Hormone Research in Paediatrics最新文献

Introduction: The early onset of pubic hair (premature pubarche [PP]) with or without adult body odor is a common reason for referral to pediatric endocrine clinics. Most children have premature adrenarche (PA), a benign variation of pubertal development, yet extensive laboratory evaluations are often performed due to concern for pathology. We aimed to determine the prevalence of adrenal pathology in children referred for PP and describe clinical characteristics of those with pathologic findings.

Methods: We performed a retrospective chart review of children referred for PP between January 2015 and December 2024.

Results: Of 1,160 children, six (0.52%) had adrenal pathology, all of whom were diagnosed with congenital adrenal hyperplasia. Age at presentation did not differ between the PA and pathology groups. There was a trend toward lower mean body mass index z-scores in those with pathology. Males comprised 83% of the pathology group compared with 22% of the PA group.

Conclusions: Adrenal pathology among children referred for PP is exceedingly rare. Routine laboratory testing in the absence of additional signs of androgen exposure is not warranted.

Introduction: Hypogonadotropic hypogonadism (HH) is characterized by insufficient gonadotropin and testosterone secretion, resulting in failure of pubertal development. This study compared the efficacy and safety of gonadotropin therapy and testosterone replacement therapy (TRT) for pubertal induction in adolescent male patients with HH.

Methods: This retrospective cohort study included 70 male patients with HH aged <18 years who were treated at a single tertiary medical center between November 2005 and December 2023. Diagnosis was based on clinical presentation, prepubertal hormone levels, and genetic evaluation. The patients received gonadotropins (n = 56) or TRT (n = 14) and were evaluated at 6-month intervals for up to 36 months.

Results: Serum testosterone levels increased significantly in both groups, with a greater rise observed in the TRT group (from 5.2 to 283.0 ng/dL in the gonadotropin group and from 5.2 to 527.5 ng/dL in the TRT group; overall p < 0.05). Height standard deviation scores improved significantly in both groups, without significant intergroup differences. Stretched penile length also increased significantly in both groups. Testicular volume increased significantly only in the gonadotropin group. Sperm were detected in 72.0% (18/25) of the patients in the gonadotropin group. In the TRT group, two patients underwent semen analysis, wherein sperm were detected. Semen analyses in both groups were performed only after completing pubertal induction and patients reached ≥19 years of age. Both patients undergoing TRT, wherein sperm were detected, received short-term gonadotropin administration in adulthood prior to testing.

Conclusion: Gonadotropin therapy and TRT were both effective and safe for pubertal induction in adolescent male patients with HH. Using TRT, a steeper increase in serum testosterone levels was achieved, whereas gonadotropin therapy uniquely promoted testicular growth, emphasizing the importance of individualized treatment strategies and long-term follow-up to optimize clinical outcomes and preserve fertility potential.

Introduction: In healthy adolescents, there is significant interindividual variation in the dynamics of pubertal growth and in the timing and progression of physical changes of puberty. Our aim was to explore the relationship between pubertal growth and pubertal maturation through an analysis of data from a longitudinal growth study.

Methods: The Edinburgh growth study included healthy children born between 1972 and 1976 with a birth weight of >2.5 kg. Anthropometric measurements and Tanner staging were undertaken twice a year. Total pubertal growth (TPG) was quantified using the QEPS growth model, which generates an individual growth curve from birth length to adult height (AH).

Results: A total of 157 adolescents were included in analysis (89 boys, 68 girls). In girls, later age at reaching all the stages of breast maturation (B2-B5) was correlated with smaller TPG. Correlation coefficient between B3 and TPG was -0.64, p < 0.01. However, there was no correlation with AH (coefficient 0.15, p = 0.24). In boys, later age at reaching the later stages of external genitalia maturation (G4-G5) was correlated with smaller TPG. G4 was negatively correlated with TPG (-0.24, p < 0.04) but not with AH (0.02, p = 0.86).

Conclusion: We found that the magnitude of the pubertal growth spurt was linked with the age at reaching Tanner landmarks of puberty in girls and boys; however, there was no association between the timing of these landmarks and AH. This new knowledge can provide reassurance for healthy children that the normal variation of pubertal timing does not have a significant influence on expected AH.

Introduction: Short stature is a common clinical feature of Turner syndrome (TS) and Noonan syndrome (NS). Growth hormone (GH) treatment increases height in patients with TS and NS. We aimed to assess treatment patterns and costs in a real-world setting of GH-treated patients with TS and NS in the USA.

Methods: Patients with TS (aged 4 to <14 years) or NS (aged ≤18 years) were included in this retrospective analysis using the Komodo Health claims database. The study period from January 1, 2016, to September 30, 2022, included ≥6 months pre-index (baseline) and ≥1 year post-index (follow-up); the index date was the first (TS) or latest of two visits (NS) with diagnostic coding for the condition. Data were analyzed descriptively.

Results: Among 2,530 patients with TS (mean age [SD] 8.4 [3.0] years) and 1,119 patients with NS (mean age 7.0 [4.4] years), 36% and 16% initiated GH treatment during follow-up, respectively. Of these patients, 48%/41% were early initiators (started ≤6 months post-index), 66%/70% had high adherence (≥80% of GH treatment days covered), and 56%/52% had long persistence (treated ≥2 years). Mean GH treatment duration was 24.9 (15.9) and 17.6 (10.1) months for patients with TS and NS, respectively. Median (IQR) total all-cause costs per patient/year were USD 10,232 (USD 2,850-USD 36,590) and USD 17,937 (USD 5,616-USD 47,552), respectively.

Conclusion: Of the few patients on GH therapy, less than half were initiated on treatment early after their TS or NS diagnosis. Greater awareness regarding early diagnosis and treatment of TS and NS is needed.

Introduction: Given the rising prevalence of childhood obesity, it is critical to understand the metabolic consequences of excess adiposity in youth. In particular, investigating alterations in glycolysis and the tricarboxylic acid (TCA) cycle in youth with obesity are essential for elucidating the underlying mechanisms contributing to metabolic dysregulation in this population.

Methods: Forty-eight adolescents and young adults aged 15-24 years had plasma obtained after a 12-h fasting to measure levels of glucose, insulin, and TCA cycle intermediates: pyruvate, lactate, fumarate, malate, α-ketoglutarate, cis/trans aconitate, and isocitrate. Additionally, participants underwent an assessment of liver proton-density fat fraction (PDFF) and a 3-h oral glucose tolerance test (OGTT).

Results: Nineteen youth without obesity (BMI 21.5 ± 0.5 kg/m2) and twenty-nine youth with obesity (BMI 37.3 ± 1.7 kg/m2) were enrolled in the study. Youth with obesity showed higher plasma concentrations of lactate (p = 0.015) and pyruvate (p = 0.096) and lower plasma concentrations of fumarate (p = 0.022), malate (p = 0.009), cis/trans aconitate (p = 0.03), and citrate/isocitrate (p = 0.012). PDFF was directly correlated with lactate (r = 0.46, p = 0.027). Adipose tissue insulin resistance was not associated with biomarkers of glycolysis.

Conclusion: The metabolomic analysis revealed distinct characteristics between adolescents with and without obesity, thus demonstrating lower rates of aerobic glucose utilization in youth with obesity, which may contribute to the development of insulin resistance, type 2 diabetes, and cardiovascular disease.

Introduction: We wanted to establish the etiologic cause of diabetes in a female subject with mild hyperglycemia since childhood, that suddenly worsened in her late 40s. We retrieved the proband's laboratory data from the age of 5 years. We assessed type 1 diabetes autoantibodies and performed genetic screening by clinical exome.

Case presentation: The proband showed stable hyperglycemia not requiring pharmacological therapy for 42 years. The proband's fasting plasma glucose increased from 120 to 130 mg/dL (6.1-7.2 mmol/L) to 150-159 mg/dL (8.3-8.8 mmol/L) at the age of 47 years. Four type 1 diabetes autoantibodies resulted repeatedly negative. A spontaneous glucokinase pathogenic variant (c.645C>A, p. Tyr215Ter) and a NEUROD1 variant (c.616dupC, p.His206ProfsTer38) were identified in the proband. Her mother, who carries the NEUROD1 variant, was diagnosed with diabetes by OGTT (120' = 211 mg/dL) when 77 years old. NEUROD1, a low penetrance maturity onset diabetes of the young (MODY) gene, is known to regulate gene transcription of GCK and SLC2A2, encoding for GLUT2, a functional partner of GCK in glucose sensing of the β cell.

Conclusions: We conclude that the low penetrance NEUROD1 variant is likely responsible of the peculiar trajectory of fasting glucose in a subject who presented with classical metabolic phenotype associated with glucokinase haploinsufficiency from childhood to adulthood.

Introduction: Transition from pediatric to adult care present challenges for patients with chronic diseases. The objective of the study was to identify factors associated with metabolic control in childhood-onset type 1 diabetes (T1D) following transfer to adult care. Additionally, we aimed to characterize sociodemographic parameters and to compare these data with those of the general population.

Methods: Contact of 281 patients transferred from pediatric to adult care between 1998 and 2021 yearly by questionnaire to provide information regarding their current hemoglobin A1c (HbA1c), type of care, type of therapy, occupational situation, living situation, marital status, and parental status. Data were analyzed using a mixed cross-sectional longitudinal approach.

Results: A total of 205 patients responded at least once (mean age: 27.7 years). Women were more frequently treated with pump therapy than men (p < 0.05). HbA1c levels reported by men did not significantly differ from those reported by women before and after transfer. Individuals employed in academic jobs after transfer had significantly lower HbA1c levels before and after transfer than those in nonacademic jobs, while the differences between individuals who were in vocational training and those pursuing studies were most pronounced (7.4 ± 1.0%, 57 ± 13 mmol/mol vs. 7.0 ± 0.8%, 53 ± 15 mmol/mol, p < 0.05). Moreover, among individuals aged 30-40, those with T1D exhibited a lower prevalence of having children (38.0% vs. 52.7%) and being married (40.5% vs. 55.3%) compared to general population.

Conclusions: Psychosocial life circumstances that are considered more stable in early adulthood, such as being a parent and working in academic occupation, were positively associated with metabolic control.