Isolated analdosteronism: II. The nature of the adrenal cortical enzymatic defect, and the influence of diet and various agents on electrolyte balance

Abstract

The effects of changes in the dietary content of sodium and potassium in a patient with isolated aldosterone deficiency are described. Poor renal sodium conservation on a low salt intake is demonstrated, as well as an inability to correct the persistent elevation in serum potassium by dietary potassium restriction. Markedly negative sodium and chloride balance occurred with dietary salt restriction, and was associated with hyponatremia and a further increase in serum potassium, as well as more frequent paralytic episodes. Correction of the biochemical and clinical abnormalities was achieved by the administration of ACTH, desoxycorticosterone, 9α-fluorohydrocortisone, and d-aldosterone. Administration of the salt-retaining steroids, however, resulted in sustained systemic arterial hypertension. Chlorothiazide, while able to lower the serum potassium concentration, also enhanced the excretion of sodium and chloride. Paper chromatographic separation of the individual urinary hydroxycorticoids disclosed an excess of tetrahydrocorticosterone, which increased after the administration of ACTH, while aldosterone remained absent in the urine. This strongly suggests the presence of a defect in the 18-aldolase enzyme system. A slight elevation in tetrahydro-S excretion raises the possibility of an associated mild defect in the 11β-hydroxylating system, although confirmatory evidence is lacking, since hydrocortisone metabolites in the urine were present in normal amounts and desoxycorticosterone metabolites were absent. The appearance of aldosterone in two consecutive 24-hour urine specimens toward the end of the study period could not be clearly related to the administration of any exogenous compound, and apparently represented at least a temporary restoration of 18-aldolase activity to normal or, perhaps, the activation of a different biosynthetic pathway for aldosterone formation.