SUN-256 Limited Usefulness of Single IGF-I Measurement as a Screening Test for Growth Hormone Deficiency in Children and Adolescents

Abstract

Introduction: IGF-I measurement has been proposed as a screening tool for the diagnosis of Growth Hormone Deficiency (GHD). However, few studies evaluated the accuracy of IGF-I measurement as a screening test and the results have been controversial. Objective: To evaluate the value of a single IGF-I measurement as screening test in the diagnosis of GHD in short children and adolescents. Patients and Methods: 439 short children (median-IQR age 10.5 (7.1-12.8) y, 273 boys), were included in this retrospective analysis. The patient group consisted of 102 subjects (54 boys) with GHD (peak GH <7.0 μg/L after two provocative tests with Arginine, Insuline Tolerance Test, and Clonidine), 60 of whom had GHD of organic or genetic origin (OGHD) and 42 were idiopathic (IGHD). The 337 subjects with a GH peak ≥7 μg/L and no other recognizable cause for their shortness were considered as controls. All provocative tests were performed between 8.00 and 9.00 am after fasting overnight, without steroid priming. GH and IGF-I were measured by the same chemiluminescence assay in all samples (Immulite, Siemens). Receiver operating characteristic (ROC) analysis was used to evaluate the optimal IGF-I cut-offs and the diagnostic accuracy of IGF-I. The analysis was repeated including only 67 patients with severe GHD (SGHD, peak GH <5.0 μg/L after two provocative tests): 54 organic/genetic (SOGHD) and 18 idiopathic (SIGHD). Results: IGF-I SDS was significantly lower in patients than in controls (-2 (-2.9 - -1.7), -1 (-1.8 - -0.1), respectively, p<0.0001). IGF-I SDS ≥ -2 was found in 42% and 69% of OGHD and IGHD patients, respectively. The Area Under the Curve (AUC, measure of discriminative ability of the test) of IGF-I SDS was 0.73. The IGF-I SDS cut-off of -2 had 50% sensitivity (Se), 80% specificity (Sp), 2.4 likelihood ratio for positive test results (LR+), and 74% diagnostic efficiency (Ef). The best pair of values for Se and Sp was found at IGF-I SDS cut-off of -1.8 (B cut-off, Se 60%, Sp 75%, LR+ 2.3, Ef 71%). For OGHD, AUC was 0.82. For cut-off -2 SDS: Se 60%, Sp 80%, LR+ 3, Ef 80%. B cut-off was -1.9 SDS (Se 68%, Sp 78%, LR+ 3.1, EF 77%). For IGHD, AUC was 0.61. For cut-off -2 SDS: Se 36%, Sp 79%, LR+ 1.7, Ef 77%. B cut-off was -1.4 SDS (Se 52%, Sp 65%, LR+ 1.5, Ef 64%). The results were similar when only patients with SGHD were analysed. Among them, 42% had IGF-I SDS ≥ -2. IGF-I SDS ≥ -2 was found in 41% of SOGHD and in 67% of SIGHD. Conclusions: In our large cohort of short children, IGF-I measurement has shown suboptimal accuracy in discriminating GHD from non-GHD patients. The accuracy is better for patients with organic or genetic GHD. IGF-I values should be interpreted in combination with other clinical and biochemical parameters, and cannot be used alone as a screening tool.