Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Clinics (Sao Paulo). 2011;66(8):1361-6. doi: 10.1590/s1807-59322011000800009.


Introduction: 21-hydroxylase deficiency is an autosomal recessive disorder that causes glucocorticoid deficiency and increased androgen production. Treatment is based on glucocorticoid replacement; however, interindividual variability in the glucocorticoid dose required to achieve adequate hormonal control has been observed.

Objective: The present study aimed to evaluate the association between polymorphic variants involved inglucocorticoid action and/or metabolism and the mean daily glucocorticoid dose in 21-hydroxylase deficiency patients.

Methods: We evaluated 53 patients with classical forms of 21-hydroxylase deficiency who were receiving cortisone acetate. All patients were between four and six years of age and had normal androgen levels.

Results: The P450 oxidoreductase A503V, HSD11B1 rs12086634, and CYP3A7*1C variants were found in 19%, 11.3% and 3.8% of the patients, respectively. The mean ± SD glucocorticoid dose in patients with the CYP3A7*1C and wild-type alleles was 13.9 ± 0.8 and 19.5 ± 3.2 mg/m²/d, respectively. We did not identify an association between the P450 oxidoreductase or HSD11B1 allelic variants and the mean glucocorticoid dose.

Conclusion: Patients carrying the CYP3A7*1C variant required a significantly lower mean glucocorticoid dose. Indeed, the CYP3A7*1C allele accounted for 20% of the variability in the cortisone acetate dose. The analysis of genes involved in glucocorticoid metabolism may be useful in the optimization of treatment of 21-hydroxylase deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Hyperplasia, Congenital / drug therapy*
  • Adrenal Hyperplasia, Congenital / enzymology
  • Adrenal Hyperplasia, Congenital / genetics*
  • Child
  • Child, Preschool
  • Cortisone / administration & dosage
  • Cortisone / analogs & derivatives*
  • Female
  • Glucocorticoids / administration & dosage*
  • Hormone Replacement Therapy
  • Humans
  • Infant
  • Male
  • Oxidoreductases / genetics*
  • Polymorphism, Genetic*


  • Glucocorticoids
  • Oxidoreductases
  • Cortisone

Supplementary concepts

  • Congenital adrenal hyperplasia due to 21 hydroxylase deficiency