ESPE Yearbook of Paediatric Endocrinology

Brief summary: This cross-sectional study provided evidence regarding the usefulness of serum IGF-1/IGFBP-3 ratio as a marker for the diagnosis of GHD in children.

Diagnosis of growth hormone deficiency (GHD) is still challenging, due to the insufficient specificity of GH stimulation tests. Serum IGF-1, IGFBP-3, and their combination have been proposed as an alternative to GH stimulation tests. However, despite relatively high specificity, their validity in the diagnosis of GHD is limited by low sensitivity (1–3). The serum IGF-1 to IGFBP-3 ratio has been suggested as a surrogate marker of biologically active IGF-1 and a few studies investigated its potential in the diagnosis of GHD in children (4, 5).

This study aimed at investigating the utility of serum IGF-1 to IGFBP-3 ratio in the diagnosis of GHD in short-statured children and adolescents referred to a university hospital in Jordan.

A cohort of 235 children with short stature was enrolled in this cross-sectional observational study. Participants were classified into GHD (n=64) and non-GHD (n=171) groups. GHD was defined as a slow growth rate (growth velocity < 25th percentile during 1 year) and reduced growth hormone response to 2 GH stimulation tests (<6.25 ng/mL). The sensitivity and specificity of serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 molar ratio were determined.

Fifty-six (87.5%) of 64 GHD participants had a low IGF-1 to IGFBP-3 ratio as compared to 29 (17.0%) of 171 non-GHD participants. The resulting sensitivity was 87.5%, whilst specificity was 83%. As expected, the combination of low IGF-1, IGFBP-3, and IGF-1 to IGFBP-3 ratio elevated the specificity to 97.7% but lowered the sensitivity to 29.7%. On the other hand, the combination of normal serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 ratio demonstrated the greatest specificity for a non-GHD cause of short stature (100.0%).

In conclusion, this study showed that serum IGF-1/IGFBP-3 ratio may be useful marker for the diagnosis of GHD in children.

References: 1. Cianfarani S, Tondinelli T, Spadoni GL, Scirè G, Boemi S, Boscherini B. Height velocity and IGF-I assessment in the diagnosis of childhood onset GH insufficiency: do we still need a second GH stimulation test? Clin Endocrinol (Oxf). 2002;57(2):161–167. 5. 2. Ranke MB, Schweizer R, Elmlinger MW, et al. Significance of basal IGF-I, IGFBP-3 and IGFBP-2 measurements in the diagnostics of short stature in children. Horm Res. 2000;54(2):60–68. 6. 3. Cianfarani S, Liguori A, Boemi S, et al. Inaccuracy of insulin-like growth factor (IGF) binding protein (IGFBP)-3 assessment in the diagnosis of growth hormone (GH) deficiency from childhood to young adulthood: association to low GH dependency of IGF-II and presence of circulating IGFBP-3 18-kilodalton fragment. J Clin Endocrinol Metab. 2005;90(11):6028–6034. 4. Rikken B, van Doorn J, Ringeling A, van den Brande JL, Massa G, Wit JM. Plasma levels of insulin-like growth factor (IGF)-I, IGF-II and IGF-binding protein-3 in the evaluation of childhood growth hormone deficiency. Horm Res. 1998;50(3):166–176. 14. 5. Giannakopoulos A, Efthymiadou A, Chrysis D. Insulin-like growth factor ternary complex components as biomarkers for the diagnosis of short stature. Eur J Endocrinol. 2021;185(5):629–635.