What causes congenital adrenal hyperplasia?

CAH is an inherited disorder. An error (mutation) in the hereditary material (DNA) causes a lack or absence of a certain substance in the adrenal glands. This substance is called an enzyme. In 95% of cases, CAH is expressed as a deficiency of the enzyme 21-hydroxylase. This enzyme is needed in the adrenal gland for the production of hormones. The enzyme deficiency creates a problem with the production of the hormones cortisol and aldosterone in the adrenal glands. Normally, the production of cortisol is accurately regulated. If there is too little cortisol, the pituitary gland produces the control hormone ACTH which stimulates the adrenal gland to make more cortisol. If the cortisol production is sufficient then a signal goes back to the brain and less ACTH is made. If too little cortisol is produced due to the lack of the enzyme, the pituitary gland produces a lot of ACTH. The ACTH hormone continues to stimulate the adrenal glands because cortisol production is not increased. The adrenal glands become larger (in medical terms this is called hyperplasia) and will work even harder. However, due to the enzyme problem, they can only produce one type of hormone: androgens. This causes excess androgens. In addition, all kinds of precursor substances of cortisol and aldosterone are produced. The cortisol and aldosterone deficiency and the excess of androgens lead to all kinds of symptoms and phenomena. The severity of the condition is strongly dependent on the enzyme deficiency. CAH can occur in a severe form (classical CAH) in which there is no or hardly any enzyme activity, but also in a milder form (non-classical CAH) with still around 30-50% enzyme activity. In classic CAH, a distinction is made between the classic form with and without aldosterone deficiency. If there is a deficiency of aldosterone this is also called “salt-losing”.

How often does congenital adrenal hyperplasia occur?

Classical CAH (based on 21 hydroxylase deficiency) occurs in 1 in 10,000-20,000 births. Annually in the Netherlands about 15-20 children are born with CAH. Non-classical CAH occurs in 0.1-0.2% of the Dutch population.

What are the effects of congenital adrenal hyperplasia?

The classic salt-losing form of CAH is the most serious form and the symptoms occur immediately after birth. After birth, after a few days (usually after the first week), serious salt loss occurs. Without treatment, this leads to dehydration and weight loss of the baby. The salinity in the blood is then too low and the potassium level is too high. This life-threatening situation is called a salt wasting (salt-losing) crisis. Due to the excess of androgens, the external genitals look masculine in girls. The internal genitalia (uterus and ovaries) are, however, normal. The genitalia of boys appear normal. Boys run the highest risk of a salt-wasting crisis because it can go unnoticed as it is not expressed through ambiguous genitalia. The heel prick screening has been set up for this purpose.

The classic non-salt wasting form of CAH is slightly milder because there is no salt loss. However, here too there is a deficiency of cortisol and an excess of androgens. This form can also often come to light in the case of girls by the masculine appearance of the external genitals. In boys, this form can now be discovered in the heel prick program.

The non-classical form of CAH is usually discovered only later in life. With this form there is no salt loss and usually no serious cortisol deficiency. The complaints and symptoms are caused by too many androgens. In women, this may involve acne of the skin, excessive hair and menstrual problems. In men, the signs are less clear. Some people are completely symptom free.

How is congenital adrenal hyperplasia diagnosed?

The detection of the classic form of CAH is included in the heel prick program. Blood is taken in the first week after birth (heel prick) from all newborns. Thanks to the heel prick, classic CAH can quickly be discovered. The amount of 17-hydroxyprogesterone is then examined. This is a precursor substance of cortisol. With CAH, the 17-hydroxyprogesterone is increased. In case of suspicion of non-classical CAH in later life, blood tests can be done. Then 17-hydroxyprogesterone, androstenedione and cortisol can be examined. Sometimes additional study is needed: a ACTH test (Synacthen test). Here, ACTH is administered through a drip. This ensures that the adrenal gland is stimulated so that mild defects can be found detected. Blood tests are done before and after administration. It is also possible to have genetic (DNA) research carried out so that CAH can be confirmed.

What is the treatment for CAH?

CAH is not curable, but can easily be treated. The treatment is aimed at supplementing the deficiency of cortisol and aldosterone and reducing the production of androgens.

The cortisol deficiency is treated with medications such as hydrocortisone. As healthy adrenal glands normally make extra cortisol in case of illness, severe stress or surgery, the dose of these drugs must be increased in such situations to prevent a serious adrenal crisis. Giving cortisol also causes the production of androgens to decrease. This is because giving cortisol also affects the production of ACTH in the brain. ACTH is then produced less, which also reduces the production of male hormones. The aldosterone deficiency is treated with the drug fludrocortisone. The correct dosage of medicines must always be carefully examined in order to prevent complaints and symptoms and long-term health problems. The treatment of CAH is a tailor-made treatment. The non-classical form of CAH often requires no treatment. Complaints of excessive male hormones can also be treated with other medications (e.g. the pill).

In girls, a first operation is often carried out within a few months after birth to reconstruct the external genitals. The operation is complex and is only done in specialized hospitals. Sometimes an operation is needed in adolescence.[/accordion-item]