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

Abstract

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.

Retesting the childhood-onset GH-deficient patient

“…These findings have been confirmed by others who also proposed an IGF1 cut-off limit of around K2 S.D. All agree that the diagnostic reliability of low IGF1 levels is satisfactory when patients with CO severe GHD or multiple pituitary deficits are considered, particularly below 40 years of age (2,4,(11)(12)(13)(14)(15). These patients therefore do not require a GH stimulation test to make the diagnosis of adult GHD; however, it remains that patients suspected for GHD showing normal IGF1 levels must undergo provocative tests (2,4).…”

Standardized centile curves and reference intervals of serum insulin-like growth factor-I (IGF-I) levels in a normal Japanese population using the LMS method

“…On the other hand, the utility of IGF-I for severe GHD in childhood was limited, as the percentage of these patients showing less than -2 SDS was 45.5% (male, 37.1%: female, 65.2%). These results may be explained by the fact that IGF-I appears to be regulated by multiple factors and a variable percentage of severe GHD patients have completely normal results [37]. However, the mean SDS of serum IGF-I levels in children with severe GHD was -2.1±1.6 (boy, -1.7±1.0: girl, -3.0±2.2), which was low enough to consider GHD as a differential diagnosis.…”

Impact of different cut-off limits of peak GH after GHRH-arginine stimulatory test, single IGF1 measurement, or their combination in identifying adult patients with GH deficiency

“…However, which peak GH cut-off limits after GHRH-Arg test should be used for identifying GHD patients is still a matter of argument; in fact, the Endocrine Society has adopted a 4.1 mg/l peak GH (6), whereas the GH Research Society in association with other Medical Societies, including the European Society of Endocrinology (2, 7), suggests peak GH cut-off limits ranging from 4.2 to 11.5 mg/l based on body mass index (BMI) (9). In addition, either a peak GH !3 mg/l, or !2.5 mg/l, has been suggested for diagnosing GHD when different stimulatory tests or different methods for measuring GH were used (10)(11)(12).…”