Background/Aims: In classical congenital adrenal hyperplasia (CAH), elevation of adrenal androgens leads to accelerated growth and bone maturation with compromised adult height. In untreated children with non-classical CAH (NC-CAH), in which adrenal androgens are generally only slightly increased, growth velocity may not be significantly elevated. Methods: Twenty-four patients were included and divided into a symptomatic and an asymptomatic group. Height was expressed as height standard deviation scores (HSDS) and corrected for target height (HSDS-THSDS). Bone maturation was expressed as bone age acceleration (BAc = bone age – calendar age). Linear mixed models with random factor patient were used for the analysis of growth and bone age. Results: In symptomatic patients (n = 17), HSDS-THSDS only slightly increased by 0.06 SDS per year (95% CI 0.02–0.10). Mean BAc was 2.21 years (SDS 0.66, p < 0.0001). In asymptomatic patients (n = 7), no significant growth acceleration or BAc was found. Conclusions: In untreated NC-CAH children, growth acceleration is small and generally not visible on their growth charts. BAc is more pronounced. Therefore, the absence of an increase in growth velocity does not exclude the diagnosis of NC-CAH. When considering this diagnosis, bone age acceleration should also be taken into account.

Keywords:
Non-classical congenital adrenal hyperplasia, Growth, Bone development, Bone age acceleration
1.
White PC, Speiser PW: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev 2000;21:245–291.
2.
New MI: An update of congenital adrenal hyperplasia. Ann NY Acad Sci 2004;1038:14–43.
3.
New MI: Nonclassical 21-hydroxylase deficiency. J Clin Endocrinol Metab 2006;91:4205–4214.
4.
Moran C, Azziz R, Carmina E, Dewailly D, Fruzzetti F, Ibanez L, Knochenhauer ES, Marcondes JAM, Mendonca BB, Pignatelli D, Pugeat M, Rohmer V, Speiser PW, Witchel SF: 21-Hydroxylase-deficient nonclassic adrenal hyperplasia is a progressive disorder: a multicentre study. Am J Obstet Gynecol 2000;183:1468–1474.
5.
Moran C: Non classic adrenal hyperplasia. Fertil Steril 2006;86(suppl 1):S3.
6.
Cameron FJ, Tebbutt N, Montalto J, Yong Ab, Zacharin M, Best JD, Warne GL: Endocrinology and auxology of sibships with nonclassical congenital adrenal hyperplasia. Arch Dis Child 1996;74:406–411.
7.
Bidet M, Bellanne-Chantelot C, Galand-Portier MB, Tardy V, Billaud L, Laborde K, Coussieu C, Morel Y, Vaury C, Golmard JL, Claustre A, Mornet E, Chakhtoura Z, Mowszowicz I, Bachelot A, Touraine P, Kuttenn F: Clinical and molecular characterization of a cohort of 161 unrelated women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency and 330 family members. J Clin Endocrinol Metab 2009;94:1570–1578.
8.
Speiser PW: Nonclassic adrenal hyperplasia. Rev Endocr Metab Dis 2009;10:77–82.
9.
Claahsen-van der Grinten HL, Noordam K, Borm GF, Otten BJ: Absence of increased height velocity in the first year of life in untreated children with simple virilizing congenital adrenal hyperplasia. J Clin Endocrinol Metab 2006;91:1205–1209.
10.
New MI, Gertner JM, Speiser PW, Del Balzo P: Growth and final height in classical and nonclassical 21-hydroxylase deficiency. J Endocrinol Invest 1989;12:91–95.
11.
Manoli I, Kanaka-Gantenbein Ch, Voutetakis A, Maniati-Christidi M, Dacou-Voutetakis: Early growth, pubertal development, body mass index and final height of patients with congenital adrenal hyperplasia: factors influencing the outcome. Clin Endocrinol 2002;57:669–676.
12.
Eugster EA, DiMeglio LA, Wright JC, Freidenburg GR, Seshadri R, Pescovitz OH: Height outcome in congenital adrenal hyperplasia caused by 21-hydroxylase deficiency: a meta-analysis. J Pediatr 2001;138:26–32.
13.
Nandagopal R, Sinaii N, Avila NA, Van Ryzin C, Chen W, Finkielstain GP, Mehta SP, McDonnell NB, Merke DP: Phenotypic profiling of parents with cryptic nonclassic congenital adrenal hyperplasia: findings in 145 unrelated families. Eur J Endocrinol 2011;164:977–984.
14.
Fredriks AM, Buuren van S, Burgmeijer RJF, Verloove-Vanhorick SP, Wit JM: Nederlandse groeidiagrammen 1997; in Wit JM (ed): De vierde landelijke groeistudie, Leiden, Boerhaave Commissie, 1998, pp 69–78.
15.
Jaaskelainen J, Voutilainen R: Growth of patients with 21-hydroxylase deficiency: an analysis of the factors influencing adult height. Pediatr Res 1997;41:30–33.
16.
Kamp van der HJ, Otten BJ, Buitenweg N, de Muinck Keizer-Schrama SMPF, Oostdijk W, Jansen M, Delemarre-de Waal HA, Vulsma T, Wit JM: Longitudinal analysis of growth and puberty in 21-hydroxylase deficiency patients. Arch Dis Child 2002;87:139–144.
17.
Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, Meyer-Bahlburg HF, Miller WL, Montori VM, Oberfield SE, Ritzen M, White PC, Endocrine Society: Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010;95:4133–4160.
18.
Clayton PE, Miller WL, Oberfield SE, Ritzen EM, Sippell WG, Speiser PW, ESPE/LWPES CAH Working Group: Consensus statement on 21-hydroxylase deficiency from the European Society for Paediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society. Horm Res 2002;58:188–195.
19.
Muthusamy K, Elamin MB, Smushkin G, Hassan Murad M, Lampropulos JF, Elamin KB, Abu Elnour NO, Gallegos-Orozco JF, Fatourechi MM, Agrwal N, Lane MA, Albuquerque FN, Erwin PJ, Montori VM: Adult height in patients with congenital adrenal hyperplasia: a systematic review and meta-analysis. J Clin Endocrinol Metab 2010;95:4161–4172.
20.
Venken K, Callewaert F, Boonen S, Vanderschueren D: Sex hormones, their receptors and bone health. Osteoporos Int 2008;19:1517–1525.
21.
Vandenput L, Ohlsson C: Sex steroid metabolism in the regulation of bone health in men. J Steroid Biochem Mol Biol 2010;121:582–588.
22.
Frank GR: Role of estrogen and androgen in pubertal skeletal physiology. Med Pediatr Oncol 2003;41:217–221.
23.
Hargitai G, Solyom J, Battelino T, Pribillincová Z, Hauspie R, Kovács J, Waldhauser F, Frisch H: Growth patterns and final height in congenital adrenal hyperplasia due to classical 21-hydroxylase deficiency. Result of a multicenter study. Horm Res 2001;55:161–171.
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2012
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