The goals of treatment are to achieve normal linear growth and bone age advancement. Long-term therapy consists of providing glucocorticoids at a dose of approximately 10 to 15 mg/m2/24 hours in three divided doses of oral hydrocortisone or its equivalent. Mineralocorticoid therapy for salt losers consists of fludrocortisone at a dose of 0.1 to 0.2 mg/24 hours, often with sodium chloride supplementation in infancy and early childhood. Surgical correction of ambiguous external genitalia may be considered. The adequacy of glucocorticoid replacement therapy is monitored by determining serum concentrations of adrenal precursors, including androstenedione and 17-OHP for 21-hydroxylase deficiency. In addition, the assessment of linear growth and skeletal age, by bone age determination, is required as a reflection of appropriate therapy. To avoid adrenal insufficiency, threefold higher doses of glucocorticoids are given during stressful states such as febrile illnesses and surgery. Intramuscular hydrocortisone is used in severe emergencies or with illnesses involving emesis. Mineralocorticoid therapy is monitored with serum sodium, potassium, and plasma renin activity levels. Prenatal treatment with dexamethasone to suppress fetal ACTH-induced
Hemorrhage Moderate to severe No No D D D D D D D D
P-450c21 deficiency Absent to severe Yes No D D I I D D I I
Unresponsiveness to † 17-KS, 17-Ketosteroid; 17-OHCS, 17-hydroxycorticosteroid; ACTH, adrenocorticotropic hormone; D, decrease; HSD, hydroxysteroid dehydrogenase; I, increase; Nl, normal; StAR, steroid acute regulatory protein. *Usually manifested after 5 days of age.
†High normal Na+ and low normal to low K+.
androgen production can reduce or eliminate the ambiguity of the external genitalia in affected female fetuses, if begun at approximately 7 weeks of gestation; this remains controversial.
Other enzyme defects are rare in contrast to 21-hydroxylase deficiency. In 11-hydroxylase deficiency, the next most common cause of CAH, virilization occurs with salt retention and hypokalemia, as a result of the buildup of deoxycorticosterone (see Fig. 178-1), a potent mineralocorticoid. Hypertension develops as a result of excessive mineralocorticoid production. Table 178-2 summarizes the clinical and biochemical features of adrenal insufficiency in infancy.
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Addison disease is a rare acquired disorder of childhood, usually associated with autoimmune destruction of the adrenal cortex. It is a form of primary adrenal insufficiency with absence of glucocorticoid and mineralocorticoid.
Clinical manifestations are hyperpigmentation, salt craving, postural hypotension, fasting hypoglycemia, anorexia, weakness, and episodes of shock during severe illness. Baseline and ACTH-stimulated cortisol values are subnormal, confirming the diagnosis; hyponatremia, hyperkalemia, and elevated plasma renin activity indicate mineralocorticoid deficiency. Addison disease may occur within the context of autoimmune polyglandular syndromes (APS I and APS II). Other rare causes of adrenal insufficiency include adrenal leukodystrophy and conditions that affect the hypothalamus-pituitary whether acquired, such as in craniopharyngioma, or iatrogenic, such as in irradiation for treatment of malignancy.