Near-final adult height after GnRHa plus growth hormone in central precocious puberty: a single-center cohort study and predicted adult height validation audit
TL;DR
Adjunctive rhGH was associated with greater growth over 24 months and a positive, imprecisely estimated NFAH difference, and the adult-height finding should be interpreted cautiously.
Abstract
Background Whether adjunctive recombinant human growth hormone (rhGH) improves near-final adult height (NFAH) during gonadotropin-releasing hormone analog (GnRHa) therapy for central precocious puberty (CPP) remains uncertain, and predicted adult height (PAH) may reflect treatment selection and prognosis. Methods We analyzed a single-center retrospective cohort of 235 children with CPP who initiated GnRHa between January 2018 and December 2020. The primary endpoint was chart-recorded NFAH in the female-only maturity-ascertained cohort (n = 91); the criterion-confirmed all-sex set included 94 patients. The primary adjusted model (M2) included treatment, baseline age, body mass index (BMI), IGF-1, BA–CA, and baseline height; baseline bone age was not entered separately because bone age = chronological age + BA–CA. Missing baseline covariates were handled using 20 imputations by chained equations. Height gain and change in height standard deviation score (SDS) from baseline to 24 months were secondary outcomes. Results: Mean NFAH was 160.17 cm with GnRHa alone and 161.87 cm with GnRHa + rhGH. The adjusted M2 association was +2.26 cm (95% CI 0.12 to 4.40); the chart-PAH-conditioned M3 estimate was +0.58 cm (−1.60 to 2.75) and was treated as diagnostic. At 24 months, M2 estimates were +3.23 cm (2.00 to 4.46) for height gain, +3.24 cm (2.03 to 4.46) in analysis of covariance (ANCOVA) of attained height, and +0.46 SDS (0.27 to 0.66). In the criterion-confirmed female bone-age cohort, M2 estimates were +0.00 years (−0.27 to 0.27) for bone age at 24 months and −0.14 years (−0.30 to 0.03) for bone-age progression. Conclusions Adjunctive rhGH was associated with greater growth over 24 months and a positive, imprecisely estimated NFAH difference. Because this was an observational study, ascertainment criteria were heterogeneous, and the NFAH estimate was sensitive to PAH adjustment and criterion restriction, the adult-height finding should be interpreted cautiously.