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58ESPE Poster presented at: Diagnostic value of random serum growth hormone, IGF-I and IGFBP-3 concentrations for the diagnosis of growth hormone deficiency in patients below one year of life. P1- 72 Design : Diagnostic validation study at a tertiary hospital. • Random serum samples. • GH (IRS 98/574), IGF-I (WHO 02/254) and IGFBP-3 (Siemens, IMMULITE 2000/Xpi); CV% < 5% • IGF-I was log-transformed • Statistics: Multiple regression analysis, Kruskal-Wallis, Fisher t Test; Receiver operating curve (ROC): GHD (true positive) versus TH (true negative) • Primary main outcomes: GH SDS, IGF-I SDS, IGFBP-3 SDS. • Measures by ROC: Diagnostic accuracy (DA), Area under the curve (AUC), Sensitivity (S), Specificity (Sp), Positive and Negative Predictive Value (PPV and NPV). 1- To establish reference intervals for serum concentration of GH, IGF-I and IGFBP-3 for the whole first year of age. 2- To investigate GH, IGF-I and IGFBP-3 usefulness for GHD diagnosis in neonates and early infancy. Patients Inclusion criteria : Infants <1 year of age, who were referred to the Endocrinology Division with clinical suspicion of GHD from March 2016 to June 2019. • Clinical follow-up was the gold standard for GHD diagnosis: growth retardation, additional pituitary hormone deficiencies, brain MRI abnormalities and/or abnormal GH stimulation test during childhood. • Non-GHD patients were diagnosed as having congenital hyperinsulinism (HI) or transient hypoglycemia (TH ). Exclusion criteria : Preterm newborns, critical sample under hypoglycemia Methods Healthy Neonates and infants MG. Ballerini, D. Braslavsky, AV. Freire, A. Keselman, ME. Rodríguez, M. Altube, PA. Scaglia, I. Bergadá, MG. Ropelato Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE) CONICET – FEI – División de Endocrinología Hospital de Niños Dr. Ricardo Gutiérrez - Buenos Aires - Argentina Healthy neonates and infants Inclusion criteria : Surplus serum corresponding to healthy neonates and infants who consulted the Endocrinology Division for presumed endocrine abnormalities during 2016- 2019 and were found to be normal. Exclusion criteria : Preterm babies, hemolysis or lipemic samples. Subjects Results Introduction Patients GH • Neonates of 1 week of age have higher GH and lower IGF-I and IGFBP-3 than other age groups. Thereafter, GH decreases and IGF-I and IGFBP-3 increase with age. • GH is always detectable in healthy neonates and early infants. Not-detectable IGF-I are more frequently observed in neonates (18%) than in infants (9%), p< 0.01. Beyond the 1 st week, IGFBP-3 is always detectable. • Sexual dimorphism is observed for GH, IGF-I and IGFBP-3. Boys aged 2-6 months have lower concentration of these biomarkers than age-matched girls. Detection Limit IGF - I IGF - I SDS • Reference data on GH, IGF-I and IGFBP-3 obtained in a large cohort of healthy controls allowed us to calculate SDS for these biomarkers using current standardized assays. • GH constitutes the biomarker of choice in the diagnostic work-out of GHD in neonates. • In infants, the presence of GH and IGF-I or IGFBP-3 values below the cut-offs confirms GHD diagnosis with high specificity. • Due to the lack of an evidence-based approach for diagnosis of GHD along the first year of life with standardized immunoassays, we conclude that the cut-offs obtained in the present study could be useful in the diagnostic work-out of neonates and early infants with clinical suspicion of GH deficiency. IGFBP - 3 Conclusions Objectives Detection Limit Detection Limit Age as median (range) Neonates IGFBP - 3 SDS Cut-off (SDS) AUC S Sp PPV NPV DA (%) GH: -1.0 0.95 (0.87 - 1.0) p< 0.0001 0.86 (0.57 - 0.98) 1.0 (0.74 - 1.0) 1.0 (0.73 - 1.0) 0.85 (0.57 - 0.98) 92.3 NS: not significant (95% confidence interval) Infants Cut-off (SDS) AUC S Sp PPV NPV DA (%) GH: - 1.0 0.84 (0.73 - 0.94) p< 0.01 0.50 (0.25 - 0.75) 0.89 (0.74 - 0.97) 0.67 (0.35 - 0.90) 0.80 (0.64 - 0.91) 75.4 IGF - I: - 1.1 0.86 (0.73 – 0.96) p< 0.0001 0.92 (0.74 - 0.99) 0.77 (0.60 – 0.89) 0.75 (0.57 - 0.88) 0.93 (0.77 - 0.99) 83.3 IGFBP - 3: - 1.1 0.95 (0.87 - 1.0) p< 0.01 0.72 (0.55 - 0.83) 0.80 (0.59 - 0.87) 0.67 (0.45 – 0.84) 0.81 (0.64 - 0.99) 78.2 -2 0 2 4 ** p< 0.01 GHD vs TH ** SDS -3 -2 -1 0 1 2 TH HI GHD SDS Roc IGF-I p= 0.08 (NS) GH SDS Combination of biomarkers Cut-off (SDS) S Sp PPV NPV DA (%) GH < -1.0 & IGF-I < -1.1 0.50 (0.25 - 0.75) 0.97 (0.84 - 0.99) 0.89 (0.51 - 0.99) 0.76 (0.60 - 0.89) 79.2 GH < -1.0 & IGFBP-3 < -1.1 0.42 (0.20 - 0.66) 1.0 (0.88 - 1.0) 1.0 (0.63 – 1.0) 0.73 (0.57 - 0.85) 77.6 IGF - I SDS IGFBP - 3 SDS GH SDS Reference: 1 Grimberg et al. Horm Res Paediatr 2016; Acknowledgements: Ms Ana María Montese, Ms Silvina González and Dra. Gabriela Gotta ; Disclosure: Nothing to disclose < -1.0 GH SDS 1st week < 6.2 μg/L 2nd to 4th week < 4.0 μg/L Roc IGFBP-3 p= 0.08 (NS) IGF-I has the highest DA in infants. -2 0 2 4 6 Cut-off: -1.0 SDS *** p< 0.0001 GHD vs TH *** SDS -3 -2 -1 0 1 2 Cut-off: -1.1 SDS *** p< 0.0001 GHD vs TH * p< 0.05 GHD vs HI *** * SDS -4 -2 0 2 4 Cut-off: -1.1 SDS * p< 0.05 GHD vs TH * TH HI GHD SDS GH and IGF-I or IGFBP-3 below the cut-offs improved Sp and PPV The diagnosis of Growth Hormone Deficiency (GHD) needs to combine clinical phenotype, imaging as well as biochemical assessment of GH-IGF-I axis 1 . The typical auxologic phenotype in neonates and early infants could be absent and therefore, a practical evidence-based approach to assess the usefulness of biomarkers of GH action is needed. To our knowledge, this study is still lacking for current standardized GH, IGF-I and IGFBP-3 in patients below one year of life. 1º w 2º w 3º w 4º w 1st m 2-6 m 7-12 m 1º w 2º w 3º w 4º w 1st m 2-6 m 7-12 m 0.01 0.1 1 10 100 Girls Boys *** *** ** p< 0.001 vs. 2º-4º w *** p< 0.0001 vs. > 1m ** ** * * p< 0.01 vs. 31-60 d p< 0.01 vs. girls ++ + + p< 0.001 vs. 2-6 m ++ p< 0.001 vs. 31-60 d Neonates Neonates Age ug/L 1º w 2º w 3º w 4º w 1st m 2-6 m 7-12 m 1º w 2º w 3º w 4º w 1st m 2-6 m 7-12 m 0 15 30 45 60 75 90 *** ** +++ ++ *** p< 0.0001 vs. 2º-4º w ** p< 0.001 vs. > 1m ++ p< 0.01 vs. 2-6 m +++ p< 0.0001 vs. 2º w to 2 m and vs. 7-12 m p< 0.01 vs. 3º w girls p< 0.01 vs. 2-6 m girls Neonates Neonates Age ug/L 1º w 2º w 3º w 4º w 31-60 d 2-6 m 7-12 m 1º w 2º w 3º w 4º w 1st m 2-6 m 7-12 m 0 1 2 3 4 *** ** *** p< 0.0001 vs. > 2º w ** p< 0.01 vs. > 2m +++ + + p< 0.01 vs. 3º w +++ p< 0.0001 vs. > 2º w p< 0.01 vs. 4º w or 2-6 m ingirls p< 0.01 vs. 3º w in girls Neonates Neonates Age ug/L -2 0 2 4 Cut-off: -1.0 SDS *** p< 0.0001 GHD vs TH and HI *** SDS P1-072 María Gabriela Ballerini DOI: 10.3252/pso.eu.58ESPE.2019 GH and IGFs

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