Congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is a group of inherited disorders affecting the adrenal glands, caused by enzyme deficiencies in the cortisol biosynthesis pathway. The most common form, accounting for approximately 95% of cases, is due to deficiency of 21-hydroxylase (encoded by the CYP21A2 gene). Less common forms include 11-beta-hydroxylase deficiency, 17-alpha-hydroxylase deficiency, 3-beta-hydroxysteroid dehydrogenase deficiency, and lipoid adrenal hyperplasia (StAR protein deficiency). The impaired cortisol production leads to increased ACTH secretion from the pituitary gland, which in turn causes adrenal hyperplasia and overproduction of adrenal androgens. CAH presents in two major clinical forms. The classic form, which is the most severe, manifests at birth or in early infancy and includes a salt-wasting type and a simple virilizing type. In the salt-wasting form, deficiency of both cortisol and aldosterone leads to life-threatening adrenal crises with hyponatremia, hyperkalemia, dehydration, and vomiting in the neonatal period. Excess androgens cause ambiguous genitalia (virilization) in affected females at birth, while males may appear normal but can develop adrenal crises if untreated. The simple virilizing form involves androgen excess without significant aldosterone deficiency. The non-classic (late-onset) form is milder and may present in childhood or adulthood with premature pubarche, accelerated growth, advanced bone age, acne, hirsutism, menstrual irregularities, and infertility. Treatment of CAH involves lifelong glucocorticoid replacement therapy (such as hydrocortisone in children) to replace deficient cortisol and suppress excess ACTH-driven androgen production. Patients with the salt-wasting form also require mineralocorticoid replacement (fludrocortisone) and sodium supplementation, particularly in infancy. Stress dosing of glucocorticoids is essential during illness, surgery, or other physiological stress to prevent adrenal crises. Newborn screening programs in many countries now detect classic 21-hydroxylase deficiency through measurement of 17-hydroxyprogesterone. Surgical management of ambiguous genitalia in affected females remains a topic of ongoing discussion. Newer therapeutic approaches under investigation include modified-release hydrocortisone formulations and CRH receptor antagonists.

Common questions about Congenital adrenal hyperplasia