Diagnostic Value of Serum Acid-Labile Subunit Alone and in combination with IGF-I and IGFBP-3 in the Diagnosis of Growth Hormone Deficiency

Horm Res Paediatr. 2020;93(6):371-379. doi: 10.1159/000512336. Epub 2020 Dec 18.

Abstract

Background: The acid-labile subunit (ALS) is a crucial factor in the tertiary complex. IGF-I and IGFBP-3 are routinely measured during the diagnostic work-up for growth hormone deficiency (GHD). The aim of the study is to evaluate the relevance of serum ALS as an additional biomarker in the diagnosis of GHD.

Methods: Ninety-one children undergoing standard diagnostic work-up for GHD were included in this retrospective study. Inclusion criteria were evidence-based auxological cutoffs, IGF-I and IGFBP-3 <-2 SDS at first presentation, at least 1 growth hormone (GH) stimulation test, and IGF-I, IGFBP-3, and ALS measurements on the same day. Statistical analysis was performed by ROC as well as by odds ratio calculations.

Results: Forty-seven of 90 participants presented with peak GH values under the cutoff of 7 ng/mL. AUC from a model containing only IGF-I was 0.76 and 0.68 when using only ALS. A model containing IGF-I, IGFBP-3, and ALS (AUC = 0.77) did not improve the result compared to the combination of IGF-I/IGFBP-3 (0.77) or IGF-I/ALS (0.76). Furthermore, the variation in the outcome (GH peak </≥7) explained by IGF-I only amounts to 20.4%, while that explained by IGFBP-3 and ALS is only 10.6 and 7.8%, respectively. The sensitivity to diagnose GHD at respective concentrations of -2.0 SDS was 48% for IGF-I, 38% for IGFBP-3, and only 8% for ALS.

Conclusion: Determination of serum ALS alone or in combination with IGF-I and IGFBP-3 did not improve definition of biochemical GHD in a cohort of short children and adolescents with suspected growth disorder. However, performance of IGFBP-3 in this context was not statistically superior to ALS.

Keywords: Acid-labile subunit; Growth hormone deficiency; IGF-binding protein-3; Insulin-like growth factor I.

Publication types

  • Evaluation Study

MeSH terms

  • Adolescent
  • Austria
  • Biomarkers / blood
  • Carrier Proteins / blood*
  • Child
  • Child, Preschool
  • Diagnostic Techniques, Endocrine
  • Dwarfism, Pituitary / blood
  • Dwarfism, Pituitary / diagnosis*
  • Female
  • Glycoproteins / blood*
  • Human Growth Hormone / deficiency
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Predictive Value of Tests
  • Reference Values
  • Retrospective Studies

Substances

  • Biomarkers
  • Carrier Proteins
  • Glycoproteins
  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • insulin-like growth factor binding protein, acid labile subunit
  • Human Growth Hormone
  • Insulin-Like Growth Factor I