Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial.

Context: Long-acting recombinant human growth hormone (rhGH) has transformed growth hormone deficiency (GHD) treatment. However, the possibility and rationality for flexible time regimen are pending. Objective: We studied the efficacy of biweekly versus weekly PEGylated rhGH (PEG-rhGH) therapy in GHD children. Design Setting and Patients: This multicenter, phase IV trial with a non-inferiority threshold ≥20% enrolled 585 Tanner stage I GHD children. Intervention: Subjects randomly received 0.20 mg/kg once-weekly or biweekly PEG-rhGH, or 0.25 mg/kg.w rhGH once daily for 26 weeks. Main Outcome Measure: The primary outcome was height SD scores for chronological age (HtSDSCA) at week 26 and safety measurements including adverse events (AEs), IGF-2, and IGFBP-2 changes. Results: At week 26, the median HtSDSCA changed from -2.75, -2.82, and -2.78 to -2.31, -2.43, and -2.28 with weekly and biweekly PEG-rhGH, and daily rhGH, respectively. The difference in HtSDSCA was 0.17 ± 0.28 between weekly and biweekly PEG-rhGH, and 0.17 ± 0.27 between daily rhGH and biweekly PEG-rhGH, failing the non-inferiority threshold. Nevertheless, the height velocity of children receiving biweekly PEG-rhGH reached 76.42%-90.34% and 76.08%-90.60% that of children receiving weekly PEG-rhGH and daily rhGH, respectively. The rate of AEs was comparable among the groups. No statistical difference was observed in IGF-2 and IGFBP-2 levels among the groups. IGFBP-2 levels decreased over time in all groups, with no notable difference in IGF-2 and IGFBP-2 changes among the three treatment groups. Conclusions: Although notably promoted height velocity, biweekly PEG-rhGH failed the non-inferiority threshold as compared with either weekly PEG-rhGH or daily rhGH. Compared with short-term rhGH, long-acting PEG-rhGH did not significantly increase tumor-associated IGF-2 and IGFBP-2 expressions. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02976675.

Corrigendum: Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial.

[This corrects the article DOI: 10.3389/fendo.2021.779365.].

The prevalence of premature thelarche in girls and gynecomastia in boys and the associated factors in children in Southern China.

BACKGROUND: To investigate the prevalence and risk factors of premature thelarche (PT) in girls and gynecomastia (GM) in boys in Southern China. METHODS: We conducted a cross-sectional study of preschool children across 9 cities in Zhejiang province. A total of 6273 children in the age-group of 2-7 years were recruited from January 2014 to March 2015. Relevant information was collected from mothers through face-to-face interviews. Logistic regression models were used to examine the correlates of PT and GM. Odds ratios (ORs) with 95% confidence intervals (CIs) are reported. RESULTS: The prevalence of PT among girls was 4.8% and that of GM among boys was 0.8%. One hundred girls were diagnosed with PT before the age of 2 years; 69 (69.0%) of these girls experienced spontaneous resolution of PT. Twenty-four boys were diagnosed with GM before the age of 2 years; 10 (41.7%) of these experienced spontaneous resolution of GM. Children borne of mothers with early onset of menarche and those belonging to high-income families were at a higher risk of premature breast development. Greater consumption of eggs was associated with premature breast development in early childhood. CONCLUSIONS: Socioeconomic status of family, early onset of menarche in mother, and consumption of eggs were strongly associated with premature breast development in early childhood.