Cut-off limits of the peak GH response to stimulation tests for the diagnosis of GH deficiency in children and adolescents: study in patients with organic GHD

Abstract

Objective: The diagnosis of GH deficiency (GHD) in children and adolescents is established when GH concentrations fail to reach an arbitrary cut-off level after at least two provocative tests. The objective of the study was to define the optimal GH cut-offs to provocative tests in children and adolescents. Design: Retrospective study in 372 subjects who underwent evaluation of GH secretion. GH and IGF-I were measured by chemiluminescence assay in all samples. Receiver operating characteristic (ROC) analysis was used to evaluate the optimal GH cut-offs and the diagnostic accuracy of provocative tests. Methods: Seventy four patients with organic GHD (GH peak <10 µg/L after two provocative tests) and 298 control subjects (GH response >10 µg/L to at least one test) were included in the study. The provocative tests used were arginine, insulin tolerance test (ITT) and clonidine. Diagnostic criteria based on cut-offs identified by ROC analysis (best pair of values for sensitivity and specificity) were evaluated for each test individually and for each test combined with IGF-I SDS. Results: The optimal GH cut-off for arginine resulted 6.5 µg/L, 5.1 µg/L for ITT and 6.8 µg/L for clonidine. IGF-I SDS has low accuracy in diagnosing GHD (AUC = 0.85). The combination of the results of provocative tests with IGF-I concentrations increased the specificity. Conclusions:The results of the ROC analysis showed that the cut-off limits which discriminate between normal and GHD are lower than those commonly employed. IGF-I is characterized by low diagnostic accuracy.

Reliability of clonidine testing for the diagnosis of growth hormone deficiency in children and adolescents

“…Not surprisingly, mean IGF‐I concentrations were significantly lower in the prepubertal and pubertal GHD children, although with overlapping values. These data are in accordance with our previous studies showing that, despite IGF‐I alone is characterized by a low diagnostic accuracy, it is useful in combination with the results of GH stimulation testing and increases the diagnostic accuracy of the latter …”

“…Although current guidelines still indicate a cut‐off of 10 μg/L, this value is not supported by robust clinical data. We have recently shown that the best cut‐off for GH peak after CT, measured by chemiluminescent immunometric assay, is 6.8 μg/L, with an efficiency of 96.3% . In this study, we found that when applying a cut‐off of 7 μg/L, 11 subjects (six prepubertal and five pubertal) failed CT but showed normal GH responses to a second stimulation test, yielding an overall false positive responses rate of 3.3%.…”

“…Gil‐Ad et al in 1979 demonstrated for the first time in 18 children that clonidine was an effective GH‐stimulating agent in prepubertal and adolescent subjects . A number of studies have confirmed the utility of the CT in the diagnosis of GHD, but most of these studies have been performed in prepubertal children, and none has specifically addressed the effect of puberty on the rate of false positive responses in a large number of subjects. Fraser et al studied 41 children and adolescents and concluded that CT produces less false subnormal responses than ITT.…”

“…Clonidine is a central alpha‐adrenergic agonist that effectively stimulates GH secretion when administered orally at a dose of 0.10‐0.15 mg/m 2 body surface area . We have recently shown that after clonidine testing the optimal peak GH cut‐off point, measured by chemiluminescent immunometric assay, is 6.8 μg/L (LR+33.97, efficiency 96.3%) …”

“…[28][29][30][31] We have recently shown that after clonidine testing the optimal peak GH cut-off point, measured by chemiluminescent immunometric assay, is 6.8 μg/L (LR+33.97, efficiency 96.3%). 32 A number of studies have addressed the diagnostic accuracy of CT in the diagnosis of GHD. Most of these studies have been performed in prepubertal children, 29,31,[33][34][35][36] and some have included adolescents or young adults.…”