ESPE2024 Rapid Free Communications GH and IGFs (6 abstracts)
Understanding the molecular basis of short stature in Fanconi Anemia: Impact of pappalysins and stanniocalcins on IGF-I bioavailability
Beatriz Corredor 1,2 , Alvaro Martín 2 , Josune Zubicaray 3,4 , Julián Sevilla 3,4,5 , Vicente Barrios 2,6 & Jesús Argente 2,5,6,7
1Pediatric Endocrinology. Hospital Universitario Toledo, Toledo, Spain. 2Pediatric Endocrinology. Hospital Universitario Niño Jesús, Madrid, Spain. 3Pediatric Hematology. Hospital Universitario Niño Jesús, Madrid, Spain. 4Centre for Biomedical Research on Rare Diseases Network (CIBERER), Madrid, Spain. 5Department of Pediatrics. Universidad Autónoma de Madrid, Madrid, Spain. 6IMDEA, Research Institute on Food and Health Sciences, CEIUAM+CSI, Madrid, Spain. 7CIBEROBN Physiopathology of Obesity and Nutrition Biomedical Research Centre. Instituto de Salud Carlos III, Madrid, Spain
Introduction: The stanniocalcins (STCs) are inhibitory factors of the growth-promoting effects of IGFs through inactivation of pappalysins that favor the release of IGFs from their binding proteins (IGFBPs). STC1 can be involved in the cellular response to stress and plays an important role in cell cycle regulation. Patients with Fanconi Anemia (FA) are more sensitive to oxidative stress that could alter the expression of STC1. Our aim was to assess whether pappalysins and STCs influence IGF-I bioavailability in these patients.
Methodoloy: A case-control study was carried out in a reference pediatric center. Thirty children with FA and 60 controls matched for age, sex and pubertal stage were included and blood samples were taken to determine the components of the GH-IGF system. Differences in serum parameters between controls and patients were determined by the Mann-Whitney U test.
Results: The FA group were shorter -1.88 SD (IQR: -2.25; -1.08) vs control 0.33 SD (IQR: -0.24-0.81) P = 0.000 and had a lower BMI -0.31 SD (IQR: -0.67-0.43) vs control 0.84 SD (IQR: -0.29; 0.97) P = 0.005. There were no differences between age groups. The following table shows the comparison of GH-IGF axis parameters (median, IQR) between controls and FA patients. No differences by sex or hematological therapy were detected.
| Variable | Control: | FA: | p: |
| IGF-I (ng/mL) | 370.72 (271.01-600.19) | 317.35 (198.29-471.74) | 0.1903 |
| Free IGF-I (ng/mL) | 3.54 (2.23-5.13) | 5.71 (2.95-8.60) | 0.0097* |
| IGF-II (ng/mL) | 147.69 (113.59-194.27) | 162.52 (138.78-262.56) | 0.0696 |
| IGFBP-2 (ng/mL) | 57.7 (40.64-80.4) | 31.23 (15.17-57.32) | 0.0020* |
| Total IGFBP-3 (ng/mL) | 3682.25 (2946.35-4552.6) | 4076.85 (3312.5-5759.1) | 0.0000* |
| Intact IGFBP-3 (ng/mL) | 836.97 (608.72-1220) | 514.26 (355.08-657.9) | 0.0127* |
| Total IGFBP-4 (ng/mL) | 23.78 (14.74-40.60) | 34.74 (24.23-54.69) | 0.0709 |
| Intact IGFBP-4 (ng/mL) | 22.54 (19.93-27.75) | 18.48 (14.90-27.45) | 0.1109 |
| IGFBP-5 (ng/mL) | 384.89 (286.07-494.65) | 501.25 (374.16-734.41) | 0.1329 |
| ALS (ng/mL) | 8839.55 (7612.2-10671.5) | 8738.1 (6647.1-10889) | 0.4113 |
| STC1 (pg/mL) | 517.4 (363.10-707.40) | 271.00 (154.16-540.49) | 0.0004* |
| STC2 (ng/mL) | 26.17 (22.29-30.08) | 25.90 (20.67-28.19) | 0.2182 |
| PAPP-A (ng/mL) | 0.56 (0.33-0.76) | 0.78 (0.53-1.11) | 0.1170 |
| PAPP-A2 (ng/mL) | 4.83 (3.27-6.37) | 3.81 (2.68-5.03) | 0.0368* |
| IGF-I (free/total) | 0.86 (0.54-1.59) | 1.54 (1.04-2.91) | 0.0006* |
| IGFBP-3 (Intact/total) | 23.60 (16.12-34.78) | 12.01 (6.68-18.53) | 0.0000* |
| IGFBP-4 (Intact/total) | 84.49 (54.91-152.38) | 60.82 (35.13-90.36) | 0.0028* |
Conclusions: The reduction in STC-1 could be involved in increased IGFBP proteolysis, promoting IGF-I bioavailability. This could act as a negative feedback on the GH-IGF-I axis leading to a state of relative GH insufficiency in FA patients.
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