RGSDC - Information For Physicians

Physicians' Frequently Asked Questions on Nonclassical 21-Hydroxylase Deficiency

Q: How reliable is the ACTH test in diagnosing NC21OHD?

A: Genetic diagnosis is recommended. The ACTH test must be done in the early morning and you must be certain that the subject is not taking over-the-counter steroid medications. Spironolactone must be discontinued for a month prior to the ACTH test. If improperly done, the test may give erroneous results.

Q: Does it matter when in a woman's menstrual cycle you perform the ACTH test?

A: No. The time of day is key; it must be in the early morning.

Q: What is the connection between polycystic ovary disease (PCO) and NC21OHD?

A: PCO is a manifestation of hyperandrogenism. While the term PCO should only be used once NC21OHD has been eliminated as a potential diagnosis, in practice PCO may prompt testing for NC21OHD if other explanations fail.

Q: Shouldn't treatment for NC21OHD be individualized? Why do all patients receive steroids?

A: In this genetic disorder, cortisol is not produced in normal amounts owing to the enzyme deficiency. Replacement of steroids is not harmful.

Q: How long do you treat?

A: Forever.

Q: How do you treat a pregnant woman?

A: If the fetus does not require treatment and the mother is affected with CAH, you treat the woman with hydrocortisone, which does not cross the placenta. For prenatal diagnosis of the fetus, you treat the mother with dexamethasone until you have determined that the fetus is not female and is not at risk for classical 21OHD; then you stop treatment. If the mother is a patient with CAH, you switch to hydrocortisone.

Q: What are the consequences of long-term glucocorticoid treatment? Should you monitor treatment?

A: In proper doses there are no long-term complications. There are no consequences from a 0.25 mg daily dose of dexamethasone. That dose is effective in all NC21OHD patients.

Q: Do you need to give stress-dose steroids?

A: Yes, for surgery, high fever, accidents, for example. I recommend doubling or tripling the dose and then tapering it.

Q: Why not treat symptoms like hirsutism with anti-androgens and then use steroids if fertility becomes an issue?

A: I prefer to treat at the level of the disease rather than to treat symptoms. Thus, if the hirsutism is the result of adrenal disease, I prefer to give the treatment at the lesion.

Q: Why do you recommend dexamethasone rather than prednisolone?

A: Dexamethasone is long-acting and works well with a once a day at bedtime routine.

Q: Do you treat asymptomatic patients?

A: No, but they should be examined annually because symptoms may appear at any time.

Q: Do you advise prenatal diagnosis for a woman with NC21OHD?

A: If the mother is a compound heterozygote (has one gene for classical 21OHD), I advise treating with dexamethasone until you know the sex of the fetus unless you know that the father is not a carrier or affected.

Q: Is there underdiagnosis of all types of CAH?

A: We only have evidence that the nonclassical form is underdiagnosed.

Q: What is the ACTH dose for the stimulation test?

A: At 8 A.M., when cortisol secretion is at its normal diurnal peak, blood is drawn before and then 60 minutes following intravenous injection of a 0.25-mg bolus of ACTH. A nomogram that relates baseline to ACTH-stimulated serum concentrations of 17-OHP (17-hydroxyprogesterone) has been constructed which can be used to identify classical affected, nonclassical affected, and heterozygote carrier status.

Q: Where can you get genetic testing?

A: There are several commercial laboratories, which are listed on the CARES patient support website (www.CARES.org).

Q: Do you do an ACTH test if you have the results of the genetic test?

A: No, but you must monitor the hormone levels to adjust the dose of hydrocortisone treatment. The genetic test is the best screening instrument.

Q: Are carriers normal?

A: Yes.

Q: How are males affected in NC21OHD?

A: They have short stature, folliculitis, particularly on their thighs, acne, and decreased fertility. They may have small testes relative to size of penis.

Q: How would you diagnose a male patient treated for NC21OHD but who is asymptomatic with very high 17OHP?

A: The patient may not be taking the medication you prescribed. If androgen levels are high, they may impair fertility. A genetic test for NC21OHD should be done.

Q: Can you use testosterone to diagnose an affected male?

A: No. Only 17OHP and D4-androstenedione. The best is the genetic test.