CONGENITAL ADRENAL HYPERPLASIA (CAH) (21-HYDROXYLASE DEFICIENCY)
CAH is an inherited condition in which children are born with ("congenital")
enlargement ("hyperplasia") of the adrenal glands, two small
structures above the kidneys in the abdomen. The adrenals are endocrine
glands which secrete hormones (chemicals which carry messsages) into the
blood. The inner part secretes adrenalin, the hormone involved in the response
to fright; this is normal in CAH. The outer part secretes three different
steroid (a particular chemical structure) hormones, hydrocortisone, which
is important in controlling the blood sugar level and also in helping the
body combat stress, such as that due to infection or serious injury, aldosterone,
which regulates the loss of salt in the urine, and androgen, male sex hormone
(secreted in both sexes).
Cause.
In CAH there is an inherited defect in the production of hydrocortisone
and usually also of aldosterone, due to malfunction of the enzyme (a chemical
which permits specific chemical reactions to take place) 21- hydroxylase.
The low level of hydrocortisone in the blood stimulates the pituitary gland
(which lies at the base of the brain) to secrete the hormone ACTH (AdrenoCorticoTrophic
Hormone) in an attempt to restore the level of hydrocortisone to normal.
Because of the block in production of hydrocortisone this does not occur
but the stimulation causes enlargement of the glands and an excessive production
of androgen, since this is made normally. This starts before birth and
the high level of androgen causes girls to become 'masculinised' with enlargement
of the clitoris and partial closure of the vaginal opening. Since boys
are already masculinised by their testes they show no abnormality at birth.
In many but not all children with CAH the lack of aldosterone results in
excessive loss of salt in the urine after birth. If untreated, this may
become critical in the first two or three weeks of life and result in a
potentially fatal 'salt-losing crisis'. The increased ACTH secretion may
also cause some pigmentation of the skin. Inheritance. CAH is inherited
as a "recessive" disorder. Affected children are born to parents
who, although apparently normal themselves, are both "carriers"
for the condition. All genes are paired and in carriers one gene for the
structure of the 21-hydroxylase enzyme is abnormal and one is normal; adequate
amounts of 21- hydroxylase are produced. Children with CAH have two abnormal
genes, one inherited from each parent, and so no normal enzyme is produced.
On average one in four children of carrier parents can be expected to inherit
both abnormal genes and have the disease, two will be carriers and one
will inherit two normal genes. Thus, in this type of inheritance, for parents
who have produced a child with CAH, each subsequent child has a 1 in 4
risk of inheriting the condition. When a person with CAH marries, it is
unlikely that the spouse will also be a carrier since the carrier rate
in the general population is only 1 in 50. All the children will inherit
one abnormal gene from the affected parent (who has two) but this is balanced
by the normal gene from the other parent so all the children will be carriers
but none will have the disease. In CAH both the degree of masculinisation
and the severity of the salt loss are variable but in general families
'breed true' and if the first affected child is not a salt- loser, it is
unlikely that subsequent affected children will be.
Prenatal diagnosis and treatment.
In a family with one affected child, by genetic testing on placental
cells it is possible to determine whether an unborn baby is affected. Since
the condition can be treated successfully and is compatible with a fully
normal life, termination is not appropriate but it is now possible to give
a steroid which crosses the placenta and prevents masculinisation of a
female fetus. If you wish to consider this option it is essential to have
preliminary tests done before conception and then to start treatment as
soon as pregnancy can be confirmed. See the separate sheet about prenatal
treatment.
Treatment.
Children with CAH need treatment with hydrocortisone in a dose which
reduces ACTH secretion and so prevents the excessive production of androgen
and permits normal growth and development. In all girls and most boys,
treatment must be continued for life. Children with salt loss also need
fludrocortisone, a steroid with a salt-retaining action, to replace the
missing aldosterone. If the correct doses of these steroids are used, there
are no side-effects whatsoever as the treatment is merely replacing the
normal secretion of the adrenal glands. If too much hydrocortisone is given
it causes weight gain and slowing of growth; too much fludrocortisone may
cause high blood pressure. The correct dose of these drugs varies from
child to child and has to be judged by regular measurement of height and
chemical measurement of steroid concentrations in blood, urine or saliva.
Girls with masculinised genitalia require genital surgery around the age
of one year.
Emergencies.
It is necessary to mimic the response of the body to stress by increasing
the dose of hydrocortisone to cover serious illness or injury (including
surgery). Parents need to double or treble the usual dose of hydrocortisone
if the child is seriously ill or has an accident. If the dose of hydrocortisone
is repeatedly vomited it MUST be given by injection. All families with
an affected child must have an injection of hydrocortisone available and
know how to give it.
Future outlook.
The child's progress requires regular review and dose adjustment is
necessary through the years of growth and development but once into adult
life control may be improved on the longer-acting steroid prednisolone
and no further dose changes should be needed. Normal development in all
respects, normal fertility and a normal life-span without restrictions
can be expected. |
