Postpartum Obesity Is Associated With Increases in Child Adiposity in Midchildhood in a Cohort of Black and Dominican Youth.

Background: Obesity disproportionately affects marginalized and low-income populations. Birth parent obesity from the prenatal period and childhood has been associated with child obesity. It is unknown whether prenatal or postnatal birth parent obesity has differential effects on subsequent changes in adiposity and metabolic health in children. Objectives: We evaluated how birth parent obesity 7 y after delivery was associated with child body composition changes and cardiometabolic health in midchildhood and further assessed the influence of the perinatal and postpartum period on associations. Methods: Black and Dominican pregnant individuals were enrolled, and dyads (n = 319) were followed up at child age 7 and 9 y. Measures included, height, weight, waist circumference (WC), and percent body fat (BF%). Multiple linear regression was used to relate postpartum weight status with child outcomes accounting for attrition, and a series of secondary analyses were conducted with additional adjustment for perinatal weight status, gestational weight gain (GWG), and/or long-term weight retention to evaluate how these factors influenced associations. Results: Almost one-quarter (23%) of birth parents and 24.1% children were classified with obesity at child age 7 y, while at 9 y, 30% of children had obesity. Birth parent obesity at child age 7 y was associated with greater changes, from ages 7 to 9 y, in child BMI z-score (ß: 0.13; 95% CI: 0.02, 0.24) and BF% (ß: 1.15; 95% CI: 0.22, 2.09) but not obesity at age 9 y. All observed associations crossed the null after additional adjustment for prenatal factors. Conclusions: Birth parent obesity at 7-y postpartum is associated with greater gains in child BMI z-score and BF% in midchildhood. These associations diminish after accounting for prenatal size, suggesting a lasting impact of the perinatal environment and that interventions supporting families from the prenatal period through childhood are needed.

Inverse associations of cord blood mitochondrial DNA copy number with childhood adiposity.

OBJECTIVE: The objective of this study was to examine associations between umbilical cord mitochondrial DNA copy number (mtDNAcn) and adiposity across childhood. METHODS: In a prospective birth cohort of Dominican and African American children from New York City, New York (1998-2006), mtDNAcn was measured in cord blood. Children (N = 336) were evaluated for their height, weight, and bioimpedance at age 5, 7, 9, and 11 years. We used linear mixed-effects models to assess associations of mtDNAcn tertiles in cord blood with child BMI, BMI z scores, fat mass index, and body fat percentage. Latent class growth models and interactions between mtDNAcn and child age or child age2 were used to assess associations between age and adiposity trajectories. RESULTS: BMI was, on average, 1.5 kg/m2 higher (95% CI: 0.58, 2.5) in individuals with mtDNAcn in the low- compared with the middle-mtDNAcn tertile. Results were similar for BMI z score, fat mass index, and body fat percentage. Moreover, children in the low-mtDNAcn group had increased odds of being in an "increasing" or "high-stable" adiposity class. CONCLUSIONS: Lower mtDNAcn at birth may predict greater childhood adiposity, highlighting the potential key role of perinatal mitochondrial function in adiposity during development.

Reference ranges for body composition indices by dual energy X-ray absorptiometry from the Bone Mineral Density in Childhood Study Cohort.

BACKGROUND: Body composition assessment aids evaluation of energy stores and the impact of diseases and interventions on child growth. Current United States pediatric reference ranges from the National Health and Nutrition Examination Survey (NHANES) include 20% of children with obesity, body mass index of ≥95th percentile. OBJECTIVES: This study aimed to develop dual energy X-ray absorptiometry (DXA) based reference ranges in a diverse cohort with low-obesity prevalence from the Bone Mineral Density in Childhood Study (BMDCS). METHODS: This is a secondary analysis of a longitudinal, prospective, observational cohort. Healthy children (height and BMI within 3rd to 97th percentiles, ages 5-19 y at enrollment), from 5 United States centers were measured annually for ≤7 visits. Whole body scans were acquired using Hologic scanners. A subsample underwent repeat measurements to determine precision. We generated reference ranges for appendicular and total lean soft tissue mass index (LSTM Index), fat mass index (FMI), and other body composition measures. Resulting curves were compared to NHANES and across subgroups. Sex and age-specific equations were developed to adjust body composition Z-scores for height Z score. RESULTS: We obtained 9846 scans of 2011 participants (51% female, 22% Black, 17% Hispanic, 48% White, 7% Asian/Pacific Islander, and 6% with obesity). Precision (percent coefficient of variation) ranged from 0.7% to 1.96%. Median and-2 standard deviation curves for BMDCS and NHANES were similar, but NHANES +2 standard deviation LSTM Index and FMI curves were distinctly greater than the respective BMDCS curves. Subgroup differences were more extreme for appendicular LSTM Index-Z (mean ± SD: Asian -0.52 ± 0.93 compared with Black 0.77 ± 0.87) than for FMI-Z (Hispanic 0.29 ± 0.98 compared with Black -0.14 ± 1.1) and were smaller for Z-scores adjusted for height Z-score. CONCLUSIONS: These reference ranges add to sparse normative data regarding body composition in children and adolescents and are based on a cohort with an obesity prevalence similar to current BMI charts. Awareness of subgroup differences aids in interpreting results.

The Relationship Between Metabolic Comorbidities and Post-surgical Weight Loss Outcomes in Adolescents Undergoing Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Little is known about the relationship between metabolic factors and weight loss success in adolescents undergoing bariatric surgery. METHODS: The objective of this study was to assess if baseline metabolic characteristics associate with weight loss in adolescents undergoing laparoscopic sleeve gastrectomy. A retrospective study was conducted in a comprehensive adolescent bariatric surgery center of 151 subjects (34 male, 117 female). Anthropometric measurements and metabolic factors including blood pressure, fasting glucose, HbA1c, Metabolic Syndrome (MeS), liver function, triglycerides, and waist circumference were collected at one pre-surgical visit, and at 6 and/or 12 months post-laparoscopic sleeve gastrectomy. Weight loss was compared between subjects with normal or abnormal baseline metabolic factors. Absolute BMI change was used to measure successful weight loss. RESULTS: Higher baseline systolic blood pressure (SBP) was associated with greater weight loss as measured by body mass index (BMI) change and BMI standard deviation score (BMI-SDS) change at 6 and 12 months. Those patients in the 6-month follow up group with an abnormal hemoglobin A1C (HbA1c) at baseline had significantly more weight loss as measured by BMI-SDS. None of the other parameters, including fasting glucose, Metabolic Syndrome (MeS), liver function, triglycerides and waist circumference showed a predictive relationship. DISCUSSION/CONCLUSION: Elevated SBP and HbA1c in adolescents with morbid obesity may reflect a population more likely to achieve successful weight loss, and thus, may be a good target for bariatric surgery, specifically laparoscopic sleeve gastrectomy, as an intervention for severe obesity. An assessment of behavioral differences in patients with and without elevated BP and HbA1c might explain the mechanism for the improved weight loss.

A Brief History of the Pediatric Endocrine Society (PES).

The Pediatric Endocrine Society (PES) was initially established in 1972 as the Lawson Wilkins Pediatric Endocrine Society (LWPES), by some of Wilkins' former fellows. As the society grew from its 37 founding members and Dr. Wilkins' influence faded, the name of the society was changed in 2010 and now counts about 1,500 members, mostly from the US and Canada. Pediatric endocrine training programs headed by (LW)PES members have welcomed fellows from throughout the world, many of whom have gone on to leadership positions in their home countries. Starting in 1981, the (LW)PES has collaborated with pediatric endocrine societies around the world in quadrennial meetings, fostering collaborations, transfer of ideas, devising joint practice guidelines, and enjoying one another's fellowship and counsel. The PES presently has committees and special interest groups concerned with all aspects of pediatric endocrinology, assuring that our clinical and academic resources reflect both breadth and depth. To celebrate our 50th anniversary, selected members have written the historical manuscripts featured in this special issue of Hormone Research in Pediatrics. These historical reviews delve into the origins of our specialty, sometimes deep into antiquity, provide useful background information, and illustrate the kinds of intellectual struggles that have led to the development of contemporary pediatric endocrinology, worldwide.

History of Polycystic Ovary Syndrome, Premature Adrenarche, and Hyperandrogenism in Pediatric Endocrinology.

Descriptions of probable PCOS can be found in ancient Roman writings and in Renaissance art. Attention to domesticated animal reproduction led ancient observers to understand the role of the testes in male phenotypes, proven experimentally by testicular transplantation (in chickens) in 1849. Testosterone was isolated and its structure determined in the 1930s, but the multiple pathways of androgen synthesis have only been delineated recently. Adrenarche as an event separate from puberty was described in 1937, but the mechanism(s) triggering its onset remains unclear, although most work points to intraadrenal events. The identification of 11-ketotestosterone as the principal adrenal androgen is very recent (2018). Definitions of PCOS have evolved with the elucidation of its complex biology. PCOS is now recognized as a complex disorder characterized by irregular menses and hyperandrogenism often associated with infertility; its prevalence may be as high as 20% of reproductive age women. Work in the 1980s associated premature exaggerated adrenarche with PCOS, linking the adrenal to an "ovarian" syndrome. Obesity has long been noted in many patients with PCOS, and associated insulin resistance was noted in the 1980s, possibly associated with fetal developmental events such as low birth weight, but the mechanistic link between carbohydrate metabolism and hyperandrogenism remains unclear, despite intensive investigation. Genome-wide association studies have identified apparently associated genes, but mechanistic links are apparent for only some of these. Adrenarche, PCOS, and adrenal and ovarian hyperandrogenism remain very active areas of clinical and basic research.

Prenatal exposure to polybrominated diphenyl ethers and BMI Z-scores from 5 to 14 years.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are flame-retardant compounds widely used in household products until phase out in 2004. PBDEs are endocrine disruptors and are suggested to influence signaling related to weight control. Prenatal exposures to PBDEs may alter childhood adiposity, yet few studies have examined these associations in human populations. METHODS: Data were collected from a birth cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners BDE-47, - 99, - 100, and - 153 were measured in cord plasma (ng/µL) and dichotomized into low (< 80th percentile) and high (>80th percentile) exposure categories. Height and weight were collected at ages 5, 7, 9, 11, and an ancillary visit from 8 to 14 years (n = 289). Mixed-effects models with random intercepts for participant were used to assess associations between concentrations of individual PBDE congeners or the PBDE sum and child BMI z-scores (BMIz). To assess associations between PBDEs and the change in BMIz over time, models including interactions between PBDE categories and child age and (child age)2 were fit. Quantile g-computation was used to investigate associations between BMIz and the total PBDE mixture. Models were adjusted for baseline maternal covariates: ethnicity, age, education, parity, partnership status, and receipt of public assistance, and child covariates: child sex and cord cholesterol and triglycerides. RESULTS: The prevalence of children with obesity at age 5 was 24.2% and increased to 30% at age 11. Neither cord levels of individual PBDEs nor the total PBDE mixture were associated with overall BMIz in childhood. The changes in BMIz across childhood were not different between children with low or high PBDEs. Results were similar when adjusting for postnatal PBDE exposures. CONCLUSIONS: Prenatal PBDE exposures were not associated with child growth trajectories in a cohort of Dominican and African American children.

Ovarian follicle count by magnetic resonance imaging is greater in adolescents and young adults with polycystic ovary syndrome than in controls.

Objective: To use magnetic resonance imaging (MRI) to quantify the follicle number per ovary (FNPO) using biplanar measurements and determine the ovarian volume (OV) using three-dimensional measurements in adolescents and young adults with polycystic ovary syndrome (PCOS) and controls and compare the differences between these groups; to examine the relationships between FNPO and OV and metabolic markers associated with PCOS; to compare OV obtained by use of MRI and ultrasound between young patients with PCOS and controls. Design: Cross-sectional study. Setting: Outpatient within a major medical center in New York City. Patients: Adolescent girls and young women aged 13-25 years with PCOS (n = 16) and body mass index-, age-, and ethnicity-comparable control subjects (n = 15). Interventions: None. Main Outcome Measures: The OV and FNPO by use of MRI, OV by use of transabdominal pelvic ultrasound, anthropometric measurements, and biochemical and hormonal evaluation. Results: The FNPO was higher in participants with PCOS (23.7 ± 4.6 follicles) than in controls (15.2 ± 4 follicles) when adjusted for menstrual age. The OV by use of ultrasound was higher in participants with PCOS (11.7 ± 5.6 mL) than in controls (8.1 ± 3.4 mL); however, OV by use of MRI did not differ between the groups. The OV by use of MRI and ultrasound correlated in participants with PCOS (r = 0.62) but not in controls. Conclusions: Our results are in line with prior studies showing that FNPO may be a more sensitive measure of polycystic ovary morphology than OV. The results of this study support the use of ovarian k, a promising diagnostic tool for PCOS, in young patients.

Trabecular Bone Score Reference Values for Children and Adolescents According to Age, Sex, and Ancestry.

Trabecular bone score (TBS) is used for fracture prediction in adults, but its utility in children is limited by absence of appropriate reference values. We aimed to develop reference ranges for TBS by age, sex, and population ancestry for youth ages 5 to 20 years. We also investigated the association between height, body mass index (BMI), and TBS, agreement between TBS and lumbar spine areal bone mineral density (aBMD) and bone mineral apparent density (BMAD) Z-scores, tracking of TBS Z-scores over time, and precision of TBS measurements. We performed secondary analysis of spine dual-energy X-ray absorptiometry (DXA) scans from the Bone Mineral Density in Childhood Study (BMDCS), a mixed longitudinal cohort of healthy children (n = 2014) evaluated at five US centers. TBS was derived using a dedicated TBS algorithm accounting for tissue thickness rather than BMI. TBS increased only during ages corresponding to pubertal development with an earlier increase in females than males. There were no differences in TBS between African Americans and non-African Americans. We provide sex-specific TBS reference ranges and LMS values for calculation of TBS Z-scores by age and means and SD for calculation of Z-scores by pubertal stage. TBS Z-scores were positively associated with height Z-scores at some ages. TBS Z-scores explained only 27% and 17% of the variance of spine aBMD and BMAD Z-scores. Tracking of TBS Z-scores over 6 years was lower (r = 0.47) than for aBMD or BMAD Z-scores (r = 0.74 to 0.79), and precision error of TBS (2.87%) was greater than for aBMD (0.85%) and BMAD (1.22%). In sum, TBS Z-scores provide information distinct from spine aBMD and BMAD Z-scores. Our robust reference ranges for TBS in a well-characterized pediatric cohort and precision error estimates provide essential tools for clinical assessment using TBS and determination of its value in predicting bone fragility in childhood and adolescence. © 2022 American Society for Bone and Mineral Research (ASBMR).

Profile of Daughters and Sisters of Women With Polycystic Ovary Syndrome: The Role of Proband's Glucose Tolerance.

CONTEXT: First-degree relatives of women with polycystic ovary syndrome (PCOS) present hormonal and metabolic alterations compared to girls unrelated to PCOS. It is unknown whether glucose intolerance in the PCOS proband confers a more severe metabolic predisposition on their first-degree relatives. OBJECTIVE: To determine whether glucose tolerance status in women with PCOS is associated with worsened glucose metabolism and sex hormone levels in their peripubertal daughters or sisters. DESIGN: Cross-sectional study. SETTING: Seven academic centers in North America, South America, and Europe. PATIENTS: Sixty-four pairs of women with PCOS and their daughters or younger sisters aged between 8 and 14 years were recruited. Twenty-five mothers or older sisters with PCOS were glucose intolerant (GI) and 39 were normal glucose tolerant (NGT). MAIN OUTCOME MEASURES: Beta-cell function estimated by the insulin secretion-sensitivity index-2 (ISSI-2) during an oral glucose tolerance test and by the disposition index during a frequently sampled IV glucose tolerance test. Free testosterone and 17-hydroxyprogesterone (17-OHP) levels. RESULTS: Being related to a GI PCOS proband was associated with a lower ISSI-2 (P-value = 0.032) after adjusting for ethnicity, body mass index z-score, and pubertal stage. They also had higher free testosterone (P-value = 0.011) and 17-OHP levels compared to girls with an NGT proband, the latter becoming significant after adjusting for confounders (P-value = 0.040). CONCLUSIONS: Compared to first-degree female relatives of women with PCOS and NGT, first-degree relatives of women with PCOS and GI display lower beta-cell function and hyperandrogenemia, putting them at higher risk of GI and PCOS development.

Disorders of Puberty in Girls.

Puberty is the process through which reproductive competence is achieved and comprises gonadarche and adrenarche. Breast development is the initial physical finding of pubertal onset in girls and typically occurs between 8 and 13 years. Menarche normally occurs 2 to 3 years after the onset of breast development. Pubertal onset is controlled by the gonadotropin-releasing hormone pulse generator in the hypothalamus; however, environmental factors such as alterations in energy balance and exposure to endocrine-disrupting chemicals can alter the timing of pubertal onset. Improvement in nutritional and socioeconomic conditions over the past two centuries has been associated with a secular trend in earlier pubertal onset. Precocious puberty is defined as onset of breast development prior to 8 years and can be central or peripheral. Delayed puberty can be hypogonadotropic or hypergonadotropic and is defined as lack of breast development by 13 years or lack of menarche by 16 years. Both precocious and delayed puberty may have negative effects on self-esteem, potentially leading to psychosocial stress. Patients who present with pubertal differences require a comprehensive assessment to determine the underlying etiology and to devise an effective treatment plan.

Salivary microbiome differences in prepubertal children with and without adrenal androgen excess.

BACKGROUND: Premature adrenarche is a condition of childhood adrenal androgen excess (AAE) in the absence of gonadotropin-dependent puberty, and has been linked to insulin resistance and progression to metabolic syndrome. Microbial dysbiosis is associated with progression of inflammatory states and chronic diseases. Here, we aimed to examine the salivary microbiomes of children with AAE and assess the relationship with adrenal androgens and metabolic parameters. METHODS: In a prospective cross-sectional study of children with AAE and healthy controls, adrenal and metabolic parameters were characterized and salivary microbiome was profiled using V3-V4 16S rDNA gene amplicon sequencing. RESULTS: There was increased α-diversity in AAE (5 M, 15 F) compared to controls (3 M, 8 F), with positive correlation of 11OHA4, 11KA4, testosterone, androstenedione, DHEA, and DHEAS. Subanalyses showed increased α-diversity in both overweight/obese AAE and normal weight AAE compared to normal weight controls. Genus Peptostreptococcus, Veillonella, and Streptococcus salivarius were increased in normal weight AAE. Genus Prevotella, Abiotrophia, and Neisseria were increased in overweight/obese AAE. CONCLUSION: These pilot data demonstrate differences in salivary microbiome profiles of children with and without AAE. Further studies are needed to assess the causal relationships between adrenal androgens, metabolic dysfunction, and salivary microbiome composition. IMPACT: This study is the first to report the salivary microbiome of prepubertal children with adrenal androgen excess (AAE). α-Diversity is increased in the salivary microbiome of children with AAE independent of weight status, and in this study cohort several serum androgens are positively associated with α-diversity. Several taxa that have been associated with periodontal disease and inflammation are found to be significantly increased in AAE.

CYP11B1 variants influence skeletal maturation via alternative splicing.

We performed genome-wide association study meta-analysis to identify genetic determinants of skeletal age (SA) deviating in multiple growth disorders. The joint meta-analysis (N = 4557) in two multiethnic cohorts of school-aged children identified one locus, CYP11B1 (expression confined to the adrenal gland), robustly associated with SA (rs6471570-A; ß = 0.14; P = 6.2 × 10-12). rs6410 (a synonymous variant in the first exon of CYP11B1 in high LD with rs6471570), was prioritized for functional follow-up being second most significant and the one closest to the first intron-exon boundary. In 208 adrenal RNA-seq samples from GTEx, C-allele of rs6410 was associated with intron 3 retention (P = 8.11 × 10-40), exon 4 inclusion (P = 4.29 × 10-34), and decreased exon 3 and 5 splicing (P = 7.85 × 10-43), replicated using RT-PCR in 15 adrenal samples. As CYP11B1 encodes 11-ß-hydroxylase, involved in adrenal glucocorticoid and mineralocorticoid biosynthesis, our findings highlight the role of adrenal steroidogenesis in SA in healthy children, suggesting alternative splicing as a likely underlying mechanism.

Genome-wide association study implicates novel loci and reveals candidate effector genes for longitudinal pediatric bone accrual.

BACKGROUND: Bone accrual impacts lifelong skeletal health, but genetic discovery has been primarily limited to cross-sectional study designs and hampered by uncertainty about target effector genes. Here, we capture this dynamic phenotype by modeling longitudinal bone accrual across 11,000 bone scans in a cohort of healthy children and adolescents, followed by genome-wide association studies (GWAS) and variant-to-gene mapping with functional follow-up. RESULTS: We identify 40 loci, 35 not previously reported, with various degrees of supportive evidence, half residing in topological associated domains harboring known bone genes. Of several loci potentially associated with later-life fracture risk, a candidate SNP lookup provides the most compelling evidence for rs11195210 (SMC3). Variant-to-gene mapping combining ATAC-seq to assay open chromatin with high-resolution promoter-focused Capture C identifies contacts between GWAS loci and nearby gene promoters. siRNA knockdown of gene expression supports the putative effector gene at three specific loci in two osteoblast cell models. Finally, using CRISPR-Cas9 genome editing, we confirm that the immediate genomic region harboring the putative causal SNP influences PRPF38A expression, a location which is predicted to coincide with a set of binding sites for relevant transcription factors. CONCLUSIONS: Using a new longitudinal approach, we expand the number of genetic loci putatively associated with pediatric bone gain. Functional follow-up in appropriate cell models finds novel candidate genes impacting bone accrual. Our data also raise the possibility that the cell fate decision between osteogenic and adipogenic lineages is important in normal bone accrual.

The effects of adolescent laparoscopic adjustable gastric band and sleeve gastrectomy on markers of bone health and bone turnover.

25-hydroxy vitamin D (25 OHD) deficiency and secondary hyperparathyroidism have been seen after metabolic and bariatric surgery, but data are lacking on the bone health outcomes of adolescent sleeve gastrectomy (SG). The purpose of this study was to examine bone-related nutrition after SG, compared to laparoscopic adjustable gastric band (LAGB), and trend bone turnover markers following SG. This is an observational study of 197 adolescents who underwent LAGB (n = 98) or SG (n = 99). Bone health labs were collected at baseline and 6 and/or 12 months after LAGB or SG, with additional analysis of bone turnover markers in the SG group. Calcium and 25 OHD levels increased at 6 and 12 months after LAGB and SG, with no difference between the surgeries. Parathyroid hormone levels decreased only in the SG group. SG patients had increased osteocalcin and carboxy-terminal cross-linking telopeptide of type 1 collagen (CTX) at 6 and 12 months post-SG, although CTX decreased between 6 and 12 months. Excess weight loss at 6 months predicted the rise in CTX, but the changes in osteocalcin and CTX could not be attributed to 25 OHD deficiency, hypocalcemia or hyperparathyroidism. Patients had improved 25 OHD levels post-surgery, which may be secondary to stringent vitamin supplementation guidelines. However, there were marked increases in bone turnover markers following SG. More studies are needed to evaluate the effects of SG on adolescent bone health and to correlate the early changes in bone turnover with bone mineral density and fracture risk.

Intermachine differences in DXA measurements vary by skeletal site, and impact the assessment of low bone density in children.

BACKGROUND: Bone mineral content (BMC) and areal-bone mineral density (aBMD) measurements of the lumbar spine (LS) and whole body less head (WBLH) by dual energy X-ray absorptiometry (DXA) are recommended for bone health assessment in children. Intermachine differences were not considered previously in formulating these recommendations. METHODOLOGY: DXA measurements of the LS, WBLH, total hip, femoral neck and distal 1/3 radius from the Bone Mineral Density in Childhood Study were examined. Healthy children, ages 6 to 16 years, from five clinical centers participated. The same spine, whole body, and femur phantoms were measured on each Center's DXA machine. Percentage of individuals with low BMC or aBMD (Z-score < -1.5) was determined. Clinical center differences were evaluated by analysis of covariance adjusting for height and BMI Z-score, calcium intake, physical activity, Tanner stage and bone age. Logistic regression assessed odds of low BMC or aBMD across clinical centers. RESULTS: Significant differences among Clinical Centers (p < 0.05) were evident in adjusted mean BMC and aBMD Z-scores (n = 1503) for all skeletal sites. WBLH BMC and aBMD Z-scores had the greatest range across centers (-0.13 to 0.24, and -0.17 to 0.56, respectively). The percentage of children with Z-scores less than -1.5 varied among Clinical Centers from 1.9 [95%CI 0.8, 4.5] to 8.1 [95%CI 5.7, 11.3] for WBLH BMC, 1.1 [95%CI 0.4, 3.5] to 6.3 [95%CI 3.8, 10.1] for WBLH aBMD, and from 4.4 [95%CI 2.8, 7.0] to 12.6 [95%CI 9.3, 16.9] for distal 1/3 radius aBMD. For each skeletal site except total hip aBMD and femoral neck BMC, at least one center had significantly lower odds of low bone density. CONCLUSIONS: By design, our reference ranges capture intermachine variability. Most clinical centers don't know where their machine falls within the range of intermachine variability, and this may affect diagnosis of children evaluated for conditions that threaten bone health. Total hip scans showed the least, and whole body scans showed the most intermachine variability. Pediatric bone health assessment recommendations should recognize intermachine differences and address this important issue.

Update on adrenarche.

PURPOSE OF REVIEW: Adrenarche is the pubertal maturation of the innermost zone of the adrenal cortex, the zona reticularis. The onset of adrenarche occurs between 6 and 8 years of age when dehydroepiandrosterone sulfate (DHEAS) concentrations increase. This review provides an update on adrenal steroidogenesis and the differential diagnosis of premature development of pubic hair. RECENT FINDINGS: The complexity of adrenal steroidogenesis has increased with recognition of the alternative 'backdoor pathway' and the 11-oxo-androgens pathways. Traditionally, sulfated steroids such as DHEAS have been considered to be inactive metabolites. Recent data suggest that intracellular sulfated steroids may function as tissue-specific intracrine hormones particularly in the tissues expressing steroid sulfatases such as ovaries, testes, and placenta. SUMMARY: The physiologic mechanisms governing the onset of adrenarche remain unclear. To date, no validated regulatory feedback mechanism has been identified for adrenal C19 steroid secretion. Available data indicate that for most children, premature adrenarche is a benign variation of development and a diagnosis of exclusion. Patients with premature adrenarche tend to have higher BMI values. Yet, despite greater knowledge about C19 steroids and zona reticularis function, much remains to be learned about adrenarche.