Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia is caused by a congenital deficiency of the 21-hydroxylase enzyme. This causes underproduction of cortisol and aldosterone and overproduction of androgens from birth. It is a genetic condition that is inherited in an autosomal recessive pattern. In a small number of cases it is caused by a deficiency of 11-beta-hydroxylase rather than 21-hydroxylase.


Steroid Hormones

Testosterone is an androgen hormone. It is found in high levels in men and low levels in women. It acts to promote male sexual characteristics.

Glucocorticoid hormones act to help the body deal with stress, raise blood glucose, reduce inflammation and suppress the immune system. Cortisol is the main glucocorticoid hormone. The level of cortisol fluctuates during the day, with higher levels in the morning and during times of stress. It is released in response to adrenocorticotropic hormone (ACTH) from the anterior pituitary.

Mineralocorticoid hormones act on the kidneys to control the balance of salt and water in the blood. Aldosterone is  the main mineralocorticoid hormone. It is released by the adrenal gland in response to renin. Aldosterone acts on the kidneys to increase sodium reabsorption into the blood and increase potassium secretion into the urine. Therefore, aldosterone acts to increase sodium and decrease potassium in the blood.


Congenital Adrenal Hyperplasia Pathophysiology

21-hydroxylase is the enzyme responsible for converting progesterone into aldosterone and cortisol. Progesterone is also used to create testosterone, but this conversion does not rely on the 21-hydroxylase enzyme. In CAH, there is a defect in the 21-hydroxylase enzyme. Therefore, because there is extra progesterone floating about that cannot be converted to aldosterone or cortisol, it gets converted to testosterone instead. The result is a patient with low aldosterone, low cortisol and abnormally high testosterone.


Presentation in Severe Cases

Female patients with CAH usually presents at birth with virilised genitalia, known as “ambiguous genitalia” and an enlarged clitoris due to the high testosterone levels.

Patients with more severe CAH present shortly after birth with hyponatraemia, hyperkalaemia and hypoglycaemia.

This leads to signs and symptoms:

  • Poor feeding
  • Vomiting
  • Dehydration
  • Arrhythmias


Presentation in Mild Cases

Patients who are less severely affected present during childhood or after puberty. Their symptoms tend to be related to high androgen levels.


Female patients:

  • Tall for their age
  • Facial hair
  • Absent periods
  • Deep voice
  • Early puberty


Male patients:

  • Tall for their age
  • Deep voice
  • Large penis
  • Small testicles
  • Early puberty


TOM TIP: A textbook and exam clue that a patient has CAH is skin hyperpigmentation. Hyperpigmentation occurs because the anterior pituitary gland responds to the low levels of cortisol by producing increasing amounts of ACTH. A byproduct of the production of ACTH is melanocyte simulating hormone. This hormone stimulates the production of melanin (pigment) within skin cells.



Management will be coordinated by specialist paediatric endocrinologists. They will be followed up closely for their growth and development. Treatment involves:

  • Cortisol replacement, usually with hydrocortisone, similar to treatment for adrenal insufficiency
  • Aldosterone replacement, usually with fludrocortisone
  • Female patients with “virilised” genitals may require corrective surgery


Last updated August 2019