Hyperaldosteronism, primary

Hyperaldosteronism is a syndrome caused by excessive secretion of aldosterone. It is characterized by renal loss of potassium. Sodium reabsorption in the kidney is increased and accompanied by an increase in extracellular fluid. Clinically, an increased blood pressure (hypertension) is observed. Primary hyperaldosteronism is caused by aldosterone-producing, benign adrenal tumors (Conn s syndrome). Secondary hyperaldosteronism is caused by activation of the renin-angiotensin-aldosterone system. Various dtugs, in particular diuretics, cause or exaggerate secondary peadosteronism. 

ACE inhibitors do not completely block aldosterone synthesis. Since this steroid hormone is a potent inducer of fibrosis in the heart, specific antagonists, such as spironolactone and eplerenone, have recently been very successfully used in clinical trials in addition to ACE inhibitors to treat congestive heart failure [5]. Formerly, these drugs have only been applied as potassium-saving diuretics in oedematous diseases, hypertension, and hypokalemia as well as in primary hyperaldosteronism. Possible side effects of aldosterone antagonists include hyperkalemia and, in case of spironolactone, which is less specific for the mineralocorticoid receptor than eplerenone, also antiandrogenic and progestational actions. 

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. 

Potassium-sparing diuretics are often coadministered with thiazide or loop diuretics in the treatment of edema and hypertension. In this way, edema fluid is lost to the urine while K+ ion balance is better maintained. The aldosterone antagonists are particularly useful in the treatment of primary hyperaldosteronism. 

Short-term preoperative treatment of patients with primary hyperaldosteronism. 

Diagnosis of primary hyperaldosteronism As initial diagnostic measure to provide presumptive evidence of primary hyperaldosteronism in patients on normal diets, as follows ... 

Long test-400 mg/day for 3 to 4 weeks. Correction of hypokalemia and hypertension provides presumptive evidence for diagnosis of primary hyperaldosteronism. 

Short test-400 mg/day for 4 days. If serum potassium increases but decreases when spironolactone is discontinued, consider a presumptive diagnosis of primary hyperaldosteronism. 

Primary hyperaldosteronism. Used as an aid in preparing patients with adrenal cortical tumors for surgery. 

Contraindications Bilateral renal artery stenosis, biliary cirrhosis or obstruction, primary hyperaldosteronism, severe hepatic insufficiency... 

When used for diagnosis of primary hyperaldosteronism, positive results are (long test) correction of hyperkalemia and hypertension (short test) serum potassium increases during administration, but falls upon discontinuation... 

Spironolactone (see p. 534) is a competitive aldosterone antagonist which also blocks the mineralocorticoid effect of other steroids it is used in the treatment of primary hyperaldosteronism and as a diuretic, principally when severe oedema is due to secondary hyperaldosteronism, e.g. cirrhosis, congestive cardiac failure. 

It has been argued that drug combinations that contain a beta-adrenoceptor antagonist in combination with a thiazide diuretic minimize the hypokalemic effect of the latter however, marked hypokalemia in the absence of primary hyperaldosteronism has been reported in a patient taking Sotazide (a combination of hydrochlorothiazide and the non-selective drug sotalol) (204). The use of a combination formulation of chlortaUdone and atenolol has also produced hypokalemia (205), in one case complicated by ventricular fibrillation after myocardial infarction (206). 

When there is severe hypokalemia, it should not be attributed immediately to diuretic treatment. It may well be due to primary hyperaldosteronism, occult chronic liver disease, or abuse of licorice or laxatives. 

Ribstein J,Guilhem DC, Pierre F, Mimran A. Relative glomerular hyperfiltration in primary hyperaldosteronism. J Am Soc Nephrol 2005 16 1320-1325. 

In humans, spironolactone is absorbed readily and is metabolized in the liver to active compounds called canrenones. It is these metabolites that compete with aldosterone for its cytosolic receptor therefore, the maximal natriuretic effect is not observed until 24-48 h after treatment has been initiated. Spironolactone is indicated for the treatment of primary hyperaldosteronism but is also used in refractory edema and in secondary hyperaldosteronism consequent to use of loop or thiazide-type diuretics (Martinez-Maldonado Cordova 1990, Rose 1989, 1991, Wilcox 1991). In one study, the administration of spironolactone via nasogastric tube (1 and 2mg/kg) to ponies more than doubled the urinary excretion of sodium and reduced the urinary excretion of potassium for a period of 72 h, although there was no difference in the volume of urine produced (Alexander 1982). This suggests that spironolactone is a potassium-sparing agent in horses however, to date, no pharmacokinetic studies have been published. 

Primary hyperaldosteronism (adrenal adenoma or rarely, carcinoma)... 

This condition is far less common than chloride responsive metabolic alkalosis and is almost always associated with either an underlying disease (primary hyperaldosteronism, Cushing s syndrome, or Bartter s syndrome) or with excess addition of exogenous base. In these conditions, urine CL will usually be >20 mmol/L. 

Luderer JR, Demers LM, Harrison TS, Hayes AH. Converting enzyme inhibition with captopril in patients with primary hyperaldosteronism. Clin Pharmacol Ther 1982 31 305-11. 

Sheaves R. Relative value of computed tomography scanning and venous sampling in establishing the cause of primary hyperaldosteronism. Eur J Endocrinol 1996 134 308-13. 

A plasma-aldosterone-to-plasma-renin-activity ratio (PA PRA) greater than 25 is indicative of primary hyperaldosteronism. 

Fardella CE, Mosso L, Gomez-Sanchez C, et al. Primary hyperaldosteronism in essential hypertensives Prevalence, biochemical profile, and molecular biology. J Clin Endocrinol Metab 2000 85 1863-1867. 

Excessive sodium intake, particularly from the use ol intravenous solutions, may cause hypernatraemia. Rarely, primary hyperaldosteronism (Conn s syndrome) may be the cause. 

Primary hyperaldosteronism (Conn s syndrome) is rare. In most cases, the disease is due to a single adrenocortical adenoma. Patients may present with polydipsia and polyuria, symptoms of neuromuscular abnormalities such as weakness, paraeslhesiae and tetany, and hypertension. All symptoms other than hyjjcrtcnsion are attributable to potassium depletion. 

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