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A patient who developed atrial fibrillation resulting from the failure to adjust the levothyroxine dose after rapid, significant weight loss while on the antiobesity drug tirzepatide (Zepbound) serves as a key reminder in managing patients experiencing rapid weight loss, either from antiobesity medications or any other means: Patients taking medications with weight-based dosing need to have their doses closely monitored.
“Failing to monitor and adjust dosing of these [and other] medications during a period of rapid weight loss may lead to supratherapeutic — even toxic — levels, as was seen in this [case],” underscore the authors of an editorial regarding the Teachable Moment case, published in JAMA Internal Medicine.
Toxicities from excessive doses can have a range of detrimental effects. In terms of thyroid medicine, the failure to adjust levothyroxine treatment for hypothyroidism in cases of rapid weight loss can lead to thyrotoxicosis, and in older patients in particular, a resulting thyrotropin level < 0.1 mIU/L is associated with as much as a threefold increased risk for atrial fibrillation, as observed in the report.
Case Demonstrates Risks
The case involved a 62-year-old man with obesity, hypothyroidism, and type 1 diabetes who presented to the emergency department with palpitations, excessive sweating, confusion, fever, and hand tremors. Upon being diagnosed with atrial fibrillation, the patient was immediately treated.
His medical history revealed the underlying culprit: Six months earlier, the patient had started treatment with the gastric inhibitory polypeptide (GIP)/glucagon-like peptide (GLP) 1 dual agonist tirzepatide. As is typical with the drug, the patient’s weight quickly plummeted, dropping from a starting body mass index of 44.4 down to 31.2 after 6 months and a decrease in body weight from 132 kg to 93 kg (a loss of 39 kg [approximately 86 lb]).
When he was prescribed tirzepatide, 2.5 mg weekly, for obesity, the patient had been recommended to increase the dose every 4 weeks as tolerated and, importantly, to have a follow-up visit in a month. But because he lived in different states seasonally, the follow-up never occurred.
Upon his emergency department visit, the patient’s thyrotropin level had dropped from 1.9 mIU/L at the first visit 6 months earlier to 0.001 mIU/L (well within the atrial fibrillation risk range), and his free thyroxine level (fT4) was 7.26 ng/ dL — substantially outside of the normal range of about 0.9-1.7 ng/dL for adults.
“The patient had 4-times higher fT4 levels of the upper limit,” first author Kagan E. Karakus, MD, of the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, told this news organization. “That is why he had experienced the adverse event of atrial fibrillation.”
Thyrotoxicosis Symptoms Can Be ‘Insidious,’ Levothyroxine Should Be Monitored
Although tirzepatide has not been approved by the US Food and Drug Administration for the treatment of type 1 diabetes, obesity is on the rise among patients with this disorder and recent research has shown a more than 10% reduction in body weight in 6 months and significant reductions in A1c with various doses.
Of note, in the current case, although the patient’s levothyroxine dose was not adjusted, his insulin dose was gradually self-decreased during his tirzepatide treatment to prevent hypoglycemia.
“If insulin treatment is excessive in diabetes, it causes hypoglycemia, [and] people with type 1 diabetes will recognize the signs of hypoglycemia related to excessive insulin earlier,” Dr. Karakus said.
If symptoms appear, patients can reduce their insulin doses on their own; however, the symptoms of thyrotoxicosis caused by excessive levothyroxine can be more insidious compared with hypoglycemia, he explained.
“Although patients can change their insulin doses, they cannot change the levothyroxine doses since it requires a blood test [thyroid-stimulating hormone; TSH] and a new prescription of the new dose.”
The key lesson is that “following levothyroxine treatment initiation or dose adjustment, 4-6 weeks is the optimal duration to recheck [the] thyrotropin level and adjust the dose as needed,” Dr. Karakus said.
Key Medications to Monitor
Other common outpatient medications that should be closely monitored in patients experiencing rapid weight loss, by any method, range from anticoagulants, anticonvulsants, and antituberculosis drugs to antibiotics and antifungals, the authors note.
Of note, medications with a narrow therapeutic index include phenytoin, warfarin, lithium carbonate, digoxin theophylline, tacrolimus, valproic acid, carbamazepine, and cyclosporine.
The failure to make necessary dose adjustments “is seen more often since the newer antiobesity drugs reduce a great amount of weight within months, almost as rapidly as bariatric surgery,” Dr. Karakus said.
“It is very important for physicians to be aware of the weight-based medications and narrow therapeutic index medications since their doses should be adjusted carefully, especially during weight loss,” he added.
Furthermore, “the patient should also know that weight reduction medication may cause adverse effects like nausea, vomiting and also may affect metabolism of other medications such that some medication doses should be adjusted regularly.”
In the editorial published with the study, Tyrone A. Johnson, MD, of the Department of Medicine, University of California, San Francisco, and colleagues note that the need for close monitoring is particularly important with older patients, who, in addition to having a higher likelihood of comorbidities, commonly have polypharmacy that could increase the potential for adverse effects.
Another key area concern is the emergence of direct-to-consumer avenues for GLP-1/GIP agonists for the many who either cannot afford or do not have access to the drugs, providing further opportunities for treatment without appropriate clinical oversight, they add.
Overall, the case “highlights the potential dangers underlying under-supervised prescribing of GLP-1/GIP receptor agonists and affirms the need for strong partnerships between patients and their clinicians during their use,” they wrote.
“These medications are best used in collaboration with continuity care teams, in context of a patient’s entire health, and in comprehensive risk-benefit assessment throughout the entire duration of treatment.”
A Caveat: Subclinical Levothyroxine Dosing
Commenting on the study, Matthew Ettleson, MD, a clinical instructor of medicine in the Section of Endocrinology, Diabetes, & Metabolism, University of Chicago, noted the important caveat that patients with hypothyroidism are commonly on subclinical doses, with varying dose adjustment needs.
“The patient in the case was clearly on a replacement level dose. However, many patients are on low doses of levothyroxine (75 µg or lower) for subclinical hypothyroidism, and, in general, I think the risks are lower with patients with subclinical hypothyroidism on lower doses of levothyroxine,” he told this news organization.
Because of that, “frequent TSH monitoring may be excessive in this population,” he said. “I would hesitate to empirically lower the dose with weight loss, unless it was clear that the patient was unlikely to follow up.
“Checking TSH at a more frequent interval and adjusting the dose accordingly should be adequate to prevent situations like this case.”
Dr. Karakus, Dr. Ettleson, and the editorial authors had no relevant disclosures to report.
A version of this article appeared on Medscape.com.
A patient who developed atrial fibrillation resulting from the failure to adjust the levothyroxine dose after rapid, significant weight loss while on the antiobesity drug tirzepatide (Zepbound) serves as a key reminder in managing patients experiencing rapid weight loss, either from antiobesity medications or any other means: Patients taking medications with weight-based dosing need to have their doses closely monitored.
“Failing to monitor and adjust dosing of these [and other] medications during a period of rapid weight loss may lead to supratherapeutic — even toxic — levels, as was seen in this [case],” underscore the authors of an editorial regarding the Teachable Moment case, published in JAMA Internal Medicine.
Toxicities from excessive doses can have a range of detrimental effects. In terms of thyroid medicine, the failure to adjust levothyroxine treatment for hypothyroidism in cases of rapid weight loss can lead to thyrotoxicosis, and in older patients in particular, a resulting thyrotropin level < 0.1 mIU/L is associated with as much as a threefold increased risk for atrial fibrillation, as observed in the report.
Case Demonstrates Risks
The case involved a 62-year-old man with obesity, hypothyroidism, and type 1 diabetes who presented to the emergency department with palpitations, excessive sweating, confusion, fever, and hand tremors. Upon being diagnosed with atrial fibrillation, the patient was immediately treated.
His medical history revealed the underlying culprit: Six months earlier, the patient had started treatment with the gastric inhibitory polypeptide (GIP)/glucagon-like peptide (GLP) 1 dual agonist tirzepatide. As is typical with the drug, the patient’s weight quickly plummeted, dropping from a starting body mass index of 44.4 down to 31.2 after 6 months and a decrease in body weight from 132 kg to 93 kg (a loss of 39 kg [approximately 86 lb]).
When he was prescribed tirzepatide, 2.5 mg weekly, for obesity, the patient had been recommended to increase the dose every 4 weeks as tolerated and, importantly, to have a follow-up visit in a month. But because he lived in different states seasonally, the follow-up never occurred.
Upon his emergency department visit, the patient’s thyrotropin level had dropped from 1.9 mIU/L at the first visit 6 months earlier to 0.001 mIU/L (well within the atrial fibrillation risk range), and his free thyroxine level (fT4) was 7.26 ng/ dL — substantially outside of the normal range of about 0.9-1.7 ng/dL for adults.
“The patient had 4-times higher fT4 levels of the upper limit,” first author Kagan E. Karakus, MD, of the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, told this news organization. “That is why he had experienced the adverse event of atrial fibrillation.”
Thyrotoxicosis Symptoms Can Be ‘Insidious,’ Levothyroxine Should Be Monitored
Although tirzepatide has not been approved by the US Food and Drug Administration for the treatment of type 1 diabetes, obesity is on the rise among patients with this disorder and recent research has shown a more than 10% reduction in body weight in 6 months and significant reductions in A1c with various doses.
Of note, in the current case, although the patient’s levothyroxine dose was not adjusted, his insulin dose was gradually self-decreased during his tirzepatide treatment to prevent hypoglycemia.
“If insulin treatment is excessive in diabetes, it causes hypoglycemia, [and] people with type 1 diabetes will recognize the signs of hypoglycemia related to excessive insulin earlier,” Dr. Karakus said.
If symptoms appear, patients can reduce their insulin doses on their own; however, the symptoms of thyrotoxicosis caused by excessive levothyroxine can be more insidious compared with hypoglycemia, he explained.
“Although patients can change their insulin doses, they cannot change the levothyroxine doses since it requires a blood test [thyroid-stimulating hormone; TSH] and a new prescription of the new dose.”
The key lesson is that “following levothyroxine treatment initiation or dose adjustment, 4-6 weeks is the optimal duration to recheck [the] thyrotropin level and adjust the dose as needed,” Dr. Karakus said.
Key Medications to Monitor
Other common outpatient medications that should be closely monitored in patients experiencing rapid weight loss, by any method, range from anticoagulants, anticonvulsants, and antituberculosis drugs to antibiotics and antifungals, the authors note.
Of note, medications with a narrow therapeutic index include phenytoin, warfarin, lithium carbonate, digoxin theophylline, tacrolimus, valproic acid, carbamazepine, and cyclosporine.
The failure to make necessary dose adjustments “is seen more often since the newer antiobesity drugs reduce a great amount of weight within months, almost as rapidly as bariatric surgery,” Dr. Karakus said.
“It is very important for physicians to be aware of the weight-based medications and narrow therapeutic index medications since their doses should be adjusted carefully, especially during weight loss,” he added.
Furthermore, “the patient should also know that weight reduction medication may cause adverse effects like nausea, vomiting and also may affect metabolism of other medications such that some medication doses should be adjusted regularly.”
In the editorial published with the study, Tyrone A. Johnson, MD, of the Department of Medicine, University of California, San Francisco, and colleagues note that the need for close monitoring is particularly important with older patients, who, in addition to having a higher likelihood of comorbidities, commonly have polypharmacy that could increase the potential for adverse effects.
Another key area concern is the emergence of direct-to-consumer avenues for GLP-1/GIP agonists for the many who either cannot afford or do not have access to the drugs, providing further opportunities for treatment without appropriate clinical oversight, they add.
Overall, the case “highlights the potential dangers underlying under-supervised prescribing of GLP-1/GIP receptor agonists and affirms the need for strong partnerships between patients and their clinicians during their use,” they wrote.
“These medications are best used in collaboration with continuity care teams, in context of a patient’s entire health, and in comprehensive risk-benefit assessment throughout the entire duration of treatment.”
A Caveat: Subclinical Levothyroxine Dosing
Commenting on the study, Matthew Ettleson, MD, a clinical instructor of medicine in the Section of Endocrinology, Diabetes, & Metabolism, University of Chicago, noted the important caveat that patients with hypothyroidism are commonly on subclinical doses, with varying dose adjustment needs.
“The patient in the case was clearly on a replacement level dose. However, many patients are on low doses of levothyroxine (75 µg or lower) for subclinical hypothyroidism, and, in general, I think the risks are lower with patients with subclinical hypothyroidism on lower doses of levothyroxine,” he told this news organization.
Because of that, “frequent TSH monitoring may be excessive in this population,” he said. “I would hesitate to empirically lower the dose with weight loss, unless it was clear that the patient was unlikely to follow up.
“Checking TSH at a more frequent interval and adjusting the dose accordingly should be adequate to prevent situations like this case.”
Dr. Karakus, Dr. Ettleson, and the editorial authors had no relevant disclosures to report.
A version of this article appeared on Medscape.com.
A patient who developed atrial fibrillation resulting from the failure to adjust the levothyroxine dose after rapid, significant weight loss while on the antiobesity drug tirzepatide (Zepbound) serves as a key reminder in managing patients experiencing rapid weight loss, either from antiobesity medications or any other means: Patients taking medications with weight-based dosing need to have their doses closely monitored.
“Failing to monitor and adjust dosing of these [and other] medications during a period of rapid weight loss may lead to supratherapeutic — even toxic — levels, as was seen in this [case],” underscore the authors of an editorial regarding the Teachable Moment case, published in JAMA Internal Medicine.
Toxicities from excessive doses can have a range of detrimental effects. In terms of thyroid medicine, the failure to adjust levothyroxine treatment for hypothyroidism in cases of rapid weight loss can lead to thyrotoxicosis, and in older patients in particular, a resulting thyrotropin level < 0.1 mIU/L is associated with as much as a threefold increased risk for atrial fibrillation, as observed in the report.
Case Demonstrates Risks
The case involved a 62-year-old man with obesity, hypothyroidism, and type 1 diabetes who presented to the emergency department with palpitations, excessive sweating, confusion, fever, and hand tremors. Upon being diagnosed with atrial fibrillation, the patient was immediately treated.
His medical history revealed the underlying culprit: Six months earlier, the patient had started treatment with the gastric inhibitory polypeptide (GIP)/glucagon-like peptide (GLP) 1 dual agonist tirzepatide. As is typical with the drug, the patient’s weight quickly plummeted, dropping from a starting body mass index of 44.4 down to 31.2 after 6 months and a decrease in body weight from 132 kg to 93 kg (a loss of 39 kg [approximately 86 lb]).
When he was prescribed tirzepatide, 2.5 mg weekly, for obesity, the patient had been recommended to increase the dose every 4 weeks as tolerated and, importantly, to have a follow-up visit in a month. But because he lived in different states seasonally, the follow-up never occurred.
Upon his emergency department visit, the patient’s thyrotropin level had dropped from 1.9 mIU/L at the first visit 6 months earlier to 0.001 mIU/L (well within the atrial fibrillation risk range), and his free thyroxine level (fT4) was 7.26 ng/ dL — substantially outside of the normal range of about 0.9-1.7 ng/dL for adults.
“The patient had 4-times higher fT4 levels of the upper limit,” first author Kagan E. Karakus, MD, of the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, told this news organization. “That is why he had experienced the adverse event of atrial fibrillation.”
Thyrotoxicosis Symptoms Can Be ‘Insidious,’ Levothyroxine Should Be Monitored
Although tirzepatide has not been approved by the US Food and Drug Administration for the treatment of type 1 diabetes, obesity is on the rise among patients with this disorder and recent research has shown a more than 10% reduction in body weight in 6 months and significant reductions in A1c with various doses.
Of note, in the current case, although the patient’s levothyroxine dose was not adjusted, his insulin dose was gradually self-decreased during his tirzepatide treatment to prevent hypoglycemia.
“If insulin treatment is excessive in diabetes, it causes hypoglycemia, [and] people with type 1 diabetes will recognize the signs of hypoglycemia related to excessive insulin earlier,” Dr. Karakus said.
If symptoms appear, patients can reduce their insulin doses on their own; however, the symptoms of thyrotoxicosis caused by excessive levothyroxine can be more insidious compared with hypoglycemia, he explained.
“Although patients can change their insulin doses, they cannot change the levothyroxine doses since it requires a blood test [thyroid-stimulating hormone; TSH] and a new prescription of the new dose.”
The key lesson is that “following levothyroxine treatment initiation or dose adjustment, 4-6 weeks is the optimal duration to recheck [the] thyrotropin level and adjust the dose as needed,” Dr. Karakus said.
Key Medications to Monitor
Other common outpatient medications that should be closely monitored in patients experiencing rapid weight loss, by any method, range from anticoagulants, anticonvulsants, and antituberculosis drugs to antibiotics and antifungals, the authors note.
Of note, medications with a narrow therapeutic index include phenytoin, warfarin, lithium carbonate, digoxin theophylline, tacrolimus, valproic acid, carbamazepine, and cyclosporine.
The failure to make necessary dose adjustments “is seen more often since the newer antiobesity drugs reduce a great amount of weight within months, almost as rapidly as bariatric surgery,” Dr. Karakus said.
“It is very important for physicians to be aware of the weight-based medications and narrow therapeutic index medications since their doses should be adjusted carefully, especially during weight loss,” he added.
Furthermore, “the patient should also know that weight reduction medication may cause adverse effects like nausea, vomiting and also may affect metabolism of other medications such that some medication doses should be adjusted regularly.”
In the editorial published with the study, Tyrone A. Johnson, MD, of the Department of Medicine, University of California, San Francisco, and colleagues note that the need for close monitoring is particularly important with older patients, who, in addition to having a higher likelihood of comorbidities, commonly have polypharmacy that could increase the potential for adverse effects.
Another key area concern is the emergence of direct-to-consumer avenues for GLP-1/GIP agonists for the many who either cannot afford or do not have access to the drugs, providing further opportunities for treatment without appropriate clinical oversight, they add.
Overall, the case “highlights the potential dangers underlying under-supervised prescribing of GLP-1/GIP receptor agonists and affirms the need for strong partnerships between patients and their clinicians during their use,” they wrote.
“These medications are best used in collaboration with continuity care teams, in context of a patient’s entire health, and in comprehensive risk-benefit assessment throughout the entire duration of treatment.”
A Caveat: Subclinical Levothyroxine Dosing
Commenting on the study, Matthew Ettleson, MD, a clinical instructor of medicine in the Section of Endocrinology, Diabetes, & Metabolism, University of Chicago, noted the important caveat that patients with hypothyroidism are commonly on subclinical doses, with varying dose adjustment needs.
“The patient in the case was clearly on a replacement level dose. However, many patients are on low doses of levothyroxine (75 µg or lower) for subclinical hypothyroidism, and, in general, I think the risks are lower with patients with subclinical hypothyroidism on lower doses of levothyroxine,” he told this news organization.
Because of that, “frequent TSH monitoring may be excessive in this population,” he said. “I would hesitate to empirically lower the dose with weight loss, unless it was clear that the patient was unlikely to follow up.
“Checking TSH at a more frequent interval and adjusting the dose accordingly should be adequate to prevent situations like this case.”
Dr. Karakus, Dr. Ettleson, and the editorial authors had no relevant disclosures to report.
A version of this article appeared on Medscape.com.