ACTH-Dependent Aldosterone Excess Due to Adrenocortical Adenoma: A Variant of Primary Aldosteronism

To investigate the alleged importance of ACTH in aldosteronism due to adrenocortical adenoma, we studied the regulation of aldosterone in this condition. Plasma concentrations of aldosterone, cortisol, and renin were measured under various circumstances, including short-term and long-term dexamethasone treatment and infusions of physiological amounts of ACTH and pressor doses of angiotensin II. Two groups of patients could be distinguished. In group 1 (6 cases) normalized plasma levels of aldosterone and cortisol during the day were significantly correlated (n % 29, r % 0.83, P < 0.001). Group 2 (4 cases) did not show such correlation (n % 20, r % 0.17, P > 0.05). One day of dexamethasone treatment (0.5 mg, every 6 h) suppressed aldosterone to subnormal levels in group 1, but had little effect in group 2. Infusion of β–1–24 ACTH (1.25 μg/h) under dexamethasone suppresson produced large increments of aldosterone in both groups with a peak level of 43.3 ± 6.9 ng/100 ml, whereas cortisol did not rise above the normal level found in unsuppressed individuals. In contrast, incremental infusions of [asp1–val5]–angiotensin II β–amide (maximally 8–16 ng kg–1 min–1) had no effect on aldosterone in group 1, but resulted in a significant response in group 2. Plasma concentrations of potassium and renin were not different in the 2 groups. Suppression of aldosterone by dexamethasone, as observed in group 1, was not maintained when this drug was continued. After 7 days, aldosterone had partly returned to pre-treatment levels, again with a cortisol–like diurnal pattern. Plasma levels of potassium and renin at that time were not higher than before treatment with dexamethasone. These results illustrate the functional heterogeneity of the group of patients with aldosterone-producing adenoma. In some cases, there is a dissociation of the aldosterone responses to ACTH and to angiotensin II. A practical point emerging from this study is thatthe presence or absence of ACTH-dependency cannot be used as an absolute criterionfor differentiating adenoma from non-adenoma cases. Furthermore, our data suggest that in some patients an unknown factor, possibly also of hypophyseal origin, is involved in the regulation of aldosterone during prolonged suppression of ACTH.