Congenital adrenal hyperplasia

Clinical information

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders in which the two adrenal glands do not function properly, most commonly due to mutations in the gene encoding the enzyme 21-hydroxylase. Without this enzyme, the adrenal glands may produce too little cortisol and/or aldosterone and too much androgens.

There are two main types of CAH: classic CAH, which is divided into two subtypes (the salt-wasting form and the simple virilising form), and non-classic CAH (also known as late-onset CAH).

Salt-wasting classic CAH is the most severe form and accounts for about 75 % of classic CAH cases. In this form the levels of cortisol and aldosterone are too low, the androgen levels are too high and the body is unable to maintain appropriate levels of salt in the blood. Signs of salt-wasting CAH usually begin within the first few weeks of life; it can be life-threatening if not diagnosed and treated promptly.

Simple virilising classic CAH is a milder form and accounts for about 25 % of classic CAH cases. In this form the adrenals produce enough aldosterone, but not cortisol. Individuals with simple virilising classic CAH experience early puberty because high androgen levels cause rapid growth and sexual development and promote development of male sexual features.

Non-classic CAH (NCCAH) is much less severe and more common than classic CAH. Individuals with NCCAH have normal levels of cortisol and aldosterone, but high levels of androgens. It is not life-threatening but can affect puberty and growth in children, and cause infertility in males and females as well as other symptoms affecting quality of life. Signs of NCCAH can begin in childhood, adolescence, or adulthood.

Diagnostics

Classic CAH is usually diagnosed soon after birth through newborn screening with a blood test from a heel prick. Positive neonatal screening results are confirmed by measuring 17-OH progesterone and additional adrenal steroids (e. g. cortisol, 11-deoxycortisol, dehydroepiandrosterone sulphate, androstenedione, testosterone). Diagnosis of classic CAH in infancy or later may also include genetic tests.

NCCAH signs and symptoms may appear at any time from infancy through adulthood and overlap with other disorders so that NCCAH is less likely to be diagnosed promptly. The diagnosis is often made accidentally when measuring adrenal steroids during the investigation of other clinical conditions and confirmed with a cosyntropin stimulation test.

While patients with classic CAH need to take medications to replace cortisol and aldosterone throughout their lives, patients with non-classic CAH may or may not require treatment, depending on their symptoms and gender.