Glucocorticoid responsive aldosteronism

The major disease clearly linked with disordered sodium homeostasis, among other diseases, is hypertension, and this is observed in very small populations with genetic defects including glucocorticoid-responsive aldosteronism, Liddle syndrome, and apparent mineralocorticoid excess (AME) (Anke 2002). Cystic fibrosis is another genetically determined defect in the chloride channels. This leads to the secretion of sweat with high NaCl concen-... 

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. 

The adrenal cortex is functionally divided into three zones, the zona glomerulosa, fasciculata, and reticularis. Only the outermost zone, the zona glomerulosa, synthesizes aldosterone. The other zones are responsible for the generation of glucocorticoids and androgens. 

I. Replacement therapy. The adrenal cortex (AC) produces the glucocorticoid cortisol (hydrocortisone) and the mine-ralocorticoid aldosterone. Both steroid hormones are vitally important in adaptation responses to stress situations, such as disease, trauma, or surgery. Cortisol secretion is stimulated by hypophyseal ACTH, aldosterone secretion by angiotensin 11 in particular (p. 124). In AC failure (primary AC insuffiency ... 

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. 

Some of the effects of glucocorticoids can be attributed to their binding to aldosterone receptors (ARs). Indeed, ARs bind aldosterone and cortisol with similar affinity. A mineralocorticoid effect of cortisol is avoided in some tissues by expression of llE>-hydroxysteroid dehydrogenase type 2, the enzyme responsible for biotransformation to its 11-keto derivative (cortisone), which has minimal affinity for aldosterone receptors. 

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. 

The adrenal cortex (AC) produces the glucocorticoid cortisol (hydrocortisone) in the zona fasciculata and the mineralocorticoid aldosterone in the zona glomerulosa. Both steroid hormones are vitally important in adaptation responses to stress situations, such as disease, trauma, or surgery. Cortisol secretion is stimulated by hypophyseal ACTH aldosterone secretion by angiotensin II in particular (p. 128). In AC failure (primary adrenocortical insuf ciency, Addison disease), both cortisol and aldosterone must be replaced when ACTH production is deficient (secondary adrenocortical insuf ciency), cortisol alone needs to be replaced. Cortisol is effective when given orally (30 mg/day, 2/3 a.m 1 /3 p.m.). In stress situations, the dose is raised 5- to 10-fold. Aldosterone is poorly effective via the oral route instead, the mineralocorticoid fludrocortisone (0.1 mg/day) is given. 

Increased end-organ responsiveness to glucocorticoids, mineralocorti-coids, and aldosterone (Section 9.3.3). Oversecretion of (and presumably also enhanced sensitivity to) any of these hormones can result in hypertension. Vitamin Bg supplementation would be expected to reduce end-organ sensitivity to these hormones, and thus might have a hypotensive action. 

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. " " ... 

Adrenocortical steroid hormones have a vast array of biological functions. Cortisol, the primary human glucocorticoid, regulates the inflammatory response (Newton and Holden, 2007), carbohydrate and lipid metabolism, and stress response (Kassel and Herrlich, 2007). Aldosterone regulates blood pressure by modulating fluid and electrolyte balance (Brizuela et ah, 2006 Foster, 2004). In the adrenal cortex, dehydroepiandrosterone (DHEA), dehy-droepiandrosterone sulfate (DHEA-S), and androstenedione are the androgens produced (Havelock et ah, 2004 Rainey et ah, 2002). 

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