibitor was “much more efficient than ezetimibe” in reaching that goal, Dr. Müller-Wieland said in a video interview.

For patients in the extreme cardiovascular risk category, as defined in recent guidelines, the AACE recommends a new LDL treatment goal of less than 55 mg/dL, Dr. Müller-Wieland noted.

Significant differences in favor of alirocumab were also reported for the proportion of patients achieving non-HDL and ApoB goals, the report showed.

Adverse events related to treatment occurred in a similar proportion of patients in the alirocumab and ezetimibe groups, according to the investigators.

SOURCE: Müller-Wieland D et al. AACE 2018. Abstract #402.

BOSTON – The PCSK9 inhibitor alirocumab was superior to ezetimibe in meeting multiple lipid goals In patients with type 2 diabetes, according to results from a pooled analysis of randomized clinical trials.

“Alirocumab is an efficient therapy to get patients at target, which is our clinical daily business and the reason to treat patients,” said investigator Dirk Müller-Wieland, MD, an internist at University Hospital Aachen, Germany.

Dr. Müller-Wieland and his colleagues conducted a pooled analysis of 407 individuals with type 2 diabetes enrolled in one of three randomized trials who had hypercholesterolemia despite background lipid-lowering treatments. They found a total of 241 patients with diabetes who had received alirocumab in the trials, and 166 who had received ezetimibe.

With alirocumab on top of statins, 75.0% of patients met a combined LDL cholesterol, non–HDL cholesterol, and apolipoprotein B threshold after 24 weeks of treatment, compared with 56.7% of patients receiving ezetimibe along with their statins, a significant difference, it was reported at the annual meeting of the American Association of Clinical Endocrinologists.

The proportion of patients achieving LDL levels of less than 70 or 100 mg/dL (depending on cardiovascular risk) was significantly larger in the alirocumab group than in the ezetimibe group, at 80.8% versus 64.3%, Dr. Müller-Wieland reported.

In patients with extreme cardiovascular risk, the proportion of patients achieving LDL levels of less than 55 mg/dL was 66.0% in the alirocumab group, compared with 36.6% in the ezetimibe group, suggesting the PCSK9 inhibitor was “much more efficient than ezetimibe” in reaching that goal, Dr. Müller-Wieland said in a video interview.

For patients in the extreme cardiovascular risk category, as defined in recent guidelines, the AACE recommends a new LDL treatment goal of less than 55 mg/dL, Dr. Müller-Wieland noted.

Significant differences in favor of alirocumab were also reported for the proportion of patients achieving non-HDL and ApoB goals, the report showed.

Adverse events related to treatment occurred in a similar proportion of patients in the alirocumab and ezetimibe groups, according to the investigators.

SOURCE: Müller-Wieland D et al. AACE 2018. Abstract #402.

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Key clinical point: The PCSK9 inhibitor alirocumab was superior to ezetimibe in meeting multiple lipid goals in patients with type 2 diabetes on background statins.

Major finding: 75.0% of alirocumab-treated individuals met a combined LDL-C, non–HDL-C, and ApoB threshold, compared with 56.7% of ezetimibe-treated individuals (P = .0003).

Study details: A pooled analysis of 407 individuals with type 2 diabetes enrolled in one of three randomized trials of alirocumab. Of them, 241 had received alirocumab, and 166 received ezetimibe.

Disclosures: Dr. Müller-Wieland reported speakers bureau and consultant/advisory board fees from Amgen, Astrazeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Novo Nordisk, and Sanofi.

Source: Müller-Wieland D et al. AACE 2018. Abstract #402.

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Hematocrit improvement with SGLT2 inhibitor: Not just a diuretic effect?

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BOSTON – The SGLT2 inhibitor dapagliflozin may increase red blood cell production by suppressing plasma levels of hepcidin, a proinflammatory inhibitor of iron transport, according to results of a randomized study.

This reduction in hepcidin provides a new mechanistic explanation for the improvement in hematocrit seen with SGLT2 inhibitor treatment and suggests a role for use of these drugs beyond their current indications, according to researcher Husam A. Ghanim, PhD, of the State University of New York at Buffalo.

Dr. Husam A. Ghanim
“While the common knowledge is that SGLT2 inhibitors increase hematocrit through hemoconcentration, it is possible that the other mechanisms are involved, including the anti-inflammatory effect that suppresses hepcidin, as well as increased erythropoiesis due to kidney function improvement,” Dr. Ghanim said in a presentation at the annual meeting of the American Association of Clinical Endocrinologists.

To see whether there were other mechanisms involved beyond hemoconcentration caused by diuretic effects of the drugs, Dr. Ghanim and his colleagues investigated the possibility that dapagliflozin might suppress concentrations of hepcidin concentrations, thereby increasing erythropoiesis.

Their study included 22 patients with type 2 diabetes and normal renal function randomized to dapagliflozin 10 mg daily or placebo for 12 weeks.

They found that the plasma concentration of hepcidin fell significantly over that time period, from 265 to 215 ng/mL in dapagliflozin-treated patients. They also saw significant decreases in hemoglobin A1c, hemoglobin concentration, and hematocrit, as well as an increase in transferrin, the major transporter of iron in the circulation, over 12 weeks.

 

 

No such significant changes in those measures were seen in the placebo group, Dr. Ghanim said.

There was a modest but nonsignificant increase in erythropoietin concentrations in the dapagliflozin-treated group, according to the researcher.

Circulating ferritin also fell by about 40% over the course of the study. “Circulating ferritin doesn’t have a clear indication or implication on iron transport,” Dr. Ghanim said. “However, it gets secreted from macrophages and from the liver, and it gets used as a marker for inflammation, and it’s also used as a marker of liver function. So a reduction in ferritin levels may have some clinical implication to what’s going on in the liver.”

On the basis of these findings, it appears that SGLT2 inhibition might increase hematocrit via anti-inflammatory effects and increased erythropoiesis, Dr. Ghanim said.
 

 

The increase in oxygenated blood available to tissues might contribute to the beneficial effects of SGLT2 inhibitors on cardiovascular disease, he added.

Also, it’s possible that SGLT2 inhibitors could have a “major impact” on the liver since hepcidin and ferritin are secreted mainly by the liver: “This could also lead us to think that it is possible that we could use SGLT2 inhibitors in conditions of liver inflammation like nonalcoholic steatohepatitis and fatty liver disease,” Dr. Ghanim said in his presentation. “These are future ideas we could explore, based on our data.”

Dr. Ghanim had no disclosures to report.

SOURCE: Ghanim HA et al. AACE 2018, Abstract 228.

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BOSTON – The SGLT2 inhibitor dapagliflozin may increase red blood cell production by suppressing plasma levels of hepcidin, a proinflammatory inhibitor of iron transport, according to results of a randomized study.

This reduction in hepcidin provides a new mechanistic explanation for the improvement in hematocrit seen with SGLT2 inhibitor treatment and suggests a role for use of these drugs beyond their current indications, according to researcher Husam A. Ghanim, PhD, of the State University of New York at Buffalo.

Dr. Husam A. Ghanim
“While the common knowledge is that SGLT2 inhibitors increase hematocrit through hemoconcentration, it is possible that the other mechanisms are involved, including the anti-inflammatory effect that suppresses hepcidin, as well as increased erythropoiesis due to kidney function improvement,” Dr. Ghanim said in a presentation at the annual meeting of the American Association of Clinical Endocrinologists.

To see whether there were other mechanisms involved beyond hemoconcentration caused by diuretic effects of the drugs, Dr. Ghanim and his colleagues investigated the possibility that dapagliflozin might suppress concentrations of hepcidin concentrations, thereby increasing erythropoiesis.

Their study included 22 patients with type 2 diabetes and normal renal function randomized to dapagliflozin 10 mg daily or placebo for 12 weeks.

They found that the plasma concentration of hepcidin fell significantly over that time period, from 265 to 215 ng/mL in dapagliflozin-treated patients. They also saw significant decreases in hemoglobin A1c, hemoglobin concentration, and hematocrit, as well as an increase in transferrin, the major transporter of iron in the circulation, over 12 weeks.

 

 

No such significant changes in those measures were seen in the placebo group, Dr. Ghanim said.

There was a modest but nonsignificant increase in erythropoietin concentrations in the dapagliflozin-treated group, according to the researcher.

Circulating ferritin also fell by about 40% over the course of the study. “Circulating ferritin doesn’t have a clear indication or implication on iron transport,” Dr. Ghanim said. “However, it gets secreted from macrophages and from the liver, and it gets used as a marker for inflammation, and it’s also used as a marker of liver function. So a reduction in ferritin levels may have some clinical implication to what’s going on in the liver.”

On the basis of these findings, it appears that SGLT2 inhibition might increase hematocrit via anti-inflammatory effects and increased erythropoiesis, Dr. Ghanim said.
 

 

The increase in oxygenated blood available to tissues might contribute to the beneficial effects of SGLT2 inhibitors on cardiovascular disease, he added.

Also, it’s possible that SGLT2 inhibitors could have a “major impact” on the liver since hepcidin and ferritin are secreted mainly by the liver: “This could also lead us to think that it is possible that we could use SGLT2 inhibitors in conditions of liver inflammation like nonalcoholic steatohepatitis and fatty liver disease,” Dr. Ghanim said in his presentation. “These are future ideas we could explore, based on our data.”

Dr. Ghanim had no disclosures to report.

SOURCE: Ghanim HA et al. AACE 2018, Abstract 228.

BOSTON – The SGLT2 inhibitor dapagliflozin may increase red blood cell production by suppressing plasma levels of hepcidin, a proinflammatory inhibitor of iron transport, according to results of a randomized study.

This reduction in hepcidin provides a new mechanistic explanation for the improvement in hematocrit seen with SGLT2 inhibitor treatment and suggests a role for use of these drugs beyond their current indications, according to researcher Husam A. Ghanim, PhD, of the State University of New York at Buffalo.

Dr. Husam A. Ghanim
“While the common knowledge is that SGLT2 inhibitors increase hematocrit through hemoconcentration, it is possible that the other mechanisms are involved, including the anti-inflammatory effect that suppresses hepcidin, as well as increased erythropoiesis due to kidney function improvement,” Dr. Ghanim said in a presentation at the annual meeting of the American Association of Clinical Endocrinologists.

To see whether there were other mechanisms involved beyond hemoconcentration caused by diuretic effects of the drugs, Dr. Ghanim and his colleagues investigated the possibility that dapagliflozin might suppress concentrations of hepcidin concentrations, thereby increasing erythropoiesis.

Their study included 22 patients with type 2 diabetes and normal renal function randomized to dapagliflozin 10 mg daily or placebo for 12 weeks.

They found that the plasma concentration of hepcidin fell significantly over that time period, from 265 to 215 ng/mL in dapagliflozin-treated patients. They also saw significant decreases in hemoglobin A1c, hemoglobin concentration, and hematocrit, as well as an increase in transferrin, the major transporter of iron in the circulation, over 12 weeks.

 

 

No such significant changes in those measures were seen in the placebo group, Dr. Ghanim said.

There was a modest but nonsignificant increase in erythropoietin concentrations in the dapagliflozin-treated group, according to the researcher.

Circulating ferritin also fell by about 40% over the course of the study. “Circulating ferritin doesn’t have a clear indication or implication on iron transport,” Dr. Ghanim said. “However, it gets secreted from macrophages and from the liver, and it gets used as a marker for inflammation, and it’s also used as a marker of liver function. So a reduction in ferritin levels may have some clinical implication to what’s going on in the liver.”

On the basis of these findings, it appears that SGLT2 inhibition might increase hematocrit via anti-inflammatory effects and increased erythropoiesis, Dr. Ghanim said.
 

 

The increase in oxygenated blood available to tissues might contribute to the beneficial effects of SGLT2 inhibitors on cardiovascular disease, he added.

Also, it’s possible that SGLT2 inhibitors could have a “major impact” on the liver since hepcidin and ferritin are secreted mainly by the liver: “This could also lead us to think that it is possible that we could use SGLT2 inhibitors in conditions of liver inflammation like nonalcoholic steatohepatitis and fatty liver disease,” Dr. Ghanim said in his presentation. “These are future ideas we could explore, based on our data.”

Dr. Ghanim had no disclosures to report.

SOURCE: Ghanim HA et al. AACE 2018, Abstract 228.

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Key clinical point: The SGLT2 inhibitor dapagliflozin suppressed hepcidin, a proinflammatory inhibitor of iron transport.

Major finding: Hepcidin plasma concentration fell from 265 to 215 ng/mL (P < 0.05) in dapagliflozin-treated patients.

Study details: A study of 22 patients with type 2 diabetes randomized to either dapagliflozin 10 mg daily or placebo for 12 weeks.

Disclosures: Dr. Ghanim had no disclosures related to the presentation.

Source: Ghanim HA et al. AACE 2018, Abstract 228.

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VIDEO: Real-world findings on hybrid closed-loop insulin system

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– Real-world experience with the Medtronic MiniMed 670G, a hybrid closed-loop insulin delivery system, showed the device was associated with improved average glucose readings and more time in euglycemia in 26 patients with type 1 diabetes.

The findings go beyond the safety data from the clinical trial of the MiniMed 670G system, Kathryn Weaver, MD, of the University of Washington, Seattle, and her colleagues reported in a poster presented at the annual meeting of the American Association of Clinical Endocrinologists.

Vidyard Video

The clinical trial included a 2-week run-in period during which the system was used in manual mode before it was switched to automated mode. Mean sensor glucose readings for participants went from 150.2 mg/dL during run-in to 150.8 mg/dL at the end of 3 months, which was not a statistically significant difference (JAMA. 2016;316[13]:1407-8).

In the real-world study, average sensor glucose readings dropped from a mean 169.46 mg/dL at baseline to 157.08 mg/dL at the end of the 3-month study period (P = .05). Also, the time spent with blood glucose levels greater than 180 mg/dL fell from 26.5% to 20% (P = .007), while the amount of time with glucose readings between 70 and 180 mg/dL increased from 61.7% to 71.1% (P = .02). Periods of hypoglycemia and severe hypoglycemia were already low at baseline and did not change, Dr. Weaver said.

“It is important to note that the initial pivotal trial was a study designed to evaluate safety not a study designed to evaluate effectiveness. And the [trial] group did demonstrate safety; they had a very significant reduction in the amount of hypoglycemia” with the pump, said Dr. Weaver. “We did not show a significant reduction in hypoglycemia in our [real-world] group, likely because we had a very low rate of hypoglycemia going into the study.”

Two of the study coauthors are employees of Medtronic, which manufactures the MiniMed 670G insulin pump/continuous glucose monitor. Medtronic did not provide funding support for the study or provide the closed-loop systems, and Dr. Weaver reported that she had no relevant financial disclosures.

SOURCE: Weaver K et al. AACE 2018, Abstract 210.

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– Real-world experience with the Medtronic MiniMed 670G, a hybrid closed-loop insulin delivery system, showed the device was associated with improved average glucose readings and more time in euglycemia in 26 patients with type 1 diabetes.

The findings go beyond the safety data from the clinical trial of the MiniMed 670G system, Kathryn Weaver, MD, of the University of Washington, Seattle, and her colleagues reported in a poster presented at the annual meeting of the American Association of Clinical Endocrinologists.

Vidyard Video

The clinical trial included a 2-week run-in period during which the system was used in manual mode before it was switched to automated mode. Mean sensor glucose readings for participants went from 150.2 mg/dL during run-in to 150.8 mg/dL at the end of 3 months, which was not a statistically significant difference (JAMA. 2016;316[13]:1407-8).

In the real-world study, average sensor glucose readings dropped from a mean 169.46 mg/dL at baseline to 157.08 mg/dL at the end of the 3-month study period (P = .05). Also, the time spent with blood glucose levels greater than 180 mg/dL fell from 26.5% to 20% (P = .007), while the amount of time with glucose readings between 70 and 180 mg/dL increased from 61.7% to 71.1% (P = .02). Periods of hypoglycemia and severe hypoglycemia were already low at baseline and did not change, Dr. Weaver said.

“It is important to note that the initial pivotal trial was a study designed to evaluate safety not a study designed to evaluate effectiveness. And the [trial] group did demonstrate safety; they had a very significant reduction in the amount of hypoglycemia” with the pump, said Dr. Weaver. “We did not show a significant reduction in hypoglycemia in our [real-world] group, likely because we had a very low rate of hypoglycemia going into the study.”

Two of the study coauthors are employees of Medtronic, which manufactures the MiniMed 670G insulin pump/continuous glucose monitor. Medtronic did not provide funding support for the study or provide the closed-loop systems, and Dr. Weaver reported that she had no relevant financial disclosures.

SOURCE: Weaver K et al. AACE 2018, Abstract 210.

– Real-world experience with the Medtronic MiniMed 670G, a hybrid closed-loop insulin delivery system, showed the device was associated with improved average glucose readings and more time in euglycemia in 26 patients with type 1 diabetes.

The findings go beyond the safety data from the clinical trial of the MiniMed 670G system, Kathryn Weaver, MD, of the University of Washington, Seattle, and her colleagues reported in a poster presented at the annual meeting of the American Association of Clinical Endocrinologists.

Vidyard Video

The clinical trial included a 2-week run-in period during which the system was used in manual mode before it was switched to automated mode. Mean sensor glucose readings for participants went from 150.2 mg/dL during run-in to 150.8 mg/dL at the end of 3 months, which was not a statistically significant difference (JAMA. 2016;316[13]:1407-8).

In the real-world study, average sensor glucose readings dropped from a mean 169.46 mg/dL at baseline to 157.08 mg/dL at the end of the 3-month study period (P = .05). Also, the time spent with blood glucose levels greater than 180 mg/dL fell from 26.5% to 20% (P = .007), while the amount of time with glucose readings between 70 and 180 mg/dL increased from 61.7% to 71.1% (P = .02). Periods of hypoglycemia and severe hypoglycemia were already low at baseline and did not change, Dr. Weaver said.

“It is important to note that the initial pivotal trial was a study designed to evaluate safety not a study designed to evaluate effectiveness. And the [trial] group did demonstrate safety; they had a very significant reduction in the amount of hypoglycemia” with the pump, said Dr. Weaver. “We did not show a significant reduction in hypoglycemia in our [real-world] group, likely because we had a very low rate of hypoglycemia going into the study.”

Two of the study coauthors are employees of Medtronic, which manufactures the MiniMed 670G insulin pump/continuous glucose monitor. Medtronic did not provide funding support for the study or provide the closed-loop systems, and Dr. Weaver reported that she had no relevant financial disclosures.

SOURCE: Weaver K et al. AACE 2018, Abstract 210.

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Transgender care mandates endocrinologists share their expertise

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BOSTON – Endocrinologists need to be familiar with new practice guidelines and changes in the landscape of transgender health care, Joshua D. Safer, MD, executive director of the Mount Sinai Center for Transgender Medicine and Surgery, New York, said in a video interview at the annual meeting of the American Association of Clinical Endocrinologists.

“We endocrinologists ... need to be able to help (gender-dysphoric/gender-incongruent) individuals, even if it’s just an occasional patient, to do what is safe and to be expert (in transgender health care), just as we are with other hormone treatments,” he said in a discussion of aspects of the Endocrine Society clinical practice guideline on endocrine treatment of gender-dysphoric/gender-incongruent individuals.

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel


The new guidelines, published in November 2017, update 2009 guidance from the society. Among the big changes are the recognition that there may be “compelling reasons” to start cross-sex hormonal therapy prior to the old age cutoff of 16 years, which is “very late if you’re thinking about it from a biological perspective,” said Dr. Safer.

Another major change challenges the idea that a mental health professional is necessary to diagnose adults. Rather, any knowledgeable clinician could make the diagnosis, according to Dr. Safer.

The guidelines also recommend that endocrinologists provide education regarding onset and time course of physical changes induced by sex hormone treatments to transgender individuals undergoing treatment.

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BOSTON – Endocrinologists need to be familiar with new practice guidelines and changes in the landscape of transgender health care, Joshua D. Safer, MD, executive director of the Mount Sinai Center for Transgender Medicine and Surgery, New York, said in a video interview at the annual meeting of the American Association of Clinical Endocrinologists.

“We endocrinologists ... need to be able to help (gender-dysphoric/gender-incongruent) individuals, even if it’s just an occasional patient, to do what is safe and to be expert (in transgender health care), just as we are with other hormone treatments,” he said in a discussion of aspects of the Endocrine Society clinical practice guideline on endocrine treatment of gender-dysphoric/gender-incongruent individuals.

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel


The new guidelines, published in November 2017, update 2009 guidance from the society. Among the big changes are the recognition that there may be “compelling reasons” to start cross-sex hormonal therapy prior to the old age cutoff of 16 years, which is “very late if you’re thinking about it from a biological perspective,” said Dr. Safer.

Another major change challenges the idea that a mental health professional is necessary to diagnose adults. Rather, any knowledgeable clinician could make the diagnosis, according to Dr. Safer.

The guidelines also recommend that endocrinologists provide education regarding onset and time course of physical changes induced by sex hormone treatments to transgender individuals undergoing treatment.

 

BOSTON – Endocrinologists need to be familiar with new practice guidelines and changes in the landscape of transgender health care, Joshua D. Safer, MD, executive director of the Mount Sinai Center for Transgender Medicine and Surgery, New York, said in a video interview at the annual meeting of the American Association of Clinical Endocrinologists.

“We endocrinologists ... need to be able to help (gender-dysphoric/gender-incongruent) individuals, even if it’s just an occasional patient, to do what is safe and to be expert (in transgender health care), just as we are with other hormone treatments,” he said in a discussion of aspects of the Endocrine Society clinical practice guideline on endocrine treatment of gender-dysphoric/gender-incongruent individuals.

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel


The new guidelines, published in November 2017, update 2009 guidance from the society. Among the big changes are the recognition that there may be “compelling reasons” to start cross-sex hormonal therapy prior to the old age cutoff of 16 years, which is “very late if you’re thinking about it from a biological perspective,” said Dr. Safer.

Another major change challenges the idea that a mental health professional is necessary to diagnose adults. Rather, any knowledgeable clinician could make the diagnosis, according to Dr. Safer.

The guidelines also recommend that endocrinologists provide education regarding onset and time course of physical changes induced by sex hormone treatments to transgender individuals undergoing treatment.

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Calcium, PTH predict permanent hypoparathyroidism

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– Low postoperative calcium serum and parathyroid hormone (PTH) levels may be strong predictors of permanent hypoparathyroidism in total thyroidectomy patients, according to results of a study presented at the annual meeting of the American Association of Clinical Endocrinologists.

With incidence of transient hypoparathyroidism at 20-30%, being able to predict at-risk patients can significantly help clinicians with postoperative management, according to Steven Brown, DO, of the University of Arizona, Phoenix.

“It’s very important to draw the preoperative lab and postoperative lab in order to help those patients who are at risk,” said Dr. Brown in an oral abstract session.

To test the predictive accuracy of PTH and calcium levels, investigators conducted a single-center, retrospective study of 176 total thyroidectomy patients recorded during 1999-2013.

Patients with hypoparathyroidism had an average age of about 47 years, was almost entirely composed of females, was majority hispanic, and had mean postop calcium and PTH levels of 7.6 mg/dL and 8.0 pg/mL, respectively.

Those without hypoparathyroidism averaged about 51 years old, were equally hispanic and white, and had postop calcium and PTH levels of 8.08 mg/dL and 30.8 pg/dL, respectively.

Patients were split into four groups: Group 1 had low calcium and PTH levels (66), group 2 had low calcium and normal PTH levels (30), group 3 had normal calcium and low PTH levels (31), and group 4 had normal levels of both (49).

Over the study period, hypoparathyroidism developed in 30% of patients in group 1, 10% in group 2, 15% in group 3, and 2% in group 4.

 

 

Permanent hypothyroidism was defined as persistently low PTH (less than 12 pg/mL), low serum calcium (less than 8.0 mg/dL), and/or requiring calcitriol to maintain a normal calcium level for more than 6 months after total thyroidectomy.

Those with both low calcium and PTH levels were 4.3 times more likely to develop permanent hypoparathyroidism than those in the other groups, according to Dr. Brown.

Patients in the permanent hypoparathyroid group had a PTH drop of 70%, compared with 39% in the nonhypoparathyroid group. There was also a significant difference in respective drops of calcium levels (17.8% vs. 14.3%).
 

 

By comparing the levels before and after a thyroidectomy, physicians can act faster and more accurately when determining how best to treat patients to prevent hypoparathyroidism, a practice which, according to Dr. Brown, has already begun to be put into place.

“We’re starting to incorporate some of the practices into our patient care routine,” said Dr. Brown. “The next part of our project is going to be to actually do a prospective study at three different institution sites in order to evaluate this further.”

Dr. Brown reported no relevant financial disclosures.

SOURCE: Brown S et al. AACE 2018, Abstract 720.

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– Low postoperative calcium serum and parathyroid hormone (PTH) levels may be strong predictors of permanent hypoparathyroidism in total thyroidectomy patients, according to results of a study presented at the annual meeting of the American Association of Clinical Endocrinologists.

With incidence of transient hypoparathyroidism at 20-30%, being able to predict at-risk patients can significantly help clinicians with postoperative management, according to Steven Brown, DO, of the University of Arizona, Phoenix.

“It’s very important to draw the preoperative lab and postoperative lab in order to help those patients who are at risk,” said Dr. Brown in an oral abstract session.

To test the predictive accuracy of PTH and calcium levels, investigators conducted a single-center, retrospective study of 176 total thyroidectomy patients recorded during 1999-2013.

Patients with hypoparathyroidism had an average age of about 47 years, was almost entirely composed of females, was majority hispanic, and had mean postop calcium and PTH levels of 7.6 mg/dL and 8.0 pg/mL, respectively.

Those without hypoparathyroidism averaged about 51 years old, were equally hispanic and white, and had postop calcium and PTH levels of 8.08 mg/dL and 30.8 pg/dL, respectively.

Patients were split into four groups: Group 1 had low calcium and PTH levels (66), group 2 had low calcium and normal PTH levels (30), group 3 had normal calcium and low PTH levels (31), and group 4 had normal levels of both (49).

Over the study period, hypoparathyroidism developed in 30% of patients in group 1, 10% in group 2, 15% in group 3, and 2% in group 4.

 

 

Permanent hypothyroidism was defined as persistently low PTH (less than 12 pg/mL), low serum calcium (less than 8.0 mg/dL), and/or requiring calcitriol to maintain a normal calcium level for more than 6 months after total thyroidectomy.

Those with both low calcium and PTH levels were 4.3 times more likely to develop permanent hypoparathyroidism than those in the other groups, according to Dr. Brown.

Patients in the permanent hypoparathyroid group had a PTH drop of 70%, compared with 39% in the nonhypoparathyroid group. There was also a significant difference in respective drops of calcium levels (17.8% vs. 14.3%).
 

 

By comparing the levels before and after a thyroidectomy, physicians can act faster and more accurately when determining how best to treat patients to prevent hypoparathyroidism, a practice which, according to Dr. Brown, has already begun to be put into place.

“We’re starting to incorporate some of the practices into our patient care routine,” said Dr. Brown. “The next part of our project is going to be to actually do a prospective study at three different institution sites in order to evaluate this further.”

Dr. Brown reported no relevant financial disclosures.

SOURCE: Brown S et al. AACE 2018, Abstract 720.

– Low postoperative calcium serum and parathyroid hormone (PTH) levels may be strong predictors of permanent hypoparathyroidism in total thyroidectomy patients, according to results of a study presented at the annual meeting of the American Association of Clinical Endocrinologists.

With incidence of transient hypoparathyroidism at 20-30%, being able to predict at-risk patients can significantly help clinicians with postoperative management, according to Steven Brown, DO, of the University of Arizona, Phoenix.

“It’s very important to draw the preoperative lab and postoperative lab in order to help those patients who are at risk,” said Dr. Brown in an oral abstract session.

To test the predictive accuracy of PTH and calcium levels, investigators conducted a single-center, retrospective study of 176 total thyroidectomy patients recorded during 1999-2013.

Patients with hypoparathyroidism had an average age of about 47 years, was almost entirely composed of females, was majority hispanic, and had mean postop calcium and PTH levels of 7.6 mg/dL and 8.0 pg/mL, respectively.

Those without hypoparathyroidism averaged about 51 years old, were equally hispanic and white, and had postop calcium and PTH levels of 8.08 mg/dL and 30.8 pg/dL, respectively.

Patients were split into four groups: Group 1 had low calcium and PTH levels (66), group 2 had low calcium and normal PTH levels (30), group 3 had normal calcium and low PTH levels (31), and group 4 had normal levels of both (49).

Over the study period, hypoparathyroidism developed in 30% of patients in group 1, 10% in group 2, 15% in group 3, and 2% in group 4.

 

 

Permanent hypothyroidism was defined as persistently low PTH (less than 12 pg/mL), low serum calcium (less than 8.0 mg/dL), and/or requiring calcitriol to maintain a normal calcium level for more than 6 months after total thyroidectomy.

Those with both low calcium and PTH levels were 4.3 times more likely to develop permanent hypoparathyroidism than those in the other groups, according to Dr. Brown.

Patients in the permanent hypoparathyroid group had a PTH drop of 70%, compared with 39% in the nonhypoparathyroid group. There was also a significant difference in respective drops of calcium levels (17.8% vs. 14.3%).
 

 

By comparing the levels before and after a thyroidectomy, physicians can act faster and more accurately when determining how best to treat patients to prevent hypoparathyroidism, a practice which, according to Dr. Brown, has already begun to be put into place.

“We’re starting to incorporate some of the practices into our patient care routine,” said Dr. Brown. “The next part of our project is going to be to actually do a prospective study at three different institution sites in order to evaluate this further.”

Dr. Brown reported no relevant financial disclosures.

SOURCE: Brown S et al. AACE 2018, Abstract 720.

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Key clinical point: Measuring calcium and parathyroid hormone can help predict permanent hypoparathyroidism.

Major finding: Patients with low calcium and low PTH were 4.3 times as likely as those without to develop permanent hypoparathyroidism after total thyroidectomy.

Study details: Retrospective, single center study of 176 total thyroidectomy patients during 1999-2013.

Disclosures: The presenter reported no relevant financial disclosures.

Source: Brown S et al. AACE 2018, Abstract 720.

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Do “VILPs” signal a new era for viral endocrinology?

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BOSTON – A new era for endocrinology could emerge based in part on the recent discovery of viral sequences that align with human peptide hormones, C. Ronald Kahn, MD, said in a plenary presentation at the annual meeting of the American Association of Clinical Endocrinologists.

Using a bioinformatics approach, researchers have identified viral sequences that align closely with 16 different human peptide hormones, including four very strongly aligned viral insulin/insulinlike growth factor–I peptides, or VILPs.

Dr. C. Ronald Khan of Harvard Medical School, Boston
Andrew Bowser/MDedge News
Dr. C. Ronald Khan
When those VILPs were chemically synthesized, the resulting peptides were able to bind to insulin and IGF-I receptors and stimulate postreceptor signaling, Dr. Kahn and colleagues reported in March 2018 in PNAS.

They also observed increased glucose uptake and activation of cell proliferation associated with VILPs, along with significantly lowered blood glucose when they were injected into mice.

Together, those results help define VILPs as the first viral hormones to be characterized, according to Dr. Kahn, head of the section on integrative physiology and metabolism at Joslin Diabetes Center, Harvard Medical School, Boston.

“We think that this is the tip of an iceberg, and could be the beginning of a new generation for endocrinologists – that of viral-hormone endocrinology,” Dr. Kahn said in his plenary presentation.

The positive outcomes seen in rodent and human cells suggest a potential role for using VILPs to treat human disease, according to Dr. Kahn.

 

 


Dr. Kahn credited Emrah Altindis, PhD, an instructor in medicine at Harvard and a research associate at Joslin, for finding the four VILPs, each encoded by a different member of the Iridoviridae family of viruses.

Iridoviridae are not known to infect humans, but they do infect fish, insects, and amphibians. In fact, iridovirus infection is the most common viral disease in saltwater fish, according to Dr. Kahn.

“What’s interesting, of course, is that we eat fish, and we can potentially eat fish that are contaminated with these viruses,” Dr. Kahn said in his presentation.

“So, could these VILPs play a role in human disease? This is really an important area of challenge,” he added.
 

 


There are many possibilities that need to be researched. If the viruses can infect human cells, then maybe they could mimic insulin signaling and cause hypoglycemia, or on the other hand, maybe they could act as competitive antagonists and impair insulin signaling, Dr. Kahn said.

The four VILPs found to date represent the tip of a potential iceberg because only about 2% of viruses have been sequenced. That means there could be 50 times as many other viral hormones out there that could influence human health and disease, Dr. Kahn said in his presentation.

Dr. Kahn reported disclosures related to CohBar, ERX Therapeutics, Kaleido Biosciences, and Merck.
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BOSTON – A new era for endocrinology could emerge based in part on the recent discovery of viral sequences that align with human peptide hormones, C. Ronald Kahn, MD, said in a plenary presentation at the annual meeting of the American Association of Clinical Endocrinologists.

Using a bioinformatics approach, researchers have identified viral sequences that align closely with 16 different human peptide hormones, including four very strongly aligned viral insulin/insulinlike growth factor–I peptides, or VILPs.

Dr. C. Ronald Khan of Harvard Medical School, Boston
Andrew Bowser/MDedge News
Dr. C. Ronald Khan
When those VILPs were chemically synthesized, the resulting peptides were able to bind to insulin and IGF-I receptors and stimulate postreceptor signaling, Dr. Kahn and colleagues reported in March 2018 in PNAS.

They also observed increased glucose uptake and activation of cell proliferation associated with VILPs, along with significantly lowered blood glucose when they were injected into mice.

Together, those results help define VILPs as the first viral hormones to be characterized, according to Dr. Kahn, head of the section on integrative physiology and metabolism at Joslin Diabetes Center, Harvard Medical School, Boston.

“We think that this is the tip of an iceberg, and could be the beginning of a new generation for endocrinologists – that of viral-hormone endocrinology,” Dr. Kahn said in his plenary presentation.

The positive outcomes seen in rodent and human cells suggest a potential role for using VILPs to treat human disease, according to Dr. Kahn.

 

 


Dr. Kahn credited Emrah Altindis, PhD, an instructor in medicine at Harvard and a research associate at Joslin, for finding the four VILPs, each encoded by a different member of the Iridoviridae family of viruses.

Iridoviridae are not known to infect humans, but they do infect fish, insects, and amphibians. In fact, iridovirus infection is the most common viral disease in saltwater fish, according to Dr. Kahn.

“What’s interesting, of course, is that we eat fish, and we can potentially eat fish that are contaminated with these viruses,” Dr. Kahn said in his presentation.

“So, could these VILPs play a role in human disease? This is really an important area of challenge,” he added.
 

 


There are many possibilities that need to be researched. If the viruses can infect human cells, then maybe they could mimic insulin signaling and cause hypoglycemia, or on the other hand, maybe they could act as competitive antagonists and impair insulin signaling, Dr. Kahn said.

The four VILPs found to date represent the tip of a potential iceberg because only about 2% of viruses have been sequenced. That means there could be 50 times as many other viral hormones out there that could influence human health and disease, Dr. Kahn said in his presentation.

Dr. Kahn reported disclosures related to CohBar, ERX Therapeutics, Kaleido Biosciences, and Merck.

 

BOSTON – A new era for endocrinology could emerge based in part on the recent discovery of viral sequences that align with human peptide hormones, C. Ronald Kahn, MD, said in a plenary presentation at the annual meeting of the American Association of Clinical Endocrinologists.

Using a bioinformatics approach, researchers have identified viral sequences that align closely with 16 different human peptide hormones, including four very strongly aligned viral insulin/insulinlike growth factor–I peptides, or VILPs.

Dr. C. Ronald Khan of Harvard Medical School, Boston
Andrew Bowser/MDedge News
Dr. C. Ronald Khan
When those VILPs were chemically synthesized, the resulting peptides were able to bind to insulin and IGF-I receptors and stimulate postreceptor signaling, Dr. Kahn and colleagues reported in March 2018 in PNAS.

They also observed increased glucose uptake and activation of cell proliferation associated with VILPs, along with significantly lowered blood glucose when they were injected into mice.

Together, those results help define VILPs as the first viral hormones to be characterized, according to Dr. Kahn, head of the section on integrative physiology and metabolism at Joslin Diabetes Center, Harvard Medical School, Boston.

“We think that this is the tip of an iceberg, and could be the beginning of a new generation for endocrinologists – that of viral-hormone endocrinology,” Dr. Kahn said in his plenary presentation.

The positive outcomes seen in rodent and human cells suggest a potential role for using VILPs to treat human disease, according to Dr. Kahn.

 

 


Dr. Kahn credited Emrah Altindis, PhD, an instructor in medicine at Harvard and a research associate at Joslin, for finding the four VILPs, each encoded by a different member of the Iridoviridae family of viruses.

Iridoviridae are not known to infect humans, but they do infect fish, insects, and amphibians. In fact, iridovirus infection is the most common viral disease in saltwater fish, according to Dr. Kahn.

“What’s interesting, of course, is that we eat fish, and we can potentially eat fish that are contaminated with these viruses,” Dr. Kahn said in his presentation.

“So, could these VILPs play a role in human disease? This is really an important area of challenge,” he added.
 

 


There are many possibilities that need to be researched. If the viruses can infect human cells, then maybe they could mimic insulin signaling and cause hypoglycemia, or on the other hand, maybe they could act as competitive antagonists and impair insulin signaling, Dr. Kahn said.

The four VILPs found to date represent the tip of a potential iceberg because only about 2% of viruses have been sequenced. That means there could be 50 times as many other viral hormones out there that could influence human health and disease, Dr. Kahn said in his presentation.

Dr. Kahn reported disclosures related to CohBar, ERX Therapeutics, Kaleido Biosciences, and Merck.
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SCVD common in women with type 1 diabetes

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BOSTON – Women with type 1 diabetes had a high prevalence of systemic collagen vascular diseases in a recent study, suggesting a global or progressive loss of immune tolerance, investigators reported at the annual meeting of the American Association of Clinical Endocrinologists.

“The median time of diagnosis for most of those autoimmune diseases was years after the diabetes diagnosis,” according to investigator Yicheng Bao, a medical student at University of Missouri-Kansas City.*


“I think there’s some loss of immune tolerance in these patients with type 1 diabetes that really deserves more study as these patients get older,” Mr. Bao said in a video interview.

The study from Mr. Bao and his colleagues was based on patient questionnaire responses and medical chart reviews for 1,167 adults with type 1 diabetes, including 628 women.

They found that SCVDs occurred in 9.2% of women, who had a significantly higher risk versus men (adjusted odds ratio, 2.57; 95% confidence interval, 1.98-3.34; P less than 0.0001).

Rheumatoid arthritis was the most commonly diagnosed SCVD, occurring in 4.3% of the women, followed by psoriasis at 2.6% and lupus at 1.8%. Others occurring in less than 1% of women included Sjögren’s, mixed connective tissue disease, granulomatosis with polyangiitis, juvenile RA, and scleroderma.

Older women were at higher risk of SCVD, with a mean age of 53.6 years versus 46.3 years for women with no SCVD (P = 0.006).

 

 


Looking at both men and women, investigators found that individuals with type 1 diabetes and an SCVD were more likely to have other autoimmune diseases, such as hypothyroidism, hyperthyroidism, and celiac disease (adjusted OR, 2.8; 95% CI, 1.71-4.60; P less than 0.0001).

Based on these findings, clinicians taking care of adults with type 1 diabetes need to be vigilant about checking for collagen vascular autoimmune diseases on review of systems, particularly in older women, Mr. Bao said.

“If the patient has a collagen vascular autoimmune disease with type 1 diabetes, they really need to be checking for these other autoimmune diseases,” he added.

Mr. Bao had no disclosures to report.

*This article was updated on May 18, 2018.

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BOSTON – Women with type 1 diabetes had a high prevalence of systemic collagen vascular diseases in a recent study, suggesting a global or progressive loss of immune tolerance, investigators reported at the annual meeting of the American Association of Clinical Endocrinologists.

“The median time of diagnosis for most of those autoimmune diseases was years after the diabetes diagnosis,” according to investigator Yicheng Bao, a medical student at University of Missouri-Kansas City.*


“I think there’s some loss of immune tolerance in these patients with type 1 diabetes that really deserves more study as these patients get older,” Mr. Bao said in a video interview.

The study from Mr. Bao and his colleagues was based on patient questionnaire responses and medical chart reviews for 1,167 adults with type 1 diabetes, including 628 women.

They found that SCVDs occurred in 9.2% of women, who had a significantly higher risk versus men (adjusted odds ratio, 2.57; 95% confidence interval, 1.98-3.34; P less than 0.0001).

Rheumatoid arthritis was the most commonly diagnosed SCVD, occurring in 4.3% of the women, followed by psoriasis at 2.6% and lupus at 1.8%. Others occurring in less than 1% of women included Sjögren’s, mixed connective tissue disease, granulomatosis with polyangiitis, juvenile RA, and scleroderma.

Older women were at higher risk of SCVD, with a mean age of 53.6 years versus 46.3 years for women with no SCVD (P = 0.006).

 

 


Looking at both men and women, investigators found that individuals with type 1 diabetes and an SCVD were more likely to have other autoimmune diseases, such as hypothyroidism, hyperthyroidism, and celiac disease (adjusted OR, 2.8; 95% CI, 1.71-4.60; P less than 0.0001).

Based on these findings, clinicians taking care of adults with type 1 diabetes need to be vigilant about checking for collagen vascular autoimmune diseases on review of systems, particularly in older women, Mr. Bao said.

“If the patient has a collagen vascular autoimmune disease with type 1 diabetes, they really need to be checking for these other autoimmune diseases,” he added.

Mr. Bao had no disclosures to report.

*This article was updated on May 18, 2018.

BOSTON – Women with type 1 diabetes had a high prevalence of systemic collagen vascular diseases in a recent study, suggesting a global or progressive loss of immune tolerance, investigators reported at the annual meeting of the American Association of Clinical Endocrinologists.

“The median time of diagnosis for most of those autoimmune diseases was years after the diabetes diagnosis,” according to investigator Yicheng Bao, a medical student at University of Missouri-Kansas City.*


“I think there’s some loss of immune tolerance in these patients with type 1 diabetes that really deserves more study as these patients get older,” Mr. Bao said in a video interview.

The study from Mr. Bao and his colleagues was based on patient questionnaire responses and medical chart reviews for 1,167 adults with type 1 diabetes, including 628 women.

They found that SCVDs occurred in 9.2% of women, who had a significantly higher risk versus men (adjusted odds ratio, 2.57; 95% confidence interval, 1.98-3.34; P less than 0.0001).

Rheumatoid arthritis was the most commonly diagnosed SCVD, occurring in 4.3% of the women, followed by psoriasis at 2.6% and lupus at 1.8%. Others occurring in less than 1% of women included Sjögren’s, mixed connective tissue disease, granulomatosis with polyangiitis, juvenile RA, and scleroderma.

Older women were at higher risk of SCVD, with a mean age of 53.6 years versus 46.3 years for women with no SCVD (P = 0.006).

 

 


Looking at both men and women, investigators found that individuals with type 1 diabetes and an SCVD were more likely to have other autoimmune diseases, such as hypothyroidism, hyperthyroidism, and celiac disease (adjusted OR, 2.8; 95% CI, 1.71-4.60; P less than 0.0001).

Based on these findings, clinicians taking care of adults with type 1 diabetes need to be vigilant about checking for collagen vascular autoimmune diseases on review of systems, particularly in older women, Mr. Bao said.

“If the patient has a collagen vascular autoimmune disease with type 1 diabetes, they really need to be checking for these other autoimmune diseases,” he added.

Mr. Bao had no disclosures to report.

*This article was updated on May 18, 2018.

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Key clinical point: The high incidence of systemic collagen vascular diseases in women with type 1 diabetes suggests a potential progressive loss of immune tolerance.

Major finding: Systemic collagen vascular diseases occurred in 9.2% of women, who had a significantly higher risk versus men (adjusted odds ratio, 2.57; 95% confidence interval, 1.98-3.34; P less than 0.0001).

Study details: A nonrandomized study including retrospective chart review and responses to questionnaires for 1,212 individuals with type 1 diabetes.

Disclosures: Mr. Bao had no disclosures to report.

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VIDEO: BMI helps predict bone fragility in obese patients

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Fri, 01/18/2019 - 17:40

 

– An index that takes into account the ratio between body mass index (BMI) and bone mineral density (BMD) correlated well with trabecular bone scores, a newer assessment of bone fragility. The index may help predict risk for fragility fractures in individuals with obesity when trabecular bone scores are not available.

“Obesity is traditionally thought to be protective against bone fractures,” said Mikiko Watanabe, MD, an endocrinologist at Sapienza University of Rome. “But recent evidence suggests that this is not entirely true, especially in morbidly obese patients.”

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel


Lumbar spine BMD alone may not accurately capture bone fragility in patients with obesity, said Dr. Watanabe in an interview at the annual meeting of the American Association of Clinical Endocrinologists.

Adding the trabecular bone score (TBS) to BMD gives additional information about bone microarchitecture, refining risk assessment for fragility fractures. This newer technology, however, may not be readily available and may be associated with extra cost.

Accordingly, said Dr. Watanabe, the study’s senior investigator, Sapienza University’s Carla Lubrano, MD, had the idea to index bone density to BMI, and then see how well the ratio correlated to TBS; obesity is known to be associated with lower TBS scores, indicating increased bone fragility.

Living in Italy, with relatively fewer medical resources available, “We were trying to find some readily available index that could predict the risk of fracture as well as the indexes that are around right now,” said Dr. Watanabe.

“We did find some very interesting data in our population of over 2,000 obese patients living in Rome,” she said. “We do confirm something from the literature, where BMD tends to go high with increasing BMI.” Further, the relatively weak correlation between TBS and BMI was confirmed in the investigators’ work (r = 0.3).

 

 


“If you correct the BMD by BMI – so if you use our index – then the correlation becomes more stringent, and definitely so much better,” she said (r = 0.54).

Dr. Watanabe and her colleagues also conducted an analysis to see if there were differences between participants with and without metabolic syndrome. The 45.7% of participants who had metabolic syndrome had similar lumbar spine BMD scores to the rest of the cohort (1.067 versus 1.063 g/cm2, P = .50754).

However, both the TBS and BMD/BMI ratio were significantly lower for those with metabolic syndrome than for the metabolically healthy participants. The TBS, as expected, was 1.21 in patients with metabolic syndrome, and 1.31 in patients without metabolic syndrome; the BMD/BMI ratio followed the same pattern, with ratios of 0.28 for those with, and 0.30 for those without, metabolic syndrome (P less than .00001 for both).

Dr. Watanabe said that she and her associates are continuing research “to see whether our ratio is actually able to predict the risk of fractures." The hope, she said, is to use the BMD/BMI index together with or instead of TBS to better assess bone strength in patients with obesity.

Dr. Watanabe reported that she had no relevant conflicts of interest.
 
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– An index that takes into account the ratio between body mass index (BMI) and bone mineral density (BMD) correlated well with trabecular bone scores, a newer assessment of bone fragility. The index may help predict risk for fragility fractures in individuals with obesity when trabecular bone scores are not available.

“Obesity is traditionally thought to be protective against bone fractures,” said Mikiko Watanabe, MD, an endocrinologist at Sapienza University of Rome. “But recent evidence suggests that this is not entirely true, especially in morbidly obese patients.”

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel


Lumbar spine BMD alone may not accurately capture bone fragility in patients with obesity, said Dr. Watanabe in an interview at the annual meeting of the American Association of Clinical Endocrinologists.

Adding the trabecular bone score (TBS) to BMD gives additional information about bone microarchitecture, refining risk assessment for fragility fractures. This newer technology, however, may not be readily available and may be associated with extra cost.

Accordingly, said Dr. Watanabe, the study’s senior investigator, Sapienza University’s Carla Lubrano, MD, had the idea to index bone density to BMI, and then see how well the ratio correlated to TBS; obesity is known to be associated with lower TBS scores, indicating increased bone fragility.

Living in Italy, with relatively fewer medical resources available, “We were trying to find some readily available index that could predict the risk of fracture as well as the indexes that are around right now,” said Dr. Watanabe.

“We did find some very interesting data in our population of over 2,000 obese patients living in Rome,” she said. “We do confirm something from the literature, where BMD tends to go high with increasing BMI.” Further, the relatively weak correlation between TBS and BMI was confirmed in the investigators’ work (r = 0.3).

 

 


“If you correct the BMD by BMI – so if you use our index – then the correlation becomes more stringent, and definitely so much better,” she said (r = 0.54).

Dr. Watanabe and her colleagues also conducted an analysis to see if there were differences between participants with and without metabolic syndrome. The 45.7% of participants who had metabolic syndrome had similar lumbar spine BMD scores to the rest of the cohort (1.067 versus 1.063 g/cm2, P = .50754).

However, both the TBS and BMD/BMI ratio were significantly lower for those with metabolic syndrome than for the metabolically healthy participants. The TBS, as expected, was 1.21 in patients with metabolic syndrome, and 1.31 in patients without metabolic syndrome; the BMD/BMI ratio followed the same pattern, with ratios of 0.28 for those with, and 0.30 for those without, metabolic syndrome (P less than .00001 for both).

Dr. Watanabe said that she and her associates are continuing research “to see whether our ratio is actually able to predict the risk of fractures." The hope, she said, is to use the BMD/BMI index together with or instead of TBS to better assess bone strength in patients with obesity.

Dr. Watanabe reported that she had no relevant conflicts of interest.
 

 

– An index that takes into account the ratio between body mass index (BMI) and bone mineral density (BMD) correlated well with trabecular bone scores, a newer assessment of bone fragility. The index may help predict risk for fragility fractures in individuals with obesity when trabecular bone scores are not available.

“Obesity is traditionally thought to be protective against bone fractures,” said Mikiko Watanabe, MD, an endocrinologist at Sapienza University of Rome. “But recent evidence suggests that this is not entirely true, especially in morbidly obese patients.”

The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel


Lumbar spine BMD alone may not accurately capture bone fragility in patients with obesity, said Dr. Watanabe in an interview at the annual meeting of the American Association of Clinical Endocrinologists.

Adding the trabecular bone score (TBS) to BMD gives additional information about bone microarchitecture, refining risk assessment for fragility fractures. This newer technology, however, may not be readily available and may be associated with extra cost.

Accordingly, said Dr. Watanabe, the study’s senior investigator, Sapienza University’s Carla Lubrano, MD, had the idea to index bone density to BMI, and then see how well the ratio correlated to TBS; obesity is known to be associated with lower TBS scores, indicating increased bone fragility.

Living in Italy, with relatively fewer medical resources available, “We were trying to find some readily available index that could predict the risk of fracture as well as the indexes that are around right now,” said Dr. Watanabe.

“We did find some very interesting data in our population of over 2,000 obese patients living in Rome,” she said. “We do confirm something from the literature, where BMD tends to go high with increasing BMI.” Further, the relatively weak correlation between TBS and BMI was confirmed in the investigators’ work (r = 0.3).

 

 


“If you correct the BMD by BMI – so if you use our index – then the correlation becomes more stringent, and definitely so much better,” she said (r = 0.54).

Dr. Watanabe and her colleagues also conducted an analysis to see if there were differences between participants with and without metabolic syndrome. The 45.7% of participants who had metabolic syndrome had similar lumbar spine BMD scores to the rest of the cohort (1.067 versus 1.063 g/cm2, P = .50754).

However, both the TBS and BMD/BMI ratio were significantly lower for those with metabolic syndrome than for the metabolically healthy participants. The TBS, as expected, was 1.21 in patients with metabolic syndrome, and 1.31 in patients without metabolic syndrome; the BMD/BMI ratio followed the same pattern, with ratios of 0.28 for those with, and 0.30 for those without, metabolic syndrome (P less than .00001 for both).

Dr. Watanabe said that she and her associates are continuing research “to see whether our ratio is actually able to predict the risk of fractures." The hope, she said, is to use the BMD/BMI index together with or instead of TBS to better assess bone strength in patients with obesity.

Dr. Watanabe reported that she had no relevant conflicts of interest.
 
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