Aldosterone deficiency

Secondary hypotension is a sign of an underlying disease that should be treated first. If stroke volume is too low, as in heart failure, a cardiac glycoside can be given to increase myocardial contractility and stroke volume. When stroke volume is decreased due to insufficient blood volume, plasma substitutes will be helpful in treating blood loss, whereas aldosterone deficiency requires administration of a mineralocor-ticoid (e.g., fludrocortisone). The latter is the drug of choice for orthostatic hypotension due to autonomic failure. A parasympatholytic (or electrical pacemaker) can restore cardiac rate in bradycardia. 

Small quantities of progesterone, testosterone, and estradiol are also produced by the adrenal gland. However, they play a minor role compared to the testicular and ovarian hormones. Progesterone, which is the precursor of cortisol, aldosterone, testosterone, and estradiol, is synthesized from 5-pregnenolone by 3-P-ol-dehydrogenase. Deficiency of this enzyme results in cortisol and aldosterone deficiencies. Such patients require replacement therapy with both glucocorticoids and mineralocorticoids. 

Concurrent acidosis in patients with trimethoprim-induced hyperkalemia is uncommon, which could be explained if the action of trimethoprim, like that of amiloride, is hmited to the cortical collecting tubule but does not affect the medullary collecting tubule, which has a large capacity to secrete hydrogen ions and may therefore prevent the development of acidosis. Predisposing factors for the rare adverse effect of renal tubular acidosis in this case may have been aldosterone deficiency or resistance, medullary dysfunction of sickle cell anemia, and renal insufficiency. All these factors could contribute to impaired renal handling of secretion of hydrogen ions (72). 

The classification of the RTAs is based upon the biochemical expression and region of defect rather than an understanding of the exact molecular defect. The three categories of RTA are distal (dRTA, type I) proximal (pRTA, type II) and type IV, which is secondary to aldosterone deficiency or resistance. The term type III RTA (mixed proximal/distal defect) has been abandoned as it is no longer considered a separate entity. 

Selective Aldosterone Deficiency (Type IV RTA). In type IV RTA, there is failure of distal potassium and hydrogen ion secretion because of aldosterone deficiency or resistance. This may occur because of a range of steroid or steroid receptor synthetic defects or because of hyporeninemic hypoaldosteronism (e.g., due to diabetic nephropathy, tubulointerstitial disease, urinary obstruction, renal transplantation, or SLE). Hyperkalemia, although mild, is a usual manifestation. 

Deficient aldosterone production occurs in conditions other than Addison s disease (Table 51-6). Isolated aldosterone deficiency accompanied by normal cortisol production is seen in patients with (1) inadequate production of renin by the kidney, which leads to secondary aldosterone deficiency... 

Patients with primary adrenal insufficiency usually also have aldosterone deficiency. Most endocrinologists, however, do not conduct tests to confirm aldosterone deficiency in these patients. 

Veldhuis JD, Melby JC. Isolated aldosterone deficiency in man Acquired and inborn errors in the biosynthesis or action of aldosterone. Endocr Rev 1981 2 495-517. 

Steroidgenic pathways in 1 lj8-hydroxylase CYPBl and CYPB2 deficiency. A CYPl IB 1 defect causes a deficiency of cortisol and the disorder congential adrenal hyperplasia (CAH). A CYPl 1B2 defect causes an aldosterone deficiency. Synthesis of steroids within the boxed areas is decreased and steroids outside the boxed area increased, respectively, for each enzyme deficiency. 

Ashouri OS. Hyperkalemic distal tubular acidosis and selective aldosterone deficiency combination in a patient with lead nephropathy. Arch Intern Med 1985 145 1306-1307. 

Type IV. Bicarbonate rcabsorption by the renal tubule is impaired as a consequence of aldosterone deficiency, aldosterone receptor defects, or drugs which block aldosterone action. 

Congenital adrenal hyperplasia Primary adrenal insufficiency Secondary adrenal insufficiency Selective aldosterone deficiency Musculoskeletal Diseases Mixed connective tissue syndromes Polymyalgia rheumatica Polymyositis Rheumatoid arthritis... 

These actions on electrolyte transport, in the kidney and in other tissues e.g., colon, salivary glands, and sweat glands), appear to account for the physiological and pharmacological activities that are characteristic of mineralocorticoids. Thus, the primary features of hyperaldosteronism are positive Na balance with consequent expansion of extracellular fluid volume, normal or slight increases in plasma Na+ concentration, hypokalemia, and alkalosis. Mineralocorticoid deficiency, in contrast, leads to Na+ wasting and contraction of the extracellular fluid volume, hyponatremia, hyperkalemia, and acidosis. Chronically, hyperaldosteronism can cause hypertension, whereas aldosterone deficiency can lead to hypotension and vascular collapse. 

Hyponatremia originates from sodium depletion caused by excessive hyperemesis, diarrhea, bums, aldosterone deficiency (Addison s disease), nephrological diseases, as well as dilution caused by liquid infusions, water shifts from intra- to extracellular space, and renal insufficiency. 

Hypoaldosteronism is defined as a deficiency of aldosterone. Renal secretion of potassium is decreased, causing hyperkalaemia. The treatment is replacement of a mineralocorticoid, e.g. fludrocortisone. 

The mineralocorticoids consist of aldosterone and des-oxycorticosterone and play an important role in conserving sodium and increasing die excretion of potassium. Because of diese activities, die mineralocorticoids are important in controlling salt and water balance Aldosterone is die more potent of these two hormones. Deficiencies of the mineralocorticoids result in a loss of sodium and water and a retention of potassium. 

Congenital adrenal hyperplasia A rare inherited condition resulting from a deficiency in cortisol and aldosterone synthesis with resulting excess androgen production. The clinical presentation depends on the variant of the condition, but it typically manifests as abnormalities in sexual development and/or adrenal insufficiency. 

Primary adrenal insufficiency (Addison s disease) most often involves the destruction of all regions of the adrenal cortex. There are deficiencies of cortisol, aldosterone, and the various androgens. Medications that inhibit cortisol synthesis (e.g., ketoconazole) or accelerate cortisol metabolism (e.g., phenytoin, rifampin, phenobarbital) can also cause primary adrenal insufficiency. 

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. 

For replacement of deficient aldosterone secretion, the fiuorinated steroid derivative fludrocortisone is used, usually in a dose of 100-200 pg per day. Replacement therapy is normally judged by monitoring blood pressure (lying and standing) and plasma electrolytes. 

Because the actions of triamterene and amiloride are independent of plasma aldosterone levels, their prolonged administration is likely to result in hyperkalemia. Both amiloride and triamterene are contraindicated in patients with hyperkalemia. Triamterene should not be given to patients with impaired renal function. Potassium intake must be reduced, especially in outpatients. A folic acid deficiency has been reported to occur occasionally following the use of triamterene. 

Congenital enzymatic defects in the adrenal biosynthetic pathways lead to diminished cortisol and aldosterone production and release. In these conditions, corticotrophin secretion is increased, and adrenal hyperplasia occurs, accompanied by enhanced secretion of steroid intermediates, especially adrenal androgens. More than 90% of cases of congenital adrenal hyperplasia are due to 21-hydroxylase deficiency, which is cre-afed by mufafions in fhe CYP21 gene encoding fhe en-... 

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. 

Outline of major pathways in adrenocortical hormone biosynthesis. The major secretory products are underlined. Pregnenolone is the major precursor of corticosterone and aldosterone, and 17-hydroxypregnenolone is the major precursor of cortisol. The enzymes and cofactors for the reactions progressing down each column are shown on the left and across columns at the top of the figure. When a particular enzyme is deficient, hormone production is blocked at the points indicated by the shaded bars. 

Patients with 11/1-hydroxylase deficiency present with features of androgen excess, including masculinization of female newborns and precocious puberty in male children. There are two human isozymes that are responsible for cortisol and aldosterone synthesis, respectively. The CYP11B1 enzyme (p45011B) converts DOC to corticosterone (B) and 11-deoxycortisol (S or 11-dihydrocortisol) to cortisol (F). It is also capable of 18-hydroxylating DOC but cannot convert to aldosterone. The latter transformation is carried out by CYP11B2 (also known as aldosterone synthase), which encompasses activity for 18-hydroxylation and subsequent 18-oxidation. When CAH is associated with hypertension, deficient lljS-hydroxylase (CYP11B1) is suspected at this time more than ten mutations have been defined in affected individuals [103]. 

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