Can Mounjaro (tirzepatide) be used in a patient with a family history of thyroid cancer, such as a sister with thyroid cancer?

Tirzepatide (Mounjaro) is Contraindicated in Patients with Family History of Medullary Thyroid Cancer

Tirzepatide (Mounjaro) is absolutely contraindicated in patients with a family history of medullary thyroid cancer, including cases where a sister had thyroid cancer. 1

Contraindication Details

The FDA label for Mounjaro (tirzepatide) explicitly states this contraindication in a black box warning:

• Tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors in rats at clinically relevant exposures
• Mounjaro is contraindicated in patients with:
  • Personal history of medullary thyroid carcinoma (MTC)
  • Family history of MTC
  • Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1

Mechanism of Concern

The concern stems from tirzepatide's potential to cause thyroid C-cell tumors. While human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been definitively determined, the FDA requires this contraindication as a precautionary measure due to the serious nature of medullary thyroid cancer. 1

Important Clinical Considerations

Types of Thyroid Cancer to Consider

• Medullary thyroid cancer (MTC) is the specific concern with tirzepatide
• MTC represents approximately 5-7% of all thyroid cancers 2
• Family history of MTC significantly increases risk, especially in genetic syndromes like MEN 2A or 2B 2

Risk Assessment

• A patient with a sister who had thyroid cancer should be evaluated to determine:
  1. The specific type of thyroid cancer the sister had (medullary vs. other types)
  2. Whether genetic testing for RET proto-oncogene mutations has been performed
  3. Whether there are other family members with thyroid cancer or related conditions 2

Alternative Medications

For patients with a family history of thyroid cancer who need treatment for type 2 diabetes or obesity, consider:

1. Other weight management medications without thyroid C-cell tumor risk:

   • Phentermine-topiramate
   • Naltrexone-bupropion
   • Orlistat 2

2. Standard diabetes medications without this contraindication:

   • Metformin
   • SGLT2 inhibitors
   • DPP-4 inhibitors
   • Sulfonylureas (if appropriate)

Recent Research Context

While recent meta-analyses suggest tirzepatide does not increase overall cancer risk in short-term studies (26-72 weeks) 3, 4, these studies:

• Are limited by short duration
• Do not override the FDA contraindication
• Cannot rule out specific risks in genetically predisposed individuals

Clinical Algorithm for Decision-Making

1. Determine thyroid cancer type in family member:

   • If confirmed NOT medullary thyroid cancer → may consider tirzepatide with caution
   • If confirmed medullary thyroid cancer → ABSOLUTE CONTRAINDICATION
   • If type unknown → treat as contraindicated until confirmed otherwise

2. If family history suggests possible MEN syndrome:

   • Refer for genetic testing for RET proto-oncogene mutations
   • Consider endocrinology consultation
   • Avoid tirzepatide until MEN 2 definitively ruled out

3. For patients with contraindication to tirzepatide:

   • Select alternative medication based on treatment goals
   • Consider referral to endocrinology for specialized management

Conclusion

The presence of a family history of thyroid cancer, particularly if it could be medullary thyroid cancer, represents a clear contraindication to using tirzepatide (Mounjaro). This contraindication is explicitly stated in the FDA-approved labeling and should be strictly observed to prioritize patient safety and avoid potentially serious complications.