Primary aldosteronism is the principal disorder of the zona glomerulosa, and a number of subsets have been identified: Unilateral adenoma, bilateral micro- or macronodular hyperplasia (idiopathicaldosteronism), primary hyperplasia, and aldosterone-producing carcinoma, either adrenal or ectopic. The diagnostic criteria for a correct differential diagnosis of these subsets arc now quite reliable, and our experience is presented in detail. Unfortunately, the pathogenesis of most of these forms is still poorly recognized and requires further investigation. An extreme sensitivity to angiotensin II is present in patients with idiopathic aldosteronism, and a role of adrenal renin is now being advocated. A peculiar form of hyperaldosteronism is the glucocorticoid-remediable subtype. An unusual sensitivity of aldosterone to ACTH is present in this form. The qualitative biochemical abnormality in this disorder consists of a marked overproduction of products of the cortisol C- 18-oxidation pathway, 18-hydroxycortisol and 18-oxocortisol. which are more abundant than aldosterone and 18-hydroxycorticosterone. A family with 3 affected sibs has been studied by our group. In other clinical situations, classical zona fasciculata mineralocorticoids (deoxycorticosterone |DOC], corticosterone, and their 18-hydroxy compounds) are secreted in excess. The hypertensive diseases of this zone are rare DOC-secret- ing tumors and two forms of congenital adrenal hyperplasia, the 1 lß-hydroxylase and 17a-hydroxylase deficiency syndromes, which are identified by the presence of hypokalemia and suppressed renin activity. DOC is the only mineralocorticoid hormone (MCH) oversecreted in the 11-hydroxylase deficiency syndromes, while all ACTH-dependent MCH levels are very high in the 17-hydroxylase deficiency syndromes. The molecular basis of the gene abnormalities in these disorders is currently under investigation, and preliminary data obtained in some of our patients are presented. Finally, a syndrome of apparent mineralocorticoid (MC) excess, which is not a primary disorder of the adrenal cortex, shows the association of unexplained hypermineralocorticoid state with a decreased rate of peripheral 1 lß-hydroxyde- hydrogenation of cortisol (F) to cortisone (E). Studies on this syndrome have led to the hypothesis that peripheral F inactivation is the normal mechanism permitting specific MC recognition. The syndrome exists in two forms, both characterized by a decreased turnover of a normal level of plasma F. but in the type 1 variant, an elevated F/E metabolite ratio is found, whereas in the type 2 variant, this ratio is normal. Three patients with the latter form have recently been described by us and are shortly illustrated. A possible role of this impaired F metabolism in the pathogenesis of other forms of hypertension, such as liquorice- and carbenoxolone-induced hypertension, has recently been suggested.
- 17α-Hydroxylase deficiency
- Mineralocorticoid excess
- Primary aldosteronism
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Pediatrics, Perinatology, and Child Health