21-hydroxylase deficiency medical therapy

Congenital adrenal hyperplasia main page
Overview
Classification 21-hydroxylase deficiency
11β-hydroxylase deficiency
17 alpha-hydroxylase deficiency
3 beta-hydroxysteroid dehydrogenase deficiency
Cytochrome P450-oxidoreductase (POR) deficiency (ORD)
Lipoid congenital adrenal hyperplasia
Differential Diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Overview

Medical treatment of 21-hydroxylase deficiency disorder depends on age: neonatal treatment is hydrocortisone or fludrocortisone as early as possible. If treatment cannot be started by 9 weeks, it should not be given at all. Surgical correction of ambiguous genitalia is the best treatment. Adults management: Hydrocortisone and Fludrocortisone acetate are the treatment of choice. CAH  patients need oral contraceptive pills to regulate the menstrual cycle and induction of ovulation.

Medical Therapy

Neonatal management

Prenatal diagnosis

Virilization of female fetus begins early; Therefore, early diagnosis and treatment are required as following :

• Maternal administration of dexamethasone; in selected case of diagnosing prenatally. Dexamethasone crosses the placenta into the fetal circulation. And suppresses cosintropin in 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.
• 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

• 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. 

• Growth suppression and shorter height in adulthood are the complications of using high d occurs in neonates treated with high doses of hydrocortisone.

Ambiguous genitalia 

• The initial evaluation is pelvic ultrasonography to evaluate internal genitalia, karyotype for sex chromosome (SRY probe) material,
• measurement of 17-hydroxyprogesterone and serum electrolytes. Until results release, glucocorticoid, mineralocorticoid and sodium chloride should be initiated
• Girls with classic CAH typically undergo reconstructive surgery, usually clitoroplasty and vaginoplasty.

Adrenal crisis

• 20 mL/kg of normal saline should be administered.
• An intravenous bolus of 2 to 4 mL/kg of 10 percent dextrose should be considered if there is significant hypoglycemia.  
• Hyperkalemia should be corrected with the administration of glucose and insulin if necessary.

Adults management

21-Hydroxylase

Glucocorticoids 

• Glucocorticoids reduce the excess production of adrenal androgens and reduce the excessive secretion of both corticotropin-releasing hormone and  ACTH.
• daily doses: hydrocortisone, a short-acting glucocorticoid, is the treatment of choice.

• Dexamethasone a very potent and long-acting glucocorticoid effectively suppresses ACTH secretion but almost always causes the development of Cushingoid features with chronic use.
• Combination therapy, with typical doses of hydrocortisone to replace the cortisol deficiency during the day and a very small dose of a long-acting glucocorticoid. We suggest this approach when standard hydrocortisone regimens are ineffective.
• Stress dosing: patients with classic 21OHD should be provided stress dosing.

Mineralocorticoid replacement 

• Fludrocortisone acetate, in a dose sufficient to restore normal serum potassium concentrations and plasma renin activity.
• The usual adult dose of fludrocortisone is 0.1 to 0.2 mg/day.
• Patients who are undertreated and in chronic poor control develop testicular adrenal rest tumors.

Infertility in men

• Sperm production is often impaired in untreated men due to defected spermatogenesis and Leydig cells suppression.
• Most of the patients have severe oligospermia. Moreover, Most of the untreated patients have testicular tumors that need surgical removal.
• An elevated FSH is a sensitive indicator for patients fertility condition but semen analysis is the specific test.

Infertility in women

• Lowering blood androgen levels helps women to control annoying cosmetic symptoms such as acne and hirsutism.
• Similar to polycystic ovary syndrome, CAH  patients need oral contraceptive pills to regulate the menstrual cycle and induction of ovulation.
• Women need pregnancy should consult a surgeon to repair previous genital malformations.
• hydrocortisone doesn’t pass placenta so, it can be used safely during pregnancy.
• Glucocorticoids doses need to increase at end of pregnancy with careful monitoring.

11-Hydroxylase

Treatment is similar to 21-hydroxylase deficiency with glucocorticoid replacement. Clinical assessment of virilization, growth velocity, hair growth, menstrual function and blood pressure are necessary. Despite adequate glucocorticoid replacement, medication may be required to control blood pressure. Spironolactone is a good choice as well as calcium blockers.