Endocrine Abstracts

Background: Growth hormone stimulation testing (GHST) is used to diagnose growth hormone deficiency (GHD) in children. Given that sex steroids impact on anterior pituitary function, there is concern around the efficacy of GH stimulation testing in pre/peripubertal children, where sex steroid levels are low. Sex steroid priming prior to GH stimulation testing is thought to improve test efficacy in these children, however evidence to support its use in clinical practice is limited.

Objectives and Rationale: In this systematic review, we addressed the following research questions: Does priming increase GH stimulation test efficacy in pre/peripubertal children? Does priming identify those who would benefit most from treatment in terms of final height?

Search Methods: The study was registered with PROSPERO (registration: CRD42021244443). We searched Medline, Cochrane Library, Scopus, EMBASE and Web of Science and included all studies that included GHST in both primed and unprimed children. A GH cut-off of 7ng/ml was used as a threshold for GHD. Study quality was assessed using the Risk Of Bias In Non-Randomized Studies (ROBINS-I) tool or the revised Cochrane risk-of-bias tool for Randomised trials.

Results: From 127 articles identified in the initial search, 15 studies (954 patients) met our inclusion criteria. This included 4 randomised controlled trials (RCTs). The majority (9/13) of studies indicated that priming increases growth hormone response upon GHST in pre/peri-pubertal children, increasing test specificity. For 3/13 studies (all non-RCTs) the mean GH was <7ng/ml (i.e. GHD) in ‘unprimed’ patients, compared with >7ng/ml in primed patients. Those treated for GHD based on ‘primed’ GHST reached a greater final height compared to those with untreated constitutional delay of growth and puberty (CDGP) (P = 0.023), whilst for those diagnosed by ‘unprimed’ GHST, there was no difference compared with untreated CDGP (P>0.05).

Conclusion: Overall, the majority of studies suggest that sex steroid priming increases GH response in pre/peripubertal children, increasing GHST specificity and reducing false positive GHD diagnoses. Further studies are required to determine optimal regimen and specific criteria (e.g. age, pubertal stage) to define those individuals who would benefit from priming.