Mineralocorticoid excess

Primary aldosteronism and other mineralocorticoid excess states... 

Metabolic alkalosis is characterized by an increased arterial pH, a primary increase in the HCOf concentration, and a compensatory increase in the PaC02. Patients will always hypoventilate to compensate for metabolic alkalosis—even if it results in profound hypoxemia. For a metabolic alkalosis to persist there must concurrently be a process that elevates serum HC03 concentration (gastric or renal loss of acids) and another that impairs renal HC03 excretion (hypovolemia, hypokalemia, or mineralocorticoid excess). The etiologies of metabolic alkalosis are listed in Table 25-5. 

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. 

If the defect is in 11-hydroxylation, large amounts of deoxycorticosterone are produced, and because this steroid has mineralocorticoid activity, hypertension with or without hypokalemic alkalosis ensues. When 17-hydroxylation is defective in the adrenals and gonads, hypogonadism is also present. However, increased amounts of 11-deoxycorticosterone are formed, and the signs and symptoms associated with mineralocorticoid excess—such as hypertension and hypokalemia—are also observed. 

Wilson RC, Krozowski ZS, Li K, Obeyesekere VR, Razzaghy-Azar M, Harbison MD, Wei JQ, Shackleton CHL, Funder JW, New MI. A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess. J Clin Endocrinology Metab 80 1995 2263-2266. 

Apparent mineralocorticoid excess syndrome (AME). 11/1HSD 2 deficiency HSD11B2 16q22 218030(207765)... 

Table 5.3.8 Diagnosis of apparent mineralocorticoid excess syndrome (AME) by urine steroid analysis...

Dave-Sharma S, Wilson RC, Harbison MD, Newfield R, Azar MR, Krozowski ZS, Funder JW, Shackleton CH, Bradlow HL, Wei JQ, Hertecant J, Moran A, Neiberger RE, Balfe JW, Fattah A, Daneman D, Akkurt HI, De Santis C, New MI (1998) Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess. J Clin Endocrinol Metab 83 2244-2254... 

Nikkila H, Tannin CM, New MI, Taylor NF, Kalaitzoglou G, Monder C, White PC (1993) Defects in the HSD11 gene encoding 11/J-hydroxysteroid dehydrogenase are not found in patients with apparent mineralocorticoid excess or 11 -oxoreductase deficiency. J Clin Endocrinol Metab 77 687-691... 

Ulick S, Levine LS, Gunczler P, Zanconato G, Ramirez LC, Rauh W, Rosier A, Bradlow HL, New MI (1979) A syndrome of apparent mineralocorticoid excess associated with defects in the peripheral metabolism of cortisol. J Clin Endocrinol Metab 49 757-764... 

New MI, Wilson RC Steroid disorders in children congenital adrenal hyperplasia and apparent mineralocorticoid excess. Proc Natl Acad Sci USA 96 12790-12797,1999. 

The active ingredients of licorice inhibit the breakdown of mineralocorticoids by inhibiting 11-beta-hydroxysteroid dehydrogenase type 2, and its adverse effects relate mainly to mineralocorticoid excess, with sodium retention, potassium loss, and inhibition of the renin-angiotensin-aldosterone system (36). 

Interpretation Responses must be defined for the assay technique used. Patients with renin-dependent forms of hypertension (e.g., renovascular hypertension) show values that are approximately five times normal. Stimulated responses are also seen in patients with high-renin essential hypertension, pheochromocytoma, and Barttei s syndrome. Patients with hypertension firom mineralocorticoid excess (e.g., primary aldosteronism) usually have PRA below the concentration of assay sensitivity. Patients with hyporeninemic hypoaldosteronism usually have low concentrations of plasma renin and low aldosterone concentrations. Figure 51-17 shows typical responses. 

Most patients with autonomous aldosterone overproduction are hypokalemic, but most patients with hypokalemia do not have primary aldosteronism. In hyperaldosteronism, urinary potassium excretion is inappropriately high, and a random urine potassium >30mraol/L is usually indicative of primary aldosteronism or some type of mineralocorticoid excess condition. If hypokalemia can be shown to he due to nonrenal potassium loss, the diagnosis of aldosteronism does not need to be considered further. ... 

Edwards CR. Primary mineralocorticoid excess syndromes. In Besser M, Burger HG, Jameson JL, eds. Endocrinology, 3rd ed. Philadelphia WB Saunders Co, 1995 1775-803. 

The type I corticosteroid receptor (mineralocorticoid receptor) binds cortisol and aldosterone with equal affinity. Because the circulating level of cortisol normally exceeds that of aldosterone by about 1000-fold (Table 32-1), activation of the receptor by aldosterone would probably not occur, were it not for the presence of a cortisolinactivating enzyme in cells responsive to aldosterone. This enzyme, llySHSD (Chapter 30), catalyzes the conversion of cortisol to cortisone, a metabolite that is not recognized by the receptor. Inhibition or absence of this enzyme leads to excessive aldosterone-like effects due to receptor activation by cortisol, a condition referred to as apparent mineralocorticoid excess (AME). AME can... 

M. New The prismatic case of apparent mineralocorticoid excess. Journal of Clinical Endocrinology and Metabolisml9, 1 (1994). 

Management of these disorders usually consists of treatment of the underlying cause of mineralocorticoid excess. In patients in whom the mineralocorticoid excess cannot be corrected, chronic pharmacologic therapy may be required. 

Mineralocorticoid excess also plays a significant role in the maintenance of metabolic alkalosis. In patients with volume-responsive metabolic alkalosis, intravascular volume depletion stimulates aldosterone secretion. As discussed earlier, excess mineralocorticoid activity may also underlie the generation of metabolic alkalosis. In either situation, the increased mineralocorticoid effect stimulates collecting duct H+ secretion. Metabolic alkalosis may also be maintained by persistent hypokalemia. Hypokalemia has a multitude of effects on renal acid-base homeostasis, enhancing proximal tubular bicarbonate reabsorption, stimulating ammoniagenesis and increasing distal tubular H secretion. ... 

Management of these disorders usually consists of treatment of the underlying cause of the mineralocorticoid excess. Patients who are taking corticosteroids may require a dosage reduction or may need to be switched to a corticosteroid with less mineralocorticoid activity. Patients with an endogenous source of excess mineralocorticoid activity may require surgery or the administration of spironolactone, amiloride, or triamterene. " " ... 

The inhibition of 1 lP-OHSD by licorice can mimic the syndrome of apparent mineralocorticoid excess produced by congenital deficiency of this enzyme. For example, there is a rise in free urinary cortisol, and a decreased urinary ratio of cortisone to cortisol metabolites in both situations (Stewart et al., 1987). However, the elevated urinary ratio of 5 3-tetrahydrocortisol to 5a-tetrahydrocortisol that occurs with licorice ingestion is the opposite of the finding expected in children with the syndrome of apparent mineralocorticoid excess (Stewart et al., 1987). 

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-... 

Corticosterone methyloxidase deficiency type I, or type II occasional CAH Chimeric enzymes causing glucocorticoid-remediable aldosteronism occasional CAH Mineralocorticoid excess syndromes, glucocorticoid, and sex hormone deficiencies association with increased risk of prostate cancer and benign prostatic hypertrophy occasional CAH... 

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