9282 Silver - Russell Syndrome and Free Insulin-like Growth Factor-1 Measurements

Abstract Disclosure: R.D. Oude Engberink: None. V. van den Bogert: None. L. IJsselstijn: None. S.A. van den Berg: None. D.C. van der Kaay: None. Introduction: Silver - Russell syndrome (SRS) is a congenital condition characterized by prenatal and postnatal growth retardation. An underlying genetic cause is identified in approximately 60% of patients clinically diagnosed with SRS. The 2 main genetic alterations are loss of methylation of chromosome 11p15 (11p15 LOM) and maternal uniparental disomy of chromosome 7 (UPD(7)mat). Patients benefit from early and appropriate growth hormone (GH) treatment. However, GH treatment in SRS patients is associated with high levels (> 2 SDS) of immunoreactive Insulin-like Growth Factor-1 (IGF-1). As a result, clinicians often lower the GH dose, resulting in a suboptimal effect on growth, body composition and quality of life. There has been increased interest in measuring free IGF-1 in these conditions. Theoretically, the unbound fraction of IGF - i.e. the fraction that is readily dissociable from IGF binding proteins - is the biologically active fraction. Measurement of free IGF-1 might better reflect IGF-1 bioavailability and may be of benefit in optimizing GH treatment. Objective and methods: We explored levels of free IGF-I versus immunoreactive (total) IGF-1 in 22 SRS patients on GH treatment. Immunoreactive IGF-1 was measured on a routine immunochemistry analyzer (IDS-iSYS) and free IGF-1 was measured manually using a two-site antibody method (AnshLabs). Results: In this group of 22 SRS patients the mean immunoreactive IGF-1 was +1.96 +/- 0.48 SDS and the mean GH dose was 0.84 +/- 0.24 mg/m2/d. Subdividing into SDS categories, 45% of patients had an immunoreactive IGF-1 > 2 SDS. In this subset, 60% of patients had levels of free IGF-1 in the normal range (< 2 SDS). Further stratification into the underlying molecular defect showed that 11p15 LOM was associated with a more pronounced discrepancy between the level of immunoreactive IGF-1 (+2.64 SDS) and free IGF-1 (+0.25 SDS). Conclusion: In the majority of SRS patients on GH treatment, immunoreactive IGF-1 levels exceeded > 2 SDS, whereas free IGF-1 levels were within normal range. Measurement of free IGF-1 could provide clinicians with an additional tool to determine the dose of GH in SRS patients. Ongoing research will reveal the full potential of free IGF-1 measurements in disorders that affect the GH - IGF-1 axis. Presentation: 6/3/2024