How do you rule out medullary thyroid carcinoma to initiate Glucagon-like peptide-1 (GLP-1) therapy?

From the Guidelines

To rule out medullary thyroid carcinoma (MTC) before starting GLP-1 receptor agonists, obtain a baseline calcitonin level, as recommended by the most recent guidelines 1. If calcitonin is normal (<10 pg/mL for men, <5 pg/mL for women), you can proceed with GLP-1 therapy. The following key points should be considered:

• If calcitonin is elevated or borderline, refer the patient to an endocrinologist for further evaluation, which may include thyroid ultrasound and possibly fine needle aspiration.
• This screening is particularly important for patients with risk factors such as family history of MTC, multiple endocrine neoplasia type 2, or personal history of thyroid nodules.
• The concern stems from animal studies showing GLP-1 receptor agonists increased the risk of C-cell tumors in rodents, though this has not been definitively established in humans, as noted in recent studies 1.
• Once MTC is ruled out, you can initiate GLP-1 therapy at the recommended starting dose for the specific medication (such as semaglutide 0.25 mg weekly for Wegovy or Ozempic, titrating up as tolerated). Some key considerations for GLP-1 receptor agonist therapy include:
• Ongoing monitoring should include awareness of symptoms like neck pain, persistent hoarseness, difficulty swallowing, or palpable neck masses, which would warrant prompt evaluation.
• The use of GLP-1 receptor agonists requires careful consideration of the potential risks and benefits, particularly in patients with a history of thyroid cancer or multiple endocrine neoplasia type 2, as highlighted in recent guidelines 1.

From the FDA Drug Label

• OZEMPIC is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). • Counsel patients regarding the potential risk of MTC and symptoms of thyroid tumors (4,5.1).

To rule out medullary carcinoma of the thyroid before starting GLP-1 receptor agonists like semaglutide, patients should be assessed for a personal or family history of MTC or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). If such a history is present, the use of semaglutide is contraindicated 2. Patients without such a history should still be counseled about the potential risk of MTC and the symptoms of thyroid tumors. However, the drug label does not provide specific guidance on diagnostic tests or procedures to rule out medullary carcinoma of the thyroid before initiating therapy with semaglutide.

From the Research

Ruling Out Medullary Carcinoma of the Thyroid

To rule out medullary carcinoma of the thyroid before starting GLP-1, the following steps can be taken:

• Perform thyroid ultrasonography to identify suspicious nodules 3, 4
• Conduct fine-needle aspiration (FNA) on suspicious nodules to assess for medullary thyroid carcinoma (MTC) 3, 4
• Measure serum calcitonin and carcinoembryonic antigen levels to aid in diagnosis and assess tumor burden 3, 4, 5
• Perform DNA analysis for RET mutations to diagnose multiple endocrine neoplasia (MEN) type 2 syndromes 3, 4, 5
• If MTC is diagnosed, consider total thyroidectomy with central lymph node dissection as the primary treatment 5, 6

Diagnostic Markers

• Calcitonin is a highly sensitive and specific tumor marker for MTC diagnosis and follow-up 4, 5
• Carcinoembryonic antigen levels can be used as prognostic factors and tumor markers 3, 5

Treatment and Management

• Total thyroidectomy with central lymph node dissection is the primary treatment for MTC 5, 6
• Adjuvant therapy, including radiotherapy and targeted therapies, may be used for metastatic disease 6, 7
• Recent guidelines emphasize individualized treatment and follow-up strategies based on molecular diagnosis and postoperative risk stratification systems 7