Purpose Circulating insulin-like growth factor 1 (IGF-1) is associated with longevity, yet its activity is tightly regulated by IGF-binding proteins (IGFBPs) and the cleavage of IGF–IGFBP complexes, mediated by pappalysins (PAPP-A and PAPP-A2) and inhibited by stanniocalcins (STC1 and STC2). However, the association of these IGF-1–regulating proteins with mortality remains unclear. This study aimed to evaluate the association between serum STC–PAPP-A–IGFBP–IGF axis proteins and all-cause mortality in middle-aged and older adults. Methods A systematic review was conducted in MEDLINE, EMBASE, Web of Science, and Scopus, following the JBI and PRISMA parameters for study inclusion through December 2025. Findings were analyzed using vote counting based on direction of effect and synthesized according to SWiM guidelines for systematic reviews without meta-analysis, given exposure heterogeneity. Risk of bias was assessed using the Newcastle-Ottawa Scale. The protocol was registered in PROSPERO (CRD42024556008). Results Thirty-eight observational studies were included across general and disease-specific cohorts, including cardiovascular, metabolic, cancer, and chronic kidney disease populations. Elevated IGFBP-1, IGFBP-2, and IGFBP-4 were associated with increased all-cause mortality, whereas higher IGFBP-3 was associated with lower risk. Overall, IGF-1 associations were inconsistent. Moreover, circulating PAPP-A was associated with increased all-cause mortality, with limited evidence suggesting a similar trend for STC2. Conclusion IGF-1 bioavailability-regulating proteins are associated with all-cause mortality in middle-aged and older adults. These findings suggest a role of IGF-1 signaling dysregulation through altered binary/ternary complexes in aging, supporting circulating STC–PAPP-A–IGFBP–IGF axis proteins as mechanistically grounded biomarkers for mortality risk stratification.
Background In the field of childhood growth hormone therapy (rhGH), patient and parent/observer-reported outcome measures (PROMs) are rarely used routinely. Aim To identify barriers and facilitators for the global implementation of PROMs for evaluating QoL in children receiving rhGH. Methods PROMs used in childhood rhGH therapy that were identified through a narrative literature search and expert group consultation were evaluated on reporter's perspective, language availability, administration mode, cost, age range, and completion time. Results Of the 50 PROMs identified, 13 were excluded due to methodological limitations. Of the remaining 37, that included 26 generic and 11 condition-specific PROMs, 16 (43%) were available in self-report and parent-proxy formats in over 30 languages and 24 (65%) had a reported completion time less than 15 min. The median lower age limit was 7 yrs (range: 3.0, 12.7). Of the 37, 7 (19%) were free to use, 12 (32%) required a fee, and for 18 (49%), the cost was unclear or varied between clinical practice and research. The mostly commonly represented domains in the condition-specific PROMs included “physical functioning & symptoms” and “emotional & mental health”. Fees for condition-specific PROMs were often not explicit, and none were unconditionally free of charge. Overall, generic PROMS tended to rank higher across the six usability parameters than condition-specific tools. Conclusion Cost and unclear fee structures represent barriers to the routine use of condition-specific PROMs for assessing rhGH therapy in real-world settings. Whilst both, generic and condition-specific PROMs play important complementary roles, the former are more likely to exhibit characteristics that support global implementation.
Objective To evaluate the local practice and short-term efficacy of recombinant human growth hormone (rhGH) therapy in children and adolescents in Hong Kong. Methods A retrospective analysis of rhGH therapy in children and adolescents between 2013 and 2022 who attended six Hong Kong centres that had enrolled in GloBE-Reg. Results The cohort comprised 161 males and 190 females with a range of clinical indications that consisted mainly of growth hormone deficiency (GHD) (n = 147, 41%). The median age at rhGH initiation was 10.1 years (range, 0.3, 18.1). Median one-year change in height standard deviation score (HtSDS) was available in 319 children (90.8%) and was 0.41 (range, −0.98, 3.4). The median starting dose of rhGH for GHD was 0.028 mg/kg/day (range, 0.008, 0.051). Conclusions This multicentre study shows the utility of GloBE-Reg for understanding the use of rhGH therapy at a regional level. Findings demonstrate a variation in clinical practice as well as in short-term growth outcomes. These results support the need for continued optimisation of rhGH therapy through local benchmarking and care quality improvement activities.
