Papillary Thyroid Carcinoma Following Semaglutide Therapy for Metabolic Syndrome: A Case Presentation and Review of Current Evidence

Background Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is widely used for the management of type 2 diabetes, metabolic syndrome, and obesity. Concerns regarding its potential association with thyroid cancer, particularly medullary thyroid carcinoma have emerged, although current human evidence remains inconclusive. Reports of papillary thyroid carcinoma (PTC) following semaglutide therapy are exceedingly rare. Case Presentation: We describe a 40-year-old man with metabolic syndrome and obesity who had been treated with semaglutide for several years before discontinuation. A routine chest computed tomography (CT) performed for an unrelated diaphragmatic hernia identified a suspicious thyroid lesion, later confirmed by ultrasound as a 1 × 1 cm irregular hypoechoic nodule in the left lobe with several small ipsilateral lymph nodes demonstrating suspicious features. Fine-needle aspiration cytology revealed classic PTC (Bethesda VI). The patient underwent total thyroidectomy with left selective neck dissection and central compartment dissection. Histopathology confirmed a unifocal classic variant PTC, 16 mm in size, with negative margins, no lymph node involvement, and no extrathyroidal extension. After an uncomplicated postoperative course, he was discharged levothyroxine for TSH suppression. Conclusion This case of PTC following semaglutide therapy highlights an important clinical scenario but does not provide evidence of causation. The totality of available human data continues to support the safety of semaglutide with respect to thyroid cancer risk. Further long-term surveillance and high-quality epidemiological studies remain warranted.