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Congenital Adrenal Hyperplasia

What are the adrenal glands and what do they do?

You have two small adrenal glands that lie just above each kidney. Each adrenal gland has an outer part (adrenal cortex) and an inner part (adrenal medulla). Cells in the adrenal glands make various hormones. A hormone is a chemical which is made in one part of the body but passes into the bloodstream and has effects on other parts of the body.

Cells in the adrenal cortex (the outer part of the adrenals) make the hormones cortisol and aldosterone. The amount of cortisol that is made is controlled by another hormone called adrenocorticotrophic hormone (ACTH). ACTH is made in the pituitary gland (a small gland that lies just under the brain). ACTH passes into the bloodstream, is carried to the adrenal glands, and stimulates the adrenal glands to make cortisol.

Cells in the adrenal cortex also make small amounts of sex hormones such as testosterone and oestrogen, although most of these are made in the testes and ovaries.

What is congenital adrenal hyperplasia?

Congenital adrenal hyperplasia (CAH) is a condition affecting the level of cortisol, a hormone produced by the adrenal gland. It is a genetic condition and can be inherited from your parents. There are different forms:

  • Classic: this is the severe form. There are two types – salt-losing and non-salt-losing.
  • Non-classic: this is milder (also known as late-onset type).

Whom does it affect and how common is it?

The severe classic form affects one in 15,000 births worldwide. About 7 in 10 affected people have the salt-losing type and the rest have the non-salt-losing type.

The milder non-classic form affects about one in 1,000 white people. It is more common in certain ethnic groups such as Jewish people of Eastern Europe, Hispanics and Yugoslavs.

What causes CAH?

  • Under normal circumstances, ACTH stimulates the adrenal glands to produce the chemical building blocks (precursors) which make cortisol.
  • There is a feedback system which controls ACTH production. The rate of release of ACTH depends on the amount of cortisol in the bloodstream. As more cortisol is produced it reduces the release of ACTH, thus slowing down the stimulation of the adrenals and production of cortisol until a balance between these two hormones is achieved.
  • In CAH there is a blockage in the assembly line that makes cortisol from the precursors. So, the blood level of cortisol is low, and there is never enough cortisol produced to slow the release of ACTH. This means the adrenal glands are constantly stimulated, causing an overgrowth of the adrenal gland (hence, the term hyperplasia).
  • The large amounts of the precursors from all this stimulation build up in the adrenals and leak out into the bloodstream. One of these is testosterone, a male hormone, which causes the virilising (male-like) features seen in the condition.
  • The blockage may also cause aldosterone production to be reduced. A drop in the level of this hormone can have an effect on the salt level in the bloodstream.

What are the symptoms of untreated CAH?

The typical symptoms depend on the type of CAH and whether you are female or male.

Classic form

What are the typical symptoms of a girl baby?
Girl babies are usually diagnosed soon after birth because of unusual looking genitalia. The clitoris may be larger than normal and the urethra (urine tube) and vagina may merge to form a larger hole. The uterus (womb) and other female organs are normal. Because the condition is recognised so early, baby girls do not usually become seriously ill through complications (see below).

What are the typical symptoms of a boy baby?

  • These babies look normal, except their skin may be slightly darker than usual. The penis may be enlarged. Other symptoms depend on whether the boy has the salt-losing form or the non-salt-losing form.
  • Boy babies with the salt-losing form: if the condition is severe, the baby may experience a salt-losing crisis and become quite ill. This happens when they are between 7-14 days old. They may get vomiting, weight loss, extreme tiredness, dehydration (severe loss of fluid) and shock.
  • Boys with the non-salt-losing form are usually diagnosed because they develop early virilisation. This means there are signs of early puberty such as an enlarged penis or an increase in body hair. This is often recognised between the ages of 2-4 years.

Non-classic form

This tends to get diagnosed in later childhood or as a young adult.

What symptoms do boys or young men get?
In severe forms, boys may become sexually mature at an early age, with pubic and armpit hair growth, enlarged penis and a height spurt. A young man may have a mild form which causes no symptoms. It may not be diagnosed unless he is tested in later life for some other condition.

What symptoms do females get?
Girls may develop sexually at an early age, with pubic hair and armpit hair growth and a height spurt. Virilisation (the development of masculine features) in girls, due to increase in male hormone levels, may take the form of excess body hair (hirsutism). You may also get infertility or oligomenorrhoea (scanty periods). Other features may include amenorrhoea (lack of periods), polycystic ovarian syndrome (a condition in which lots of cysts are found in the ovaries) or acne. If you have a mild form you may not get any symptoms at all.

With either form, you may find that it affects your sexuality. You may become less feminine in your appearance and behaviour.

How is CAH diagnosed?

  • Blood tests are the first tests to be done and may show that the levels of chemicals in the blood are outside the normal range. For example, you may have a low sodium level or a high potassium level. You may also get a low blood glucose level or a high level of the hormone 17-hydroxyprogesterone.
  • If there is still doubt about the diagnosis, you may have to have a corticotropin stimulation test. Corticotropin is a hormone which stimulates the adrenal gland. You will have an injection of this hormone and a blood test an hour later to measure how your adrenals have responded.
  • An ultrasound scan of the pelvis is done on baby girls who have unusual-looking genitalia. This shows whether a uterus is present or absent and whether the kidneys look unusual.
  • X-rays of a child’s bones are sometimes done to check the rate of development of the skeleton (the bone age). In CAH this rate may be faster than normal.
  • If the baby’s gender is in doubt, a karyotype test (a blood test to examine the sex genes in a single cell) may be performed.
  • Other tests to examine gene defects may also be necessary.
  • An unborn baby may be suspected of having classic CAH if both parents have been identified as carriers. In this case, tests are done to check the sex of the baby and whether it is affected. One test, called an amniocentesis, involves taking a sample of amniotic fluid (the liquid that surrounds the baby in the womb). Another test, called villous sampling, involves taking a sample of placental tissue.

What are the treatments for classic CAH?

Treatment may include:

  • Glucocorticoids: these are steroid medicines that are similar to cortisol. Cortisol and glucocorticoids have various effects on the body including helping to regulate the glucose (blood sugar) level. You need a certain level of cortisol or glucocorticoid to keep well. One of this group, hydrocortisone, is used in children because it does not have much effect on growth rate. Stronger steroids such as prednisolone and dexamethasone may be used in adults. Hydrocortisone is still used in short bursts in adults during illness, or after injury or surgery.
  • Mineralocorticoids: these are a type of steroid similar to aldosterone. One of these may be needed to control the salt concentration in the blood and the level of a kidney hormone called renin. The most common used is fludrocortisone.
  • Babies with salt-losing CAH may need extra sodium chloride (salt) for the first six months of life. Salt replacement is particularly important in hot weather.

What other precautions should people with classic CAH take?

  • Extra care should be taken during situations which put extra stress on the adrenal glands. Examples include surgery, infection and injury. You may (in consultation with your GP or hospital specialist) need a higher dose of steroid than you normally take. You may also need extra fluid administered through a drip into a vein.
  • Your blood glucose level may drop with exercise, illness or fasting and you may need to increase your intake of glucose and carbohydrates to compensate.
  • You should wear or carry medical alert identification so that any health professional treating you in an emergency will know you have CAH.

What are the treatments for non-classic CAH?

  • Treatment is not necessary unless you have symptoms, in which case a glucocorticoid steroid is used. Boys or girls who have features of androgen excess (see above) may need hydrocortisone. An adult woman may need extra treatment to control the androgen effect, such as a steroid called flutamide.
  • If you are on a glucocorticoid, you may need extra doses of steroid in situations in which the adrenal glands are stressed, such as illness, surgery or injury.

What treatment is available if my unborn baby is suspected of being affected?

If you and your partner are both carriers of the CAH gene, the mother may be offered treatment with dexamethasone tablets. This helps to reduce the effect that the condition has on the unborn baby’s genitalia if it is a girl. The treatment is controversial because there is only a 1 in 8 chance that the baby will be affected: the specialist will discuss the risks and benefits of this treatment with you. If the tests show that the baby is a boy or a girl who is not affected, treatment should be stopped straightaway.

What treatment is available to a newborn baby who has classic CAH?

Two thirds of affected babies with classic CAH are salt-losers. They may need treatment through a drip to replace fluid, salt and glucose.

What surgical treatment is available?

  • Surgery to improve the appearance is sometimes offered when a baby girl has unusual genitalia.This is usually done between 2-6 months because it is technically easier than at later ages.
  • Surgery to remove both adrenal glands is sometimes performed. The operation reduces androgen effects of the condition and prevents weight gain. However, if you have this procedure you would have to be on large amounts of steroid treatment for life. There have been reports of adrenal crisis (a life-threatening condition that happens when there is not enough cortisol in the blood circulation); deaths have occurred.

Will CAH go away?

  • CAH is a lifelong condition. However, if you have the correct treatment, either medical or surgical, the outlook is mainly good.
  • If you are a woman with a genital abnormality, you may develop masculine interests and have problems with sexual adjustment. You may not grow very tall and you may have infertility problems. Proper treatment and counselling will be able to help with all these difficulties.
  • It is important that you have a thorough understanding of your condition. The most important point regarding your physical health is to check with your doctor whether you need steroids at times of illness, injury or surgery.

Further help and information

CAH – Congenital Adrenal Hyperplasia Support Group

2 Windrush Close, Flitwick, Bedfordshire, MK45 1PX
Tel: 01525 717536 Web: www.livingwithcah.com

National Centre for Adolescent and Adult Females with Congenital Abnormalities of the Genital Tract

Queen Charlotte’s and Chelsea Hospital, Du Cane Road, London, W12 OHS
Tel: 0203 313 5363 Web: www.imperial.nhs.uk/femgenab

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References

  • Wilson TA, Congenital Adrenal Hyperplasia, Medscape, Sep 2010
  • van der Kamp H, Wit J; Neonatal screening for congenital adrenal hyperplasia European Journal of Endocrinology (2004) 151 U71–U75

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