How is congenital adrenal hyperplasia differentiated from hyperaldosteronism?

Updated: Sep 08, 2020
  • Author: George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London); Chief Editor: Robert P Hoffman, MD  more...
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Congenital adrenal hyperplasia

11β-Hydroxylase deficiency is the second most common form of congenital adrenal hyperplasia (accounting for about 5% of all cases), with a frequency of 1 in 100,000 live births. Because conversion of 11-deoxycortisol to cortisol and 11-deoxycorticosterone to aldosterone are both reduced, hypersecretion of adrenocorticotropic hormone (ACTH) leads to excessive production of adrenal androgens as well as steroid hormone precursors. 11-Deoxycorticosterone has mineralocorticoid activity and can produce hypertension and sometimes hypokalemia.

The extent of virilization varies widely, ranging from newborn female infants with ambiguous genitalia to early male virilization to hirsutism and infertility in adult women.

The diagnosis should be considered in patients with features of hyperandrogenism and hypertension of the mineralocorticoid-excess type. The age at presentation correlates with the severity of the defect.

Treatment in younger children is with hydrocortisone or cortisone acetate. Those who have finished growing may be treated with dexamethasone. This treatment must be administered carefully; it may precipitate a salt-losing state, because this synthetic steroid has no mineralocorticoid activity and suppresses levels of 11-deoxycorticosterone by inhibiting ACTH release. Patients with 11β-hydroxylase deficiencies who are treated with glucocorticoids may require mineralocorticoid therapy during acute intercurrent illness.

Various mutations of the P-450c11 gene have been described. The diagnosis can be made on the basis of elevated levels of 11-deoxycorticosterone after ACTH stimulation, though basal levels are often diagnostic in affected neonates and infants. Treatment involves glucocorticoid replacement at physiologic doses.

Lyase and 17α-hydroxylase deficiencies are very rare. P-450c17 mutations produce a block in production of a single enzyme with both 17α-hydroxylase and 17,20-lyase activities.

Blockade of sex steroid production can lead to failure of female pubertal development and variable degrees of incomplete virilization with ambiguous genitalia in males. Deficient cortisol production results in ACTH hypersecretion with increased production of aldosterone precursors, including 11-deoxycorticosterone. Plasma renin activity and aldosterone are low.

Treatment involves glucocorticoid treatment similar to that employed for 11β-hydroxylase deficiencies. Males respond to testosterone in the neonatal period with phallic growth that may improve the outcome of corrective surgery. Both sexes also need pubertal induction.

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