Circulating soluble interleukin 2 receptor concentration is increased in both immunogenic and nonimmunogenic hyperthyroidism

High serum concentration of soluble interleukin-2 receptor (sIL-2R) is considered a reliable marker of T lymphocyte activation. It has been recently reported that sIL-2R levels are increased in untreated Graves’ disease. This finding has been interpreted as the consequence of an active autoimmune state, but the relevance of the thyroid function per se was not investigated. In the present study we assayed sIL-2R by ELISA in 20 normal subjects and in a series of patients with immunogenic (Graves’ disease, GD) or nonimmunogenic (toxic adenoma, TA) hyperthyroidism. Significantly increased concentrations of sIL-2R were found in 46 patients with untreated hyper-thyroid GD (mean ± SD: 1,683 ± 1016 U/ml, vs 461 ± 186 U/ml in normal controls, p < 0.0001) and in 21 with untreated TA (1,111 ± 617 U/ml, p < 0.0001 vs normals). Restoration of the euthyroid state by antithyroid drugs or ¹³¹I administration was associated with a normalization of sIL-2R (516 ± 174 U/ml in 38 patients with GD and 365 ± 90 U/ml in 12 with TA; p = NS vs normals and p < 0.001 vs the untreated state for both groups). A highly significant positive correlation between serum sIL-2R and free triiodothyronine (FT₃) (r = 0.724, p < 0.0001) or free thyroxine (FT₄) (r = 0.698, p < 0.0001) concentrations was found in combined sera obtained from all untreated and treated patients, irrespectively of the autoimmune or nonautoimmune nature of the underlying hyperthyroid disease. No relationship was found between sIL-2R and the presence or the titer of anti-thyroglobulin and anti-thyroid peroxidase autoantibodies. In conclusion, sIL-2R concentrations are increased in immunogenic and nonimmmunogenic hyperthyroidism. This phenomenon prevents the use of sIL-2R as a reliable marker of autoimmune activation in hyperthyroid conditions.