Hormone Research in Paediatrics最新文献

In the article by Bayrak Demirel et al. entitled "Thyrotoxic Hypokalemic Periodic Paralysis Induced by High-Dose Insulin in an Adolescent Male with Type 1 Diabetes Mellitus" [Horm Res Paediatr. 2024, DOI: 10.1159/000543329] the license was incorrect, and it has been changed from CCC to CC BY-NC 4.0.

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.

Introduction: Managing exercise remains challenging for adolescent athletes with type 1 diabetes (T1D), especially in contact sports. Even the use of hybrid closed loops can cause problems due to the need to disconnect the pump during some training or competitions. This study evaluated the efficacy of a novel protocol for the use of an advanced hybrid closed-loop system in adolescent football players with T1D during a sports camp.

Methods: Eleven boys aged 14.9 years (25-75th percentile: 14-15.5), with a diabetes duration of 5.7 years (5.2-7) and regular training schedules in junior football leagues, participated in the study. They started AHCL (MiniMed780G, Medtronic) therapy a month before a week-long sports camp and were observed during the sports camp and the preceding week. Daily camp activities included two 1.5-h training sessions. Protocol included a 90-min temporary target of 150 mg/dL before and insulin pump disconnection during training. Physical activity was tracked using wGT3X-BT Actigraph monitors.

Results: The camp provided conditions of demanding physical activity (6.6 [6-6.9] h/day of moderate-to-vigorous intensity). After starting AHCL, the average participant time spent in the target glucose range (70-180 mg/dL) was 79.34 ± 8.46%, and no significant change was observed during the camp (mean difference +0.79 ± 8.24%, p = 0.7581). Median glucose levels dropped by 10.91 ± 12.08 mg/dL (p = 0.0134), and time in the tight target range increased by 11.41 ± 11.60% (p = 0.0008) without increasing the time below range (<70 mg/dL) or glycemic variability. During the camp, daily insulin dose and basal/bolus ratio remained comparable with baseline, but the relative amount of automated bolus insulin decreased by 14.24 ± 4.65% (p < 0.0001).

Conclusion: The predefined regimen, including a temporary target before and disconnection of AHCL during football training, was safe and may provide satisfactory glucose control in active adolescents with T1D. This protocol could be adapted for use in other intensive contact sports.

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: 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.

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: 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: Severe childhood obesity can be caused by pathogenic variants in several genes involved in monogenic and syndromic obesity. Recently, heterozygous variants in pleckstrin homology domain interacting protein (PHIP) have been identified in patients with obesity as part of Chung-Jansen syndrome.

Case presentation: The index patient is a 5-year-old boy with severe obesity since 1 year of age, developmental delay, facial dysmorphism, and behavior problems. Whole-exome sequencing identified a novel missense variant in PHIP (c.3182C>A, p.Ala1061Glu) in the index patient. Further genetic testing in family members revealed segregation of the same PHIP variant in the brother and mother, who both presented with severe childhood obesity and developmental delay or learning difficulties. The PHIP missense variant was predicted pathogenic by multiple in silico tools and affects a highly conserved residue.

Conclusion: Early-onset obesity may be monogenic. Our finding expands the spectrum of disease-causing variants in PHIP and demonstrates variable intrafamilial clinical expressivity and severity. Screening for PHIP variants should be included in genetic testing in patients with severe early-onset obesity.

Introduction: Individuals with differences of sex development (DSD) experience complex, often competing, medical and psychosocial challenges surrounding fertility. The study aimed to characterize how "success" in fertility-related care is conceptualized and attained among individuals with a DSD, their parents or caregivers, healthcare providers, and other stakeholders.

Methods: As part of a larger study, DSD stakeholders (n = 110) participated in semi-structured interviews covering the clinical care of patients with DSD. Primary questions included "What is a successful outcome in DSD care?" and "How do you achieve it?" with fertility as either a spontaneous or suggested topic of discussion. Transcripts were analyzed utilizing a phenomenological approach. This analysis focuses on the extracted themes related to fertility.

Results: Fertility was discussed by 19/24 individuals with DSD, 12/19 parents or caregivers, 35/37 healthcare providers, and 19/30 other stakeholders. Components of successful fertility-related care included (1) specific discussions surrounding the relationship between DSD and fertility potential, options for fertility preservation, and options for non-biologic parenthood; (2) early and repeated introduction of these topics; and (3) consideration of age, developmental maturity, and cultural context on decisions around fertility. Challenges included the lack of fertility outcome data in this population and the irreversibility of gonadectomy. Trade-offs identified included anatomic typicality versus function, fertility preservation versus cancer risk reduction, and balancing the different priorities of stakeholders.

Discussion/conclusions: A wide range of DSD stakeholders highlighted the importance of addressing fertility concerns in achieving favorable outcomes for individuals with DSD. These stakeholder perspectives should inform fertility-related education, shared decision-making processes, and clinical care.

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.