Hyper-responsiveness of aldosterone to metoclopramide in aldosteronism.

Metoclopramide, a dopamine antagonist, stimulates aldosterone secretion in normal man. We studied the response of plasma aldosterone, plasma renin activity, cortisol, sodium, potassium and serum prolactin to a 10-mg intravenous dose of metoclopramide in six dexamethasone suppressed patients with aldosteronism (four with adrenal adenoma, two with bilateral adrenal hyperplasia) and in six dexamethasone suppressed normal male volunteers. All subjects were studied on an ad libitum sodium diet. Patients were supplemented with oral potassium prior to study. Sodium and potassium were not different between groups and did not change following metoclopramide. Cortisol was suppressed to less than 3 pg/dl throughout the study in all subjects. Basal plasma renin activity was significantly lower in the patients as compared with controls (P<O.O5), and did not change in either group following metoclopramide. Basal aldosterone levels were not significantly different in patients as compared with controls, although patients did tend to have higher levels. The incremental and integrated response of aldosterone to metoclopramide in patients was significantly greater than controls (P < 0.01). The percentage increase in aldosterone was greater than controls in five of the six patients. Basal prolactin was higher in the patients than in the controls. All subjects had a significant rise in prolactin to metoclopramide (Px0.05). Five of six patients had an increased response of prolactin when compared to the controls and the four female patients had a significantly greater rise in prolactin as compared to the normals (P< 0.01). These data suggest that increased dopaminergic activity plays a compensatory role in inhibiting aldosterone secretion in patients with aldosteronism. It appears unlikely that a decrease of dopaminergic inhibition is involved in the pathogenesis of aldosteronism due to either adenoma or bilateral hyperplasia.