Converging Growth Trajectories During Recombinant Human Growth Hormone Therapy in Children With Isolated and Combined Pituitary Hormone Deficiency.
Children with combined pituitary hormone deficiency showed greater catch-up growth during rhGH therapy compared to those with isolated growth hormone deficiency, despite starting with more severe growth impairment.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This study measured longitudinal growth trajectories in children with isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD) during recombinant human growth hormone (rhGH) therapy. A total of 120 patients (72 IGHD and 48 CPHD) were included, with assessments of height standard deviation score (SDS) at baseline and after 12, 24, 36, and 48 months. It was found that CPHD patients had greater catch-up growth compared to IGHD patients over the treatment period.
Abstract
<h4>Objective</h4>Growth hormone deficiency (GHD) is an important cause of growth failure in children. Although recombinant human growth hormone (rhGH) promotes catch-up growth, longitudinal differences in treatment response between isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD) remain unclear. This study compared longitudinal growth trajectories during rhGH therapy between IGHD and CPHD patients.<h4>Design and patients</h4>A retrospective cohort study included 72 IGHD and 48 CPHD patients.<h4>Measurements</h4>Height standard deviation score (SDS) was assessed at baseline and after 12, 24, 36 and 48 months of rhGH therapy. Longitudinal trajectories were analysed using linear mixed-effects models adjusted for age at treatment initiation, bone age, BMI SDS and pituitary MRI findings.<h4>Results</h4>CPHD patients had more severe growth impairment at baseline than those with IGHD (height SDS: -5.00 ± 1.57 vs. -3.20 ± 1.12; p < 0.001). However, CPHD demonstrated greater catch-up growth, achieving larger cumulative height SDS gains after 48 months (3.10 ± 1.36 vs. 1.92 ± 0.87 SDS; p < 0.001). Mixed-effects modelling confirmed significantly different longitudinal growth trajectories (time-by-diagnosis interaction: χ<sup>2 </sup>= 66.62, p < 0.001). Adjusted height SDS improved from -3.40 to -1.49 in IGHD and from -4.56 to -1.55 in CPHD. At 48 months, the adjusted CPHD-IGHD difference was -0.06 SDS (95% CI, -0.63 to 0.51), consistent with substantial convergence of the two growth trajectories. Older age at treatment initiation and abnormal pituitary MRI findings were independently associated with lower height SDS across follow-up.<h4>Conclusions</h4>Despite more severe baseline growth impairment, children with CPHD experienced greater catch-up growth during rhGH therapy, resulting in substantial convergence of longitudinal height SDS trajectories toward those of children with IGHD over 4 years.
Background
This paper addresses the differences in growth response to rhGH therapy between children with isolated growth hormone deficiency (IGHD) and those with combined pituitary hormone deficiency (CPHD). Prior research has established that rhGH can promote catch-up growth, but the longitudinal differences in treatment response between these two groups were not well understood. Understanding these differences is important for optimizing treatment strategies in pediatric patients with growth hormone deficiencies.
Methods
This was a retrospective cohort study involving 120 patients, with 72 diagnosed with IGHD and 48 with CPHD. Height standard deviation score (SDS) was measured at baseline and after 12, 24, 36, and 48 months of rhGH therapy. Longitudinal growth trajectories were analyzed using linear mixed-effects models, adjusted for age at treatment initiation, bone age, BMI SDS, and pituitary MRI findings.
Results
At baseline, CPHD patients had a height SDS of -5.00 ± 1.57, while IGHD patients had a height SDS of -3.20 ± 1.12 (p < 0.001). After 48 months, CPHD patients showed greater cumulative height SDS gains of 3.10 ± 1.36 compared to 1.92 ± 0.87 in IGHD patients (p < 0.001). The adjusted height SDS improved from -3.40 to -1.49 in IGHD and from -4.56 to -1.55 in CPHD. The adjusted CPHD-IGHD difference at 48 months was -0.06 SDS (95% CI, -0.63 to 0.51).
Interpretation
The findings indicate that despite starting with more severe growth impairment, children with CPHD experienced greater catch-up growth compared to those with IGHD, leading to a convergence of growth trajectories over the study period. This suggests that treatment may be more effective in CPHD patients, but the clinical significance of the small adjusted difference at 48 months (-0.06 SDS) raises questions about the long-term implications of these findings. Limitations such as the retrospective design and potential biases should be considered when interpreting the results.
Key findings
- Height SDS at baseline: -5.00 ± 1.57 for CPHD vs. -3.20 ± 1.12 for IGHD; p < 0.001.
- Cumulative height SDS gains after 48 months: 3.10 ± 1.36 for CPHD vs. 1.92 ± 0.87 for IGHD; p < 0.001.
- Adjusted height SDS improved from -3.40 to -1.49 in IGHD and from -4.56 to -1.55 in CPHD.
- At 48 months, the adjusted CPHD-IGHD difference was -0.06 SDS (95% CI, -0.63 to 0.51).
- Time-by-diagnosis interaction: χ² = 66.62, p < 0.001.
Limitations
- Retrospective cohort design may introduce biases.
- Limited generalizability due to specific patient populations.
- No information on long-term outcomes beyond 48 months.