21-hydroxylase deficiency medical therapy

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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], Mohammed Abdelwahed M.D[3]

Medical Therapy

Neonatal management

Medical therapy in 21 hydroxylase deficiency in prenatal period, neonates, children and adults, is as below:

Prenatal treatment

In the prenatal period virilization of female fetus begins early; therefore, early diagnosis and treatment are required as following:

• If classic CYP21A2 gene mutations exist in parents, maternal administration of dexamethasone should be applied. Dexamethasone crosses the placenta into the fetal circulation and prevents ambiguous genitalia in female fetus.
• This treatment should be started before nine weeks of pregnancy age; if treatment cannot be started by 9 weeks, it should not be given at all.
• If in cell-free fetal DNA testing male fetus detected, treatment should be discontinued
• Approximately 85% of managed cases appear quite normal after delivery.
• Side effects of prenatal dexamethasone are:   
  • Postnatal failure to thrive
  • Psychomotor developmental delay
  • Increased risk of cleft lip and palate
  • Increased risk for psychiatric disturbances and ADHD

Neonatal treatment

21 hydroxylase deficiency therapy medications in the neonates are as following:

• Hydrocortisone is 20 to 30 mg/m²/day divided in three doses. 
• Fludrocortisone 100 mcg twice daily.
• One gram or 4 mEq/kg/day of sodium chloride divided in several doses.
• One first time high doses of hydrocortisone, 50 mg/m²/day, can be used in order to suppress adrenal hormones.  
• The minimization of steroid doses should be considered to avoid steroid complications in infants. 
• Growth suppression and shorter height in adulthood are the complications of using high dose steroids which occurs in neonates.

Ambiguous genitalia 

• Ambiguous genitalia should be managed immediately. Infants with ambiguous genitalia and non palpable gonads should be considered to have congenital adrenal hyperplasia and empirical treatment should be start early after obtaining blood sample for 17-hydroxyprogesterone.
• Initial empiric therapy should contains doses of glucocorticoid and mineralocorticoid and sodium chloride supplementation
• Reconstructive surgery can be done in patients.

Adrenal crisis

• Normal saline 0.9 percent, 20 mL/kg should be administered.
• An intravenous bolus of 2 to 4 mL/kg of 10 percent dextrose should be considered if there is significant hypoglycemia.  
• Initial dose of hydrocortisone of 50 to 100 mg/m² should be administered as an intravenous bolus bolus, then 50 to 100 mg/m² IV per day divided four times a day.  
• The blood sample should be obtained for steroid hormone levels before giving hydrocortisone.  
• Hyperkalemia should be corrected on the base of its level and complications.

Children management

• Hydrocortisone (cortisol) in a dose of 10 to 15 mg/m2 body surface area/day orally.

• Mineralocorticoid replacement should be started in all children and often may be tapered after six months of age.

• Response to therapy can be monitored by below items:
  • Serum 17-hydroxyprogesterone
  • Androstenedione
  • Plasma renin activity or direct renin
  • Height measurements

Adults management

21 hydroxylase deficiency should be managed as follows:

Treatment goals

• Provide proper dosing of glucocorticoid and mineralocorticoid.
• Decrease secretion of cosyntropin; therefore decrease adrenal overstimulation and androgen production.

Glucocorticoids 

• Glucocorticoids reduce the excess production of adrenal androgens and reduce the excessive secretion of both corticotropin-releasing hormone and  ACTH.
• Preferred Regimen
  • Hydrocortisone 15-30 mg/d divided into three doses orally.
• Alternative Regimen:
  • Dexamethasone 0.75 mg/d orally.
    • Dexamethasone is very potent and long-acting glucocorticoid effectively suppresses ACTH secretion but almost always causes the development of cushingoid appearance with chronic use.
  • Prednisone 5mg/d orally.
• Stress dosing: in patients with 21 hydroxylase deficiency and serious illness glucocorticoids stress dosing is necessary.

Mineralocorticoid replacement 

• Fludrocortisone acetate 0.1 to 0.2 mg/day.
• The proper dose of fludrocortisone acetate should be used to restore normal serum potassium concentrations and plasma renin activity.

Therapy consideration in women

• Lowering blood androgen levels with glucocorticoids, can helps women to control annoying cosmetic symptoms such as acne and hirsutism.
• In  21 hydroxylase deficient patients oral contraceptive pills in combination with glucocorticoids can be used to regulate the menstrual cycle and induction of ovulation.