Role of 21-deoxyaldosterone in human hypertension.
21-Deoxyaldosterone has been postulated to be a precursor of aldosterone in an alternative biosynthesis pathway and Kelly's-M1 is considered to be its metabolite. In healthy volunteers, the excretion rate of 21-deoxyaldosterone and of Kelly's-M1 are significantly lower than the aldosterone metabolites, aldosterone-18-glucuronide and tetrahydro-aldosterone and than the aldosterone precursor 18-OH-corticosterone. Essential hypertension patients (with low and normal renin) excrete comparable values of 21-deoxyaldosterone and Kelly's-M1 as normotensives. In 66% of aldosterone-producing adenoma cases (APA) and in 60% of idiopathic hyperaldosteronism (IHA) patients, significantly raised values of 21-deoxyaldosterone and Kelly's-M1 were found. The patients with the high excretion rates of both steroids showed only moderately increased values of the aldosterone metabolites, aldosterone-18-glucuronide and tetrahydro-aldosterone, as well as of the aldosterone precursor 18-OH-corticosterone. In contrast, the latter mentioned steroids were excreted in higher amounts in those patients with normal excretion of 21-deoxyaldosterone and Kelly's-M1. Hence, it is suggested that aldosterone is produced alternatively either via 18-OH-corticosterone alone or additionally via 21-deoxyaldosterone. Furthermore, in three cases of "incidentally" discovered adrenal adenomas, 21-deoxyaldosterone and Kelly's-M1 were the only elevated steroids. After adrenalectomy, excretion of 21-deoxyaldosterone and of Kelly's-M1 and blood pressure returned to normal, which proves that these steroids play a role in blood pressure regulation. In essential hypertension, ACTH infusion induced a significant increase of 21-deoxyaldosterone and Kelly's-M1. However, the increase after angiotensin II was 3- to 6-fold higher than after ACTH. IHA patients proved to be more responsive to angiotensin II; and, in contrast, APA cases proved to be more sensitive to ACTH. The data suggest that beside the main route of aldosterone biosynthesis via 11-deoxycorticosterone, corticosterone and 18-OH-corticosterone an alternative pathway exists via 21-deoxyaldosterone in healthy and in hypertensive patients. There are similarities between the regulation of 21-deoxyaldosterone and the regulation of aldosterone. The determination of 21-deoxyaldosterone and its possible metabolite Kelly's-M1 might be appropriate in the diagnosis of mineralocorticoid-induced forms of hypertension, especially when an adrenal adenoma is discovered.
Abdelhamid
S
S
Hypertension and Nephrology Unit, Deutsche Klinik für Diagnostik, Wiesbaden, Germany.
Lewicka
S
S
Bige
K
K
Haack
D
D
Lorenz
H
H
Nensel
U
U
Röckel
A
A
Fiegel
P
P
Walb
D
D
Vecsei
P
P
D000236:Adenoma / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D000450:Aldosterone / Q000031:analogs & derivatives* / Q000652:urine; D000804:Angiotensin II / Q000494:pharmacology; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011278:Pregnanes / Q000652:urine*
D011278:Pregnanes; D000804:Angiotensin II; C032486:21-deoxyaldosterone; D000450:Aldosterone; C055569:11,18-18,20-diepoxypregnan-3-ol; D000324:Adrenocorticotropic Hormone