What is the effect of Mounjaro (tirzepatide) on patients with thyroid disorders?

Effect of Mounjaro (Tirzepatide) in Patients with Thyroid Disorders

Mounjaro (tirzepatide) is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), and should be used with extreme caution and counseling in patients with other thyroid disorders due to the risk of thyroid C-cell tumors observed in animal studies. 1

Absolute Contraindications

The FDA explicitly contraindicates tirzepatide in the following populations:

• Patients with a personal history of medullary thyroid carcinoma (MTC) 1
• Patients with a family history of MTC 1
• Patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1

Thyroid C-Cell Tumor Risk

Critical safety concern: Tirzepatide caused dose-dependent and treatment-duration-dependent increases in thyroid C-cell tumors (adenomas and carcinomas) in both male and female rats at clinically relevant plasma exposures in 2-year studies. 1

• The human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined, making the actual risk in humans uncertain 1
• All patients must be counseled about the potential risk for MTC and informed of thyroid tumor symptoms including neck mass, dysphagia, dyspnea, and persistent hoarseness 1

Monitoring Considerations

Routine thyroid monitoring has uncertain value but specific findings warrant action:

• Routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value for early detection of MTC in tirzepatide-treated patients 1
• Such monitoring may increase unnecessary procedures due to low test specificity for serum calcitonin and high background incidence of thyroid disease 1
• However, if serum calcitonin is measured and significantly elevated (MTC patients usually have values >50 ng/L), the patient requires further evaluation 1
• Patients with thyroid nodules noted on physical examination or neck imaging should be further evaluated 1

Use in Hyperthyroidism

For patients with hyperthyroidism or thyrotoxicosis who also have type 2 diabetes:

• Hyperthyroidism itself is preferably treated with nonselective beta-blockers (propranolol), diltiazem, verapamil, or ivabradine 2
• The decision to use tirzepatide in patients with hyperthyroidism requires careful risk-benefit assessment, as there is no specific contraindication beyond MTC/MEN 2, but the thyroid C-cell tumor risk adds complexity 1
• Thyroid function should be monitored at 2-4 month intervals during treatment and regularly for 1 year after termination if tirzepatide is used 2

Use in Hypothyroidism

For patients with hypothyroidism on levothyroxine replacement:

• There is no specific contraindication to tirzepatide use in patients with adequately treated hypothyroidism 1
• Ensure TSH is normalized with levothyroxine before initiating tirzepatide 2
• Monitor TSH levels every 6-12 months once stable, as is standard practice for hypothyroid patients 3
• Be aware that overtreatment with levothyroxine increases risks of osteoporosis, fractures, and cardiac complications 3

Clinical Decision Algorithm

When considering tirzepatide in patients with thyroid disorders:

1. Screen for absolute contraindications: Personal or family history of MTC, or MEN 2 diagnosis → Do not prescribe tirzepatide 1

2. For patients with hyperthyroidism: Assess severity and etiology → Ensure adequate treatment of hyperthyroidism first → Consider alternative diabetes medications given uncertain thyroid tumor risk → If tirzepatide is chosen, counsel extensively about MTC risk and symptoms 2, 1

3. For patients with hypothyroidism: Confirm adequate levothyroxine replacement with normal TSH → Tirzepatide can be used → Maintain standard thyroid monitoring 2, 3

4. For all patients on tirzepatide: Counsel about thyroid tumor symptoms (neck mass, dysphagia, dyspnea, persistent hoarseness) → Evaluate any thyroid nodules found on examination → If calcitonin is checked and >50 ng/L, pursue further evaluation 1

Important Caveats

• The boxed warning for thyroid C-cell tumors is based on animal data; human relevance remains undetermined, but the FDA considers this risk significant enough to warrant contraindication in high-risk populations 1
• Tirzepatide has demonstrated superior glycemic control and weight loss compared to GLP-1 receptor agonists, but this efficacy must be weighed against thyroid safety concerns in patients with any thyroid disorder 4, 5
• The evidence provided does not address direct interactions between tirzepatide and thyroid hormone metabolism, but the primary concern remains the C-cell tumor risk 1