11β-hydroxylase deficiency medical therapy
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Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency Microchapters |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]
Overview
Medical Therapy
Children are generally treated with glucocorticoids only, including hydrocortisone (10 to 25 mg/m2), prednisolone (0.1 mg/kg), and dexamethasone (up to 0.5 mg/day), to lower ACTH secretion. Despite the proclivity for hypertension in 11OHD, hypotensive adrenal crises due to glucocorticoid deficiency occur during significant illness.
● Mineralocorticoid therapy is rarely necessary, and spironolactone is sometimes added to antagonize both androgens and mineralocorticoids, allowing reduce glucocorticoid dosing. Given the phenotypic variability in this disease, treatment must be tailored to the individual in order to minimize the dose of glucocorticoid and to mitigate the consequences of chronic glucocorticoid therapy and iatrogenic Cushing's syndrome. (See "Epidemiology and clinical manifestations of Cushing's syndrome".)
The response to therapy should be monitored both biochemically and clinically: ● Serum DHEAS should be suppressed, normokalemia should be restored, and 11-deoxycortisol concentrations should fall although not necessarily to normal.
● Serum testosterone concentrations should be brought to age and gender-specific normal range.
● A measurable plasma renin activity indicates suppression of mineralocorticoid synthesis, which can take months after starting therapy.
● Clinical monitoring includes assessment of virilization, growth velocity, and skeletal maturation (bone age) with attention to glucocorticoid-related side effects such as bruising, weight gain, and glucose intolerance. (See "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children", section on 'Monitoring therapy'.)
● In adolescent girls, facial hair growth and acne should be examined. As in 21OHD, genital malformations in affected females may require surgical correction with one or more surgeries and vaginal dilation. (See "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children" and "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in adults".)
In adult women with 11OHD, growth and bone age advancement are no longer concerns, but androgen excess and hypertension remain indications for treatment. ● Spironolactone, 25 to 200 mg/day, treats both the mineralocorticoid-mediated hypertension with hypokalemia and the androgen excess by blocking both the mineralocorticoid and androgen receptors.
• The main drawbacks of spironolactone are vaginal bleeding between menses and contraindication during pregnancy.
• If pregnancy is not desired, spironolactone and an oral contraception pill can be combined with replacement doses of hydrocortisone only as a glucocorticoid-sparing regimen, as in 17OHD.
• There has been one successful pregnancy reported in a woman with 11OHD. A 26-year old who had been on dexamethasone and metformin conceived when clomiphene citrate was added to induce ovulation. Increasing doses of dexamethasone were used to manage her hyperandrogenemia during pregnancy [102].
In adult males, at least replacement doses of hydrocortisone should be administered to avoid the development of adrenal rest tumors. Spironolactone can cause gynecomastia and sexual dysfunction in males, whereas eplerenone and the potassium-sparing diuretics triamterene and amiloride are alternatives. As with other forms of mineralocorticoid excess, the hypertension may persist even after adequate treatment. (See "Treatment of primary aldosteronism", section on 'Medical therapy'.) Prenatal diagnosis of 11OHD may be established by measuring tetrahydro-11-deoxycortisol in amniotic fluid [103] or by sequencing the CYP11B1 gene amplified from DNA in chorionic villus biopsy samples [104]. As in 21OHD, prenatal dexamethasone reduces genital virilization in affected girls, but experience is much more limited than in 21OHD. In one report, a woman with two affected daughters was treated with dexamethasone (20 mcg/kg daily in three divided doses) from the fifth week of pregnancy to term and delivered a female infant with normal external genitalia [104]. (See "Treatment of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in adults".)
- Salt-wasting in infancy responds to intravenous saline, dextrose, and high dose hydrocortisone, but prolonged fludrocortisone replacement is usually not necessary. The hypertension is ameliorated by glucocorticoid suppression.
- Long term glucocorticoid replacement requires a careful balance between doses sufficient to suppress androgens while avoiding suppression of growth. Because the enzyme defect does not affect sex steroid synthesis, gonadal function at puberty and long-term fertility should be normal if adrenal androgen production is controlled.