This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Charmandari, E. Search for Related Content PubMed Articles by Charmandari, E.

Author’s Response: Serum Cortisol and 17-Hydroxyprogesterone Concentrations in Children with Classic Congenital Adrenal Hyperplasia

National Institute of Child Health and Human Development, National Institutes of Health, Pediatric and Reproductive Endocrinology Branch Bethesda, Maryland 20892-1583

Address correspondence to: Evangelia Charmandari, M.D., Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, Building 10, Room 9D42, Bethesda, Maryland 20852-1583.

To the editor:

We thank Dr. R. L. Rosenfield for his comments on our paper (1) and for the opportunity to clarify these points further.

We recommend administration of the higher portion of the daily hydrocortisone dose in the morning because serum cortisol concentrations attained after the administration of the evening hydrocortisone dose decline and reach undetectable concentrations by 0400 h, when a precipitous rise in 17-hydroxyprogesterone is observed. This point is illustrated in Fig. 2 of our paper (1). Of course, one could suggest that administration of a higher dose of hydrocortisone in the evening might successfully suppress the early morning rise in ACTH and 17-hydroxyprogesterone concentrations because of the higher peak cortisol concentrations attained. However, in our studies of cortisol pharmacokinetics, we have demonstrated that the half-life of serum cortisol is short (80–90 min) and that after the iv administration of hydrocortisone sodium succinate in a dose of 15 mg/m², serum cortisol concentrations decline monoexponentially and reach undetectable levels within 4–6 h (2). Therefore, it is likely that even if we give the higher portion of daily hydrocortisone dose in the evening, we may not achieve sufficient suppression of the hypothalamic-pituitary-adrenal axis between 0400 and 0800 h.

As for prednisone or dexamethasone, we suggest that they be given for a few days only in patients with inadequate control, in whom standard therapy with hydrocortisone failed to control adrenal hyperandrogenism. However, we would be reluctant to recommend their regular use in the management of patients with congenital adrenal hyperplasia because of their well documented detrimental effects on growth and the associated adverse effects of long-acting glucocorticoids (3, 4, 5, 6).

Received February 22, 2002.

References

1. Charmandari E, Matthews DR, Johnston A, Brook CG, Hindmarsh PC 2001 Serum cortisol and 17-hydroxyprogesterone interrelation in classic 21-hydroxylase deficiency: is current replacement therapy satisfactory? J Clin Endocrinol Metab 86:4679–4685[Abstract/Free Full Text]
2. Charmandari E, Hindmarsh PC, Johnston A, Brook CGD 2001 Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: alterations in cortisol pharmacokinetics at puberty. J Clin Endocrinol Metab 86:2701–2708[Abstract/Free Full Text]
3. Guest G, Rappaport R, Philippe F, Thibaud E 1983 Occurrence of severe striae in adolescents with congenital adrenal hyperplasia and 21-hydroxylation deficiency treated with dexamethasone. Arch Fr Pediatr 40:453–456[Medline]
4. Job JC, Munck A, Chaussain JL, Canlorbe P 1985 Treatment of virilizing adrenal hyperplasia in adolescents. Use and side-effects of dexamethasone. Arch Fr Pediatr 42:765–769[Medline]
5. Horrocks PM, London DR 1987 Effects of long-term dexamethasone treatment in adult patients with congenital adrenal hyperplasia. Clin Endocrinol (Oxf) 27:635–642[Medline]
6. Young MC, Hughes IA 1990 Dexamethasone treatment for congenital adrenal hyperplasia. Arch Dis Child 65:312–314[Abstract/Free Full Text]

This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Charmandari, E. Search for Related Content PubMed Articles by Charmandari, E.