C-11 Hydroxylase Deficiency Treatment & Management

Updated: Jan 10, 2017
  • Author: Gabriel I Uwaifo, MD; Chief Editor: George T Griffing, MD  more...
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Treatment

Medical Care

Treatment for 11-beta-hydroxylase deficiency is similar to that for all the other variants of congenital adrenal hyperplasia (CAH). It centers on suppressing the ACTH-driven adrenal hyperplasia and subsequent mineralocorticoid and/or androgen excess.

  • Glucocorticoid replacement therapy [18]
    • Glucocorticoid replacement is vital, because it reduces ACTH secretion and thus reduces the production of ACTH-dependent androgens and mineralocorticoids.
    • Clues that suggest inadequate glucocorticoid replacement include persistent hypertension, suppressed renin activity, elevated DOC or 11-deoxycortisol levels, and continued virilization in women or children.
    • Clues that suggest excess glucocorticoid replacement include obesity, decreased growth velocity in children, hyperlipidemia, osteoporosis, and suppressed 11-deoxycortisol levels.
    • Oral hydrocortisone is the ideal glucocorticoid for replacement therapy in children. A typical dose is 12-25 mg/m2/d in 2-3 divided doses.
    • Monitor patients for inadequate (virilization) and excess (cushingoid features) steroid treatment, even if the dose is within the indicated range.
    • If the response to hydrocortisone is poor, dexamethasone may be used in adults. The major problem associated with dexamethasone use is its relative short duration of action, which thus necessitates multiple daily dosing (ideally q4-6h). Other glucocorticoid formulations also may be used, and prednisone has a significantly longer duration of action than does dexamethasone, making bid to tid dosing adequate in most cases.
    • In situations involving fever or non–life-threatening illness, increase glucocorticoid dosages 2-3 times above the maintenance dose.
    • Treat patients with high doses of glucocorticoids for surgical procedures, life-threatening illness (eg, sepsis), and/or major trauma (hydrocortisone at 100 mg/m2 IV q6h as needed).
  • Antihypertensive therapy often is needed. Potassium-sparing diuretics, such as spironolactone or amiloride, with or without a calcium channel blocker, such as nifedipine, often are used. [19]
  • Prenatal treatment [14, 15, 17]
    • Prenatal treatment is an option for fetuses known to be at risk for classic 11-beta-hydroxylase deficiency. The only setting in which this therapy should be considered is if both parents are known carriers of virilizing CAH.
    • Prenatal therapy is controversial, because the long-term effects on the child are unknown.
    • Dexamethasone may be used in mothers during pregnancy at a dose of 20 mcg/kg/day in multiple divided doses initiated as soon as the pregnancy is confirmed, starting at approximately 4-5 weeks’ gestation.
    • Genetic testing is performed on the fetus, typically via chorionic villus sampling or less ideally by amniocentesis. Dexamethasone is discontinued if the fetus is XY or unaffected XX.
    • Once such therapy is initiated, the mother and fetus must be monitored closely. While this sort of therapy has the potential to reduce virilization in affected female babies, it does not obviate the need for subsequent CAH therapy in the child. In addition, the treatment's price is often great for the mother, because the required dose of dexamethasone invariably causes her to develop a cushingoid state.
  • Several preliminary trials of gene therapy for CAH in animal models of 21-hydroxylase deficiency are ongoing. Trials include gene transfer experiments in 21-hydroxylase–deficient mice and adenoviral vector/direct intra-adrenal transfer of the CYP21 gene in other animal models. At present, no human studies are underway.
  • Fertility and pregnancy [20]
    • Many women with congenital adrenal hyperplasia (CAH) wish to have children.
    • Reduced fertility may be caused by inadequately suppressed adrenal androgen production. [21]
    • Polycystic ovarian syndrome (PCOS) may develop secondary to adrenal hyperandrogenism.
    • The effect of ovarian exposure to adrenal androgens prenatally and during childhood is unknown, but it may predispose women with CAH to PCOS.
    • Other reasons for reduced fertility may include an inadequate vaginal vault for coitus and psychological factors leading to reduced sexual activity. [21]
    • Whether the increase in adrenal androgens associated with pregnancy requires increased glucocorticoid therapy is unclear. Placental aromatase appears to have a large reserve and is able to convert large amounts of ambient androgen to estrogen. This may prevent virilization of the fetus, even in cases of poorly controlled CAH in the mother.
    • Prednisone is the ideal glucocorticoid for use during pregnancy in patients with 11-hydroxylase deficiency and other CAH variants.
    • Dexamethasone or any other semisynthetic glucocorticoid crosses the placenta and suppresses the fetal hypothalamic-pituitary-adrenal (HPA) axis. This treatment should be used only when there is a high risk that a fetus will have virilizing CAH. In such a case, suppression of the fetal HPA axis is desirable.
    • During pregnancy, closely monitor glucocorticoid dosages and hormone levels.
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Surgical Care

Surgical care generally is limited to the reconstruction of ambiguous genitalia in female patients, a treatment that remains a subject of debate. [22]

The surgical procedure usually involves clitoroplasty and vaginoplasty in infancy, or clitoroplasty in infancy and vaginoplasty in late adolescence. Use of vaginal dilators sometimes is necessary to prevent restenosis.

Suggested treatment options for CAH have included the use of bilateral adrenalectomy. This has been proposed for infants, as well as for older patients. It is still considered experimental and should be reserved for cases that are difficult to control using standard medical therapy.

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Consultations

Because 11-beta-hydroxylase deficiency often is associated with ambiguous genitalia or precocious puberty, patients and families may require psychological counseling and support.

A small number of studies have suggested that women with CAH have a higher incidence of negative body self-image, have fewer sexual thoughts and fantasies, and are less sexually active. Endocrine, anatomical, surgical, and psychological factors may contribute to this observed reduction in sexual activity. [21]

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Diet

Hypertensive phenotypic variants may require a low-salt diet.

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