A 78-year-old woman started on hydrochlorothiazide for hypertension returns after three weeks with confusion. Serum sodium is 118 mEq/L. The mechanism of her hyponatremia is best explained by:

• A Direct stimulation of hypothalamic ADH release by the drug
• B Excessive sodium loss exceeding water loss, creating pure volume depletion
• C Impaired free water dilution due to interference with medullary concentrating gradient ✓
• D Enhanced free water reabsorption through upregulated urea transporters

Explanation

Thiazides impair renal diluting capacity: they block sodium reabsorption in the cortical diluting segment, so the kidney cannot generate maximally dilute urine. They also cause mild volume depletion that stimulates ADH release, allowing continued water retention. Elderly women are the classic risk group. The result is impaired water excretion, not isolated salt wasting, and not direct ADH stimulation.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th ed.

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