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Karger Publishers, Hormone Research in Paediatrics, 3(93), p. 197-205, 2020

DOI: 10.1159/000509840

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A Bayesian Approach to Diagnose Growth Hormone Deficiency in Children: Insulin-Like Growth Factor Type 1 Is Valuable for Screening and IGF-Binding Protein Type 3 for Confirmation

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

<b><i>Background:</i></b> The utility of insulin-like growth factor type 1 (IGF-1) is well established in the diagnosis of growth hormone deficiency (GHD), whereas IGF-binding protein type 3 (IGFBP-3) has a more controversial role. Most studies evaluated the value of these peptides by assessing their sensitivity and specificity but not considering the low prevalence of GHD among short children (&#x3c;2%). <b><i>Objective:</i></b> To evaluate the utility of basal IGF-1 and IGFBP-3 values in the GHD diagnosis process with a Bayesian approach, based on pre- and post-test probability. <b><i>Methods:</i></b> We determined ROC curves, sensitivity, specificity, and positive and negative predictive values for IGF-1 and IGFBP-3 obtained from patients with GHD (<i>n</i> = 48) and GH-sufficient children (<i>n</i> = 175). The data were also analyzed by classifying the children into early childhood and late childhood (girls and boys younger and older than 8 and 9 years, respectively). <b><i>Results:</i></b> The area under the curve (AUC) of the receiver operating characteristic curve of IGF-1-SDS (standard deviation score) was greater than that of IGFBP-3-SDS (AUC 0.886 and 0.786, respectively, <i>p</i> = 0.001). In early childhood, the AUC of IGFBP-3-SDS was significantly improved (0.866) and similar to IGF-1-SDS (0.898). IGF-1-SDS, in comparison to IGFBP-3-SDS, had a greater sensitivity (92 vs. 45.8%, respectively), lower specificity (69 vs. 93.8%, respectively), and lower positive predictive value (5.7 vs. 13.1%, respectively), with similar negative predictive values. <b><i>Conclusion:</i></b> IGF-1-SDS is a useful screening tool in the diagnosis of GHD. Although IGFBP-3-SDS lacks sensitivity, its high specificity supports the role to confirm GHD in short children, especially in early childhood. This strategy could simplify and reduce the necessity of a second laborious and expensive GH stimulation test to confirm the diagnosis of GHD.