Transient stimulatory effects on pituitary-thyroid axis in patients treated with interleukin-2

It has been shown that various cytokine therapies may influence thyroid hor mone parameters that may lead to serious side effects including nonthyroida l illness. Interleukin-2 is effective in increasing CD4-T cell numbers in h uman immunodeficiency virus (HIV)-infected patients and it is used in the t reatment of various malignant tumours. However, the association of interleu kin-2 (IL-2) therapy and thyroid function is not clearly established as ser ial systematic measurements of thyroid parameters have not been performed w ith interleukin-2 as the sole therapeutic agent. Therefore, it was the aim of this study to examine prospectively the impact of a 5-day interleukin-2 therapy on thyroid parameters in asymptomatic HIV-infected patients. Twenty male euthyroid patients (mean age, 42.6 +/- 3.2 years; body weight, 73.4 /- 3.0 kg) received 9,000,000 IU/d interleukin-2. Thyroid function was eval uated by measurements of serum thyrotropin (TSH), triiodothyronine (T-3), t hyroxine (T-4), free thyroxine (FT4), reverse T-3 (rT(3)), thyroglobulin (T g), thyroxine-binding globulin (TBG), and anti-thyroid-peroxidase (TPO)-ant ibodies from day 1-4 and on days 7, 14, 20, 40, 60, 80, and 100. All result s are given as mean +/- SD. On day 4, we observed a significant increase th at was still within normal range of T-4 and T-3 (p < 0.05). TSH increased f rom 1.33 +/- 0.57 to 4.53 +/- 1.39 mU/I (p = 0.0001) and FT4 from 18.1 +/- 4.2 to 48.9 +/- 10.9 pmol/L (p = 0.0001) on day 4 with a gradual decrease t hereafter. Normalization to baseline levels for TSH (1.45 +/- 0.75 mU/L) an d FT4 (18.1 +/- 3.0 pmol/L) was achieved only on day 14. The increase of FT 4 was more pronounced (well in the hyperthyroid range) than the increase in total T-4 in the presence of normal TBG and albumin concentrations whereas TBG was not affected. We did not observe changes in anti-TPO-antibody leve ls up to day 100. Our data clearly demonstrate that the administration of i nterleukin-2 has a stimulatory effect on the pituitary-thyroid axis. The in crease of TSH suggests a central stimulation directed by the action of IL-2 as the major mechanism.