Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency

=Congenital Adrenal Hyperplasia due to 11-Beta-Hydroxylase Deficiency = Congenital adrenal hyperplasia (CAH) due to 11-beta-hydroxylase deficiency is a rare genetic disorder affecting the adrenal glands, which are responsible for producing certain hormones. This condition is a form of CAH, a group of inherited disorders characterized by enzyme deficiencies that impair hormone production.

Pathophysiology

11-beta-hydroxylase deficiency is caused by mutations in the CYP11B1 gene, which encodes the enzyme 11-beta-hydroxylase. This enzyme is crucial for the biosynthesis of cortisol and aldosterone in the adrenal cortex. The deficiency leads to:

• Decreased cortisol production: Cortisol is a vital hormone for stress response, metabolism, and immune function.
• Decreased aldosterone production: Aldosterone helps regulate sodium and potassium levels, affecting blood pressure and fluid balance.
• Increased androgen production: Due to the enzyme block, precursor molecules are shunted towards androgen synthesis, leading to excess androgens.

Clinical Features

The clinical presentation of 11-beta-hydroxylase deficiency can vary but often includes:

• Hypertension: Due to excess deoxycorticosterone, a mineralocorticoid with hypertensive effects.
• Virilization: In females, excess androgens can cause ambiguous genitalia or virilization.
• Precocious puberty: In males, early onset of puberty may occur due to elevated androgens.
• Electrolyte imbalances: Although less common than in other forms of CAH, some patients may experience imbalances.

Diagnosis

Diagnosis of 11-beta-hydroxylase deficiency involves:

• Hormonal assays: Elevated levels of 11-deoxycortisol and 11-deoxycorticosterone in the blood.
• Genetic testing: Identification of mutations in the CYP11B1 gene.
• Imaging studies: Adrenal hyperplasia may be observed on imaging.

Treatment

Management of 11-beta-hydroxylase deficiency includes:

• Glucocorticoid replacement therapy: To suppress excess androgen production and replace deficient cortisol.
• Mineralocorticoid antagonists: To manage hypertension if necessary.
• Surgical intervention: In cases of significant virilization, surgical correction may be considered.

Prognosis

With appropriate treatment, individuals with 11-beta-hydroxylase deficiency can lead normal lives. However, lifelong monitoring and management are essential to prevent complications.

See Also

• Congenital adrenal hyperplasia
• CYP11B1 gene
• Endocrine disorders

,

 Congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency, 
 Endocrinology, 
 2001, 
 Vol. 142(Issue: 6), 
 pp. 2381-2386,

,

 Genetic Disorders of the Adrenal Gland, 
  
 Springer, 
 2013,

NIH genetic and rare disease info

• NIH info on Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency

Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency is a rare disease.