The Importance of Disease Specific Growth Charts for Children with Congenital Adrenal Hyperplasia

Abstract

Background: Children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency typically have height, weight and BMI growth patterns that differ from the general population due to increased androgen and/or glucocorticoid exposures. With the recent surge in the development of new therapies, CAH-specific growth charts are needed to evaluate the effectiveness of these new treatments.

Methods: Retrospective data from patients aged 0-20 years with classic CAH, confirmed by hormonal testing and/or CYP21A2 genotyping, from two large clinical databases were analyzed. Specialized charts were developed using the Lamda-Mu-Sigma semi-parametric modeling method to generate CAH-specific percentile curves from 0-20 years. Nodal-point analyses were conducted to assess differences in incremental growth at 4, 8, 12, 16 and 20 years of age relative to CDC-2000 normative charts using one-sided quantile tests and age of adiposity rebound estimated with curve derivative solutions.

Results: A total sample of 8692 visits from 515 patients were used. Growth (height-, weight-, BMI-for-age) channels of CAH patients were significantly different over the entire growing period and characterized by diminished pubertal spurt relative to the CDC reference. Onset of adiposity rebound based on BMI-for-age occurred earlier for CAH patients (females 3.3 years, males 3.9 years) compared to their normative counterparts (5-8 years).

Conclusion: Our study showed that at incremental time points throughout childhood, children with CAH collectively follow specific differences in growth trajectories than unaffected children. These variations highlight the need for CAH-specific charts to assist in clinical management, appraisal of growth trajectories and to assess the impact of new therapies.

Keywords: 21-hydroxylase deficiency; Congenital adrenal hyperplasia; growth; growth chart.