Familial Hyperaldosteronism

Genetically inherited endocrine disorder entity that is clinically characterized by fatigue, ileus (from hypokalemia), hypertension, strokes, and other significant cardiovascular events in young persons because of overproduction of aldosterone.

ACTH-Dependent Hyperaldosteronism Syndrome.

Type I: Aldosteronism Sensitive to Dexamethasone; Glucocorticoid-Suppressible Hyperaldosteronism; Glucocorticoid-Remediable Aldosteronism.

Type II: Aldosteronism Insensitive to Dexamethasone; Glucocorticoid Nonsuppressible Hyperaldosteronism; Glucocorticoid Nonremediable Aldosteronism.

Fewer than 150 validated cases reported in the literature.

Autosomal dominant. The glucocorticoid-sensitive form (type I) of familial hyperaldosteronism is related to a chimeric gene product combining (by crossover) the promoter of the 11β-hydroxylase gene with the coding region of the aldosterone synthetase gene on chromosome 8q21 (anti-Lepore-type fusion of Cyp11B1 and Cyp11B2). Type II is caused by a mutation in chromosome 7p22.

Hyperaldosteronism is a consequence of aldosterone-producing adenoma. The effects of aldosterone are mediated through activation of the epithelial sodium channel, and activating mutations of this channel lead to signs of mineralocorticoid excess.

Hypertension, polyuria, polydipsia, fatigue, tinnitus, paresthesia, and paralysis of variable duration (from 1 hour to weeks), failure to thrive, and muscle loss. Laboratory investigations include hypokalemia (<3.5 mmol/liter), metabolic alkalosis associated with inappropriate kaliuresis, increased plasma levels of aldosterone (>40 ng/dl), decreased plasma renin activity (<0.3 ng/ ml/hour), and nonsuppressible aldosterone response to ambulation. Dexamethasone test did not suppress aldosterone level. Magnetic resonance imaging is better for locating the adenoma than is CT. The left gland is four times more frequently involved than the right gland. In Conn syndrome, the ratio of deoxycorticosterone to corticosterone is unaffected by adrenocorticotropic hormone.

The clinical presentation of familial hyperaldosteronism is not distinctive, and diagnosis requires expertise on the part of the physician. Familial hyperaldosteronism patients usually have a long history of fatigue, muscle loss, paresthesia (even paralysis), tinnitus, and headache (caused by hypertension). Polyuria and polydipsia are common features. The main physical symptom is hypertension. It is not unusual for the diagnosis to be established when a severe complication of hypertension occurs (stroke, cardiac problem). Laboratory examinations reveal hypokalemia (often severe), metabolic alkalosis, inappropriate kaliuresis, decreased plasma rennin activity, and high basal plasma levels of aldosterone. Imaging reveals either diffuse adrenocortical hyperplasia or multiple adrenocortical adenomas. Depending on the efficacy of glucocorticoid given to correct the symptomatology, two types of this familial disease exist: type I, which is glucocorticoid sensitive and caused by multiple adrenocortical adenomas, and type II, which is caused by adrenal hyperplasia and is not glucocorticoid remediable. Otherwise the two forms are clinically similar.

Evaluate electrolytes status and correct hypokalemia. Restrict sodium intake. Administrate spironolactone (5-10 mg/kg/d) . Stop captopril or enalapril 24 hours before general anesthesia. Evaluate immune status because of treatment by agents that inhibit angiotensin-converting enzyme.

If hypokalemia has not been corrected prior to anesthesia, hyperventilation could be dangerous by decreasing further potassium plasma levels. Regional anesthesia technique such as epidural anesthesia can be used safety in children, especially in patients less than 8 years of age, because of the absence of induced hemodynamic effects in this age group. No specific anesthetic agents can be recommended or contraindicated considering the risk of acute hypotension. Monitoring of arterial blood pressure as well as central venous pressure is recommended perioperatively.

Pay close attention to the possible interaction between hypotensive drugs that can be used, such as captopril or enalapril and spironolactone, and the risk of hyperkalemia. Clonidine must be avoided because it decreases plasma renin activity. Enflurane may be questionable if a nephropathy exists preoperatively. Supplementation with exogenous cortisol (cortisone hemisuccinate) is indicated only in cases of excision of multiple adenomas with bilateral mobilization of adrenal glands.

Bartter Syndrome: Family of disorders characterized by hypokalemic, hypochloremic, metabolic alkalosis, and normotensive, hyperreninemic hyperaldosteronism.

Conn Syndrome: Rare and potentially curable endocrine disorder caused by hyperaldosteronism. Presenting symptoms associate hypertension to severe hypokalemia.

Gitelman Syndrome: Inherited renal tubular defect resulting in urinary loss of magnesium, sodium, potassium, and chloride with otherwise normal kidneys.