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

CYP21 Genotype, Adult Height, and Pubertal Development in 55 Patients Treated for 21-Hydroxylase Deficiency

Department of Pediatrics, University of Bologna and S. Orsola-Malpighi Hospital, 40138 Bologna, Italy

Address all correspondence and requests for reprints to: Prof. E. Cacciari, Dipartimento di Scienze Pediatriche Mediche e Chirurgiche, Az. Ospedaliera S. Orsola-Malpighi, Via Massarenti 11, 40138 Bologna, Italy. E-mail: antonio.balsamo{at}unibo.it.

In a retrospective study we evaluated long-term growth, pubertal developmental patterns to final height (FH), and medication in 55 patients (35 females) affected by 21-hydroxylase deficiency. The patients were classified into 3 groups according to predicted mutation severity: group A (11 women and 9 men), homozygous or compound heterozygous for null or In2 splice mutations [residual enzymatic activity (RA), <1%]; group B (11 women and 4 men), homozygous for I172N or R341P or R426H mutations (RA, 2–3%) or compound heterozygous with any of the group A or B mutations; and group C (13 women and 7 men), homozygous for P30L or V281L or P453S mutations (RA, >30%) or compound heterozygous with any of the group A, B, or C mutations. Three patients showed unclassifiable genotypes. FH was similar in the female groups, whereas male patients in group B were shorter than males in groups A and C. Fifty-five percent of patients in group A, 33% in group B, and 40% in group C reached an FH within 0.5 SD of target height. Four of the 7 patients diagnosed via neonatal screening achieved an FH equal to or above the target height. In the entire group, early diagnosis (<1 yr) improved height outcome. Early diagnosed CAH patients who received lower cortisol equivalent doses during the first year of life reached a better FH. Our results underline the importance of mineralocorticoid therapy, as CAH subjects in groups A and B who did not receive this treatment showed reduced FH. Early diagnosis, the use of more physiological cortisol equivalent dosages during the first year of life, and the extension of mineralocorticoid therapy to all classical patients are shown to improve the auxological outcome. Genotypic analysis helped to interpret the height results of our cases and prospectively may represent a useful tool for improving the therapeutic choice and the height outcome.

This work was supported in part by Grant Università Quota 60%: 60CICOGN02. Part of these data were presented at the 38th Annual Meeting of the European Society for Pediatric Endocrinology, Warsaw, Poland, August 29 to September 1, 1999.

Abbreviations: ⁴A, ⁴-Androstenedione; BMI, body mass index; C, cortone acetate; CA, chronological age; CAH, congenital adrenal hyperplasia; D, dexamethasone; F, fluorohydrocortisone; FH, final height; HCASD, height for chronological age SD; NC, nonclassical; 21OHD, 21-hydroxylase deficiency; 17OHP, 17-hydroxyprogesterone; P, prednisone; PRA, plasma renin activity; RA, residual enzymatic activity; SGA, small for gestational age; SV, simple virilizing; SW, salt-wasting; TH, target height.

This article has been cited by other articles:

				Z. Chakhtoura, A. Bachelot, D. Samara-Boustani, J.-C. Ruiz, B. Donadille, J. Dulon, S. Christin-Maitre, C. Bouvattier, M.-C. Raux-Demay, P. Bouchard, et al. Impact of total cumulative glucocorticoid dose on bone mineral density in patients with 21-hydroxylase deficiency. Eur. J. Endocrinol., June 1, 2008; 158(6): 879 - 887. [Abstract] [Full Text] [PDF]

				W. Bonfig, S. Bechtold, H. Schmidt, D. Knorr, and H. P. Schwarz Reduced Final Height Outcome in Congenital Adrenal Hyperplasia under Prednisone Treatment: Deceleration of Growth Velocity during Puberty J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1635 - 1639. [Abstract] [Full Text] [PDF]

				H. Falhammar, H. Filipsson, G. Holmdahl, P.-O. Janson, A. Nordenskjold, K. Hagenfeldt, and M. Thoren Metabolic Profile and Body Composition in Adult Women with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 110 - 116. [Abstract] [Full Text] [PDF]

				M. I. New Nonclassical 21-Hydroxylase Deficiency J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4205 - 4214. [Abstract] [Full Text] [PDF]

				K. Lin-Su, M. G. Vogiatzi, I. Marshall, M. D. Harbison, M. C. Macapagal, B. Betensky, S. Tansil, and M. I. New Treatment with Growth Hormone and Luteinizing Hormone Releasing Hormone Analog Improves Final Adult Height in Children with Congenital Adrenal Hyperplasia J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3318 - 3325. [Abstract] [Full Text] [PDF]

				M. G. Forest Recent advances in the diagnosis and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency Hum. Reprod. Update, November 1, 2004; 10(6): 469 - 485. [Abstract] [Full Text] [PDF]