Does tirzepatide (a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist) have any impact on thyroid disease?

Impact of Tirzepatide on Thyroid Disease

Tirzepatide may potentially cause thyroid dysfunction, specifically painless thyroiditis, though this is not common and the overall risk appears similar to that of GLP-1 receptor agonists. 1

Thyroid-Related Concerns with Tirzepatide

Thyroid C-Cell Tumors

• The FDA label for tirzepatide (Mounjaro) includes a boxed warning regarding the risk of thyroid C-cell tumors 2
• In animal studies, tirzepatide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) in rats at clinically relevant plasma exposures 2
• However, human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined 2

Contraindications

• Tirzepatide is contraindicated in patients with:
  • Personal or family history of medullary thyroid carcinoma (MTC)
  • Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 2

Case Reports of Thyroid Dysfunction

• A recent case report documented a 32-year-old woman with no personal or family history of thyroid disease who developed painless biphasic thyroiditis (initial thyrotoxicosis followed by transient hypothyroidism) after two months of tirzepatide therapy 1
• The patient's thyroid function normalized two months after discontinuing tirzepatide without requiring treatment 1

Pharmacovigilance Data

• Analysis of the FDA Adverse Event Reporting System (FAERS) database showed disproportionate reporting of medullary thyroid cancer with tirzepatide (ROR 13.67,95% CI 4.35-42.96) 3
• However, tirzepatide exhibited a similar risk of medullary thyroid cancer compared to GLP-1 receptor agonists 3
• This suggests that the thyroid-related adverse events profile of tirzepatide is comparable to that of other GLP-1 receptor agonists 3

Monitoring Recommendations

• Patients should be counseled regarding the potential risk for MTC and informed about symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness) 2
• Routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with tirzepatide 2
• If serum calcitonin is measured and found to be elevated, particularly values >50 ng/L, the patient should be further evaluated 2
• Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated 2

Clinical Implications

• Healthcare providers should:
  • Screen for personal or family history of MTC or MEN 2 before initiating tirzepatide
  • Be aware of the possibility of drug-induced thyroiditis as a potential adverse effect
  • Monitor for signs and symptoms of thyroid dysfunction in patients on tirzepatide
  • Consider thyroid function testing if symptoms of hyper- or hypothyroidism develop

Conclusion

While tirzepatide carries a warning about thyroid C-cell tumors based on animal studies, the clinical significance in humans remains uncertain. Recent case reports suggest a potential association with painless thyroiditis, but the overall risk appears similar to that of other GLP-1 receptor agonists. Clinicians should be vigilant about thyroid-related adverse events when prescribing tirzepatide, particularly in patients with pre-existing thyroid conditions or risk factors for thyroid disease.