title: Glucocorticoid-suppressible aldosteronism: a disorder of the adrenal transitional zone.
abstract: Glucocorticoid-suppressible aldosteronism (GSA) is a rare form of hyperaldosteronism in which the increased secretion of aldosterone and the elevation of blood pressure are corrected when ACTH secretion is suppressed. Two 17-hydroxylated analogs of 18-hydroxycorticosterone and aldosterone, 18-hydroxycortisol and 18-oxocortisol, which had been identified in the urine of patients with hyperaldosteronism due to an adrenal adenoma and in bullfrog adrenal tissue incubated with cortisol, are produced in greater than normal quantities in patients with GSA. The excretion of 18-hydroxycortisol and 18-oxocortisol in nine patients with GSA was 2914 +/- 923 (+/- SD) nmol/day [1108 +/- 351 micrograms/day; normal, 165 +/- 94 nmol/day (63 +/- 36 micrograms/day)] and 141 +/- 77 nmol/day [53 +/- 29 micrograms/day; normal, 3.2 +/- 2.4 nmol/day (1.2 +/- 0.9 micrograms/day)], respectively. The excretion of aldosterone 18-oxoglucuronide was 53 +/- 18 nmold/day [19.4 +/- 6.8 micrograms/day; normal, 16.9 +/- 7.5 nmol/day (6.1 +/- 2.7 micrograms/day)]. Aldosterone excretion was elevated in six patients and within the normal range in three patients. The degree of abnormality in 18-hydroxycortisol and 18-oxocortisol excretion was significantly greater than that in aldosterone. Dexamethasone administration decreased excretion of the three steroids to the normal range. ACTH administration for 3 days resulted in an exaggerated increase in the excretion of these steroids, suggesting ACTH dependence of these steroids in patients with GSA. The excessive production of these steroids, which are 17- and 18-hydroxylated, indicate that they are produced by hybrid-type cells which we have called transitional cells, which are also capable of producing aldosterone. These findings are consistent with the postulate that cytochrome P-450-corticosterone methyl oxidase fails to disappear normally in the zona glomerulosa cells as they migrate to the zona fasciculata and acquire 17-hydroxylase activity. This abnormality explains the supernormal conversion of cortisol to 18-hydroxycortisol and 18-oxocortisol and the ACTH dependence of aldosterone secretion in GSA.
authors.affiliation: Department of Internal Medicine, University of South Florida College of Medicine, Tampa.
authors.forename: C E
authors.initials: CE
authors.lastname: Gomez-Sanchez
authors.forename: J R
authors.initials: JR
authors.lastname: Gill
authors.forename: A
authors.initials: A
authors.lastname: Ganguly
authors.forename: R D
authors.initials: RD
authors.lastname: Gordon
mesh_terms: D000293:Adolescent; D000302:Adrenal Cortex / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D002648:Child; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000652:urine; D006929:Hyperaldosteronism / Q000503:physiopathology* / Q000652:urine; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011892:Rana catesbeiana
chemical_list: C038135:18-oxocortisol; D000450:Aldosterone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; C033689:18-hydroxycortisol; D006854:Hydrocortisone