Analysis of differences in response to long-acting growth hormone therapy and influencing factors between patients with idiopathic short stature (ISS) and growth hormone deficiency (GHD)

Background: Long-acting growth hormone [pegylated recombinant human growth hormone (PEG-rhGH)] is increasingly used for pediatric short stature, yet its differential effects between growth hormone deficiency (GHD) and idiopathic short stature (ISS) remain unclear. This study aims to compare the 52-week efficacy and safety of PEG-rhGH in prepubertal children with GHD versus ISS within a Chinese clinical cohort.

Methods: A single-center retrospective cohort study enrolled prepubertal children (3–10 years for girls, 3–11 years for boys) with GHD/ISS (June 2023–June 2024). All received once-weekly PEG-rhGH [starting dose: 0.2 mg/kg/week, adjusted by insulin-like growth factor 1 standard deviation score (IGF-1 SDS)/height velocity (HV)] and completed 12-month follow-up. Primary endpoint: 12-month Δheight standard deviation score (ΔHt-SDS); secondary endpoints: HV, ΔIGF-1 SDS, target height achievement rate. Safety was assessed via adverse events (AEs) and metabolic/hepatorenal parameters. Regression analyses identified influencing factors.

Results: There were 132 children (68 GHD, 64 ISS) included, with balanced baselines. At 12 months: (I) efficacy: GHD had higher ΔHt-SDS (0.92±0.31 vs. 0.65±0.27, P<0.001), HV (9.8±1.6 vs. 8.2±1.4 cm/year, P<0.001), target height achievement rate (64.7% vs. 43.8%, P=0.009), and ΔIGF-1 SDS (1.8±0.7 vs. 1.1±0.6, P<0.001); (II) safety: AE incidence was similar (GHD: 32.4%, ISS:35.9%, P=0.63), with no serious AEs. ISS had slightly higher fasting insulin (15.8±4.2 vs. 12.3±3.5 µU/mL, P<0.001) and low-density lipoprotein cholesterol (LDL-C) (2.8±0.5 vs. 2.5±0.4 mmol/L, P=0.002), all within normal ranges; (III) influencing factors: diagnosis type (β=0.32), baseline IGF-1 (β=0.21), and PEG-rhGH dose (β=0.18) independently affected ΔHt-SDS (all P<0.01).

Conclusions: GHD children respond better to PEG-rhGH than ISS children; both have good safety. Diagnosis type is the key efficacy factor, supporting subtype-specific PEG-rhGH strategies.