What are the recommendations for using semaglutide (glucagon-like peptide-1 receptor agonist) in patients with a Thyroid Imaging Reporting and Data System (TIRADS) 4 thyroid nodule?

Recommendations for Using Semaglutide in Patients with TIRADS 4 Thyroid Nodules

There are no specific contraindications to using semaglutide in patients with TIRADS 4 thyroid nodules, but caution is warranted due to theoretical risks related to thyroid C-cell tumors, and patients should be monitored appropriately. 1

Understanding TIRADS 4 Thyroid Nodules

TIRADS (Thyroid Imaging Reporting and Data System) is a standardized ultrasound classification system for thyroid nodules that stratifies cancer risk:

• TIRADS 4 nodules have a malignancy risk of 5-80% 2
• These nodules typically require fine needle aspiration (FNA) biopsy for further evaluation 1
• TIRADS 4 is further subdivided into 4A, 4B, and 4C categories with increasing risk of malignancy 3

Semaglutide and Thyroid Considerations

Safety Profile

• GLP-1 receptor agonists like semaglutide are not recommended in patients at risk for thyroid C-cell tumors (e.g., multiple endocrine neoplasia) based on theoretical risks from preclinical models 1
• Important contraindications include personal or family history of medullary thyroid cancer and multiple endocrine neoplasia syndrome type 2 4

Clinical Approach for Patients with TIRADS 4 Nodules

1. Initial Assessment

   • Complete evaluation of the thyroid nodule according to guidelines, including FNA if indicated based on size and TIRADS category 1
   • For TIRADS 4 nodules, FNA is typically recommended for nodules ≥1 cm 5
   • Smaller nodules (<1 cm) with TIRADS 4 classification still have higher malignancy risk 5

2. Before Starting Semaglutide

   • Rule out personal or family history of medullary thyroid cancer 4
   • Confirm absence of multiple endocrine neoplasia syndrome type 2 4
   • Consider baseline thyroid function tests

3. During Semaglutide Treatment

   • Monitor for any changes in nodule size or characteristics during follow-up ultrasounds
   • Continue standard surveillance of the TIRADS 4 nodule according to endocrinology guidelines

Special Considerations

Perioperative Management

• If thyroid surgery is planned, semaglutide should be held for at least three half-lives (approximately 3 weeks) before surgery 4
• This precaution is due to the risk of delayed gastric emptying, which could increase aspiration risk 1
• Multiple case reports have documented regurgitation and aspiration in patients taking GLP-1 receptor agonists despite appropriate fasting 1

Dosing and Administration

• Standard semaglutide dosing applies:
  • For weight management: Start at 0.25 mg once weekly for 4 weeks, then gradually titrate to 2.4 mg 4
  • For diabetes: Start at 0.25 mg once weekly, with gradual titration to 0.5-1.0 mg 4

Monitoring

• Regular thyroid ultrasound follow-up as indicated for TIRADS 4 nodules
• Be vigilant for any symptoms suggesting nodule growth or local compression

Key Pitfalls to Avoid

1. Don't assume TIRADS 4 automatically means cancer

   • While higher risk, many TIRADS 4 nodules are benign 6
   • Complete the diagnostic workup before making treatment decisions

2. Don't withhold semaglutide solely due to TIRADS 4 classification

   • The presence of a TIRADS 4 nodule alone is not a contraindication
   • Only withhold if there's confirmed medullary thyroid cancer or family history

3. Don't neglect appropriate thyroid nodule follow-up

   • Continue standard surveillance regardless of semaglutide therapy
   • Follow cytology results and endocrinology recommendations

4. Don't forget perioperative considerations

   • If thyroid surgery becomes necessary, plan for appropriate discontinuation of semaglutide
   • Consider risk reduction strategies for aspiration if urgent surgery is needed 1

By following these guidelines, semaglutide can be used safely in most patients with TIRADS 4 thyroid nodules while maintaining appropriate monitoring of the thyroid condition.