Wegovy (Semaglutide) and Thyroid Effects
Wegovy (semaglutide) carries a boxed warning for risk of thyroid C-cell tumors based on rodent studies, and is contraindicated in patients with personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. 1
Thyroid-Related Risks and Concerns
Risk of Thyroid C-Cell Tumors
- Semaglutide caused dose-dependent and treatment-duration-dependent increases in thyroid C-cell tumors (adenomas and carcinomas) in mice and rats during lifetime exposure studies 1
- The human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined 1
- Cases of medullary thyroid carcinoma (MTC) have been reported in patients treated with liraglutide (another GLP-1 receptor agonist), but data is insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans 1
Contraindications
- Wegovy is contraindicated in patients with personal or family history of medullary thyroid carcinoma 1
- Wegovy is contraindicated in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1
Mechanism of Action Related to Thyroid
- GLP-1 receptors are expressed in multiple organs, including the thyroid gland 2
- This ubiquitous expression of GLP-1 receptors may explain the pleiotropic effects of GLP-1 receptor agonists 2
Monitoring and Management
Recommended Monitoring
- Patients should be counseled regarding the potential risk for MTC with Wegovy use and informed about symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness) 1
- Routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Wegovy 1
- Such monitoring may increase the risk of unnecessary procedures due to low test specificity for serum calcitonin and high background incidence of thyroid disease 1
When to Evaluate Further
- Significantly elevated serum calcitonin values may indicate MTC, and patients with MTC usually have calcitonin values >50 ng/L 1
- If serum calcitonin is measured and found to be elevated, the patient should be further evaluated 1
- Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated 1
Clinical Considerations
Impact on Thyroid Hormone Levels
- There is limited data regarding the effect of GLP-1 receptor agonists on serum thyroid hormone levels in patients without thyroid disease 3
- A case report described suppressed thyroid stimulating hormone (TSH) levels after initiation of subcutaneous semaglutide in a post-thyroidectomy patient managed with levothyroxine, necessitating a 25% dose reduction of levothyroxine 3
- The etiology of these changes may be related to direct effects of GLP-1 receptor agonists on TSH levels, changes in absorption related to delayed gastric emptying, secondary to GLP-1 RA-associated weight loss, or a combination of these proposed mechanisms 3
Pretreatment Assessment
- Despite the importance of investigating personal and family disease histories related to thyroid abnormalities before initiating semaglutide, one study found that such checks were conducted in only 1.8% of patients 4
- More frequent monitoring of medications that require weight-based dosing and those with a narrow therapeutic index (such as levothyroxine) may be prudent when initiating and titrating GLP-1 receptor agonist therapies 3
Common Pitfalls and Caveats
- Failure to screen for personal or family history of medullary thyroid carcinoma or MEN 2 before prescribing Wegovy 1
- Inadequate monitoring of thyroid function in patients on thyroid hormone replacement therapy who start Wegovy, as dose adjustments may be necessary 3
- Overreliance on routine calcitonin monitoring, which may lead to unnecessary procedures due to low test specificity 1
- Lack of pretreatment assessment of thyroid function, which could predispose patients to risk of adverse outcomes 4