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Free and Total Insulin-Like Growth Factor (IGF)-I, -II, and IGF Binding Protein-1, -2, and -3 Serum Levels in Patients with Active Thyroid Eye Disease

Department of Endocrinology and Metabolism (G.E.K., N.P., T.K.), Panagia General Hospital, 55132 Thessaloniki, Greece; Hippokrates (A.D.), Nuclear Medicine Center, 54622 Thessaloniki, Greece; and Medical Research Laboratories (J.F., J.W.C., A.F.), Aarhus Kommunehospital, University Hospital in Aarhus, DK-8000 Aarhus Center, Denmark

Address all correspondence and requests for reprints to: Prof. G. E. Krassas, M.D., Associate Professor of Medicine, Chairman, Department of Endocrinology, and Metabolism, Panagia Hospital, Tsimiski 92, 546 22 Thessaloniki, Greece. E-mail: krassas{at}the.forthnet.gr.

To determine whether serum levels of total (T) and free (F) IGF-I and -II and IGF binding protein (IGFBP),-1, -2, and -3 are normal in euthyroid patients with Graves’ disease and active thyroid ophthalmopathy, we investigated the above-mentioned parameters in 21 patients (11 male, 10 female) aged 50.8 ± 11.8 yr (range 35–70) and 19 healthy individuals matched for age, gender, and body mass index. All patients had active thyroid eye disease (TED) with clinical activity scores 4 and positive orbital octreoscan in both eyes. Serum T and F IGF-I and IGF-II were determined using noncompetitive time-resolved monoclonal immunofluorometric assays, IGFBP-1 was determined by an in-house RIA, IGFBP-2 by a novel in-house time-resolved immunofluorometric assay, whereas IGFBP-3 by an immunoradiometric assay. All data are expressed as mean ± SD. Our results show that T and F IGF-I, -II, and IGFBP-1, -2, and -3 levels in patients were similar to controls and did not show any significant difference. Specifically, mean T IGF-I for patients group was 131 (61), F IGF-I was 0.47 (0.16), T IGF-II was 1056 (300), F IGF-II was 1.45 (0.54), IGFBP-1 was 33 (14), IGFBP-2 was 848 (377), and finally IGFBP-3 was 3953 (1422). For controls, mean T IGF-I was 146 (51), F IGF-I was 0.85 (0.43), T IGF-II was 939 (197), F IGF-II was 1.53 (0.53), IGFBP-1 was 44 (24), IGFBP-2 was 764 (316) and finally IGFBP-3 was 3721 (1017). Furthermore, no statistically differences emerged in the ratio between molar weights of T IGF-I/IGFBP-3 and T IGF-II/IGFBP-3, as well as to the F/T IGF-I and F/T IGF-II. Finally, no relationship was found between the levels of the above-mentioned parameters and clinical activity scores, octreoscan scores, and thyroid hormones. Our data demonstrate for the first time that serum levels of IGFs (including free fractions) and IGFBPs are not increased in euthyroid Graves’ patients with active TED. The increased IGF levels in retrobulbar tissues previously described, appear to be independent of serum IGFs concentration and probably represent autocrine and/or paracrine activity.

Abbreviations: CAS, Clinical activity scores; CV, coefficient of variation; F, free; IGFBP, IGF binding protein; rh, recombinant human; SM, somatostatin; SM-a, SM analogs; T, total; TED, thyroid eye disease.

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