AUTHOR=Felício João Soares , Janaú Luísa Corrêa , Moraes Marcelle Alves , Zahalan Nathalie Abdallah , de Souza Resende Fabrício , de Lemos Manuela Nascimento , de Souza Neto Norberto Jorge Kzan , Farias de Franco Isabela Imbelloni , Leitão Loyane Tamyres Costa , Silva Lilian de Souza d'Albuquerque , de Oliveira Maria Clara Neres Iunes , de Alcântara Angélica Leite , Contente Braga de Souza Ana Carolina , da Silva Wanderson Maia , dos Santos Márcia Costa , de Queiroz Natércia Neves Marques , de Moraes Lorena Vilhena , de Figueiredo Antônio Bentes , Farinassi Ana Luiza Prieto , Farias Luciana Marques da Costa , da Silva Danielle Dias , Felício Karem Miléo , Abrahão Neto João Felício 

TITLE=Diagnosis of Idiopathic GHD in Children Based on Response to rhGH Treatment: The Importance of GH Provocative Tests and IGF-1

JOURNAL=Frontiers in Endocrinology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00638

DOI=10.3389/fendo.2019.00638

ISSN=1664-2392

ABSTRACT=<p><bold>Purpose:</bold> Serum IGF-1 (Insulin like growth factor 1) and Growth Hormone (GH) provocative tests are reasonable tools for screening and diagnosis of idiopathic GH Deficiency (IGHD). However, the average cut-off points applied on these tests have a lower level of evidence and produce large amounts of false results. The aim of this study is to evaluate the sensitivity, specificity, and accuracy of IGF-1 and GH stimulation tests as diagnostic tools for IGHD, using clinical response to recombinant human GH (rhGH) treatment as diagnostic standard [increase of at least 0.3 in height standard deviation (H-SD) in 1 year].</p><p><bold>Methods:</bold> We performed a prospective study with 115 children and adolescents presenting short stature (SS), without secondary SS etiologies such as organic lesions, genetic syndromes, thyroid disorders. They were separated into Group 1 [patients with familial SS or constitutional delay of growth and puberty (CDGP), not treated with rhGH], Group 2 (patients with suspicion of IGHD with clinical response to rhGH treatment), and Group 3 (patients with suspicion of IGHD without growth response to rhGH treatment). Then, they were assessed for diagnostic performance of IGF-1, Insulin Tolerance Test (ITT) and clonidine test (CT) alone and combined at different cut-off points.</p><p><bold>Results:</bold> Based on the ROC curve, the best cut-off points found for IGF-1, ITT, and CT when they were used isolated were −0.492 SDS (sensitivity: 50%; specificity: 53.8%; accuracy: 46.5%), 4.515 μg/L (sensitivity: 75.5%; specificity: 45.5%; accuracy: 52.7%), and 4.095 μg/L (sensitivity: 54.5%; specificity: 52.6%; accuracy: 56.9%), respectively. When we had combined IGF-1 with−2SD as cut-off alongside ITT or CT, we found 7 μg/L as the best cut-off point. In this situation, ITT had sensitivity, specificity and accuracy of 93.9, 81.8, and 90.1%, while CT had 93.2, 68.4, and 85.7%, respectively.</p><p><bold>Conclusion:</bold> Our data suggest that diagnosis of IGHD should be established based on a combination of clinical expertise, auxologic, radiologic, and laboratorial data, using IGF-1 at the −2SD threshold combined, with ITT or CT at the cut-off point of 7 μg/L. Additional studies, similar to ours, are imperative to establish cut-off points based on therapeutic response to rhGH in IGHD, which would be directly related to a better treatment outcome.</p>