21-hydroxylase deficiency medical therapy

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.

Early-onset: Severe 21-hydroxylase deficient congenital adrenal hyperplasia

Salt-wasting crisis in infancy

• Hydrocortisone and intravenous saline and dextrose are mainstay treatment of adrenal crisis
• This treatment 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 and androgen escape from too little glucocorticoid.
• 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 is recommended.
• 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

• Combination of very low dose of glucocorticoid (to reduce adrenal androgen production) and androgen blockers (to induce ovulation) are used in late onset congenital adrenal hyperplasia