SUPPRESSED THYROID-STIMULATING HORMONE-SECRETION IN PATIENTS TREATED WITH INTERLEUKIN-2 AND INTERFERON-ALPHA(2B) FOR METASTATIC MELANOMA

Recent reports suggest that combined therapy with recombinant interleu kin (IL)-2 and interferon (IFN) alpha(2b) may result in autoimmune-ind uced thyroid dysfunction. We prospectively analyzed thyroid function f or 6 weeks in two groups of patients with progressive metastatic melan oma treated according to two different protocols. In group I (n=17) th ree treatment cycles were given, each with three weeks of subcutanous administration of rIL-2 and INF-alpha(2b), at different doses. In grou p II (n=13) the chemotherapeutic agent dacarbazine was given in additi on. In group 1 three patients developed frank hyperthyroidism, which r equired antithyroid drug therapy in one case. Autoantibodies against t hyroid microsomal antigen, thyroglobulin, and the thyroid-stimulating hormone (TSH) receptor were not significantly elevated in any of these patients. However, the remaining 14 patients showed a significant dec rease in TSH after 6 weeks of treatment, from 1.8+/-0.9 to 0.7+/-0.7 m u U/ml (P < 0.02). Thyroid hormones (triiodothyronine, thyroxine, free thyroxine) also increased during the observation time, but this did n ot parallel the drop in TSH levels. Only thyroxine increased above the upper limit of normal, while triiodothyronine and free thyroxine stay ed within the normal range. In group II, 6 of 13 patients (46%) had a decreased TSH after 6 weeks of treatment. Mean TSH was 1.5+/-1.4 befor e and 0.8+/-0.6 mu U/ml after 6 weeks and was totally suppressed in th ree cases. None of these patients showed ouvert hyperthyroidism. Hypot hyroidism was not observed in either group. We conclude that treatment with rIL-2 and INF-alpha(2b) may not only be associated with autoimmu ne thyroiditis and hyperthyroidism but also results in suppression of TSH levels while the patients remain euthyroid.