A. Cushing’s syndrome.
C. True hermaphrodite.
D. congenital adrenal hyperpasia.
The term congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive disorders, each of which involves a deficiency of an enzyme involved in the synthesis of cortisol, aldosterone, or both. Deficiency of 21-hydroxylase, resulting from mutations or deletions of CYP21A, is the most common form of CAH, accounting for more than 90% of cases.
Signs and symptoms
The clinical phenotype of CAH depends on the nature and severity of the enzyme deficiency. Although the presentation varies according to chromosomal sex, the sex of a neonate with CAH is often initially unclear because of genital ambiguity.
Clinical presentation in females
- Females with severe CAH due to deficiencies of 21-hydroxylase, 11-beta-hydroxylase, or 3-beta-hydroxysteroid dehydrogenase have ambiguous genitalia at birth (classic virilizing adrenal hyperplasia); genital anomalies range from complete fusion of the labioscrotal folds and a phallic urethra to clitoromegaly, partial fusion of the labioscrotal folds, or both
- Females with mild 21-hydroxylase deficiency are identified later in childhood because of precocious pubic hair, clitoromegaly, or both, often accompanied by accelerated growth and skeletal maturation (simple virilizing adrenal hyperplasia)
- Females with still milder deficiencies of 21-hydroxylase or 3-beta-hydroxysteroid dehydrogenase activity may present in adolescence or adulthood with oligomenorrhea, hirsutism, and/or infertility (nonclassic adrenal hyperplasia).
- Females with 17-hydroxylase deficiency appear phenotypically female at birth but do not develop breasts or menstruate in adolescence; they may present with hypertension
Clinical presentation in males
- Males with 21-hydroxylase deficiency have normal genitalia
- If the defect is severe and results in salt wasting, these male neonates present at age 1-4 weeks with failure to thrive, recurrent vomiting, dehydration, hypotension, hyponatremia, hyperkalemia, and shock (classic salt-wasting adrenal hyperplasia)
- Males with less severe deficiencies of 21-hydroxylase present later in childhood with early development of pubic hair, phallic enlargement, or both, accompanied by accelerated linear growth and advancement of skeletal maturation (simple virilizing adrenal hyperplasia)
- Males with steroidogenic acute regulatory (StAR) deficiency, classic 3-beta-hydroxysteroid dehydrogenase deficiency, or 17-hydroxylase deficiency generally have ambiguous genitalia or female genitalia; they may be raised as girls and seek medical attention later in life because of hypertension or a lack of breast development
- Patients with aldosterone deficiency of any etiology may present with dehydration, hyponatremia, and hyperkalemia, especially with the stress of illness
- Males or females with 11-hydroxylase deficiency may present in the second or third week of life with a salt-losing crisis; later in life, these patients develop hypertension, hypokalemic alkalosis, or both
- Infants with StAR deficiency (lipoid adrenal hyperplasia) usually have signs of adrenal insufficiency (eg, poor feeding, vomiting, dehydration, hypotension, hyponatremia, hyperkalemia)
- Hyperpigmentation: Occurs in patients with deficiencies of enzyme activity involved in cortisol synthesis; may be subtle and is best observed in the genitalia and areolae.