Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency
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eMedicine	article 117012
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Human steroidogenesis. The action of 11β-hydroxylase is seen in red box at right.

11β-OH CAH is autosomal recessive.

Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is a rare, autosomal recessive disorder that is part of the larger family of congenital adrenal hyperplasia (CAH) disorders. It is caused by a deficiency in the enzyme 11β-hydroxylase, which is crucial for the synthesis of corticosteroids in the adrenal glands. This deficiency leads to an accumulation of precursor steroids, which are then diverted to androgen synthesis, resulting in symptoms of androgen excess.

Etiology and Pathophysiology

The disorder is caused by mutations in the CYP11B1 gene, which encodes the enzyme 11β-hydroxylase. This enzyme is responsible for the conversion of 11-deoxycortisol to cortisol and deoxycorticosterone (DOC) to corticosterone in the adrenal cortex. A deficiency in 11β-hydroxylase leads to decreased production of cortisol and corticosterone, with a consequent increase in ACTH secretion by the pituitary gland. The increased ACTH levels stimulate the adrenal gland, leading to an overproduction of androgenic steroids.

Clinical Features

Patients with 11β-hydroxylase deficiency typically present with signs of androgen excess, such as virilization in females, precocious puberty in males, and accelerated growth and bone maturation in both sexes, which may lead to short stature as growth plates close early. Hypertension is a distinguishing feature of this form of CAH, due to the accumulation of deoxycorticosterone, a potent mineralocorticoid.

Diagnosis

Diagnosis is based on clinical presentation, biochemical testing showing elevated levels of 11-deoxycortisol and androgens, and genetic testing confirming mutations in the CYP11B1 gene. The differential diagnosis includes other forms of CAH, particularly 21-hydroxylase deficiency, which is more common.

Treatment

Treatment focuses on replacing deficient corticosteroids, usually with glucocorticoids such as hydrocortisone, to suppress ACTH production and reduce androgen synthesis. Mineralocorticoid replacement is not typically required, as hypertension is usually due to the mineralocorticoid effect of DOC. Blood pressure management is also crucial. In cases of severe virilization, additional treatments may be necessary.

Prognosis

With early diagnosis and appropriate treatment, individuals with 11β-hydroxylase deficiency can lead normal lives, although they require lifelong monitoring and medication. The main complications arise from improper management of glucocorticoid therapy and the consequences of excess androgen exposure.

See also

• Inborn errors of steroid metabolism
• Congenital adrenal hyperplasia
• Adrenal insufficiency
• Disorders of sexual development
• Intersexuality, pseudohermaphroditism, and ambiguous genitalia
• Steroid 11β-hydroxylase

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