Hypothyroidism after Treatment with Interleukin-2 and Lymphokine-Activated Killer Cells

Abstract

The development of a goiter and hypothyroidism in a 28-year-old man in whom metastatic melanoma had been treated with interleukin-2 and lymphokine-activated killer cells (LAK cells) prompted us to assess thyroid function in patients undergoing this therapy. Thirty-four patients with advanced neoplasms who had received interleukin-2 and LAK cells were followed for at least four weeks after treatment. Seven patients (21 percent) had laboratory evidence of hypothyroidism, with a decline in the serum thyroxine concentration to below normal (less than or equal to 35 nmol per liter; normal, 65 to 148), a decline in the serum free thyroxine index, and a rise in the serum thyrotropin concentration (peak values, 7.2 to 166 mU per liter; normal, 0.5 to 5.5) 6 to 11 weeks after treatment. Two patients had elevated serum thyrotropin levels before treatment, which increased further after treatment. In two patients, these abnormal values returned to normal within 10 months. All five symptomatic patients had borderline or elevated serum antimicrosomal antibody titers after treatment; two had serum antibodies to thyroglobulin. Five of the seven patients with hypothyroidism (71 percent) but only 5 of the 27 euthyroid patients (19 percent) had evidence of tumor regression (P less than 0.02). None of 11 patients treated with interleukin-2 but not LAK cells had hypothyroidism. We conclude that treatment with interleukin-2 and LAK cells can cause hypothyroidism, possibly by exacerbating preexisting autoimmune thyroiditis, and that it may be associated with a favorable tumor response.

Thyroid dysfunction can predict response to immunotherapy with interleukin-2 and interferon-2α

“…The development of abnormal thyroid function has been well documented in association with treatment with alpha-interferon alone, IL-2 alone, IL-2 plus LAK cells, and IL-2 plus alpha-interferon (Atkins et al, 1988;Pichert et al, 1990). …”

Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy

“…the development of thyroid autoantibodies was associated with improved outcomes in patients with metastatic rCC who received interleukin 2 or iFnα immuno therapy. 14,15 limitations of this study include the small number of patients assessed, the absence of control partici pants, and the fact that baseline tFt measure ments were lacking in some patients. since a proportion of patients were pretreated with cytokines, it would be of interest to know whether hypo thyroidism is prevalent in pretreated or naive patients.…”

“…[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] some small molecule tyrosine kinase inhibitors (tKis) have been shown to cause hypothyroidism related symptoms to a variable extent, which can reduce a patient's quality of life. we review the available data for tKi related thyroid dysfunction and the hypothesized patho physiological mechanisms of this toxicity.…”

“…interleukin 2 and interferons (iFns) could induce functional thyroid damage in patients affected by melanoma or renal cell carcinoma (rCC), by causing thy roiditis. [12][13][14][15][16] increased levels of thyroid auto antibodies 14,15 or hypothyroidism without autoantibodies 16,17 have been associ ated with improved outcome in patients with competing interests The authors declared no competing interests. reviews (Flt3), colony stimulating factor 1 receptor (CsF1r), ret, Kit, and platelet derived growth factor receptor.…”

Cytokines and autoimmunity

“…In support of this hypothesis, administration of IL-2 was able to induce or accelerate the development of haemolytic anaemia and IDDM [91]. Furthermore, some patients undergoing IL-2 treatment for neoplasia developed hypothyroidism with lymphomonocytic infiltration of the aflected thyroid tissue [92]. Additional evidence that IL-2 is needed in order to provoke autoimmune reaction is derived from studies using transgenic mice expressing IL-2 in association with the insulin promoter in fi cells [93] which developed insulitis but not IDDM.…”