Tirzepatide-Induced Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Presenting With Seizures

Tirzepatide (Mounjaro), a novel, dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, is increasingly prescribed for type 2 diabetes and off-label weight loss. While gastrointestinal adverse effects are common, hyponatremia induced by tirzepatide is rarely reported. We report a 63-year-old woman with no significant past medical history who developed tonic-clonic seizures 4 days after starting tirzepatide for weight loss. Laboratory evaluation revealed severe hyponatremia (serum sodium 122 mmol/L), low serum osmolality, and high urine osmolality and urine sodium consistent with syndrome of inappropriate antidiuretic hormone secretion (SIADH). No other causes were identified. Discontinuation of tirzepatide and fluid restriction led to gradual normalization of sodium levels and full clinical recovery. This case highlights tirzepatide as a potential cause of SIADH and severe hyponatremia leading to seizures, even in low-risk individuals. Clinicians should monitor electrolytes when initiating GLP-1 receptor agonists, especially off-label.