Semaglutide linked to transient hyperprolactinemia in a patient with Hashimoto's thyroiditis

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like semaglutide are widely used for weight management and glycemic control, demonstrating significant metabolic and gastrointestinal benefits. However, their broader influence on pituitary function remains largely unexplored. While the metabolic effects are well-characterized, the potential for GLP-1 RAs to modulate neuroendocrine pathways, specifically those regulating prolactin secretion, represents a gap in current understanding. This case highlights a rare, yet important, potential endocrine side effect not typically associated with GLP-1 RA therapy.

This case report describes a middle-aged woman with well-controlled Hashimoto's thyroiditis who developed elevated prolactin levels while on semaglutide therapy. The patient presented without typical clinical symptoms of hyperprolactinemia. Diagnostic workup included serial measurement of serum prolactin levels and a pituitary MRI to rule out structural abnormalities. Following the detection of elevated prolactin, semaglutide was discontinued. Prolactin levels were subsequently monitored without any additional pharmacologic intervention to assess for spontaneous normalization.

The patient experienced a significant, transient elevation in prolactin levels, which approached 100 ng/mL during semaglutide therapy. Importantly, despite this elevation, the patient remained asymptomatic, experiencing no galactorrhea, menstrual irregularities, or visual disturbances. A pituitary MRI revealed no evidence of an adenoma or other structural pathology that could account for the hyperprolactinemia.

After semaglutide discontinuation, the patient's prolactin levels normalized spontaneously, without requiring any pharmacologic intervention, strongly suggesting a direct association with the GLP-1 RA. This observation raises the hypothesis that GLP-1R agonism may influence prolactin regulation through central neuroendocrine pathways, potentially involving prolactin-releasing peptide (PrRP) signaling or modulation of dopaminergic pathways, which are known to inhibit prolactin secretion.