Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia is an inherited (genetic) condition causing swelling of the adrenal glands. The condition is associated with a decrease in the blood level of a hormone called cortisol and an increase in the level of male sex hormones (androgens) in both sexes. Some people get a mild condition that produces no symptoms. Others (mainly baby boys) develop a severe form that can be life-threatening. Medical treatment to correct hormone levels is available. Surgery to improve the appearance of unusual genitalia (in girls) is sometimes considered.
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).
What are the adrenal glands and what do they do?
There is an adrenal gland 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 outer part of the adrenals (the adrenal cortex) 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 a small gland which lies just under the brain (the pituitary gland). 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 testicles (testes) and ovaries.
Who is affected by it and how common is it?
The severe classic form affects 1 in 18,000 births in Great Britain. About three quarters of affected people have the salt-losing type and the rest have the non-salt-losing type. Similar numbers of girls and boys are affected when they are born, but boys tend to have the more severe symptoms.
The milder non-classic form is more common. It affects about 1 in 1,000 white people. It is more common in certain ethnic groups such as Ashkenazi Jewish people of Eastern Europe.
What causes congenital adrenal hyperplasia?
- 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 male-like (virilising) 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 congenital adrenal hyperplasia?
The typical symptoms depend on the type of CAH and whether you are female or male.
What are a baby girl's typical symptoms?
Baby girls are usually diagnosed soon after birth because of unusual looking genitalia. The clitoris may be larger than normal. The urine tube (urethra) and vagina may merge to form a larger hole. The womb (uterus) 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 a baby boy's typical symptoms?
- 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.
- Baby boys 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 develop symptoms such as:
- Weight loss.
- Extreme tiredness.
- Severe loss of fluid (dehydration).
- Boys with the non-salt-losing form: these children 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.
This tends to be diagnosed in later childhood or as a young adult.
What symptoms do males get?
In severe forms, boys may become sexually mature at an early age. For example, they may develop:
- Early pubic and armpit hair growth.
- An enlarged penis.
- An early 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?
Possible symptoms girls or women may develop include:
- Early sexual development - ie early pubic hair and armpit hair growth and a height spurt.
- Excess body hair in a masculine distribution (hirsutism).
- Light periods (oligomenorrhoea).
- Lack of periods (amenorrhoea).
- Polycystic ovary syndrome - a condition in which lots of cysts are found in the ovaries.
If you have a mild form you may not have 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 congenital adrenal hyperplasia diagnosed?
- Blood tests are the first tests to be done. These may show a high level of the hormone 17-hydroxyprogesterone. Blood tests may also 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 have a low blood glucose level.
- 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 may be done on baby girls who have unusual-looking genitalia. This shows whether a womb (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 blood test to examine the sex genes in a single cell (a karyotype test) may be performed.
- Other tests to examine gene defects may also be necessary if the diagnosis is unclear.
- 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 amniocentesis, involves taking a sample of the liquid surrounding the baby in the womb (the amniotic fluid). Another test, called villous sampling, involves taking a sample of placental tissue.
What are the treatments for classic congenital adrenal hyperplasia?
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 blood sugar (glucose) 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 medicine used is fludrocortisone.
- Babies with salt-losing CAH may need extra salt (sodium chloride) for the first six months of life. Salt replacement is particularly important in hot weather.
What other precautions should people with classic congenital adrenal hyperplasia 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 congenital adrenal hyperplasia?
- 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 oral contraceptive pills or 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.
- If you are on a glucocorticoid, you may be able to stop this once your symptoms have improved.
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 congenital adrenal hyperplasia?
Two thirds of affected babies with classic CAH are salt losers. They may need treatment through a drip to replace fluid, salt and glucose. They will need long-term glucocorticoid treatment.
What surgical treatment is available?
- Surgery is sometimes offered when a baby girl has unusual genitalia. This is usually done when the baby is very young because it is technically easier than at later ages. This has been offered in the past not only to make the appearance more normal but also to prevent complications such as urine infections. However, there is a growing body of opinion that these babies should not be subjected to surgery and that even though their appearance is different, they should not be considered 'abnormal'.
- Surgery to remove both adrenal glands is very occasionally 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. This puts you at risk of a life-threatening condition that happens when there is not enough cortisol in the blood circulation (adrenal crisis).
Will congenital adrenal hyperplasia 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 reading and references
Dreger A, Feder EK, Tamar-Mattis A; Prenatal Dexamethasone for Congenital Adrenal Hyperplasia: An Ethics Canary in the Modern Medical Mine. J Bioeth Inq. 2012 Sep9(3):277-294. Epub 2012 Jul 31.
Auchus RJ, Arlt W; Approach to the patient: the adult with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2013 Jul98(7):2645-55. doi: 10.1210/jc.2013-1440.
Mooij CF, Webb EA, Claahsen van der Grinten HL, et al; Cardiovascular health, growth and gonadal function in children and adolescents with congenital adrenal hyperplasia. Arch Dis Child. 2017 Jun102(6):578-584. doi: 10.1136/archdischild-2016-311910. Epub 2016 Dec 14.