SUN-388 - A Case of Medullary Thyroid Carcinoma and MEN2A in A Patient on Compounded Semaglutide

GLP-1 (glucagon-like peptide-1) agonists are used to treat diabetes and obesity. They are contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type IIA (MEN2A) due to increased thyroid cancer risk. Although not fully understood, the mechanism is thought to be due to medication-mediated activation of GLP-1 receptors expressed on thyroid C-cells, the same cell type involved in MTC.

A 40-year-old female with hypertension, vitamin D deficiency, obesity, and treated cervical cancer was evaluated for hypercalcemia. She reported fatigue, frontal hair loss, and brain fog. Family history was notable for osteoporosis in her mother and negative for calcium-related disease or thyroid disease. She was taking compounded semaglutide 2.4 mg weekly and hydrochlorothiazide daily. Exam revealed a palpable non-tender right thyroid nodule and tremors when her hands were outstretched. Vitals were normal. Labs revealed high calcium level (10.8 mg/dL), high parathyroid hormone level (119.4 pg/mL), improved vitamin D level (37 ng/mL, 19 ng/mL one month prior), high calcitonin level (395 pg/mL), high CEA level (18.4 ng/mL), and normal phosphorus, magnesium, and albumin. 24-hour urine calcium and creatinine levels were high (301 g, 1679 mg). Thyroid ultrasound revealed a 1.0 cm right nodule and a 1.7 cm left nodule, both TIRADS 4, meeting criteria for FNA. Fine-needle aspiration showed atypia of determined significance. ThyraMIRv2 molecular testing revealed over-expression of microRNA-375, strongly suggestive of MTC. On SPECT CT and soft tissue contrast CT, an 8 mm parathyroid adenoma was seen at the inferior aspect of the right thyroid. DEXA scan showed low bone mineral density based on age and sex. She began vitamin D supplementation. Genetic testing revealed a heterozygous, pathogenic RET C609Y mutation, confirming the diagnosis of MEN2A. She was evaluated by ENT who recommended total thyroidectomy, right inferior parathyroidectomy, and central neck dissection. Before surgery, pheochromocytoma was ruled out. Surgical pathology confirmed MTC and hypercellular parathyroid tissue. Post-operatively, she was started on levothyroxine.

We present a case of a patient being treated for obesity with a compounded GLP-1 agonist who developed hypercalcemia and was found to have MTC and MEN2A. While evaluation did eventually find a genetic predisposition to MTC, this case highlights the relationship between GLP-1 agonists, MTC, and MEN2A. Currently, there are no guidelines for screening for MEN2A prior to initiation of GLP-1 agonists. Given the increasing use of GLP-1 agonists in clinical practice, we encourage physicians to educate patients about contraindications and thoroughly screen for MTC and MEN2A before prescribing GLP-1 agonists.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*