Endocrine Abstracts

Background: The diagnosis of growth hormone deficiency (GHD) is based on a combination of clinical suspicion supported by growth hormone stimulation testing. IGF-1 and IGFBP-3 are used as supportive markers. Reports over the last decade have examined the performance of IGF-I and IGFBP-3 in the diagnosis of GHD. It is important that each unit evaluates the utility of these markers in the assay used by their laboratory based on relevant normative data.

Aim: To evaluate the diagnostic accuracy of IGF-I and IGFBP-3 serum levels in relation to the diagnosis of GHD in short children using updated reference ranges with different cut offs.

Methods: Data from every short child in our unit, who had been investigated for short stature with GH stimulation testing and measurements of IGF-1 and IGFBP-3 between March 2017 and January 2018, were evaluated. Their performance in relation to the diagnosis of GHD was examined using updated IDS-iSYS reference ranges for both at a cut off value of −2 SDS and cut-off levels of −1.6 SDS for IGF-1 and −1.8 SDS for IGFBP-3 (based on levels in previous studies).

Results: Seventy-three patients (44 males) fulfilled the entry criteria. 30 patients were classified as GHD based on either two failed stimulation tests or a single failed test with abnormal pituitary imaging. Using the updated reference ranges, IGF-1 had a sensitivity of 55% and a specificity of 83%. IGFBP-3 had a sensitivity of 35% and a specificity of 90%. The sensitivity for IGF-1 increased to 77% and the specificity reduced to 64% when using −1.6 SDS as a cut off value. Similarly, the sensitivity of IGFBP-3 using −1.8 SDS increased to 52%, but the specificity reduced to 88%.

Conclusion: IGF-I and IGFBP-3 at levels below −2 SDS increase the likelihood of confirming GHD. Modifying the cut-off values improves concordance with the diagnosis of GHD, but increases false positives. However it must be recognised that these ‘tried and tested’ markers are only modestly accurate markers of GH status as defined by stimulation testing.