Are there concerns with using Zepbound (generic name not specified) in patients with thyroid nodules?

Thyroid Nodules and Zepbound (Tirzepatide): Safety Considerations

There are no specific contraindications or concerns regarding the use of Zepbound (tirzepatide) in patients with benign thyroid nodules, but caution is warranted in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia type 2 (MEN 2), as tirzepatide is contraindicated in these populations.

Background on Thyroid Nodules

Thyroid nodules are extremely common in the general population:

• Prevalence of 2-6% with palpation
• 19-35% with ultrasound examination
• Most thyroid nodules (approximately 95%) are benign 1

Zepbound (Tirzepatide) and Thyroid Safety

The FDA label for tirzepatide (Zepbound) includes a boxed warning regarding thyroid C-cell tumors 2:

• Tirzepatide causes thyroid C-cell tumors in rats
• Unknown whether it causes thyroid C-cell tumors, including MTC, in humans
• Contraindicated in patients with:
  • Personal or family history of MTC
  • Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)

Clinical Approach for Patients with Thyroid Nodules Considering Zepbound

Step 1: Evaluate the thyroid nodule(s)

• Perform fine needle aspiration cytology (FNAC) for any thyroid nodule >1 cm or for nodules <1 cm with suspicious features 3
• Suspicious features include:
  • History of head/neck irradiation
  • Family history of thyroid cancer
  • Suspicious palpation findings
  • Cervical adenopathy
  • Ultrasonographic suspicion (hypoechogenicity, microcalcifications, absence of peripheral halo, irregular borders) 3

Step 2: Rule out medullary thyroid carcinoma

• Consider measurement of serum calcitonin as part of diagnostic evaluation 3
• If MTC is suspected, genetic testing for RET proto-oncogene mutations should be performed 3

Step 3: Management decisions based on nodule characteristics

• For benign nodules:

  • No contraindication to using Zepbound
  • Continue routine surveillance of nodules as clinically indicated 3

• For indeterminate or suspicious nodules:

  • Complete evaluation before initiating Zepbound
  • Consider referral to endocrinology for management 3

• For confirmed MTC or family history of MTC/MEN2:

  • Zepbound is absolutely contraindicated 2

Monitoring Recommendations for Patients on Zepbound with Thyroid Nodules

1. Continue standard monitoring of benign thyroid nodules
2. Counsel patients about potential risk of MTC and symptoms of thyroid tumors 2
3. Be vigilant for symptoms such as:
   • Neck mass
   • Dysphagia
   • Dysphonia
   • Persistent hoarseness

Special Considerations

• Patients with previous thyroid surgery: Limited data available, but no specific contraindication to Zepbound use in patients with previous lobectomy or thyroidectomy
• Patients with subclinical hyperthyroidism: Evaluate and treat the underlying thyroid condition before considering Zepbound 3
• Patients with differentiated thyroid cancer (DTC): Consult with treating endocrinologist or oncologist regarding the appropriateness of Zepbound, particularly if on TSH-suppressive therapy 3

In summary, benign thyroid nodules do not present a specific contraindication to using Zepbound, but patients with MTC or MEN2 should not receive the medication due to the boxed warning regarding thyroid C-cell tumors.