What is CAH?
CAH (congenital adrenal hyperplasia) occurs approximately once in every 15,000 people worldwide. It is an inherited condition which prevents the adrenal glands functioning correctly. To stay healthy, people with CAH must take daily life-long medication to replace the hormones which their adrenal glands don’t make.
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The Adrenal Gland & CAH
The adrenal glands sit above each kidney – one on each side of the body. Each adrenal gland is made up of the medulla (middle) and the adrenal cortex (outer). The medulla makes adrenaline, and this part works perfectly normally in CAH (congenital adrenal hyperplasia). The adrenal cortex is in three ‘layers’ and makes three main hormones from cholesterol – 1. corticosteroids, which regulate the body’s response to stress; 2. mineralocorticoids, which regulate salt and water levels; and 3. androgens, which are male sex hormones).
In CAH, an enzyme deficiency caused by a deleted or mutated gene prevents the adrenal gland from making enough of these hormones correctly.
In order to compensate for the low levels of these hormones, the pituitary gland makes ACTH which pushes the adrenal gland to work harder. The constant unsuccessful rise in these hormones causes the adrenal cortex to increase in size and become ‘hyperplastic’. This in turn, makes the adrenal cortex produce more androgens while corticosteroid and mineralocorticoid levels remain low.
Steroids and CAH
The 3 main steroids involved in CAH are:
This controls how the body copes with emotional and physical stress, such as infection or injury. It also helps to control blood sugar levels, raising these levels if they become too low particularly in children.
This 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 less Aldosterone is secreted, allowing the excess salt to be passed in the urine.
These are a group of male hormones, one of which is testosterone. Testosterone is produced by the adrenal cortex in both males and females controls the formation of pubic hair at the onset of puberty. Testosterone is also produced by the testis and in small amounts by the ovary.
Types of CAH
Although there are many different grades of severity of CAH (congenital adrenal hyperplasia), there are three main types of CAH (over 90% of cases) which are caused by a deficiency of an enzyme called 21 hydroxylase. The three main types of CAH are ‘Salt-wasting’ (most cases), ‘Non-salt wasting’ and ‘late onset CAH’.
Another type of CAH is caused by a deficiency of the enzyme 11-beta hydroxylase and while deficiencies of other enzymes occur they are exceedingly rare.
Over 90% of people with CAH have a deficiency of an enzyme called 21 hydroxylase.
The most common types of CAH – 21 hydroxylase deficiency
The three main types of CAH caused by a deficiency of the 21 hydroxylase enzyme are salt-wasting, non-salt wasting and late onset. In these forms of CAH the production of Cortisol and Aldosterone is low.
In salt-wasting CAH, the hormone aldosterone in completely lacking which results in uncontrolled loss of salt from the body through urine.
In non-salt wasting CAH, the salt balance is usually normal. However, in stressful situations, those with non-salt wasting CAH may begin to lose salt and hence require extra treatment.
In both ‘salt wasting’ and ‘non-salt wasting’ types of CAH, the salt loss can cause acute dehydration, very low blood pressure (hypotension) and vomiting. As salt (sodium and chloride) and sugar (glucose) levels fall in the blood, potassium levels rise and if left untreated, a potentially life-threatening Adrenal Crisis can result.
Untreated CAH, or illness in a person with CAH, can cause a potentially life-threatening Adrenal Crisis.
‘Salt wasting’ and ‘non-salt wasting’ CAH can cause differences in early sexual development due to the body producing excess testosterone to compensate for the low levels of cortisol and aldosterone. In boys, this excess of testosterone causes early sexual development. In females, the excess in testosterone can cause differences in sexual development before birth.
Only by correcting the levels of Cortisol with substitute therapy does the body recognise normal levels and stop producing excessive amounts of testosterone.
CAH can cause differences in sexual development due to the body producing excess testosterone to compensate for the low levels of cortisol and aldosterone.
The mildest form of CAH – Late onset CAH
Last onset CAH can affect men and women at any age. As with other forms of CAH, the body tries to correct the low levels of aldosterone and cortisol by producing excess testosterone.
For women, 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.
For men, late onset CAH usually goes unrecognised although it may cause the sperm count to be low.
11-beta hydroxylase deficiency and other enzyme deficiencies
These types of CAH are much rarer that 21 hydroxylase deficiency. Treatment of these types 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.