Congenital adrenal hyperplasia 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 hydro cortisone 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

• Early diagnosis and treatment are required for female fetuses because virilization begins early.
• Ideal treatment: maternal administration of dexamethasone which crosses the placenta into the fetal circulation.
• If treatment cannot be started by 9 weeks, it should not be given at all.
• If the gender of a fetus has been defined as a male by early tests such as cell-free fetal DNA, treatment should be stopped as no need for treatment for male fetuses.
• Eighty-five percent of managed cases appear quite normal after delivery.
• Side effects of prenatal dexamethasone:
  • Postnatal failure to thrive.
  • Psychomotor developmental delay but without effect on Intelligence Quotient..
  • Increased risk of cleft lip and palate.    
  • Increased risk for psychiatric disturbances and ADHD.

Neonatal treatment

• Hydrocortisone: intravenous 20 to 30 mg/m²/day. 
• Fludrocortisone: intravenous 100 mcg or 4 mEq/kg/day of sodium chloride.

• Growth suppression 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 is the treatment of choice as it is a short-acting glucocorticoid with fewer side effects.

• Dexamethasone is a very potent and long-acting glucocorticoid suppresses ACTH secretion but almost always causes the development of Cushing syndrome 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: in periods of acute illness or before surgery, patients with classic CAH should be provided with additional cortisol stress dosing as the physiological increase of cortisol level in this patient is impaired.

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.

Infertility in men

• Patients who are undertreated and in chronic poor control develop testicular adrenal rest tumors.

• 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 who 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 be increased 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.