Question

• 11 yo girl with late onset congenital adrenal hyperplasia (21 hydroxylase deficiency, non salt wasting type) presents to pediatric endocrine clinic for follow up visit. It is discovered that she has frequently been noncompliant with hydrocortisone dosing regimen. Is dexamethasone once a day an effective therapy to suppress adrenal androgen secretion while maintaining normal statural growth?

Clinical Bottom Lines

1. Dexamethasone treated patients grow normally, have normal rates of skeletal maturation, undergo puberty at a normal age, and can reach acceptable adult stature with the convience of once a day dosing in most cases. (1)
2. Glucocorticoid treatment of congenital adrenal hyperplasia involves a delicate balance of suppressing adrenal androgen secretion while maintaining normal growth.
3. Dexamethasone has been avoided in children with CAH based on previous studies which described over-suppression of adrenal steroidogenesis along with development of cushingoid features and stunted growth. The previous studies used higher potency dexamethasone than were used in this study.
4. This study suggests that carefully adjusted doses of dexamethasone are at least as effective as hydrocortisone
5. Randomized, controlled trials need to be conducted comparing dexamethasone to hydrocortisone.

Summary of Key Evidence

1. 17 boys and 9 girls were treated long-term with dexamethasone. 13 boys and 8 girls were diagnosed with 21-hydroxylase deficiency, 4 boys and 1 girl were diagnosed with 11-hydroxylase deficiency. (1)
2. Patients were divided into two groups based on the bone ages at the onset of dexamethasone therapy. The distinction was made because statural outcome was worse in children with advanced skeletal age at the start of therapy.
3. During treatment with dexamethasone, growth was observed for an average of 7.3 years for males and 6.8 years for females.
4. Mature heights were available for 6 males and 3 females. The 3 males without significant bone age advancement had final heights of 171.8 +/- 6cm compared to midparental heights of 176.1 +/- 4.1 cm, p>0.05). The one female without significant bone age advancement had a final height of 161cm compared to with midparental height of 160 cm. For the boys who were still growing, predicted heights was 176.8 +/- 2.0cm compared with midparental heights of 177.2cm ( p>0.05). For growing females, the predicted adult height was 161.4 +/- 2.8cm compared with midparental height of 158.2 +/- 2cm (p<0.05).
5. Dexamethasone was given in a dilute elixir preparation to offer better titration of dosage. The morning doses ranged between 0.24-0.33 mg/m2/d. 5 patients did require lower doses 0.04-0.17mg/m2/d.
6. This report is a retrospective cohort study without a control group.

Additional Comments

• The standard of care treatment of congenital adrenal hyperplasia, discussed in the 16th edition of Nelson's Textbook of Pediatrics, uses hydrocortisone three times a day dosing of 8-20mg/m2/day with careful monitoring of bone age, and adrenal androgen levels.(2)
• Hydrocortisone is rapidly eliminated from the circulation, requiring 3 or 4 times a day dosing. It has been associated with breakthrough adrenal androgen secretion resulting in below average adult and midparental heights.
• The loss in adult stature associated with hydrocortisone therapy is believed to reflect cumulative adverse effects on growth and inadequate suppression of adrenal androgen secretion.
• It has been suggested that because of dexamethasone's long half-life, it can provide more continuous suppression of adrenal androgen secretion in CAH compared to hydrocortisone.
• Another advantage of using dexamethasone, according to this study, is that missing one dose of dexamethasone does not cause adrenal secretion excess. In comparison, missing or delaying a dose of hydrocortisone results in adrenal secretion excess which may affect growth as well as other symptoms associated with androgen excess.

Citation

1. Rivkees S, Crawford J. Dexamethasone Treatment of Virilizing Congenital Adrenal Hyperplasia: The Ability to Achieve Normal Growth. Pediatrics 2000; 767-773
2. Behrman. Nelson Textbook of Pediatrics, 16th Edition; 2000: 1729-1743.

CAT Author: Dana Gillespie, MD

CAT Appraisers: Kathryn Layton, MD

Date appraised: November 20, 2000