Plasma corticosteroids in hyperreninemic hypoaldosteronism: evidence for diffuse impairment of the zona glomerulosa.
A subgroup of critically ill patients with selective hypoaldosteronism despite hyperreninemia has recently been defined. The mechanism underlying the subnormal response of aldosterone secretion is poorly understood. As cortisol secretion remains intact and the condition usually follows hypotensive episodes, ischemic or functional impairment restricted to the adrenal glomerulosa may be involved. To evaluate the possibility that a specific biosynthetic pathway deficiency exists in hyperreninemic hypoaldosteronism (HH), basal and ACTH-stimulated levels of aldosterone and its immediate precursors 18-hydroxycorticosterone (18-OHB) and corticosterone (B) were determined in eight HH patients, six critically ill subjects with normal aldosterone responsiveness, and nine healthy subjects. Baseline aldosterone (8.2 +/- 3.2 vs. 44.7 +/- 23.6 ng/dl) and 18-OHB (44.7 +/- 13.6 vs. 547.6 +/- 300.4 ng/dl) were lower in HH patients than in Intensive Care Unit controls (both P less than 0.01) despite similarly increased renin concentration and activity. ACTH-stimulated aldosterone and 18-OHB were significantly lower in HH patients, although the percent increase was similar to Intensive Care Unit controls. Plasma B was also lower in HH patients, though not significantly. After ACTH, B was markedly lower than both ICU controls (1764 +/- 576 vs. 6299 +/- 1266 ng/dl, P less than 0.01) and healthy controls (3261 +/- 248 ng/dl, P less than 0.01). All groups had appropriate cortisol responses demonstrating normal zona fasciculata function. Since 18-OHB arises predominantly from the zona glomerulosa, whereas B also derives in part from the zona fasciculata, the data suggest generalized impairment of the adrenal zona glomerulosa probably affecting both early and late pathway corticosteroid biosynthesis.
D015069:18-Hydroxycorticosterone / Q000097:blood; D000302:Adrenal Cortex / Q000503:physiopathology*; D000305:Adrenal Cortex Hormones / Q000097:blood*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D000450:Aldosterone / Q000096:biosynthesis / Q000172:deficiency*; D003345:Corticosterone / Q000097:blood; D005260:Female; D006801:Humans; D007022:Hypotension / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood*
D000305:Adrenal Cortex Hormones; D000450:Aldosterone; D015069:18-Hydroxycorticosterone; D000324:Adrenocorticotropic Hormone; D012083:Renin; D003345:Corticosterone