Mineralocorticoid Biosynthesis in Patients with Hyporeninemic Hypoaldosteronism*

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Abstract
Aldosterone and several of its steroid precursors were measured in patients with hyporeninemic hypoaldosteronism to examine adrenal biosynthesis in this disorder. Five hyperkalemic patients with diabetes mellitus and mild to moderate renal insufficiency and six controls were studied on both 120- and 10-meq sodium diets. Plasma levels of aldosterone (PA), 18- hydroxycorticosterone (18-OHB), corticosterone (B), H-deoxycorticosterone (DOC), 18-hydroxydeoxycorticosterone (18-OHDOC), cortisol, and PRA were measured on both sodium diets and after a 4-h infusion of ACTH. PAand 18-OHB levels were also measured during angiotensin II infusion. Mean PRA (1.1 ± 0.2 ng⁄ml-h) and PA (2.8 ± 0.8 ng⁄dl) were low and failed to increase after sodium restriction and ACTH administration in all patients. However, the levels of 18-OHB, B, DOC, 18-OH-DOC, and cortisol were within the normal range on both sodium diets and responded normally to ACTH administration. A 30-min angiotensin II infusion failed to increase PA levels but produced normal increments in plasma 18-OHB. The normal levels of DOC, B, and cortisol indicate intact adrenal 21- and 11-hydroxylase activities in hyporeninemic hypoaldosteronism. Likewise, the normal levels of 18-OH-DOC and cortisol imply normal integrity of adrenal zona fasciculata 18-hydroxylase activity in this disorder. The lack of accumulation of 18- OHB in our patients differs from the findings in patients with inborn errors in aldosterone biosynthesis (corticosterone methyl oxidase defect, type 2) and could suggest intact zona glomerulosa function in hyporeninemic hypoaldosteronism. However, the normal levels of 18-OHB in the face of suppressed PRA levels in our patients could be interpreted as a partial enzymatic blockade in the conversion of 18-OHB to aldosterone. The normal 18-OHB response to angiotensin II accompanied by subnormal aldosterone responses further supports an adrenal zona glomerulosa biosynthetic defect in hyporeninemic hypoaldosteronism. Although our results cannot exclude that chronic renin suppression may also contribute to the subnormal aldosterone response, the findings do point out a possible adrenal abnormality in addition to the proposed defects in the renin-angiotensin system in this disorder.