PRENATAL TREATMENT FOR VIRILISING (21-hydroxylase deficient) CONGENITAL
ADRENAL HYPERPLASIA
Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition
with an incidence of about 1 in 10,000; the risk to children of carrier
parents is 1 in 4. Girls are virilised in utero by excessive fetal adrenal
androgen production; this can be suppressed by treatment with a glucocorticoid.
Prenatal treatment can be achieved by giving the mother a steroid which
crosses the placenta freely, such as dexamethasone. If such treatment is
started early enough in pregnancy (as soon as possible and at the latest
by 7 weeks) virilisation can be reduced or prevented.
Before pregnancy .
- 1.Couples with an affected child should be asked as soon as possible
whether they wish to consider prenatal treatment in any future pregnancies.
Clearly they need to understand fully the risks and potential benefits.
- 2. If they want treatment, first confirm that it is possible to make
a genetic diagnosis in this family by DNA analysis of blood from both parents,
the affected child and any siblings. (Discuss requirements with the molecular
genetics lab, AH ext 3971). As long as this is informative the diagnosis
can be confirmed in utero by chorionic villus sampling (CVS).
- 3. If treatment is planned ensure that the parents and theGP understand
the need to confirm pregnancy and start treatment as soon as possible.
Early obstetric referral for a dating scan and CVS booking will also be
needed. Note that maternal hyperglycaemia, hypertension or other conditions
likely to be exacerbated by dexamethasone might contraindicate treatment.
In pregnancy
- 1. Confirm the pregnancy as promptly as possible by a test as soon
as a period is missed.
- 2. Start treatment immediately with dexamethasone 20-25mcg/kg/day in
three divided doses. (Treatment must be started before 7 weeks.)
- 3. Inform all involved (GP, obstetrician, endocrinologist, geneticist)
so that plans for investigation and management can be made.
- 4. At 10-12 weeks arrange chorionic villus sampling for: i. sex ii.
diagnosis of CAH by DNA analysis and/or HLA typing If the fetus is female
and affected continue dexamethasone in a dose of 20- 25ug/kg/day until
delivery. If male and/or unaffected, stop.
- 5. At 16 weeks, if CVS was not done because of high risk or if the
result was equivocal, amniocentesis can be done for: i. sex ii. DNA analysis
and/or HLA typing iii. measurement of 17-OHP in amniotic fluid after stopping
dexamethasone for one week (this may increase the risk of virilisation)
Again, continue dexamethasone only if the fetus is female and affected.
- 6. Consider measuring plasma and/or urinary oestriols regularly as
a monitor of compliance and adequacy of suppression.
Notes:
- 1. No serious side-effects of dexamethasone treatment in the mother
have occurred but excessive weight gain, Cushingoid facial changes, severe
striae, hyperglycaemia, hypertension and irritability have been described
with very variable incidence form study to study.
- 2. No adverse effects on the fetus have been described.
- 3. In most cases in which adequate treatment was started sufficiently
early, the evidence suggests that virilisation was completely or partially
prevented.
- 4. Amniotic 17-OHP levels probably do not accurately reflect adequate
suppression on treatment but maternal urinary oestriol levels may do so.
References:
1. Pang S., Pollack M.S., Marshall R.N., Immken L. Pre-natal treatment
of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. NEJM
1990, 3;22, 111-115.
2.New M.I., Genetic disorders of adrenal hormone synthesis. Hormone
Research, 1992; 3: 22-33.3 Pang S., Clark A.T., Freeman L.C., Dolan L.M.,
Immken L., Mueller O.T., Stiff D., Schulman D.I. Maternal side effects
of prenatal dexamethasone therapy for fetal congenital adrenal hyperplasia.
J Clin Endocrinol Metab 1992, 75, 249-53. NDB |
