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Congenital Adrenal Hyperplasia

Also known as: 21 Hydroxylase Deficiency

Background

Congenital adrenal hyperplasia (CAH) is the name given to a group of disorders causing impaired production of a hormone called cortisol (hydrocortisone) from the adrenal glands. Cortisol is released in response to stress, and is important for several processes in the body, such as increasing blood sugar levels; the adrenal glands are two small glands that sit at the top of the kidneys.

By far the most common type of CAH is 21 hydroxylase deficiency, which occurs in roughly 1 in 2,500 births. 21 hydroxylase is responsible for the production of cortisol. In 21 hydroxylase deficiency, production of cortisol and aldosterone is impaired. Aldosterone helps the body regulate blood pressure by reabsorbing sodium and water and then releasing potassium in the kidneys. The brain, sensing the low levels of cortisol, produces large amounts of adrenocorticotrophin hormone (ACTH), which stimulates the adrenal glands and causes hyperplasia (enlargement), which then results in over-production of androgen (the hormone responsible for production of testosterone).

Credits

Last updated February 2015 by Dr R Stanhope, Consultant Paediatric Endocrinologist, The Portland Hospital, London, UK.

What are the symptoms?

The symptoms of 21 hydroxylase deficiency seen in a child depends on the severity of the enzyme defect and the sex of the child. Boys with a severe defect will show symptoms at about ten days of age with vomiting, dehydration and weight loss - also known as the 'salt-losing crisis'.

Girls with a severe defect will have ambiguous (non-feminised) genitalia at birth due to the effect of androgen over production in the developing baby. Unless treated promptly these girls will also develop a 'salt-losing crisis'. Boys and girls with a mild defect will have symptoms later in childhood with signs of androgen excess - tall stature, enlargement of penis or clitoris, and early development of pubic hair but no salt-losing crisis.

How is it treated?

Treatment consists of surgery in girls to reduce the size of the clitoris and open up the lower end of the vagina. Both sexes require hydrocortisone to suppress ACTH secretion and switch off androgen production, fludrocortisone to replace aldosterone and (during the first year of life) salt supplements.

The dose of hydrocortisone has to be carefully adjusted since under-treatment will result in over-production of androgen with excessive growth and virilisation (abnormal development of male sexual characteristics in a female), while over-treatment will cause slow growth and obesity.

By adjusting the dose of hydrocortisone against the child's size, growth rate, skeletal maturity ('bone age') and adrenal steroid levels, the treatment can be optimised and the general health of these children is good. It is important for parents to learn how to increase the hydrocortisone dose during acute illness, so as to mimic the normal cortisol response to stress. In particular, there is a need for an emergency regimen of hydrocortisone injection and salt replacement in severe illness.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Autosomal recessive.

Prenatal diagnosis
Once an affected child has been diagnosed, genetic testing can be carried out on the parents and patient. Diagnosis can then be done in the developing baby by chorionic villus sampling (CVS) at 9 to 10 of pregnancy.

Antenatal treatment (for the baby before birth) is available by treating the mother throughout pregnancy with dexamethasone (a strong cortisol equivalent) which will prevent the virilisation of an affected female fetus.

Is there support?

Information and support in the UK for congenital adrenal hyperplasia is provided by Climb (see entry Inherited Metabolic diseases).

Families can use Contact a Family's freephone helpline for advice, information and, where possible, links to other families. Contact a Family's web-based linking service can be acessed at community.cafamily.org.uk