Steroids and hypertension

Primary aldosteronism is the principal disorder of zona glomerulosa and a number of subsets have been identified: unilateral adenoma; bilateral micro- or macro-nodular hyperplasia (idiopathic aldosteronism); primary hyperplasia and aldosterone-producing carcinoma either adrenal or ectopic. The diagnostic criteria for a correct differential diagnosis of these subsets are 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 for 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. A qualitative biochemical abnormality in this disorder consists of marked over-production of products of the cortisol C18-oxidation pathway, 18-hydroxycortisol and 18-oxocortisol, which are more abundant than aldosterone and 18-hydroxycorticosterone. A family with three 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-secreting tumors and two forms of congenital adrenal hyperplasia (CAH), the 11 beta-hydroxylase (11-OHDS) and the 17 alpha-hydroxylase deficiency syndromes (17-OHDS), which are identified by the presence of hypokalemia and suppressed renin activity. DOC is the only mineralocorticoid hormone (MCH) oversecreted in the 11-OHDS, while all ACTH-dependent MCH are very high in the 17-OHDS. The molecular basis of gene abnormalities of this disorder are currently under investigation, and preliminary data obtained in some of our patients are presented. Finally a syndrome of apparent mineralocorticoid excess, which is not a primary disorder of the adrenal cortex, describes the association of an unexplained hypermineralocorticoid state with a decreased rate of peripheral 11 beta-hydroxy dehydrogenation of cortisol to cortisone. Studies on this syndrome have led to the hypothesis that peripheral cortisol inactivation is the normal mechanism permitting specific mineralocorticoid recognition. The syndrome exists in two forms both characterized by a decreased turnover of a normal level of plasma cortisol, but in the type I variant an elevated cortisol/cortisone metabolite ratio is found, whereas in the type II variant this ratio is normal. Three patients of the latter form have recently been described by us and are shortly illustrated.(ABSTRACT TRUNCATED AT 400 WORDS)     

Steroids and thermogenesis

Apart from thyroid hormones, as the main hormonal regulators of obligatory thermogenesis, and catecholamines, as major hormonal regulators of facultative thermogenesis, production of heat in homeotherms can also be influenced by steroids. Generally, hormones can influence heat production by regulating the activity of various enzymes of oxidative metabolism, by modulating membrane protein carriers and other membrane or nuclear protein factors. Proton carriers in the inner mitochondrial membrane, known as uncoupling proteins, play the key role in heat dissipation to the detriment of the formation of energy-rich phosphates. In this minireview we have focused on the effects of steroids and thyroid hormones on heat production in brown adipose tissues and in skeletal muscles, with particular respect to their effect on uncoupling protein expression. Apart from hormonal steroids, dehydroepiandrosterone, an important precursor in the metabolic pathway leading to hormonal steroids which possess many, mostly beneficial effects on human health, modulates metabolic pathways which may lead to increased heat production. Recent studies demonstrate that 7-oxo-dehydroepiandrosterone, one of its 7-oxygenated metabolites, is even more effective than dehydroepiandrosterone. Recent findings of various actions of these steroids support the view that they may also participate in modulating thermogenic effects.     

Steroids and oxygen solubility

Determinations of oxygen solubility in serum were made utilizing various concentrations of corticosteroids in the serum. Within a certain concentration range dexamethasone and betamethasone caused an increase in oxygen solubility. None of the other steroids tested demonstrated this property.