Hormone Research in Paediatrics最新文献

Introduction: Precocious puberty is defined as the appearance of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Central precocious puberty (CPP) is a rare condition that is diagnosed when premature activation of the hypothalamic-pituitary-gonadal axis is detected, in association with precocious breast development or testicular growth. Idiopathic CPP is historically considered to be the most common form, but in recent years defects in a small but growing number of genes regulating the timing of puberty have been identified in an increasing proportion of cases of CPP. Delta-like non-canonical Notch ligand 1 (DLK1) is understood to be one of the key genes involved in the etiology of CPP, although its mechanistic role is not yet fully understood.

Case presentation: We identified a novel de novo variant of DLK1 (c.835C>T; p.Gln279*) in an 8-year-old girl of Bangladeshi origin. She presented with an advanced Tanner staging of B4P4A2, significantly advanced bone age (BA, 13 years), a near-adult proportioned uterus, with a history of menarche at the age of 7.4 years. Diagnosis was confirmed by raised basal luteinizing hormone concentration. She was found to have truncal obesity associated with abnormal fasting insulin levels and mildly elevated cholesterol levels. These findings are consistent with previous literature describing an association between patients with DLK1 deficiency and an impaired metabolic profile. The patient was treated for 2 years with GnRH agonists with ongoing biochemical follow-up into adolescence.

Conclusion: This case illustrates the susceptibility to metabolic derangement for patients with mutations in DLK1 and the need for ongoing monitoring after puberty. Our summary of previously identified DLK1 variants and their metabolic consequences demonstrates the frequency of obesity, lipid abnormalities, and insulin dysregulation in this patient cohort in childhood and beyond. This knowledge can guide future clinical practice for patients with CPP patients due to DLK1 deficiency.

Introduction: Diabetic ketoacidosis (DKA) is the leading cause of mortality among youth with type 1 diabetes (T1D). Guidelines for DKA prevention exist; however, specific guidance about when to check ketones and how to manage youth using insulin pumps and automated insulin delivery (AID) systems is lacking.

Methods: A 35-item online survey exploring clinical ketone management practices for youth with T1D in the USA was distributed to diabetes healthcare professionals (HCPs). Survey responses, including multiple-choice and Likert scale questions, were summarized and rates of agreement and disagreement (Likert scale 4, 5 vs. 1, 2, 3) are reported.

Results: In total, 123 HCPs (51% physicians, 26% diabetes educators, 19% nurse practitioners) from 47 institutions completed the survey. Seventy percent worked at academic specialty centers. Ninety-seven percent reported >50% continuous glucose monitoring use in their clinic and 72% reported >50% insulin pump use. Although 79% reported having ketone management protocols, the level and duration of hyperglycemia at which ketone monitoring was advised ranged from >200 to 350 mg/dL and from 0 min to >6 h of duration. While 72% had distinct ketone management protocols for pump users, only 29% had specific protocols for AID. Sixty-two percent agreed that DKA due to infusion site failure was a significant problem in their practice, and 70% agreed there was a need to standardize ketone management guidelines.

Conclusions: The preventable nature and high incidence of DKA highlight the need to build consensus for clinical ketone management and to develop tools to facilitate management, especially as the use of diabetes technologies continues to increase.

Background: Type 1 diabetes (T1D) is more than an insulin-deficiency disease - it is an autoimmune disease, and the field is moving toward adopting disease-modifying immunotherapy as part of clinical care during T1D development.

Summary: Recent successful immunotherapies as well as therapies that missed the mark are reviewed. T cell-directed therapies may allow for the greatest preservation of β cell function but also come with more side effects. Anti-cytokine therapies are very promising but likely need chronic administration. Antigen-specific therapies while safe have not produced meaningful results. Most successful trials have been conducted in adolescents and adults with stage 3 T1D (clinical T1D) with preserved C-peptide (up to 60% more compared to placebo) demonstrated 1-2 years post treatment. HbA1c and total insulin dose are less likely to be significantly different between treated and placebo groups because most participants in studies are meeting glycemic targets and because of the heterogeneous nature of these measures. In the prevention space (delaying progression from stage 2 to stage 3 T1D), the outcome is more discrete, and a T cell-directed therapy, teplizumab, has received FDA approval. Even negative studies with promising mechanistic and safety profiles have added value.

Key messages: What is clear, a single administration or short course of an immunotherapy is unlikely to provide sustained freedom from exogenous insulin.

Introduction: Polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) are endocrine-disrupting chemicals (EDCs) that may have a combined effect on sex hormone levels in children. This study investigated the correlations between co-exposure to PAHs and HMs and levels of sex steroid hormones in children.

Methods: We employed the data from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016, including 1,167 participants aged 6-19 years. Sex hormone indicators include testosterone (TT), estradiol (E2), sex hormone-binding globulin (SHBG), free androgen index (FAI), and the TT/E2 ratio. Weighted multivariate linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were used to analyze the associations between co-exposure to PAHs and HMs and sex steroid hormone levels.

Results: Co-exposure to PAHs and HMs was associated with a 16.2% reduction (95% CI [-0.321, -0.004]) in SHBG level among prepubertal males and a 16% reduction (95% CI [-0.30, -0.03]) in E2 level among pubertal males by the WQS regression, and cadmium (Cd) and mercury (Hg) contributed the highest weight, respectively. In the Bayesian kernel machine regression (BKMR) model, co-exposure to PAHs and HMs was positively associated with TT/E2 in pubertal males and negatively correlated with FAI in pubertal females, and 1-hydroxypyrene (1-PYR) and Cd were the most important components, respectively.

Conclusions: Co-exposure to PAHs and HMs was associated with sex hormone levels in children. These findings highlight the necessity for preventing the effects of these chemicals on sex hormones.

Introduction: Pathogenic variants in the genes involved in the formation of thyroid tissue and thyroid hormone secretion have been reported to cause congenital hypothyroidism (CH) in some cases. This study aimed to evaluate the clinical and genetic findings of CH cases thought to be due to genetic variants.

Methods: The study included cases whose genetic analysis was performed in accordance with the Congenital Hypothyroidism: A 2020-2021 Consensus Guidelines Update Guidelines recommendations criteria and analyzed them using the next-generation sequencing panel.

Results: Sixty one Turkish patients from 45 families were included in the study. The overall frequency of variant detection was 37.7% (out of 45 families, 17 had a positive mutation). Segregation was carried out for all families with positive variants. Variants in the TPO gene are the most frequently encountered, and this situation was identified in 10 families. Variants followed this in the TSHR gene in 7 families, variants in the DUOX2 gene in 5 families, and two variants in the TG and NKX2-1 genes in 2 families each, which are six novel variants. Furthermore, among the NKX2-1 cases, one had thyroid involvement only, while the other had chorea only. We did not find differences between cases with detected mutations and mutation-negative cases regarding gender, neonatal/perinatal parameters, initial thyroid function values, and thyroid morphology.

Conclusion: In the current investigation, rare new variations in genes known to be related to CH were discovered, adding to the molecular genetic spectrum. When we compare the overall variant detection frequency, the selection criterion for genetic analysis based on the current guidelines is quite rational, considering the benefits and costs, on the other hand, present in new genes awaiting discovery. Also, TSHR mutations are likely to be common and may account for more than 5% of thyroid dysgenesis cases if we include nonfamilial thyroid dysgenesis.

Introduction: To address disparities in clinical research, we present strategies to optimize recruitment of underrepresented families into the Building the Evidence to Address Disparities in Type 1 Diabetes (BEAD-T1D) study.

Methods: A bilingual/bicultural Latino research assistant (RA) was hired to facilitate culturally congruent recruitment for pediatric type 1 diabetes families. The RA screened, approached, and consented families using their preferred language, time of contact, and answered personal concerns around research. Families were given the option to consent during outpatient clinic visits (in-person, or virtually via video/phone call) at a pace set by the parent/guardian to ensure understanding.

Results: Sixty-four families (Hispanic-65%, Non-Hispanic White [NHW]-17%, Non-Hispanic Black-1%, and Other-4%) were eligible. Of 49 approached, 32 consented (39 ± 7.9 years; female-81%; Hispanic-72%, NHW-28%, <50K income-69%, Spanish-speaking-50%). Clinic approaches were important to successful consent: 87% of the clinic approaches resulted in consent. Barriers to clinic approaches for RA included late/no response from clinicians, care team ending visit, and bandwidth/connectivity issues. Facilitators to clinic approaches included collaborative clinic care teams, flexible RA hours, and patient screening days in advance. We exceeded our recruitment goals for surveys (31/30), focus groups/interviews (26/20), and advisory board (22/10).

Conclusions: We identified that culturally and linguistically congruent staff, flexible recruitment practices, and prioritizing participant availability were solutions to recruit a diverse study cohort resulting exceeding recruitment goals. Cultural interpersonal relationships formed with families addressed barriers to research participation within and outside of the medical system. These strategies suggest equitable clinical trial recruitment is feasible in diabetes research.

Introduction: The COVID-19 pandemic necessitated worldwide lockdowns in 2020 and 2021, with restrictions on physical activity and changes in eating habits. The aim of this study was to investigate temporal trends in body mass index (BMI) and BMI Standard Deviation Score (SDS) in three international type 1 diabetes (T1D) registries between 2018 and 2021.

Methods: Data were extracted from DPV (Germany/Austria/Luxembourg/Switzerland), T1D Exchange Quality Improvement Collaborative (T1DX-QI, USA), and the Australasian Diabetes Data Network (ADDN, Australia/New Zealand). The period affected by the COVID-19 pandemic was defined as March to December 2020 and March to December 2021 and compared with the respective 9-month periods in 2018 and 2019. Estimated mean BMI (adults ≥19 years) and WHO BMI SDS (children and adolescents 5 to <19 years) were calculated, adjusted for sex, age, HbA1c, and diabetes duration. Adjusted mean proportions overweight (BMI ≥25 in adults or BMI SDS >1 in children and adolescents 5 to <19 years) and obese (BMI ≥30 kg/m2 or BMI SDS >2 in children and adolescents 5 to <19 years) were also calculated, adjusted for sex, age, HbA1c, and diabetes duration.

Results: The study population comprised: ADDN (n = 14,624, median age 15.7 years, 51% male); DPV (n = 62,732, 16.1 years, 53.3% male); and T1DX-QI (n = 22,942, 17.1 years, 52.1% male). In the DPV registry, BMI SDS in children and adolescents and BMI in adults increased consistently between 2018 and 2021 (p < 0.001). In ADDN and T1DX-QI, variable changes in BMI and BMI SDS were seen in adults and young people. Close to 50% of people in all registries were either overweight or obese. Proportions overweight remained relatively stable across the 4 years. The proportion of obesity increased in children 5 to <10 years.

Conclusions: A slight increase in BMI and BMI SDS observed before the pandemic continued during the pandemic years. The proportion of overweight and obesity was overall high. Healthy weight remains a priority for people with T1D.

Introduction: This survey investigates brain MRI practices for isolated GHD among Pediatric Endocrine Society (PES) members, focusing on gadolinium-based contrast agents (GBCAs) versus non-contrast MRI.

Methods: A 15-question survey was distributed to 1,553 PES members, capturing data on GBCA usage, non-contrast imaging access, and awareness of gadolinium retention.

Results: A total of 85% of respondents routinely order brain MRIs for isolated GHD, with 60% using GBCAs. Most respondents have access to high-resolution non-contrast imaging, though 54% are unaware of gadolinium retention risks.

Conclusion: High-resolution non-contrast MRI demonstrates diagnostic efficacy, suggesting a shift away from GBCAs in clinic practice for isolated GHD. The survey forms the basis to update PES guidelines in the evaluation of isolated GHD.