Characteristics of Growth in Children With Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency During Adrenarche and Beyond

Abstract

Context: Patients with classic congenital adrenal hyperplasia (CAH) often do not achieve their full growth potential. Adrenarche may accelerate bone maturation and thereby result in decreased growth in CAH.

Objective: The study aimed to analyze the impact of growth during adrenarche on final height of adequately treated classic CAH patients.

Methods: This retrospective, multicenter study (4 academic pediatric endocrinology centers) included 41 patients with classical CAH, born 1990-2012. 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 (-0.4 SDS ± 0.8 SD) and their parents (corrected final height -0.6 SDS ± 1.0 SD). Analysis of growth during adrenarche revealed 2 different growth patterns: patients with accelerating bone age (49%), and patients with nonaccelerating bone age relative 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 lower adult height SDS (-0.9 SDS [95% CI, -1.3; -0.5]) than nonaccelerating patients when assessed during adrenarche (0.2 SDS [95% CI, -0.3; 0.8]). Final adult height was similarly reduced in both accelerating and nonaccelerating BA-CA groups (-0.4 SDS [95% CI, -0.9; 0.1] vs -0.3 SDS [95% CI, [-0.8; 0.1]).

Conclusion: 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.

Keywords: adrenarche; classic CAH; final height prediction; growth.

Figure 1.

Recruitment scheme. Figure 1 depicts the patients recruited according to the inclusion criteria age, informed consent, and diagnosis with classical CAH in the 4 recruitment centers.

Figure 2.

Growth characteristics of boys and girls with classic CAH before, during and after adrenarche. Shown are growth data of boys and girls, depicted in box plots and divided into 3 age groups: before adrenarche, adrenarche, and puberty. From top left to bottom right, parameters depicted as box plots are A, mean BMI SDS; B, mean height SDS; C, mean growth velocity SDS; D, mean bone age—chronological age (BA-CA); E, mean estimated height SDS according to Bayley and Pinneau (24); and F, mean estimated height SDS according to Bonfig and Schwarz (25).

Figure 3.

Growth data of CAH children showing accelerating or nonaccelerating bone age. Shown are dichotomized growth data of accelerating and nonaccelerating CAH children, and of all patients combined, depicted as line graphs and divided into 3 age groups: before adrenarche, adrenarche, and puberty. From top left to bottom right, parameters depicted are A, individual bone age − chronological age (BA-CA) of accelerating individuals (black) vs nonaccelerating (light gray) over time; B, mean BA-CA; C, individual height of accelerating individuals (black) vs nonaccelerating (light gray) over time; D, mean height SDS; E, mean growth velocity SDS; F, mean BMI SDS; G, mean estimated height SDS according to Bayley and Pinneau (24); and H, mean estimated height SDS according to Bonfig and Schwarz (25).

Figure 4.

Coefficient plots showing factors associated with height outcome in CAH. This figure shows linear mixed effects models to identify factors associated with estimated final height SDS according to Bayley and Pinneau (24), separately for A, adrenarche and B, puberty.