Etiology

Aldosterone-secreting adenomas are unilateral and have been reported in children as young as  yr of age; they mainly affect girls. Bilateral micronodular adrenocortical hyperplasia tends to occur in older children and is more frequent in males. Primary aldosteronism due to unilateral adrenal hyperplasia may also occur. Glucocorticoid-suppressible hyperaldosteronism is discussed in Chapter 570.

Epidemiology

These conditions are thought to be rare in children, but they may account for 5-10% of cases of hypertension in adults. Although usually sporadic, kindreds with several affected members have been reported. Genetic linkage to chromosome 7p22 has been identified in some of these kindreds, but the involved gene has not yet been identified.

Clinical Manifestations

Some affected children have no symptoms, the diagnosis being established after incidental discovery of moderate hypertension. Others have severe hypertension (up to 240/150 mm Hg), with headache, dizziness, and visual disturbances. Chronic hypokalemia, if present, may lead to polyuria, nocturia, enuresis, and polydipsia. Muscle weakness and discomfort, tetany, intermittent paralysis, fatigue, and growth failure affect children with severe hypokalemia.

Laboratory Findings

Hypokalemia occurs frequently. Serum pH and the carbon dioxide and sodium concentrations may be elevated and the serum chloride and magnesium levels decreased. Serum levels of calcium are normal, even in children who manifest tetany. The urine is neutral or alkaline, and urinary potassium excretion is high. Plasma levels of aldosterone may be normal or elevated. Aldosterone concentrations in 24-hr urine collections are always increased. Plasma levels of renin are persistently low.

The diagnostic test of choice for primary aldosteronism is controversial. Both renin and aldosterone levels may vary by time of day, posture, and sodium intake, making it difficult to establish consistent reference ranges. It is desirable to establish a consistent sampling protocol, for example, mid-morning after the patient has been sitting for 15 min. If possible, antihypertensive drugs or other medications that can affect aldosterone or renin secretion should be avoided for several weeks prior to testing, including diuretics, β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, clonidine, and nonsteroidal anti-inflammatory agents. Patients taking these agents may need to be changed to α-adrenergic blockers or calcium channel blockers that have smaller effects on the biochemical measurements. The ratio of plasma aldosterone concentration to renin activity is always high, and this represents a cost-effective screening test for primary aldosteronism. Aldosterone does not decrease with administration of saline solution or fludrocortisone, and renin does not respond to salt and fluid restriction. Urinary and plasma levels of 18-oxocortisol and 18-hydroxycortisol may be increased but not to the extent seen in glucocorticoid-suppressible hyperaldosteronism.

Differential Diagnosis

Primary aldosteronism should be distinguished from glucocorticoid-suppressible hyperaldosteronism (Chapter 570.8), which is specifically treated with glucocorticoids. An autosomal dominant pattern of inheritance should raise suspicion for the latter disorder. Glucocorticoid-suppressible hyperaldosteronism is diagnosed by dexamethasone suppression tests or by specific genetic testing. More generally, primary aldosteronism should be distinguished from other forms of hypertension by means of the testing previously discussed.

Treatment

The treatment of an aldosterone-producing adenoma is surgical removal. This has been performed primarily by laparotomy and adrenalectomy; successful enucleation of aldosterone-producing adenomas as well as laparoscopic adrenalectomy has been reported. Hyperaldosteronism due to bilateral adrenal hyperplasia is treated with the mineralocorticoid antagonists spironolactone or eplerenone, often normalizing blood pressure and serum potassium levels. There is greater experience with spironolactone, but this agent has antiandrogenic properties that may be unacceptable in pubertal males. Eplerenone is a more specific antimineralocorticoid, but there is little experience with this agent in the pediatric age group. As an alternative, an epithelial sodium channel blocker such as amiloride may be used and other antihypertensive agents added as necessary. In patients whose condition cannot be controlled medically, unilateral adrenalectomy may be considered.