Mineralocorticoids production

Labs lytes, blood urea nitrogen (BUN)/creatinine, urine albumin, plasma aldosterone/plasma renin ratio to screen for excess aldosterone or mineralocorticoid production, or renin for renal artery stenosis (RAS) or renin-secreting tumor. 

G-12) (G-13) 21-bydroxylase deficiency. This is the most common hereditary enzyme defect in steroid biosynthesis. There is decreased glucocorticoid and mineralocorticoid production, as the enzyme is common to both pathways. This leads to increased ACTH production, which in turn causes adrenal hyperplasia and increased pregnenolone production. This results in increased androgen production and virilization. Therapy consists in administering glucocorticoids. This decreases ACTH production by negative feedback. 

DE Avalos, S.V., Lima, C., Martin, C., Lederkremer, R.M., and Vila, M.C. ACTH-mediated glucocorticoid and mineralocorticoid production is inhibited by an inositolphosphoglycan and a glyco-sylphosphatidylinositol-phospholipase C is activated by the hormone in mammalian adrenocortical cells. Steroids, 1998,... 

The major mineralocorticoid, aldosterone, is secreted by cells of the zona glomerulosa. Primary hyperaldosteronism (Conn s syndrome) is associated with potassium depletion which is, in mm, responsible for the observed neuromuscular abnormalities seen in the disorder. These are similar to those seen in hypokalemic periodic paralysis (PP), with episodic and severe exacerbations of fixed muscle weakness. Muscle biopsy shows occasional muscle necrosis and vacuoles often these feamres are accompanied by mbular aggregates as in hypokalemic PP. All these changes can be attributed to the hypokalemia and not to excess aldosterone production per se. 

The zona glomerulosa is responsible for the production of the mineralocorticoids aldosterone, deoxycorticosterone, and 18-hydroxy-deoxycorticosterone. Aldosterone promotes renal sodium retention and excretion of potassium. Its synthesis and release are regulated by renin in response to decreased vascular volume and renal perfusion. Adrenal aldosterone production is regulated by the renin-angiotensin-aldosterone system. 

Carbenoxolone (B) is a derivative of glycyrrhetinic acid, which occurs in the sap of licorice root (succus Uquiri-tiae). Carbenoxolone stimulates mucus production. At the same time, it has a mineralocorticoid-like action (due to inhibition of 11-p-hydroxysteroid dehydrogenase) that promotes renal reabsorption of NaCl and water. It may, therefore, exacerbate hypertensioa congestive heart failure, or edemas. It is obsolete. 

Addison s disease), both cortisol and aldosterone must be replaced when ACTH production is deficient (secondary AC insufficiency), cortisol alone needs to be replaced. Cortisol is effective when given orally (30 mg/d, 2/3 a.m., 1/3 p.m.). In stress situations, the dose is raised by 5- to 10-fold. Aldosterone is poorly effective via the oral route instead, the mineralocorticoid fludrocortisone (0.1 mg/d) is given. 

Cortical hormones include glucocorticoids (cortisol/corticosterone) and mineralocorticoids (aldosterone) medullar hormones are adrenaline and noradrenaline Pancreas Regulates glucose in blood via production of the hormones glucagon and insulin... 

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 next major class of drugs for peptic ulcer disease is the mucoprotectants and other protective agents. Sucralfate (4.158) is a carbohydrate-based drug (chapter 8) which forms an impenetrable paste that adheres to the stomach lining defect, providing a protective barrier. Misoprostol (4.159) is a semisynthetic prostaglandin derivative that promotes mucus production. Carbenoxolone (4.160) has a mineralocorticoid-type action that also promotes mucus production. 

Figure 12.6 Mechanism of action of mineralocortjcoid receptor antagonists in the collecting tubule. Aldosterone enters the tubular cell by the basolateral surface and binds to a specific mineralocorticoid receptor (MNR) in the cytoplasm. The hormone receptor complex triggers the production of an aldosterone-induced protein (AlP) by the cell nucleus (NUC). The AIP acts on the sodium ion channel (ic) to augment the transport of Na+across the basolateral membrane and in to the cell. An increase in AIP activity leads to the recruitment of dormant sodium ion channels and Na pumps (P) in the cell membrane. AIP also leads to the synthesis of new channels and pumps within the cell. The increase in Na+conductance causes electrical changes in the luminal membrane that favour the excretion of intracellular cations, such as K+and H-h. Spironolactone competes with aldosterone for the binding site on the MNR and forms a complex which does not excite the production of AIP by the nucleus.

See Table 15-6. Potassium-sparing diuretics are most useful in states of mineralocorticoid excess or hyperaldosteronism (also called aldosteronism), due either to primary hypersecretion (Conn s syndrome, ectopic adrenocorticotropic hormone production) or secondary hyperaldosteronism (evoked by heart failure, hepatic cirrhosis, nephrotic syndrome, or other conditions associated with diminished effective intravascular volume). Use of diuretics such as thiazides or loop agents can cause or exacerbate volume contraction and may cause secondary hyperaldosteronism. In the setting of enhanced mineralocorticoid secretion and excessive delivery of Na+ to distal nephron sites, renal K+ wasting occurs. Potassium-sparing diuretics of either type may be used in this setting to blunt the K+ secretory response. 

Primary aldosteronism usually results from the excessive production of aldosterone by an adrenal adenoma. However, it may also result from abnormal secretion by hyperplastic glands or from a malignant tumor. The clinical findings of hypertension, weakness, and tetany are related to the continued renal loss of potassium, which leads to hypokalemia, alkalosis, and elevation of serum sodium concentrations. This syndrome can also be produced in disorders of adrenal steroid biosynthesis by excessive secretion of deoxycorticosterone, corticosterone, or 18-hydroxycorticosterone—all compounds with inherent mineralocorticoid activity. 

Mineralocorticoid disorders can have high or low aldosterone production. Even in hyperaldosteronism disorders, circulating aldosterone and aldosterone metabolite excretion can be in the upper normal range. For this reason it is important to determine the aldosteroneirenin ratio. 

Increased production of mineralocorticoid causes sodium and fluid retention and, therefore, hypertension. 

Mineralocorticoids follow a mechanistic route similar to that of glucocorticoids, though differing in the proteins expressed. The activated MR-DNA complex promotes the expression of aldosterone-induced proteins (AIPs), which then act to increase Na+ conductance of the luminal membrane and concurrendy increase Na+ pump activity of the basolateral membrane. These actions result from a number of AlP-infiuenced cellular characteristics, including a modification of tight junction permeability, an increase in membranous Na+ channels and pumps, activation of silent Na+ channels and pumps, and an increase in mitochondrial ATP-production-related enzymes. 

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