eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Congenital Adrenal Hyperplasia: Treatment & Medication

Author: Thomas A Wilson, MD, Professor of Clinical Pediatrics, Department of Pediatrics; Director of Pediatric Endocrinology, Division of Pediatric Endocrinology, Department of Pediatrics, State University of New York at Stony Brook
Contributor Information and Disclosures

Updated: Nov 18, 2009

Treatment

Medical Care

Infants with ambiguous genitalia should be closely observed for symptoms and signs of salt wasting while a diagnosis is being established. Clinical clues include abnormal weight loss or lack of expected weight gain. Electrolyte abnormalities generally take from a few days to 3 weeks to appear because the placenta maintains the fetal electrolytes in utero. In mild forms of salt-wasting adrenal hyperplasia, salt wasting may not become apparent until an illness stresses the child.

• Patients with dehydration, hyponatremia, or hyperkalemia and a possible salt-wasting form of adrenal hyperplasia should receive an intravenous (IV) bolus of isotonic sodium chloride solution (20 mL/kg or 450 mL/m²) over the first hour, as needed, to restore their intravascular volume and blood pressure.
  • This dosage may be repeated if the blood pressure remains low.
  • Dextrose must be administered if the patient is hypoglycemic and must be included in the rehydration fluid after the bolus dose to prevent hypoglycemia.
  • After samples are obtained to measure electrolyte, blood sugar, cortisol, aldosterone, and 17-hydroxyprogesterone concentrations, the patient should be treated with glucocorticoids based on suspected adrenal insufficiency. Treatment should not be withheld while confirmatory results are awaited because it may be life preserving (see Medication).
• After the patient's condition is stabilized, treat all patients who have adrenal hyperplasia with long-term glucocorticoid or aldosterone replacement (or both), depending on which enzyme is involved and on whether cortisol and/or aldosterone synthesis is affected.
• Another approach currently under investigation is the combined use of glucocorticoid (to suppress ACTH and adrenal androgen production), mineralocorticoid (to reduce angiotensin II concentrations), aromatase inhibitor (to slow skeletal maturation), and flutamide (an androgen blocker to reduce virilization).
• Some patients develop precocious puberty, which further compromises adult height. Suppression of puberty with long-acting gonadotropin-releasing hormone (GnRH) agonists while simultaneously stimulating growth with growth hormone may partially improve the patient's height.

Surgical Care

Infants with ambiguous genitalia require surgical evaluation and, if needed, plans for corrective surgery.

• The traditional approach to the female patient with ambiguous genitalia due to adrenal hyperplasia is clitoral recession early in life followed by vaginoplasty after puberty.
  • Vocal groups of patients with disorders of sexual differentiation (eg, Intersex Society of North America) have recently challenged this approach.
  • Some female infants with adrenal hyperplasia have only mild virilization and may not require corrective surgery if they receive adequate medical therapy to prevent further virilization.
• Bilateral adrenalectomies have been suggested in the management of virilizing forms of adrenal hyperplasia in order to prevent further virilization and advancement of skeletal maturation.⁶ This approach is experimental and should be considered only in the context of a controlled study.

Consultations

• An endocrinologist should be consulted when adrenal insufficiency is suspected.
• An experienced surgeon is required if genitalia are ambiguous or inconsistent with genetic sex and corrective surgery is contemplated.
• A consultation with a geneticist is useful in establishing the genetic defect causing the disorder. In parents contemplating a subsequent pregnancy, genetic counseling for prenatal diagnosis and treatment of this disorder is important.

Diet

• Patients with congenital adrenal hyperplasia should be on an unrestricted diet.
• Patients should have ample access to salt because salt wasting is common in some forms of the disease.
• Infants who have salt wasting generally benefit from supplementation with NaCl (2-4 g/d) added to their formula.
• Caloric intake may need to be monitored and restricted if excess weight gain occurs because glucocorticoids stimulate appetite.

Activity

• Activity restriction is not necessary if appropriate glucocorticoid and mineralocorticoid therapy is provided.

Medication

Short-term medical therapy

In patients with hypotension, 0.9% (isotonic) sodium chloride solution (450 mL/m² or 20 mL/kg IV) must be rapidly administered over the first hour. This is followed by a continuous IV infusion of 3200 mL/m²/d or 200 mL/kg per 100 cal/d of estimated resting energy expenditure as isotonic or half-isotonic sodium chloride solution to restore intravascular volume. Dextrose must also be provided.

If the patient is hypoglycemic, 2-4 mL of dextrose 10% in water (D10W) should be administered to increase the blood sugar, followed by a continuous infusion of dextrose 5% in water (D5W). If the patient is not hypoglycemic, D5W should be administered to prevent hypoglycemia. Patients with salt-wasting forms of adrenal hyperplasia do not need potassium supplementation because they are usually hyperkalemic. However, patients with 11-hydroxylase and 17-alpha-hydroxylase deficiency may be hypokalemic and may require potassium. After appropriate diagnostic studies are performed or after the results are known, glucocorticoid therapy, mineralocorticoid therapy, or both may be started.

In patients who are sick and who have signs of adrenal insufficiency, therapy should consist of stress dosages of hydrocortisone (50-100 mg/m² or 1-2 mg/kg IV administered as an initial dose), followed by 50-100 mg/m²/d IV divided every 6 hours. Comparable stress dosages include 10-20 mg/m² of methylprednisolone administered IV or intramuscularly (IM) and 1-2 mg/m² of dexamethasone. Methylprednisolone and dexamethasone have negligible mineralocorticoid effects. Therefore, if the patient is hypovolemic, hyponatremic, or hyperkalemic, large dosages of hydrocortisone (double or triple the stress dosages mentioned above) are preferred because of its mineralocorticoid effect.

No parenteral form of mineralocorticoid is currently available in the United States; however, if the patient has good GI function, administer 0.05-0.2 mg of fludrocortisone by mouth (PO).

Long-term medical therapy

The goal of therapy for adrenal hyperplasia is the replacement of glucocorticoid and mineralocorticoid to prevent signs of adrenal insufficiency and to prevent the accumulation of precursor hormones that cause virilization. Adequate glucocorticoid replacement should prevent excessive concentrations of ACTH from stimulating the adrenal glands to produce abnormal concentrations of adrenal androgens that result in further virilization. In the growing child with adrenal insufficiency, long-term glucocorticoid replacement must be balanced to prevent symptoms of adrenal insufficiency while still allowing the child to grow at a normal rate and prevent symptoms of glucocorticoid excess. The dosage must be tailored to each patient, but the general average dosage is 10-25 mg/m²/d of hydrocortisone PO divided in 2-3 doses.

Hydrocortisone is available in 5-mg, 10-mg, and 20-mg tablets. Hydrocortisone is recommended in the pediatric population because of its lower potency, which permits easier titration of appropriate doses. Unfortunately, hydrocortisone suspension (Cortef solution) is no longer available in the United States.

Prednisone, prednisolone, or even dexamethasone suspensions may be used. Prednisone is available in a suspension of 1 mg/mL, and prednisolone is available in a solution of 5 or 15 mg/5 mL. The estimated equivalencies are as follows:⁷

• One mg of prednisone is equal to 4 mg of hydrocortisone.
• One mg of prednisolone is equal to 5 mg of hydrocortisone.
• One mg of dexamethasone is equal to 50 mg of hydrocortisone.

These forms of glucocorticoid have the advantage of half-lives longer than those of hydrocortisone, permitting twice-daily or even once-daily dosing (dexamethasone), which often aids compliance. However, because of their increased potency, growth suppression and other signs of glucocorticoid excess are common.

Administer fludrocortisone (0.05-0.2 mg/d PO) to patients with mineralocorticoid deficiency. Administer NaCl (2-5 g/d) to infants to counteract salt wasting. Older children can usually scavenge adequate salt to provide for their needs and may lose their salt-wasting tendencies as they mature. The dose of glucocorticoid is adjusted by clinically evaluating the patient (for an absence of symptoms of glucocorticoid deficiency and normal growth) and by periodically measuring the concentrations of precursor hormones. For example, in 21-hydroxylase deficiency, keeping plasma concentrations of 17-hydroxyprogesterone in the 200- to 500-ng/dL range and keeping androstenedione in the normal physiologic range is desirable.

Plasma ACTH concentrations are of little help in adjusting doses of glucocorticoid in patients with primary adrenal insufficiency. Monitoring symptoms of salt craving and blood pressure, PRA, and electrolyte levels are helpful in adjusting the dose of fludrocortisone. High blood pressure with suppressed PRA should prompt a reduction in fludrocortisone dose.

Stress or illness

One of the important physiologic responses to stress is an increase in the cortisol production that ACTH mediates. Patients with adrenal insufficiency of any etiology cannot mount this response and must be given stress doses of glucocorticoid. In the patient with a minor illness (temperature of <38°C), the dosage of hydrocortisone should be at least doubled. For patients with relatively severe illness (temperature of >38°C), the dosage of glucocorticoid should be tripled. If the patient is vomiting or listless, administer parenteral glucocorticoid (50-75 mg/m² of hydrocortisone IM or IV or an equivalent dosage of methylprednisolone or dexamethasone). Because hydrocortisone succinate has a short duration of action, the dose must be repeated every 6-8 hours at a dosage of 50-100 mg/m²/d until the patient is well.

All patients with adrenal insufficiency must have injectable glucocorticoid available, and the caretaker must be instructed in its use and importance. Glucocorticoid or mineralocorticoid replacement has no contraindications when it is needed, and it has few drug-drug interactions.

Glucocorticoids

The purpose of glucocorticoid therapy in congenital adrenal hyperplasia is (1) to replace the body's requirement for glucocorticoids under normal conditions and during stress and (2) to suppress ACTH secretion, thereby reducing the stimulus for the adrenal glands to overproduce adrenal androgens in virilizing forms of congenital adrenal hyperplasia. Unfortunately, no currently available preparation is able to mimic the diurnal rhythm of physiologic cortisol secretion. Thus, in an attempt to suppress androgen secretion from the adrenal glands in response to early morning rises in ACTH, overtreatment often occurs, resulting in inhibition of linear growth and Cushingoid features. Delayed-release preparations of hydrocortisone have been formulated but are not commercially available.

Hydrocortisone (A-Hydrocort, Cortef, Hydrocort)

Same as cortisol, which is the primary steroid hormone secreted by adrenal zona fasciculata and reticularis. DOC in children due to short half-life and decreased potential for growth suppression. Mineralocorticoid effect at large doses.

Mineralocorticoids

Replacement of mineralocorticoids is required in patients who have salt-wasting congenital adrenal hyperplasia. This treatment is necessary to replace the aldosterone that is insufficiently produced by the adrenal cortex.

Fludrocortisone acetate (Florinef)

Synthetic steroid with predominantly mineralocorticoid activity. Acts on renal tubule to promote sodium retention in exchange for potassium or hydrogen ion and thus maintain intravascular and extracellular volume. For patients who require parenteral mineralocorticoid therapy, high-dose hydrocortisone must be used. Available only as tab; may be crushed for infants and children.

• Search for CME/CE on This Topic »

• C-17 Hydroxylase Deficiency (Endocrinology)
• C-11 Hydroxylase Deficiency (Endocrinology)
• Follicle-Stimulating Hormone Abnormalities (Endocrinology)
• Androgen Excess (Obstetrics and Gynecology)

• Recent Advances in Adrenal Autoimmunity
• Autism Spectrum Disorder-associated Biomarkers for Case Evaluation and Management by Clinical Geneticists
• Vomiting in the Pediatric Age Group