Suppressed thyroid-stimulating hormone secretion in patients treated with interleukin-2 and interferon-α2b for metastatic melanoma
Recent reports suggest that combined therapy with recombinant interleukin (IL)-2 and interferon (IFN) alb may result in autoimmune-induced thyroid dysfunction. We prospectively analyzed thyroid function for 6 weeks in two groups of patients with progressive metastatic melanoma treated according to two different protocols. In group I (n =17) three treatment cycles were given, each with three weeks of subcutanous administration of rIL-2 and INF-α2b at different doses. In group 11 (n=13) the chemotherapeutic agent dacarbazine was given in addition. In group 1 three patients developed frank hyperthyroidism, which required antithyroid drug therapy in one case. Autoantibodies against thyroid 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 decrease in TSH after 6 weeks of treatment, from 1.8 ± 0.9 to 0.7 ± 0.7 μU/ml (P < 0.02). Thyroid hormones (triiodothyronine, thyroxine, free thyroxine) also increased during the observation time, but this did not parallel the drop in TSH levels. Only thyroxine increased above the upper limit of normal, while triiodothyronine and free thyroxine stayed within the normal range. In group 11, 6 of 13 patients (46%) had a decreased TSH after 6 weeks of treatment. Mean TSH was 1.5±1.4 before and 0.8 ± 0.6 μU/ml after 6 weeks and was totally suppressed in three cases. None of these patients showed ouvert hyperthyroidism. Hypothyroidism was not observed in either group. We conclude that treatment with rIL-2 and INF-α2b may not only be associated with autoimmune thyroiditis and hyperthyroidism but also results in suppression of TSH levels while the patients remain euthyroid.