Growth Patterns and Final Height in Congenital Adrenal Hyperplasia due to Classical 21-Hydroxylase Deficiency

AbstractThe objective of this study was to identify variables that might interfere with reaching the near final height (NFH) in Congenital adrenal hyperplasia (CAH) due to classic 21-hydroxylase deficiency (21-OHD).A cross-sectional study of 82 (24 males and 58 females) classic (23 salt-wasting form [SW] and 59 simple-virilizing form [SV]) CAH 21-OHD patients seen in our institution between 1989 and 2015 with 10.6 (0.5~25.5) years of follow-up who reached their NFH was conducted. The variables related to NFH were explored.NFH (153.35±8.31) cm, (–1.9±1.1) SD was significantly lower than the normal population (p<0.001). The treated patients reached a significantly higher NFH (–1.7±1.1) SD than those untreated (–2.6±1.0) SD (p<0.05). Both of early treatment and late treatment group were taller than untreated group (p<0.001, p=0.013, respectively), and early treatment group had a taller height trend than late treatment group (p=0.089). A better height outcome was observed in patients with advantage in target height, good compliance, and low hydrocortisone dose by multivariate Cox regression analysis in 62 treatment patients. NFH and hydrocortisone dose was negatively correlated (r=–0.23, p=0.078) in treated group. Patients complicated by central precocious puberty (CPP) received gonadotropin-releasing hormone analogue (GnRHa) plus letrozole had increased NFH with height SD for bone age and Ht SD improved after treatment compare to no intervention group (p=0.001, p=0.035).Patients with classic 21-OHD have blunted final height, as compared with their target height and the population norm, not-treated even worse. Careful treatment adjustments have a favorable influence on growth. Alternative treatments, such as the use of puberty inhibitors GnRHa in addition to anti-estrogen therapy letrozole can somewhat improve NFH in children with 21-OHD complicated by CPP.

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Characteristics of growth in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency during adrenarche and beyond

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab701 ◽

2021 ◽

Author(s):

Tobias Troger ◽

Grit Sommer ◽

Mariarosaria Lang-Muritano ◽

Daniel Konrad ◽

Beatrice Kuhlmann ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Adult Height ◽

Final Height ◽

Bone Age ◽

Growth Patterns ◽

Adrenal Hyperplasia ◽

Classic Congenital Adrenal Hyperplasia ◽

Classic Cah ◽

21 Hydroxylase Deficiency ◽

The Impact

Abstract Context Patients with classic congenital adrenal hyperplasia (CAH) often fail to achieve their full growth potential. Adrenarche may accelerate bone maturation and thereby result in decreased growth in CAH. Objective To analyze the impact of growth during adrenarche on final height of adequately treated classic CAH patients. Design Retrospective, multi-center study. Setting Four academic pediatric endocrinology centers. Participants Fourty-one patients with classical CAH, born between 1990 and 2012. Main outcome measures We assessed skeletal maturation (bone age), growth velocity and (projected) adult height outcomes, and analyzed potential influencing factors, such as sex, genotype, and glucocorticoid therapy. Results Patients with classic CAH were shorter than peers (-0.4SDS±0.8SD) and their parents (corrected final height -0.6SDS±1.0SD). Analysis of growth during adrenarche revealed two different growth patterns: patients with accelerating bone age (49%), and patients with non-accelerating bone age compared to chronological age (BA-CA). Patients with accelerating BA-CA were taller than the normal population during adrenarche years (p=0.001) and were predicted to achieve a lower adult height SDS (-0.9SDS, 95%CI -1.3;-0.5) than non-accelerating patients when assessed during adrenarche (0.2SDS, 95%CI -0.3;0.8). Final adult height was similarly reduced in both accelerating and non-accelerating BA-CA groups (-0.4SDS, 95%CI -0.9;0.1 vs -0.3SDS, 95%CI -0.8;0.1). Conclusions Patients with and without significant bone age advancement, and thus differing height prediction during adrenarche, showed similar (predicted) final height when reassessed during pubertal years. Bone age alone should not be used during adrenarche as clinical marker for metabolic control in CAH treatment.

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