What is Congenital Adrenal Hyperplasia?

What is Congenital Adrenal Hyperplasia? (CAH)

The adrenal gland sits above each kidney – one on each side of the body. It is made up of a medulla (middle) which makes adrenaline – this part works perfectly normally in CAH. The outer part of the adrenal gland is the adrenal cortex which makes three main hormones called steroids. These steroids are secreted into the blood stream and are necessary for normal health. It is the adrenal cortex and its hormones which are involved in CAH.

The 3 main steroids involved in CAH are:

There are five main enzymes in the adrenal gland which convert cholesterol into the important steroid Cortisol. If any of these enzymes are missing or defective then not enough Cortisol is made for the needs of the body. The body, recognising the low levels of Cortisol, will try to stimulate the adrenal cortex to make more by ‘pushing’ the gland harder by a stimulating hormone called ACTH made in the pituitary gland. The constant unsuccessful stimulation causes the cortex to increase in thickness and become ‘hyperplastic’.

In the most common form of CAH there is a deficiency of an enzyme called 21 hydroxylase. In this form of CAH the production of Cortisol and Aldosterone is low while testosterone, the male hormone, is produced normally. As the body pushes the adrenal gland harder trying to correct the low Cortisol level more and more testosterone is made. In boys, this excess of testosterone causes early sexual development. In females, the excess in testosterone can cause abnormal genital development before birth while in adults it causes irregular periods, unwanted hair growth and acne. Only by correcting the levels of Cortisol with substitute therapy does the body recognise normal levels and stop producing excessive amounts of testosterone and the circulating levels become normal.

The hormone disturbances caused by CAH:

Different types of CAH

There are many different grades of severity of CAH depending on the degree of impairment of production of cortisol and aldosterone. In the most severe type of CAH aldosterone is completely lacking and loss of salt from the body is the most prominent problem – salt losing CAH accounts for 80% of children with CAH. The loss of salt in the urine is uncontrolled and can cause acute dehydration, very low blood pressure and vomiting. The levels of salt (sodium and chloride) and sugar (glucose) fall in the blood, and the potassium level rises. This is an ‘Adrenal Crisis’ needing very urgent treatment as a potentially life threatening condition.

In the 20% of children with less severe CAH, non-salt losing CAH, the salt balance is normal. In stressful situations, however, some people with non-salt losing CAH may become salt losers and need extra treatment. Girls born with non-salt losing CAH are usually healthy, but often born with an enlarged clitoris and the labia may be partially fused because of the excess of testosterone. Generally, this is less severe than that seen in salt losing cases. In boys, non-salt losing CAH produces no detectable signs at birth and the diagnosis is made when the penis enlarges at a very early age along with early pubic hair and rapid growth in height the result of high levels of testosterone. These changes may not occur until 4 or 5 years old.

The mildest form of CAH – late onset CAH - affects women at any age. Symptoms of unwanted hair growth or irregular periods can start at any time after puberty. Often treatment with steroids is not necessary in women with late onset CAH. Instead, giving oestrogen as in the oral contraceptive can regulate testosterone from the ovary. In fact, the treatment of late onset CAH is usually the same as for the polycystic ovary syndrome because the two conditions are so similar. In men, late onset CAH usually goes unrecognised although it may cause the sperm count to be low.

All of the types of CAH above are deficiencies of the enzyme 21 hydroxylase which account for over 90% of people with CAH. The next most common deficiency is of the enzyme 11-beta hydroxylase. Treatment of this type of CAH is more complicated because high blood pressure can be severe if treatment inadequate. The balance of treatment in 11-beta hydroxylase deficiency is very difficult and an experienced specialist is essential. Deficiencies of other enzymes are exceedingly rare.

Written By - Dr Gerard Conway The Middlesex Hospital Mortimer Street London W1N 8AA

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