Glucocorticoid-suppressible aldosteronism

Primary aldosteronism implies that the physiologic abnormality is within the adrenal cortex. The most common causes include a solitary adrenal adenoma (60%) or idiopathic adrenocortical hyperplasia (35% bilateral and 5% unilateral). Other rare causes include adrenal cortex carcinoma, primary adrenocortical hyperplasia, renin-responsive adrenocortical adenoma, and genetic mutations, such as in glucocorticoid-suppressible hyperaldosteronism. " " ... 

The second group of diseases includes rare defects in the final step in the biosynthesis of mineralocorticoid and glucocorticoid that lead to water-sodium disequilibrium. Adrenal corticosterone methyl oxidase II deficiency impairs the synthesis of aldosterone with consequent salt-loss in the neonatal period. Some patients, however, become completely asymptomatic later in life. Glucocorticoid suppressible hyperaldosteronism is an autosomal dominant... 

The steroid-inhibiting properties of metyrapone have also been used in the treatment of Cushing s syndrome, and it remains one of the more effective drugs used to treat this syndrome. However, the compensatory rise in corticotrophin levels in response to falling cortisol levels tends to maintain adrenal activity. This requires that glucocorticoids be administered concomitantly to suppress hypothalamic-pituitary activity. Although metyrapone interferes with lip- and 18-hydroxylation reactions and thereby inhibits aldosterone synthesis, it may not cause mineralocorticoid deficiency because of the compensatory increased production of 11-desoxycorticosterone. 

The adrenocorticosteroids have several important physiologic and pharmacologic functions. The glucocorticoids (cortisol, corticosterone) are primarily involved in the control of glucose metabolism and the body s ability to deal with stress. Glucocorticoids have other attributes, such as their ability to decrease inflammation and suppress the immune system. Mineralocorticoids, such as aldosterone, are involved in maintaining fluid and electrolyte balance in the body. 

The two principal groups of adrenal steroids are the glucocorticoids and mineralocorticoids. These hormones are synthesized from cholesterol within cells of the adrenal cortex. The primary glucocorticoid produced in humans is cortisol (hydrocortisone), and the primary mineralocorticoid is aldosterone. Glucocorticoids exert a number of effects such as regulation of glucose metabolism, attenuation of the inflammatory response, and suppression of the immune system. Mineralocorticoids are involved primarily in the control of fluid and electrolyte balance. 

Cortisol, corticosterone, aldosterone, and the synthetic steroids used in steroid therapy (e.g., prednisolone, dexamethasone, and triamcinolone) are glucocorticoid agonists and therefore elicit glucocorticoid responses. A number of other steroids bind to the glucocorticoid receptor and thus suppress glucocorticoid responses. 

Addison s disease results from reduction in glucocorticoid secretion, which maybe caused by infection or autoimmune disease. In the latter, proliferation of immunocytes against specific antibodies occurs because of a deficiency of immune suppresser cells in the adrenocortical cells. This causes chronic reduction in the levels of aldosterone and cortisol. Reduced aldosterone secretion decreases renal sodium and water reabsorption, leading to hypovolaemia and... 

An II -hydroxylase deficiency is confirmed by finding elevated plasma concentrations of 11-deoxycortisol and deoxycorticosterone, increased concentrations of their metabolites in urine, and their suppression by glucocorticoid therapy (see Chapter 51). Plasma renin activity and aldosterone concentrations are low in this deficiency. 

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