Growth Hormone (GH) AssayStandardization: Clinical Implication onSerum GH Cut-off Value for PharmacologicalTests Used to Diagnose GH Deficiency (GHD)in Children

BALLERINI, MARÍA GABRIELA; CHALER, EDUARDO A.; FRUSTI, MAURO; LAZZATI, JUAN MANUEL; MACEIRAS, MERCEDES; BERGADÁ, IGNACIO; RIVAROLA, MARCO A.; BELGOROSKY, ALICIA; ROPELATO, MARÍA GABRIELA

Montevideo

Congreso; XXIII Annual Meeting of the Paediatrics Endocrinology Latinoamerican Society; 2012

XXIII Annual Meeting of the Paediatrics Endocrinology Latinoamerican Society

GH deficiency (GHD) needs to be biochemically confirmed by measurements of GH concentrations during pharmacological stimulation tests (PhT). Recently, it has been introduce a new recombinant highly purified standard (IS) for GH calibration assays by manufactures and as a consequence, cut-off of PhT should be revised. Aims: To evaluate the cut-off PhT value for recently modified ICMA-GH calibrated with IS-98/574 and to determine the diagnostic efficiency (DE) of the recalculated PhT cut-off. Material and Methods: Serum GH concentration from 157 samples (baseline and in response to arginine-clonidine stimulation tests) from 92 short children were measured concomitantly by ICMA IS-80/505 (withdrawn by Siemens) and current ICMA IS-98/574 assay from Siemens. Passing-Bablok and ratio plot analyses were used for between-assay comparisons. We calculated a new PhT cut-off in terms of IS 98/574 for fixed x value of 6.1 ng/mL (ICMA IS-80/505) using the regression curve obtained. DE of the new ICMA IS-98/574 GH cut-off to define GHD in children, was studied using other independent 43 peak GH serum samples (13/43 from GHD children, peak ICMA GH IS-80/505<6.1 ng/mL) by ROC curve analysis. Results: ICMA-GH IS-98/574 results were negatively biased compared to ICMA-GH IS-80/505 (GH IS-98/574=0.74xGH IS-80/505+0.26, r2=0.979); mean ratio (IS-98/574/IS-80/505): 0.79±0.17. The calculated cut-off value for considering GH sufficient response to PhT was >4.7 ng/ mL in terms of GH IS-98/574 assay. Using this cut-off of 4.7 ng/mL, all 13 GHD children were correctly diagnosed in terms of the recalibrated GH IS-98/574 assay [DE: 100%; Sensitivity: 100% (95 IC%: 88.4–100); Specificity: 100% (75.3–100%)]. Conclusions: We found a shift to lower GH results (in average: 20%) after the standardization of the widely used ICMA-GH assay. Regarding our results, the proposed cut-off value in terms of IS-98/574 (4.7 ng/mL) constitutes a useful diagnostic tool for GHD in pediatric patients.Aims: To evaluate the cut-off PhT value for recently modified ICMA-GH calibrated with IS-98/574 and to determine the diagnostic efficiency (DE) of the recalculated PhT cut-off. Material and Methods: Serum GH concentration from 157 samples (baseline and in response to arginine-clonidine stimulation tests) from 92 short children were measured concomitantly by ICMA IS-80/505 (withdrawn by Siemens) and current ICMA IS-98/574 assay from Siemens. Passing-Bablok and ratio plot analyses were used for between-assay comparisons. We calculated a new PhT cut-off in terms of IS 98/574 for fixed x value of 6.1 ng/mL (ICMA IS-80/505) using the regression curve obtained. DE of the new ICMA IS-98/574 GH cut-off to define GHD in children, was studied using other independent 43 peak GH serum samples (13/43 from GHD children, peak ICMA GH IS-80/505<6.1 ng/mL) by ROC curve analysis. Results: ICMA-GH IS-98/574 results were negatively biased compared to ICMA-GH IS-80/505 (GH IS-98/574=0.74xGH IS-80/505+0.26, r2=0.979); mean ratio (IS-98/574/IS-80/505): 0.79±0.17. The calculated cut-off value for considering GH sufficient response to PhT was >4.7 ng/ mL in terms of GH IS-98/574 assay. Using this cut-off of 4.7 ng/mL, all 13 GHD children were correctly diagnosed in terms of the recalibrated GH IS-98/574 assay [DE: 100%; Sensitivity: 100% (95 IC%: 88.4–100); Specificity: 100% (75.3–100%)]. Conclusions: We found a shift to lower GH results (in average: 20%) after the standardization of the widely used ICMA-GH assay. Regarding our results, the proposed cut-off value in terms of IS-98/574 (4.7 ng/mL) constitutes a useful diagnostic tool for GHD in pediatric patients.Material and Methods: Serum GH concentration from 157 samples (baseline and in response to arginine-clonidine stimulation tests) from 92 short children were measured concomitantly by ICMA IS-80/505 (withdrawn by Siemens) and current ICMA IS-98/574 assay from Siemens. Passing-Bablok and ratio plot analyses were used for between-assay comparisons. We calculated a new PhT cut-off in terms of IS 98/574 for fixed x value of 6.1 ng/mL (ICMA IS-80/505) using the regression curve obtained. DE of the new ICMA IS-98/574 GH cut-off to define GHD in children, was studied using other independent 43 peak GH serum samples (13/43 from GHD children, peak ICMA GH IS-80/505<6.1 ng/mL) by ROC curve analysis. Results: ICMA-GH IS-98/574 results were negatively biased compared to ICMA-GH IS-80/505 (GH IS-98/574=0.74xGH IS-80/505+0.26, r2=0.979); mean ratio (IS-98/574/IS-80/505): 0.79±0.17. The calculated cut-off value for considering GH sufficient response to PhT was >4.7 ng/ mL in terms of GH IS-98/574 assay. Using this cut-off of 4.7 ng/mL, all 13 GHD children were correctly diagnosed in terms of the recalibrated GH IS-98/574 assay [DE: 100%; Sensitivity: 100% (95 IC%: 88.4–100); Specificity: 100% (75.3–100%)]. Conclusions: We found a shift to lower GH results (in average: 20%) after the standardization of the widely used ICMA-GH assay. Regarding our results, the proposed cut-off value in terms of IS-98/574 (4.7 ng/mL) constitutes a useful diagnostic tool for GHD in pediatric patients.Serum GH concentration from 157 samples (baseline and in response to arginine-clonidine stimulation tests) from 92 short children were measured concomitantly by ICMA IS-80/505 (withdrawn by Siemens) and current ICMA IS-98/574 assay from Siemens. Passing-Bablok and ratio plot analyses were used for between-assay comparisons. We calculated a new PhT cut-off in terms of IS 98/574 for fixed x value of 6.1 ng/mL (ICMA IS-80/505) using the regression curve obtained. DE of the new ICMA IS-98/574 GH cut-off to define GHD in children, was studied using other independent 43 peak GH serum samples (13/43 from GHD children, peak ICMA GH IS-80/505<6.1 ng/mL) by ROC curve analysis. Results: ICMA-GH IS-98/574 results were negatively biased compared to ICMA-GH IS-80/505 (GH IS-98/574=0.74xGH IS-80/505+0.26, r2=0.979); mean ratio (IS-98/574/IS-80/505): 0.79±0.17. The calculated cut-off value for considering GH sufficient response to PhT was >4.7 ng/ mL in terms of GH IS-98/574 assay. Using this cut-off of 4.7 ng/mL, all 13 GHD children were correctly diagnosed in terms of the recalibrated GH IS-98/574 assay [DE: 100%; Sensitivity: 100% (95 IC%: 88.4–100); Specificity: 100% (75.3–100%)]. Conclusions: We found a shift to lower GH results (in average: 20%) after the standardization of the widely used ICMA-GH assay. Regarding our results, the proposed cut-off value in terms of IS-98/574 (4.7 ng/mL) constitutes a useful diagnostic tool for GHD in pediatric patients.Results: ICMA-GH IS-98/574 results were negatively biased compared to ICMA-GH IS-80/505 (GH IS-98/574=0.74xGH IS-80/505+0.26, r2=0.979); mean ratio (IS-98/574/IS-80/505): 0.79±0.17. The calculated cut-off value for considering GH sufficient response to PhT was >4.7 ng/ mL in terms of GH IS-98/574 assay. Using this cut-off of 4.7 ng/mL, all 13 GHD children were correctly diagnosed in terms of the recalibrated GH IS-98/574 assay [DE: 100%; Sensitivity: 100% (95 IC%: 88.4–100); Specificity: 100% (75.3–100%)]. Conclusions: We found a shift to lower GH results (in average: 20%) after the standardization of the widely used ICMA-GH assay. Regarding our results, the proposed cut-off value in terms of IS-98/574 (4.7 ng/mL) constitutes a useful diagnostic tool for GHD in pediatric patients.2=0.979); mean ratio (IS-98/574/IS-80/505): 0.79±0.17. The calculated cut-off value for considering GH sufficient response to PhT was >4.7 ng/ mL in terms of GH IS-98/574 assay. Using this cut-off of 4.7 ng/mL, all 13 GHD children were correctly diagnosed in terms of the recalibrated GH IS-98/574 assay [DE: 100%; Sensitivity: 100% (95 IC%: 88.4–100); Specificity: 100% (75.3–100%)]. Conclusions: We found a shift to lower GH results (in average: 20%) after the standardization of the widely used ICMA-GH assay. Regarding our results, the proposed cut-off value in terms of IS-98/574 (4.7 ng/mL) constitutes a useful diagnostic tool for GHD in pediatric patients.Conclusions: We found a shift to lower GH results (in average: 20%) after the standardization of the widely used ICMA-GH assay. Regarding our results, the proposed cut-off value in terms of IS-98/574 (4.7 ng/mL) constitutes a useful diagnostic tool for GHD in pediatric patients.