Available online 17 October 2025, 102063

Thiazide diuretics are widely used antihypertensive agents, but their use can be complicated by thiazide-induced hyponatremia (TIH), a more common adverse effect than previously recognized. TIH may present acutely or chronically, with neurological symptoms varying by onset. Acute cases may require hypertonic saline, while chronic TIH is managed by discontinuing the thiazide, fluid restriction, and solute repletion. TIH appears to be idiosyncratic and is more common in older adults, those with low-normal plasma sodium and potassium levels, poor solute intake, or concurrent use of other hyponatremia-inducing drugs. TIH likely results from combined sodium and potassium depletion, increased water intake, and impaired water excretion, possibly involving prostaglandin E2 or low solute intake. This review discusses new aspects of the epidemiology, clinical presentation, and mechanisms of TIH and offers guidance on its diagnosis and management. Emerging insights into renal and extra-renal thiazide targets may enhance the prediction of both therapeutic and adverse responses to these medications.

arginine vasopressin

diuretics

electrolytes

epidemiology

prostaglandin

sodium-chloride cotransporter

© 2025 The Author(s). Published by Elsevier Ltd.