Effect of spironolactone on fluid volumes and adrenal steroids in primary aldosteronism

Plasma volume (PV) and extracellular fluid volume (ECF) were determined in 7 patients with essential hypertension (controls) and in 10 patients with primary aldosteronism, while on a high Na diet (342 mEq/day) and on a low Na diet (12 mEq/day). The volume studies were repeated in 6 of the primary aldosteronism patients during treatment with spironolactone for over 3 months. Plasma renin activity (PRA), plasma aldosterone concentration (PAC), cortisol concentration, and serum Na and K concentrations were measured in all patients while on a Na-restricted diet (85 mEq/day) as well as on high-Na and low-Na diets. There were no significant changes in arterial pressure during different Na diets in any groups of patients with essential hypertension, or primary aldosteronism with and without spironolactone therapy. Spironolactone treatment normalized the arterial pressure in patients with primary aldosteronism at all Na intakes. These patients had greater values for PV and ECF than did those with essential hypertension. Spironolactone treatment reduced PV during the low-Na diet, but did not alter it during the high-Na diet. Spironolactone did not produce significant changes in ECF during either the high-Na or low-Na diets. Although there were no changes in PV and ECF in patients with primary aldosteronism due to changes in Na intake, both PV and ECF were significantly less in these patients during spironolactone treatment and in patients with essential hypertension during low-Na intake than during high-Na intake. With primary aldosteronism, PRA was depressed and PAC was elevated when compared to essential hypertension, these were not altered by different Na diets in the patients with primary aldosteronism as they were in those with essential hypertension. During treatment with spironolactone the PRA was restored to normal and showed normal changes with variations in dietary Na, but PAC remained elevated during spironolactone. Plasma cortisol was the same among those with essential hypertension and patients with untreated and spironolactone-treated primary aldosteronism. Serum K was less in untreated primary aldosteronism during all Na diets than in essential hypertension, but during spironolactone it was restored to normal. These results suggest that in primary aldosteronism the reduction in arterial pressure by spironolactone treatment does not occur simply by reductions in body fluid volumes. The long-term treatment of patients with primary aldosteronism with spironolactone does not inhibit the production of aldosterone, possibly because of enhanced activity of the renin-angiotensin system and an increase in serum K.