ROLE OF 21-DEOXYALDOSTERONE IN HUMAN HYPERTENSION

21-Deoxyaldosterone has been postulated to be a precursor of aldostero ne 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 a ldosterone metabolites, aldosterone-18-glucuronide and tetrahydro:aldo sterone and than the aldosterone precursor 18-OH-corticosterone. Essen tial hypertension patients (with low and normal renin) excrete compara ble values of 21-deoxyaldosterone and Kelly's-M1 as normotensives. In 66% of aldosterone-producing adenoma cases (APA) and in 60% of idiopat hic hyperaldosteronism (IHA) patients, significantly raised values of 21-deoxyaldosterone and Kelly's-M1 were found. The patients with the h igh 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 excret ed in higher amounts in those patients with normal excretion of 21-deo xyaldosterone and Kelly's-M1. Hence, it is suggested that aldosterone is produced alternatively either via 18-OH-corticosterone alone or add itionally via 21-deoxyaldosterone. Furthermore, in three cases of ''in cidentally'' discovered adrenal adenomas, 21-deoxyaldosterone and Kell y'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 press ure regulation. In essential hypertension, ACTH infusion induced a sig nificant 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 sugg est that beside the main route of aldosterone biosynthesis via 11-deox ycorticosterone, corticosterone and 18-OH-corticosterone an alternativ e pathway exits via 21-deoxyaldosterone in healthy and in hypertensive patients. There are similarities between the regulation of 21-deoxyal dosterone and the regulation of aldosteorne. The determination of 21-d eoxyaldosterone and its possible metabolite Kelly's-M1 might be approp riate in the diagnosis of mineralocorticoid-induced forms of hypertens ion, especially when an adrenal adenoma is discovered.