Endocrine Abstracts

Background: Immuglobulin 4 (IgG4) is the least common subtype of Immoglobulin G. However due to its unique characteristic it has been the focal point of many research projects, which eventualy led to the discovery of the sytemic fibro-inflammatory disorder called IgG4-Related Disease. The potential role of IgG4 in the pathogenesis of autoimmune thyroid diseases has been also suggested. However, the amount of evidence is still limited, especially in Graves Disease (GD).

Objective: In this study we aimed to assess the prevalence of patients with high IgG4 GD and the corelations between IgG4 and other clinical, ultrasounographic and biochemical parameters.

Methods: 60 patients with GD were recruited. The study group was divided into 3 subgroups: Group 1 – hyperthyroid patients with newly diagnosed GD (n=29); Group 2 – euthyroid patients with GD after antythyroid treatment (n=19); Group 3 – patients with moderate to sever Graves Orbitopathy (GO) (n=12). Only patients who had not been previously treated with thyroidectomy or radioiodine were included in the study. All patients underwent a detailed laboratory assessment and ultrasonographic evaluation. IgG4 serum concentration was evaluated with the ELISA method. High IgG4 GD was defined as IgG4 serum >135 mg/dl.

Results: The prevalence of high IgG4 GD was low among GD patients without orbitopathy (4%) and substantially higher in patients with GO (33%). IgG4 serum concentration was higher in GO group than in the hyperthyroid and euthyroid GD groups (87.9 [61.55; 143.78] vs 31.4 [23.7; 41.7] mg/dl, P<0.001 and vs 30.1 [26.95; 79.6] mg/dl, P=0.015, respectively). There was no difference in IgG4 levels between the hyperthyroid and euthyroid GD groups, despite massive differences in anti-TSH receptor antibodies (TRAb) (29 [12.92; 6.38] vs 1.93 [0.78; 3.46] P<0.001), anti-thyroperoxidase antibodies (TPOAb) (274 [62; 522.75] vs 37 [21.5; 122.5] P=0.005). There were no statistically significant correlations between IgG4 levels and thyroid stimulating hormone (TSH), free thyroid hormones, TRAb, TPOAb and anti-thyroglobulin antibodies (TgAb) levels nor with thyroid volume, thyroid echogenicity, intrathyroidal blood flow. Patients with multiple thyroid nodules (>=3) had significantly lower IgG4 levels than those with <3 nodules (41.35 [29.5; 91.93 vs 25.7 [23.8; 26.3] mg/dl, P=0.026).

Conclusions: Our results suggest that IgG4 serum concentration is associated with the occurence of Graves Orbitopathy. The IgG4 serum concentration seems to be unrelated to TRAb, TPOAb or TgAb levels. Further studies, especially with a longitudinal design, are needed to determine the influence of IgG4 levels on the treatment outcomes and prognosis of GD patients.