Background: The acid-labile subunit (ALS) is the crucial third player in the tertiary complex for its function of prolonging the half-life of the IGF1-IGFBP3 binary complexes. IGF1 and IGFBP3 are routinely determined 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, alone or in combination with IGF1 and IGFBP3, in the diagnosis of GHD.
Methods: In a retrospective study, we had selected 91 children and adolescents (62 males) undergoing standard diagnostic work-up at the Department of Pediatrics and Adolescent Medicine of the Vienna General Hospital from 2010 and 2017. All patients met the inclusion criteria: short stature according to the SOP (height< -2.5 SDS, height deflection > 1 SDS, delta target height > 1.6 SDS), IGF1 and IGFBP3 lower as -2 SDS at first presentation, with at least one growth hormone stimulation tests and available baseline IGF1, IGFBP3 and ALS measurements. Excluded were pathologies that could explain short stature as well as those with no available baseline IGF1, IGFBP3 and ALS. Statistical analysis of different models consisting of ROC for various combinations of the measured parameters, as well as Odds ratio calculations were conducted using SAS software.
Results: 48 participants presented with GH values under 7 ng/ml and 43 above it. Mean IGF1, IGFBP3 and ALS were slightly lower in the participants with insufficient GH secretion.4 participants with ALS levels < -2 SDS. The area under the ROC curve (AUC) from a model containing only IGF1 was 0.76, 0.68 when only ALS. A model containing both IGF1 and IGFBP3, (AUC=0.77) was unchanged if ALS is added as a second or third parameter (AUC=0.76, AUC=0.77). Furthermore, the variation in the outcome (GH-peak < / >= 7) explained by IGF1 only, amounts to 20.4% while that explained by IGFBP3 and ALS is only 10.6% and 7.8%. For IGF1, a -2 SDS cut-off delivers a sensitivity of 48% and a specificity of 83%. -1,5 SDS limit comes with similar sensitivity and specificity of 65%. For IGFBP-3, -2 SDS registered also an extremely low sensitivity of 65%, by -1,5 SDS of only 53%.An ALS cut-off value of -2 SDS comes with a sensitivity between 8-10%. Sensitivity values above 80% were seen starting with -0,4 SDS, point where specificity is already under 50%.
Conclusion: Serum ALS measurement alone should not be used in the diagnostic work-up of short stature. Combining the measurement of ALS with IGF-I and IGFBP-3 does not improve the chances of diagnosing GHD.
Keywords: IGF-1, IGFBP-3, ALS, Growth Hormone Deficiency
19 Sep 2019 - 21 Sep 2019