Congenital adrenal hyperplasia is an autosomal recessive genetic condition causing a deficiency of the 21-hydroxylase enzyme, which converts progesterone to aldosterone and cortisol. Deficiency of this enzyme causes the underproduction of cortisol and aldosterone and overproduction of androgens from birth.
A small proportion of cases are caused by a deficiency of other enzymes (e.g., 11-beta-hydroxylase).
Steroid Hormones
Testosterone is an androgen hormone. It is found in high levels in men and low levels in women. It has many functions, including increasing muscle mass, bone density, facial hair growth, libido and competitiveness.
Glucocorticoid hormones (e.g., cortisol) help the body cope with stress. Cortisol increases alertness, raises blood glucose, reduces inflammation and suppresses the immune system.
Mineralocorticoids (e.g., aldosterone) help regulate the balance of electrolytes and blood pressure. They act on the nephrons in the kidneys to:
- Increase sodium reabsorption from the distal tubule
- Increase potassium secretion from the distal tubule
- Increase hydrogen secretion from the collecting ducts
Pathophysiology
21-hydroxylase is the enzyme responsible for converting progesterone to aldosterone and cortisol. Progesterone is also used to create testosterone, but this conversion does not require the 21-hydroxylase enzyme.
In CAH, there is a defect in the 21-hydroxylase enzyme, reducing the conversion of progesterone to aldosterone and cortisol, leaving additional progesterone that gets converted to testosterone instead. The result is:
- Low aldosterone
- Low cortisol
- High testosterone
Presentation
The severity of the symptoms varies depending on the genetic mutation. It can be divided into three forms:
- Salt-wasting congenital adrenal hyperplasia
- Simple virilising congenital adrenal hyperplasia
- Non-classical congenital adrenal hyperplasia
Patients with salt-wasting congenital adrenal hyperplasia (the most severe form) present shortly after birth with hyponatraemia, hyperkalaemia and hypoglycaemia, leading to signs and symptoms of lethargy, poor feeding, dehydration, vomiting and arrhythmia. Female patients have virilised genitalia due to high testosterone, with clitoral enlargement and labial fusion, causing ambiguous genitalia.
Simple virilising congenital adrenal hyperplasia causes virilised genitalia in female patients and other features of high testosterone. However, aldosterone production is adequate.
Patients with non-classical congenital adrenal hyperplasia are less severely affected and may present during childhood or after puberty. Their symptoms are related to high androgen levels. Features may include:
- Early puberty
- Acne
- Hirsutism (male-pattern facial hair)
- Reduced or absent periods
TOM TIP: Congenital adrenal hyperplasia can cause skin hyperpigmentation when the cortisol levels are low. Low cortisol levels mean less negative feedback to the anterior pituitary, so it produces excessive ACTH. High ACTH causes skin pigmentation by stimulating melanocytes in the skin to produce melanin.
Management
Specialist paediatric endocrinologists will coordinate management. Patients will be followed up closely for their growth and development. Treatment depends on the severity and may involve:
- Cortisol replacement with hydrocortisone
- Aldosterone replacement with fludrocortisone
- Surgery may be considered for genital abnormalities in female patients
Last updated February 2025
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