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Evaluation of Diagnostic Accuracy of Insulin-Like Growth Factor (IGF)-I and IGF-Binding Protein-3 in Growth Hormone-Deficient Children and Adults Using ROC Plot Analysis

Endocrinology Unit, Department of Medicine, Hospital T Alvarez (H.R.B., P.G.V.S., H.L.F., A.M.S., A.V.G., M.G.S., G.F.R.), Buenos Aires C1406FWY, Argentina; and Department of Endocrinology, Hospital de Niños (M.M.), Córdoba, Argentina X 5000 ANM

Address all correspondence and requests for reprints to: H. L. Fideleff, M.D., Ph.D., Hospital T. Alvarez, Endocrinology Unit. Aranguren 2701, Buenos Aires C1406FWY, Argentina. E-mail: .

We critically evaluated the diagnostic value of IGF-I and IGF-binding protein-3 (IGFBP-3) in GH deficiency (GHD) in children and adults using receiver operating characteristic (ROC) plot analysis. Sixty-six children (chronological age, 1.3–15 yr) were studied: 34 GHD and 32 idiopathic short stature (ISS). Ninety-two adults (chronological age, 18–70 yr) were also evaluated: 72 GHD, 34 of childhood onset (AGHD-CO), and 38 of adult onset (AGHD-AO); and 20 healthy volunteers. The SD score (SDS) for IGF-I was calculated from 596 normal subjects (212 children and 384 adults), and the SDS for IGFBP-3 was calculated from 350 normal subjects (212 children and 138 adults). The ROC plot showed that the best IGF-I SDS cut-off line was -1.65 for children [sensitivity (S), 68%; specificity (Sp), 97%, diagnostic efficiency (DEf), 81%], the cut-off line for AGHD was -1.65 for AGHD-CO (S, 91%; Sp, 100%; DEf, 94%), and the cut-off line for AGHD-AO was -1.80 (S, 81%; Sp, 100%; DEf, 88%). For IGFBP-3 SDS, the best cut-off line was -1.80 for children (S, 90%; Sp, 60%; DEf, 78%); it was -1.45 for AGHD-CO (S, 90%; Sp, 75%; DEf, 82%) and -0.90 for AGHD-AO (S, 90%; Sp, 68%; DEf, 77%). An accurate diagnosis was obtained using IGF-I SDS alone in GHD children 65%; ISS, 97%; AGHD-CO, 92%; AGHD-AO, 86%, with IGFBP-3 SDS alone in GHD children 60%; ISS, 90%; AGHD-CO, 75%; AGHD-AO, 68%. Considering both, an accurate diagnosis was obtained in GHD children 60%; ISS, 87%; AGHD-CO, 71%; AGHD-AO, 64%. In conclusion, our findings support the need to use cut-off lines expressed in SDS obtained using an appropriate statistical methodology for better characterization of the various clinical presentations. IGF-I proved to be more useful because of its good diagnostic efficiency and accuracy in both children and adults, whereas IGFBP-3 did not significantly contribute to the diagnosis of GHD.

This work was supported in part by Pharmacia Argentina and presented in part at the 33rd International Symposium, GH and Growth Factors in Endocrinology and Metabolism, Barcelona, Spain, April 2002.

Abbreviations: AGHD-AO, Adults with GH deficiency of adult onset; AGHD-CO, adults with GH deficiency of childhood onset; BMI, body mass index; CV, coefficient of variation; DEf, diagnostic efficiency; GHD, GH deficiency; IGFBP-3, IGF-binding protein-3; IGHD, isolated GH deficiency; IRMA, immunoradiometric assay; ISS, idiopathic short stature; MPHD, multiple pituitary hormone deficiencies; ROC, receiver operating characteristic; S, sensitivity; SDS, SD score; Sp, specificity.

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