Diuretic-Induced Hyponatremia

Severe hyponatremia (serum Na, 91 to 120 mEq/liter) secondary to the use of diuretics was observed in 25 nonedematous patients with clinically normal hydration and creatinine clearances; it was distinguishable from other hyponatremic syndromes by the presence of hypokalemia and alkalosis, the return of serum Na to normal and unimpaired excretion of a water load of 20 ml/kg body weight 3 to 10 days after withdrawing diuretics, and the recurrence of hyponatremia within 2 to 12 days of readministering the drugs. Bioassay of plasma samples in ethanol-anesthetized rats showed elevated (1 to 15 µunits/ml) antidiuretic hormone (ADH) activity in 10 of 10 patients with diuretic-induced hyponatremia, 20 of 23 patients with inappropriate-ADH syndrome, but in none of 10 patients with hypopituitarism. Simultaneous isotope dilution studies in 10 diuretic-induced hyponatremic patients showed a marked decrease in measured exchangeable potassium in relation to a 75%-predicted mean but only a borderline decrease in mean exchangeable sodium. Increasing potassium intake improved hyponatremia. Hyponatremia apparently results from potassium depletion, which exaggerates the volume receptor release of vasopressin that is the response to minimal diuretic-induced sodium loss.