Transient Stimulatory Effects on Pituitary-Thyroid Axis in Patients Treated with Interleukin-2

Abstract

It has been shown that various cytokine therapies may influence thyroid hormone parameters that may lead to serious side effects including nonthyroidal illness. Interleukin-2 is effective in increasing CD4-T cell numbers in human immunodeficiency virus (HIV)-infected patients and it is used in the treatment of various malignant tumours. However, the association of interleukin-2 (IL-2) therapy and thyroid function is not clearly established as serial systematic measurements of thyroid parameters have not been performed with 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 evaluated by measurements of serum thyrotropin (TSH), triiodothyronine (T₃), thyroxine (T₄), free thyroxine (FT₄), reverse T₃ (rT₃), thyroglobulin (Tg), thyroxine-binding globulin (TBG), and anti-thyroid-peroxidase (TPO)-antibodies from day 1-4 and on days 7, 14, 20, 40, 60, 80, and 100. All results are given as mean ± SD. On day 4, we observed a significant increase that was still within normal range of T₄ and T₃ (p < 0.05). TSH increased from 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 thereafter. Normalization to baseline levels for TSH (1.45 ± 0.75 mU/L) and FT₄ (18.1 ± 3.0 pmol/L) was achieved only on day 14. The increase of FT₄ was more pronounced(well in the hyperthyroid range) than the increase in total T₄ in the presence of normal TBG and albumin concentrations whereas TBG was not affected. We did not observe changes in anti-TPO-antibody levels up to day 100. Our data clearly demonstrate that the administration of interleukin-2 has a stimulatory effect on the pituitary-thyroid axis. The increase of TSH suggests a central stimulation directed by the action of IL-2 as the major mechanism.