What is Congenital Adrenal Hyperplasia?
The 3 main steroids involved in CAH are:
· Cortisol controls how the body copes with stress, emotional and physical, such as infection or injury. It also helps to control blood sugar levels, raising these levels if they become too low particularly in children.
· Aldosterone helps to regulate the salt levels in the body. Aldosterone causes the kidneys to conserve salt if there is too little salt in the diet, or if a lot of salt is lost due to excessive sweating. Conversely, if a lot of salt is eaten the adrenal cortex reduces the amount of aldosterone secreted, allowing the excess salt to be passed in the urine.
· Androgens are a group of male hormones, one of which is testosterone. For the rest of this booklet the term testosterone will be used to refer to the androgen group. Testosterone is produced by the adrenal cortex in both males and females and they control the formation of pubic hair at the onset of puberty. Testosterone is also produced by the testis and in small amounts by the ovary.
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:
Lack of cortisol
Lack of aldosterone
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. 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 and beyond the scope of this pamphlet. A specialist will be able to offer more information on the rarer forms of CAH. Adrenogenital syndrome is an older name for CAH which is still used occasionally.
Treatment of CAH
People with CAH have a normal life expectancy and for most people there is very little interference in every day life if the condition is well managed. Adults with CAH require life long follow up in specialist hospital clinics in order to maintain the correct level of medical care and to provide early advice on fertility when needed.
It is advisable to have regular medical checks even if everything is well controlled. For women, checks should be made 2 - 3 times per year. For men, once per year is usually sufficient. The main aim of treatment is to maintain normal cortisol levels and control of salt loss, in those who are salt losers. In women, good management of CAH brings about control of testosterone levels, regular periods and improved fertility. In men, good management can reduce an aggressive behaviour and control excessive libido. Also, the sperm count can fall if CAH is not well treated and an increase in the dose of steroid treatment for some months can restore fertility in men.
Replacement of cortisol
The object of cortisol treatment in CAH is to replace inadequate production of cortisol by the adrenal glands allowing the body to recognise normal levels of cortisol in the body, which reduces the need for the adrenal gland to produce excessive amounts of testosterone.
How do doctors work out how much cortisol to take?
If the cortisol dosage is too low the adrenal gland will try and make more, but only succeed in making more testosterone. The effect of these excess androgens is growth of body hair in women and infertility in both sexes. In severe forms of CAH, too little cortisol treatment may make the body unable to cope with stress and infection, so that major surgery or an illness like ‘flu’ can be life threatening. If the dose of cortisol treatment is too low, a blood test will establish this by showing high levels of several adrenal hormones of which the most commonly measured are:
Other side effects of steroid treatment are:
Headaches (sometimes associated with taking prednisolone and dexamethasone)
Feeling sick / nausea / tiredness
Finding it difficult to cope with stress
Water retention (sometimes associated with taking Hydrocortisone and Cortisone acetate)
There are four types of cortisol replacement treatment: Hydrocortisone, Cortisone acetete (now rarely available in the UK), Prednisolone and Dexamethasone. They vary in their dose and duration of action. Hydrocortisone is another name for cortisol. Prednisolone is 5 times more potent, and dexamethasone is 40 times more potent than cortisol. Both prednisolone and dexamethasone are comparatively long acting, where as cortisone acetate and hydrocortisone are shorter acting, and need to be taken 2 to 3 times a day. The dose in each dexamethasone tablet is not convenient for fine-tuning of treatment leading to a danger of taking too high a dose. Dexamethasone is established for use in pregnancy for women who are at risk of having a child with CAH. Hydrocortisone is also used as an injection at times of adrenal crisis or when vomiting prevents the tablets from being taken.
continued on next page......