Excess Mineralocorticoid Receptor Activity in Patients with Dexamethasone-Suppressible Hyperaldosteronism Is under Adrenocorticotropin Control*

Abstract

Total mineralocorticoid activity in human serum was assessed by the rat renal slice receptor assay (RRA). RRA values were compared to RIA-derived aldosterone (aldo) equivalents. Our data demonstrate that in normal subjects, mineralocorticoid receptor-binding steroids can be almost totally accounted for by immunoreactive deoxycorticosterone, corticosterone, cortisol, and aldo (RRA, 4.73 +/- 1.34 ng/ml aldo; RIA, 3.91 +/- 1.52 ng/ml aldo equivalents), while in 8 patients with dexamethasone-suppressible hyperaldosteronism (DSH), RRA values were greater than RIA values in the basal state (RRA, 7.57 +/- 0.75; RIA, 3.24 +/- 0.34; P less than 0.01). DSH patients had a RRA to RIA ratio after ACTH stimulation similar to the ratio in these patients in the basal state (basal, 2.34; ACTH-stimulated, 2.04). During dexamethasone treatment, RRA values fell markedly (1.82 +/- 0.26). Thus, total mineralocorticoid activity, as measured by RRA in DSH patients, was greater than RIA-measurable deoxycorticosterone, corticosterone, cortisol, and aldo, indicating the presence of an unidentified steroid which is dexamethasone suppressible and ACTH stimulable.

Glucocorticoid-Remediable Aldosteronism

“…The chimeric gene duplication results from an unequal crossing over event between the highly homologous 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes located in close proximity on chromosome 8 [5,7]. As a result, aldosterone synthesis occurs ectopically in the ZF, under transcriptional control by ACTH (rather than by angiotensin II (AII), which is suppressed) [4,7,8]. As a result, aldosterone synthesis occurs ectopically in the ZF, under transcriptional control by ACTH (rather than by angiotensin II (AII), which is suppressed) [4,7,8].…”