A Proposal for the Interpretation of Serum IGF-I Concentration as Part of Laboratory Screening in Children with Growth Failure

Wit, Jan M.; Bidlingmaier, Martin; Bruin, Christiaan de; Oostdijk, Wilma

doi:10.4274/jcrpe.galenos.2019.2019.0176

Cited by 27 publications

(47 citation statements)

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“…Considering a GH stimulation test with a sensitivity of 88.5% and a specificity of 97.4% [29] and applying a Bayesian modeling approach, the probability of GHD of a short stature child with an insufficient GH response at one stimulation test rises from 41 to 93.8% if a low IGFBP-3-SDS is also present. It is important to emphasize that a patient with a high pre-test probability of GHD (typical facial features, severe short stature, decreased growth velocity, and combined pituitary hormones deficiency) should be evaluated with a confirmatory test irrespective of the IGF-1 and IGFBP-3 values, in agreement with the literature [5, 7].…”

Section: Resultsmentioning

confidence: 58%

“…Additionally, the interpretation of these confirmatory tests is not trivial in conditions with a low prevalence, such as GHD. Hence, it is important to elaborate a stepwise approach, considering not only the sensitivity and specificity of a test but also the prevalence of a specific condition and the pre- and post-test probability, that is, a Bayesian approach [7, 17].…”

Section: Resultsmentioning

confidence: 99%

“…IGF-1 values in comparison to IGFBP-3 values have a higher sensitivity and lower specificity in the diagnosis of GHD. In patients with normal IGF-1 values, GHD is highly improbable and the necessity of GH stimulation tests is precluded [5, 7]. Conversely, low IGF-1 values support the diagnosis of GHD as long as all conditions that could decrease IGF-1 serum concentrations are excluded (malnourishment, chronic decompensated diseases, and sex steroids).…”

Section: Introductionmentioning

confidence: 99%

“…Overall, the low sensitivity and high specificity of this test make it unsuitable for the initial evaluation of the GH/IGF-1 axis, as a screening test. The usefulness of IGFBP-3 serum concentrations is greater in children younger than 3 years, when the reliability of IGF-1 values is diminished [1, 7]. Other advantages of IGFBP-3 values are the lesser influence of nutritional status or acute illness compared to IGF-1 values [11] and the non-interference of IGF-1 and IGF-2 serum concentrations on its measurement [5].…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2020

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Background: 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 (<2%). Objective: 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 posttest probability. Methods: We determined ROC curves, sensitivity, specificity, and positive and negative predictive values for IGF-1 and IGFBP-3 obtained from patients with GHD (n = 48) and GH-sufficient children (n = 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). Results: 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, p = 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. Conclusion: 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.

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Section: Resultsmentioning

confidence: 58%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

et al. 2020

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“…Hormonal assessment should follow the guidelines, published previously ( 40 ) and reviewed in the recent GRS Consensus Statement ( 5 ). Important messages are highlighted in this publication such as an IGF-1 assay with reliable reference data with ranges for paediatric ages should be used, and serum IGF-1 is influenced by many factors such as assay methodology, age, nutrition and chronic illness ( 88 ). An IGF-1 level >0 SDS at any age makes GHD less likely but not impossible ( 5 , 88 ).…”

Section: Diagnostic Approach and Investigations Of Patients With Iss mentioning

confidence: 99%

Growth failure: ‘idiopathic’ only after a detailed diagnostic evaluation

Rapaport

Wit

Savage

2021

Endocrine Connections

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The terms idiopathic short stature (ISS) and small for gestational age (SGA) were first used in the 1970s and 1980s. ISS described non-syndromic short children with undefined aetiology who did not have growth hormone (GH) deficiency, chromosomal defects, chronic illness, dysmorphic features or low birth weight. Despite originating in the pre-molecular era, ISS is still used as a diagnostic label today. The term SGA was adopted by paediatric endocrinologists to describe children born with low birth weight and/or length, some of whom may experience lack of catch-up growth and present with short stature. GH treatment was approved by the FDA for short children born SGA in 2001, and by the EMA in 2003, and for the treatment of ISS in the US, but not Europe, in 2003. These approvals strengthened the terms SGA and ISS as clinical entities. While clinical and hormonal diagnostic techniques remain important, it is the emergence of genetic investigations that have led to numerous molecular discoveries in both ISS and SGA subjects. The primary message of this article is that the labels ISS and SGA are not definitive diagnoses. We propose that the three disciplines of clinical evaluation, hormonal investigation and genetic sequencing should have equal status in the hierarchy of short stature assessments and should complement each other to identify the true pathogenesis in poorly growing patients.

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