21-hydroxylase deficiency medical therapy
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Congenital adrenal hyperplasia due to 21-hydroxylase deficiency Microchapters |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ahmad Al Maradni, M.D. [2]
Overview
The mainstay of therapy for congenital adrenal hyperplasia due to 21-hydroxylase deficiency is glucocorticoid replacement.
Medical Therapy
Early-onset: Severe 21-hydroxylase deficient congenital adrenal hyperplasia
Salt-wasting crises in infancy
As ill as these infants can be, they respond rapidly to treatment with hydrocortisone and intravenous saline and dextrose quickly restores blood volume, blood pressure, and body sodium content, and reverses the hyperkalemia. With appropriate treatment, most infants are out of danger within 24 hours.
Long-term management of congenital adrenal hyperplasia
Management of infants and children with congenital adrenal hyperplasia is complex and warrants long term care in a pediatric endocrine clinic. After the diagnosis is confirmed, and any salt-wasting crisis averted or reversed, major management issues include:
- Initiating and monitoring hormone replacement
- Stress coverage, crisis prevention, parental education
- Reconstructive surgery
- Optimizing growth
- Optimizing androgen suppression and fertility in women with congenital adrenal hyperplasia
Hormone replacement
- Glucocorticoids provide a reliable substitute for cortisol and reduce ACTH level, reducing ACTH also reduces the stimulus for continued hyperplasia and overproduction of androgens in both sexes
- Hydrocortisone or liquid prednisolone is preferred in infancy and childhood
- Prednisone or dexamethasone are often more convenient for adults
- Dose is typically started at the low end of physiologic replacement (6-12 mg/m2 but is adjusted throughout childhood to prevent both growth suppression from too much glucocorticoid and androgen escape from too little
- Serum levels of 17OHP, testosterone, androstenedione, and other adrenal steroids are followed for additional information, but may not be entirely normalized even with optimal treatment.
- Mineralocorticoids are replaced in all infants with salt-wasting and in most patients with elevated renin levels
- Fludrocortisone is the only pharmaceutically available mineralocorticoid
- Doses of 0.05 to 2 mg daily
- Electrolytes, renin, and blood pressure levels are followed to optimize the dose.
Optimizing growth in congenital adrenal hyperplasia
- Glucocorticoids are essential for health and dosing is always a matter of approximation. In even mildly excessive dose, glucocorticoids can slow growth
- Adrenal androgens are readily converted to estradiol, which accelerates bone maturation and can lead to early epiphyseal closure
- Rate of growth is assessed by checking the bone age every year or two through periodic measurement of 17OHP and testosterone levels
- Gonadotropin-releasing hormone agonists such as leuprolide are used to slow bone maturation and suppress precocious puberty
- Antiandrogen such as flutamide reduce the conversion of testosterone to estradiol
- Aromatase inhibitor such as testolactone also block conversion of testosterone to estradiol
- Bilateral adrenalectomy rarely used to remove the androgen sources
- Growth hormone treatment is used to enhance growth
Childhood onset (simple virilizing) congenital adrenal hyperplasia
The mainstay of treatment is:
- Suppression of adrenal testosterone production by a glucocorticoid such as hydrocortisone
- Mineralocorticoid in cases where the plasma renin activity is high.
- Suppression of central precocious puberty by leuprolide.
- Aromatase inhibitior to slow bone maturation by reducing the amount of testosterone converted to estradiol, estrogen blockers are also used for the same purpose.
- Stress steroid coverage for significant illness or injury.
Late onset (nonclassical) congenital adrenal hyperplasia
Treatment may involve a combination of very low dose of glucocorticoid to reduce adrenal androgen production and any of various agents to block the androgen effects and/or induce ovulation.