ESPE Yearbook of Paediatric Endocrinology

Brief summary: This retrospective case-control observational study assessed body composition of children with non-classic congenital adrenal hyperplasia (NCCAH) using bioelectrical impedance analysis (BIA). It showed that children with NCCAH have an imbalance between muscle and fat tissues compared with control subjects, which may place them at increased risk for early-onset cardiometabolic morbidity.

Non-classic congenital adrenal hyperplasia (NCCAH) is a group of enzymatic disorders characterized by a mild defect in cortisol biosynthesis (1). Glucocorticoid therapy is not always indicated but rather reserved for symptomatic cases of hyperandrogenism, in an attempt to alleviate androgen overproduction (2). Chronic androgen excess has been reported in association with increased visceral adiposity, insulin resistance and their metabolic consequences (1, 2).

In this study, the authors explored the interaction between muscle-to-fat ratio (MFR) and components of metabolic syndrome in pediatric patients with NCCAH. The study group consisted of 75 subjects [12.3 years (interquartile range: 8.9, 15.4), 26 males] with NCCAH [61 hydrocortisone-treated (21 males) and 14 untreated (5 males)] and 134 healthy sex- and age-matched subjects (41 males) with normal puberty served as controls. Body composition was measured by bioelectrical impedance analysis (BIA) and muscle-to-fat ratio (MFR) z-scores were calculated. Stepwise linear regression models were applied to evaluate explanatory variables for MFR z-scores, blood pressure percentiles, lipid profiles and glucose metabolism.

Children and adolescents with NCCAH had higher mean BMI z-scores and lower median MFR z-scores compared with their healthy sex- and age-matched controls. Factors, including lower socioeconomic position and higher birthweight z-scores adversely affected their body composition while the duration of hydrocortisone therapy was found to be beneficial.

The novelty of the study comes from the paucity of BIA data on NCCAH. In this study, subjects with NCCAH did not have an increased rate of obesity, but did have higher BMI z-scores on average compared to healthy controls. Interestingly, the BIA study of the NCCAH subjects was characterized by a low MFR z-score due to higher fat mass, indicating that muscle mass was relatively low compared to their fat mass, thus placing them at risk for sarcopenic obesity (3). This unfavorable body composition in NCCAH patients, characterized by an imbalance between muscle and adipose tissue may be attributed to the complex interaction between circulating androgens and body composition parameters (4, 5).

In summary, children with NCCAH have a body composition characterized by an imbalance between muscle and fat tissue, placing them at increased risk for early onset cardiometabolic derangements. Implementation of BIA as a part of routine assessment may assist in the identification of cardiometabolic risk factors in NCCAH. It is reassuring that low-dose glucocorticoid therapy in pediatric patients with NCCAH aimed to alleviate androgen overproduction does not appear to adversely affect body composition.

References: 1. Merke DP, Auchus RJ. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. N Engl J Med. 2020; 383(13):1248–61. 2. Speiser PW, Arlt W, Auchus RJ, Baskin LS, Conway GS, Merke DP, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2019; 104(1):39–40. 3. Stefanaki C, Paltoglou G, Mastorakos G, Chrousos GP. Chronic Stress and Steatosis of Muscles, Bones, Liver, and Pancreas: A Review. Horm Res Paediatr. 2023;96(1):66–73. 4. Ben-Shachar S, Ayalon I, Reznik-Wolf H, Tenenbaum-Rakover Y, Zuckerman-Levin N, Cohen O, et al. Androgen receptor CAG repeat length in relation to phenotype among females with nonclassical 21-hydroxylase deficiency. Horm Metab Res. 2015; 47(7):491–6. 5. Speiser PW, Arlt W, Auchus RJ, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2018;103 (11):4043–4088.