Nocturnal Dexamethasone versus Hydrocortisone for the Treatment of Children with Congenital Adrenal Hyperplasia

Andrew Dauber, Henry A Feldman, Joseph A Majzoub, Andrew Dauber, Henry A Feldman, Joseph A Majzoub

Abstract

Classic congenital adrenal hyperplasia affects approximately 1 in 15,000 children. Current treatment strategies using multiple daily doses of hydrocortisone lead to suboptimal outcomes. We tested the hypothesis that nocturnal administration of dexamethasone will suppress the hypothalamic-pituitary-adrenal axis more effectively than standard hydrocortisone treatment by blocking the inherent diurnal secretion of ACTH. We performed a pilot study of five prepubertal patients comparing CAH control during two 24-hour hospitalizations, one on hydrocortisone and the other on dexamethasone. The patterns of adrenal suppression differed markedly between hydrocortisone and nocturnal dexamethasone, with significant suppression of the morning rise in ACTH, 17-hydroxyprogesterone, and androstenedione while on dexamethasone. On hydrocortisone therapy, there is a marked variation in ACTH and adrenal hormones depending on time of day and timing of hydrocortisone administration. Longer-term studies are needed to investigate the lowest effective dose and potential toxicity of nocturnal dexamethasone to determine its utility as a therapy for CAH.

Figures

Figure 1
Figure 1
Subject 1 blood ACTH (squares) and 17 hydroxyprogesterone (17OHP, triangles) over 23-hour period while on hydrocortisone (HC, black) or dexamethasone (Dex, brown). Androstenedione levels were less than assay at all time points on both regimens in this patient. To convert to SI units, multiply ACTH by 0.2222 (pmol/L), 17OHP by 30.2572 (pmol/L), and Androstenedione by 34.9162 (pmol/L).
Figure 2
Figure 2
Subject 2 blood ACTH, 17 hydroxyprogesterone and androstenedione (circles) over 23-hour period while on hydrocortisone or dexamethasone. Abbreviations and symbols as in Figure 1.
Figure 3
Figure 3
Subject 3 blood ACTH, 17 hydroxyprogesterone, and androstenedione (circles) over 23-hour period while on hydrocortisone or dexamethasone. Abbreviations and symbols as in Figures 1 and 2.
Figure 4
Figure 4
Subject 4 blood ACTH, 17 hydroxyprogesterone, and androstenedione (circles) over 23-hour period while on hydrocortisone or dexamethasone. Abbreviations and symbols as in Figures 1 and 2.
Figure 5
Figure 5
Subject 5 blood ACTH, 17 hydroxyprogesterone, and androstenedione (circles) over 23-hour period while on hydrocortisone. Subject 5 did not complete the dexamethasone admission due to technical difficulties. Abbreviations and symbols as in Figures 1 and 2.
Figure 6
Figure 6
Percent difference in area under the curve on dexamethasone versus hydrocortisone for ACTH, 17 hydroxyprogesterone, androstenedione, and urinary 17-ketosteroids (17-KS) for subjects 1–4. Subject 1 had androstenedione levels less than assay at all time points on both regimens and did not perform a urine collection for 17-ketosteroids.

References

    1. Cutler GB, Jr., Laue L. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. The New England Journal of Medicine. 1990;323(26):1806–1813.
    1. Bonfig W, Pozza SBD, Schmidt H, Pagel P, Knorr D, Schwarz HP. Hydrocortisone dosing during puberty in patients with classical congenital adrenal hyperplasia: an evidence-based recommendation. Journal of Clinical Endocrinology and Metabolism. 2009;94(10):3882–3888.
    1. Silva IN, Kater CE, Cunha CDF, Viana MB. Randomised controlled trial of growth effect of hydrocortisone in congenital adrenal hyperplasia. Archives of Disease in Childhood. 1997;77(3):214–218.
    1. Eugster EA, DiMeglio LA, Wright JC, Freidenberg GR, Seshadri R, Pescovitz OH. Height outcome in congenital adrenal hyperplasia caused by 21-hydroxylase deficiency: a meta-analysis. Journal of Pediatrics. 2001;138(1):26–32.
    1. Stewart PM. The adrenal cortex. In: Melmed S, Kronenberg H, Polonsky K, Larsen PR, editors. Williams Textbook of Endocrinology. Philadelphia, Pa, USA: Saunders Elsevier; 2008. pp. 445–504.
    1. Micromedex. Drugdex Consults. Thomson Reuters; 2006. Comparative dosage data—corticosteroids properties and potencies; pp. 445–504.
    1. Rivkees SA, Crawford JD. Dexamethasone treatment of virilizing congenital adrenal hyperplasia: the ability to achieve normal growth. Pediatrics. 2000;106(4):767–773.
    1. Rivkees SA. Dexamethasone therapy of congenital adrenal hyperplasia and the myth of the “growth toxic” glucocorticoid. International Journal of Pediatric Endocrinology. 2010;2010:7 pages. Article ID 569680.
    1. Clayton PE, Oberfield SE, Martin Ritzén E, et al. Consensus: consensus statement on 21-hydroxylase deficiency from The Lawson Wilkins Pediatric Endocrine Society and The European Society for Pediatric Endocrinology. Journal of Clinical Endocrinology and Metabolism. 2002;87(9):4048–4053.
    1. White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocrine Reviews. 2000;21(3):245–291.
    1. Winterer J, Chrousos GP, Loriaux DL, Cutler GB., Jr. Effect of hydrocortisone dose schedule on adrenal steroid secretion in congenital adrenal hyperplasia. Journal of Pediatrics. 1985;106(1):137–142.
    1. Frisch H, Parth K, Schober E, Swoboda W. Circadian patterns of plasma cortisol, 17-hydroxyprogesterone, and testosterone in congenital adrenal hyperplasia. Archives of Disease in Childhood. 1981;56(3):208–213.
    1. Huseman CA, Varma MM, Blizzard RM, Johanson A. Treatment of congenital virilizing adrenal hyperplasia patients with single and multiple daily doses of prednisone. Journal of Pediatrics. 1977;90(4):538–542.
    1. Moeller H. Chronopharmacology of hydrocortisone and 9α-fluorhydrocortisone in the treatment for congenital adrenal hyperplasia. European Journal of Pediatrics. 1985;144(4):370–373.
    1. Verma S, Vanryzin C, Sinaii N, et al. A pharmacokinetic and pharmacodynamic study of delayed- and extended-release hydrocortisone (Chronocort) versus conventional hydrocortisone (Cortef) in the treatment of congenital adrenal hyperplasia. Clinical Endocrinology. 2009;72(4):441–447.
    1. Shen SX, Young MC, Hinohosa-Sandoval M, Hughes IA. 17OH-progesterone response to acute dexamethasone administration in congenital adrenal hyperplasia. Hormone Research. 1989;32(4):136–141.
    1. Horrocks PM, London DR. A comparison of three glucocorticoid suppressive regimes in adults with congenital adrenal hyperplasia. Clinical Endocrinology. 1982;17(6):547–556.
    1. Horrocks PM, London DR. Effects of long term dexamethasone treatment in adult patients with congenital adrenal hyperplasia. Clinical Endocrinology. 1987;27(6):635–642.
    1. Young MC, Cook N, Read GF, Hughes IA. The pharmacokinetics of low-dose dexamethasone in congenital adrenal hyperplasia. European Journal of Clinical Pharmacology. 1989;37(1):75–77.
    1. Young MC, Hughes IA. Dexamethasone treatment for congenital adrenal hyperplasia. Archives of Disease in Childhood. 1990;65(3):312–314.
    1. Hayek A, Crawford JD, Bode HH. Single dose dexamethasone in treatment of congenital adrenocortical hyperplasia. Metabolism. 1971;20(9):897–901.
    1. Rivkees SA, Stephenson A. Low-dose dexamethasone therapy from infancy of virilizing congenital adrenal hyperplasia. International Journal of Pediatric Endocrinology. 2009;2009:4 pages. Article ID 274682.
    1. LaFranchi S. Plasma adrenocorticotrophic hormone in congenital adrenal hyperplasia. Importance in long-term management. American Journal of Diseases of Children. 1980;134(11):1068–1072.
    1. Wilkins L. The Diagnosis and Treatment of Endocrine Disorders in Childhood. Springfield, Ill, USA: Charles C Thomas; 1950.
    1. Motson RW, Glass DN, Smith DA, Daly JR. The effect of short- and long-term corticosteroid treatment on sleep-associated growth hormone secretion. Clinical Endocrinology. 1978;8(4):315–326.
    1. Lee PA, Urban MD, Gutai JP, Migeon CJ. Plasma progesterone, 17-hydroxyprogesterone, androstenedione and testosterone in prepubertal, pubertal and adult subjects with congenital virilizing adrenal hyperplasia as indicators of adrenal suppression. Hormone Research. 1980;13(6):347–357.
    1. Cavallo A, Corn C, Bryan GT, Meyer WJ., III The use of plasma androstenedione in monitoring therapy of patients with congenital adrenal hyperplasia. Journal of Pediatrics. 1979;95(1):33–37.
    1. Korth-Schutz S, Virdis R, Saenger P. Serum androgens as a continuing index of adequacy of treatment of congenital adrenal hyperplasia. Journal of Clinical Endocrinology and Metabolism. 1978;46(3):452–458.
    1. Young MC, Walker RF, Riad-Fahmy D, Hughes IA. Androstenedione rhythms in saliva in congenital adrenal hyperplasia. Archives of Disease in Childhood. 1988;63(6):624–628.
    1. German A, Suraiya S, Tenenbaum-Rakover Y, Koren I, Pillar G, Hochberg Z. Control of childhood congenital adrenal hyperplasia and sleep activity and quality with morning or evening glucocorticoid therapy. Journal of Clinical Endocrinology and Metabolism. 2008;93(12):4707–4710.
    1. Hughes IA, Winter JSD. The relationships between serum concentrations of 170H progesterone and other serum and urinary steroids in patients with cogenital adrenal hyperplasia. Journal of Clinical Endocrinology and Metabolism. 1978;46(1):98–104.

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