Comparison of ICMA Versus RIA Measurements in Monitoring IGF-I Levels during rhGH Treatment in Short Children with Growth Hormone Deficiency (GHD), Turner Syndrome (TS), and Small for Gestational Age (SGA)

MARIA G BALLERINI; MARIA E RODRIGUEZ; DEBORA BRASLAVSKY; HORACIO M DOMENE; ALICIA MARTINEZ; ANA KESELMAN; PAULA SCAGLIA; ANALIA V FREIRE; IGNACIO BERGADA; HECTOR JASPER ; MARIA G ROPELATO

Houston

Congreso; 94th. Annual Meeting of the Endocrine Society; 2012

Endocrine Society

Introduction: Monitoring IGF-I levels during rhGH treatment is useful to ascertain efficacy, compliance and safety. To reach this purpose a reliable IGF-I assay is required. There is no data on the performance of ICMA IGF-I assays in children under rhGH therapy in comparison with classical extracted RIA. Aim: To compare ICMA versus RIA assay´s performance for measuring IGF-I in children under rhGH treatment. Subjects and Methods: Serum IGF-I and IGFBP3 concentrations were measured in 13 GHD children (61 samples), 7 SGA children (30 samples) and 5 TS girls (16 samples), on rhGH (GHD dose: 0.16 mg/kg/week, SGA and TS: 0.33 mg/kg/week) for up to 3 years. IGF-I measurements: ICMA (IMMULITE 2000, Siemens), and an in house RIA (with prior alcohol-acid extraction followed by cryoprecipitation) (1). IGF-I levels were expressed in SDS according to reference values obtained in our laboratory. IGFBP-3 was measured by ICMA (IMMULITE 2000, Siemens). Results: IGF-I ICMA values (ng/ml) were positively biased compared to RIA (ICMA =1.49 x RIA-13.7; r=0.97, p<0.0001). Considering all samples no relationship was found between the ratio IGF-I ICMA/RIA with neither the IGF-I RIA nor the IGFBP-3 levels; but a significant positive correlation was found for the SGA group between the IGF-I ICMA/RIA and IGFBP-3 levels (r=0.40, p=0.036). ICMA SDS results were systematically and significantly higher than RIA SDS (Mean ± SEM 1.20 ± 0.19 vs 0.57 ± 0.19, Wilcoxon test p< 0.0001). Considering IGF-I + 2 SDS the cutoff for safety for patients on GH treatment, values above this limit were found in 13.1%, 36.7% and 68.8% by ICMA and in 4.9%, 26.7% and 56.3% by RIA of GHD, SGA, and TS samples respectively. The difference in proportions between groups was not significant (p>0.05). In 12/107 (11%) samples, ICMA gave IGF-I levels above the safety cutoff while RIA results were below that limit. Conclusions: ICMA assay overestimated IGF-I concentration in comparison with an extractive RIA in children under GH therapy. The positive relationship between the IGF-I ICMA/RIA ratio and IGFBP-3 concentration in SGA on high dose rhGH treatment suggests that ICMA procedure is not totally effective to circumvent IGFBPs interference. Both assays showed similar proportion of samples with IGF-I levels higher than 2SDS. It should be noted that ICMA, even when the results are expressed in SDS, would lead to a misinterpretation of IGF-I results, giving falsely elevated values in 11% of the samples.