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Congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH), sometimes called adrenogenital syndrome, is a group of autosomal recessive defects in the enzymes responsible for secretion of adrenal cortical hormones.

The name comes from the compensatory adrenal hyperplasia which occurs due to decreased negative feedback on the pituitary, causing ACTH to increase.

Thanks to neonatal screening the more severe forms are rare nowadays, so the clinical presentation has shifted from presenting acutely with shock in the neonatal period to presenting with symptoms of increased androgens in young adults.

Classification

There are three enzymes which can be affected, each giving one type of CAH:

  • 21β-hydroxylase – accounts for 95% of cases
  • 11β-hydroxylase – accounts for approx. 5% of cases
  • 17α-hydroxylase – very rare

We’ll focus on the most common type. When we speak about CAH we generally mean 21β-hydroxylase deficiency.

There are two main types of CAH depending on the degree to which 21β-hydroxylase is deficient. In the early onset type, the deficiency is severe. In the late onset type, the deficiency is mild. The latter is most common. There are two subtypes of early onset CAH, the salt-wasting type and the virilizing type, with the former being the most severe.

  • Early onset CAH (or classic CAH)
    • Salt-wasting type
    • Simple virilizing type
  • Late onset CAH (or non-classic CAH)

In salt-wasting type the 21β-hydroxylase activity is insufficient to maintain the aldosterone and cortisol level. In the virilizing type the activity is sufficient to maintain aldosterone levels but not cortisol. In late-onset CAH, the deficiency is even milder and so the patient presents much later.

Clinical features

Salt-wasting CAH presents in the neonatal period. Patients present with symptoms of adrenal crisis, like hyponatraemia, hyperkalaemia, metabolic acidosis, hypotension, and shock, because of insufficient aldosterone and cortisol. Females also have ambiguous genitalia at birth because of increased androgens.

Virilizing CAH is diagnosed at different times in the different sexes. Males present with puberty at age 2 – 4, while females present in the neonatal period with ambiguous genitalia.

Late onset CAH is diagnosed in young adulthood. A typical late onset CAH patient is female, has hirsutism and menstrual disturbances due to increased androgens. Male patients are almost always asymptomatic.

Diagnosis and evaluation

Nowadays early-onset CAH is screened for during neonatal screening and therefore rarely presents with symptoms. 17-hydroxy-progesterone is measured in neonates and is elevated in both 21β-hydroxylase and 11β-hydroxylase deficiency.

Late onset CAH is screened for by 17-hydroxy-progesterone levels as well. The diagnosis is confirmed if 17-hydroxyprogesterone levels are high after ACTH stimulation.

Treatment

All early onset CAH patients should receive lifelong hormone replacement therapy of corticosteroids and mineralocorticoids. Glucocorticoid doses must be increased in periods of stress, infection, surgery, etc.

Like any adrenal crises, salt-wasting CAH presenting with adrenal crisis is acutely treated with fluid replacement and glucocorticoids, as well as supportive treatment to correct glucose and electrolytes.

Late onset CAH can be treated by oral contraceptives or glucocorticoids in females. Men do not require treatment.