Evidence map and gap analysis of metabolic change in pediatric growth hormone deficiency treated with growth hormone.
This evidence map and systematic review of 63 studies involving 6,158 children with growth hormone deficiency reports generally small or absent effects of growth hormone treatment on several metabolic outcomes, inconsistent lipid and anthropometric findings, and possible changes in selected exploratory biomarkers.
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This evidence map and systematic review of 63 studies involving 6,158 children with growth hormone deficiency reports generally small or absent effects of growth hormone treatment on several metabolic outcomes, inconsistent lipid and anthropometric findings, and possible changes in selected exploratory biomarkers.
Research significance
The supplied evidence supports using metabolic outcomes to guide further study and monitoring of growth hormone therapy in pediatric growth hormone deficiency; it only indirectly suggests, rather than demonstrates, that biomarkers or patient stratification could reduce treatment-related metabolic risk, and no pediatric-oncology-specific therapeutic benefit is established.
Source abstract
IMPORTANCE: Recombinant human growth hormone (rhGH) improves height in children with growth hormone deficiency (GHD). However, its metabolic effects remain unclear. OBJECTIVE: To synthesize evidence regarding the metabolic effects of rhGH or growth hormone (GH) derivatives in GHD, identify knowledge gaps, and highlight future research priorities. METHODS: PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc, and Wanfang databases were searched in July 2023 to identify studies on metabolic effects of GH treatment. Bubble plots were used to visualize GH treatment effects on metabolic parameters according to treatment duration by comparison with baselines, nonpharmacological interventions, and healthy controls. Random-effects meta-analyses were conducted for outcomes with inconsistent findings across original studies when randomized controlled trial data were sufficient. The study was registered with INPLASY (INPLASY202450064). RESULTS: Sixty-three studies (6158 participants) analyzed the effects of GH treatment on metabolic outcomes in children with GHD. Overall, GH treatment slightly affected glucose levels; lipid effects were inconsistent. GH treatment did not influence bone mineral density, bone mineral content, or parathyroid hormone levels. Most studies showed no significant effects on thyroid hormone levels, body composition, or body mass index (BMI). GH treatment may increase serum asymmetric dimethylarginine and gastrin levels while reducing tumor necrosis factor and serum urea levels. INTERPRETATION: Glucose and thyroid outcomes are consistent with clinical observations; effects on lipids, calcium, phosphorus, body composition, BMI, and waist-to-hip ratio require further validation owing to data inconsistency. New biomarkers are warranted. Further clinical studies are needed in children across age groups, GHD severities, and nutritional statuses.