Tirzepatide-associated severe euvolemic hyponatremia with syndrome of inappropriate antidiuretic hormone secretion-compatible biochemical features

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist that is being increasingly used for the management of type 2 diabetes mellitus and obesity. Gastrointestinal adverse effects associated with incretin-based therapies can influence water balance through nonosmotic vasopressin release and reduced oral solute intake. In this case report, we report a patient who developed severe symptomatic hyponatremia with biochemical features compatible with the syndrome of inappropriate antidiuretic hormone secretion temporally associated with tirzepatide therapy. A woman with type 2 diabetes mellitus and morbid obesity on regular insulin and chronic torsemide therapy presented with anorexia, weakness, and drowsiness 10 days after tirzepatide administration. Serum sodium was 104 mmol/L, and she was clinically euvolemic. Renal, hepatic, hematologic, acid-base, and other endocrine parameters were normal. The calculated serum osmolality was 224 mOsm/kg. Urinary sodium remained elevated after withdrawal of the diuretic. The patient was managed with fluid restriction and hypertonic saline, and this resulted in progressive correction of sodium and clinical improvement. This case suggests a potential association between tirzepatide therapy and severe euvolemic hyponatremia. Clinicians should consider electrolyte monitoring in patients receiving incretin-based therapy who develop significant gastrointestinal symptoms or reduced oral intake.