Lower body weight and BMI at birth were associated with early adiposity rebound in 21-hydroxylase deficiency patients

Abstract

21-HYDROXYLASE DEFICIENCY (21-OHD) isthe most common type of congenital adrenal hyperplasia (CAH). Its major clinical manifestations are adrenal crisis, virilization of external genitalia, short stature, and infertility due to adrenal androgen excess. A major part of the treatment for 21-OHD is glucocorticoid therapy, which reduces the excessive production of androgen and its metabolites by the adrenal gland [1][2][3].Obesity and metabolic syndrome during young adulthood are of serious concern for 21-OHD patients. Body mass index (BMI) is elevated in most 21-OHD patients [4,5] Abstract. 21-hydroxylase deficiency (21-OHD) is the most common type of congenital adrenal hyperplasia. In addition to the clinical problems caused by adrenal insufficiency and androgen excess, a risk for obesity and metabolic syndrome during young adulthood is a major ramification of the disease. Although glucocorticoid therapy is very likely to be one of the contributory factors, the precise causes of the metabolic status of adult 21-OHD patients remain to be clarified.Previously we reported that 21-OHD patients developed early onset AR, a condition which might create a risk for obesity and metabolic syndrome in adulthood. In order to elucidate the association between the onset of AR and factors during the fetal period to early infancy, we conducted a retrospective longitudinal analysis of 29 21-OHD patients (male: 14 cases, female: 15 cases, salt wasting type: 16, simple virilizing type: 13), who were identified by newborn screening and followed up at least until the age 10 years. Body size at birth, lower body weight, and lower BMI were found to precipitate the timing of AR. On the other hand, no significant association was observed between the timing of AR and sex, gestational age, treatment regimen (including cumulative dose of HDC), and disease severity (the type of the disease, the value of DHEA-S and 17-OHP). There are two points to consider: first, in 21-OHD patients treated with glucocorticoid substitution therapy, the risk for early AR cannot be reduced by adjusting the dose of glucocorticoid; second, fetal factors might affect the metabolic status of 21-OHD patients.Key words: 21-hydroxylase deficiency, Adiposity rebound, Glucocorticoid, Metabolic syndrome that adult 21-OHD patients tend to have metabolic syndrome [6,7]. Although the precise factors affecting the metabolic status of 21-OHD adults have not been identified, glucocorticoid therapy is thought to play some role [8,9]. 21-OHD patients require a supra-physiological dose of glucocorticoid in order to reduce the effects of androgen excess [10]. Previous reports including ours showed that the onset of adiposity rebound (AR), the point at which the BMI starts to increase after its nadir, occurred earlier in 21-OHD patients than in normal children [5,11]. Premature AR has been identified as one of the possible contributory factors in adult obesity and metabolic syndrome [9,7,[12][13][14][15][16]. We hypothesized that fetal and early infantile factors, including birth size...

Age at adiposity rebound in childhood is associated with PCOS diagnosis and obesity in adulthood—longitudinal analysis of BMI data from birth to age 46 in cases of PCOS

“…In general, there were no correlations between serum testosterone or FAI and timing of AR, and women with PCOS were hyperandrogenic compared with controls regardless of the timing of AR. Despite this finding, androgen levels during childhood have been shown to be associated with the timing of AR, since children with premature adrenarche or 21-hydroxylase deficiency do have early AR [28, 29]. Regarding 21-hydroxylase deficiency, one study hypothesized that low birth weight with concomitant excess androgen exposure during the fetal and perinatal periods may contribute to timing of AR, whereas in cases of premature adrenarche it is thought that early growth acceleration leads to obesity that may results into premature adrenarche [28, 29].…”

“…Despite this finding, androgen levels during childhood have been shown to be associated with the timing of AR, since children with premature adrenarche or 21-hydroxylase deficiency do have early AR [28, 29]. Regarding 21-hydroxylase deficiency, one study hypothesized that low birth weight with concomitant excess androgen exposure during the fetal and perinatal periods may contribute to timing of AR, whereas in cases of premature adrenarche it is thought that early growth acceleration leads to obesity that may results into premature adrenarche [28, 29]. To support this, previous studies have revealed high testosterone levels in obese adolescent girls [27], but unfortunately, data on serum testosterone levels in adolescence were not available in our study cohort.…”

Childhood obesity: rapid weight gain in early childhood and subsequent cardiometabolic risk

“…The benefits of CUG for later neurodevelopment favors the promotion of rapid growth in infants born preterm; however, CUG in infants born at term (normal or low birth weight for gestation) is likely to have adverse effects on long-term health ( 75 ). Children born with low birth weight or SGA have an increased risk for non-communicable diseases (NCDs) such as type 2 diabetes and cardiovascular disease later in life, as illustrated by the concept of Developmental Origins of Health and Disease (DOHaD) ( 76 , 77 , 78 , 79 , 80 ). Poor maternal nutritional status or smoking during pregnancy are major causes of intrauterine growth restriction ( 76 , 77 ).…”

Cardiovascular Health in Children and Adolescents With Congenital Adrenal Hyperplasia Due to 21-Hydroxilase Deficiency

“…Interestingly, adiposity rebound, consisting in the re-increase of BMI after its nadir, occurs significantly earlier in CAH patients than non-affected children, possibly predicting development of obesity (15, 34). In a recent study (35) on 29 classic CAH patients identified by neonatal screening and followed-up for at least 10 years, multivariate regression analysis identified lower BMI at birth as an independent predictor of early adiposity rebound, thus suggesting that early alterations in fetal life may predispose to the development of metabolic problems.…”