Plasma immunoreactive gamma melanotropin in patients with idiopathic hyperaldosteronism, aldosterone-producing adenomas, and essential hypertension

A non-ACTH aldosterone-stimulating factor(s) has been implicated in the pathogenesis of idiopathic hyperaldosteronism (IHA). Although this factor has not been fully characterized, some evidence suggests that it may be related to a pro-γ-melanotropin (pro-γ-MSH), derived from the NH₂-terminal region of pro-opiomelanocortin. In the present study, plasma immunoreactive (IR-) γ-MSH levels at 0800 h in patients with IHA were evaluated (90 ± 17 fmol/ml; range: 13-173 fmol/ml) and found to be significantly higher (P < 0.05) than those in subjects with aldosterone-producing adenomas (33 ± 8 fmol/ml), essential hypertension (33 ± 6 fmol/ml), and normotensive controls (19 ± 2 fmol/ml). Seven of nine IHA subjects had circulating IR-γ-MSH levels above the normal range (>35 fmol/ml). In plasma sampled at 1200 h, IR-γ-MSH was significantly higher in patients with IHA (95 ± 26 fmol/ml) and adenomas (63 ± 23 fmol/ml), as compared with essential hypertensive (31 ± 6 fmol/ml) and normotensives (19 ± 3 fmol/ml). Mean plasma IR-ACTH, plasma cortisol, and urinary cortisol levels did not differ significantly between any of these groups. In order to evaluate the effect of pro-γ-MSH in vitro, adrenal adenoma tissue was obtained from two patients, one with elevated IR-γ-MSH (61 fmol/ml) and a second with low IR-γ-MSH (12 fmol/ml). Aldosterone secretion by dispersed adenoma cells from the former, but not the latter, underwent a fourfold dose-dependent (10^-14-10^-9 M) increase in response to human Lys-γ3-MSH. These data suggest that a pro-γ-MSH may be implicated as a pathogenic factor in a subset of patients with primary aldosteronism, particularly among those differentially diagnosed as having IHA.