CONGENITAL ADRENAL HYPERPLASIA (CAH) (11-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 function 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 (which is 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 girl babies 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. The 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 11-hydroxylase enzyme is
abnormal and one is normal; adequate amounts of 11-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 comes to marry, it is unlikely that the spouse will
also be a carrier since the carrier rate in the general population is only
about 1 in 500. 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.
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
the mother a steroid which crosses the placenta and prevents masculinisation
of the 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 prgnency can be confirmed. See the separate sheet on 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. If the correct doses of hydrocortisone
is 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. The correct dose
varies from child to child and has to be judged by regular measurement
of height and chemical measurement of hydrocortisone in blood, urine or
saliva. Girls with masculinised genitalia will require genital surgery
whcih is usually undertaken at about 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 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 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. |
