TY - JOUR
T1 - Hypothyroidism during immunotherapy with interleukin-2 is associated with antithyroid antibodies and response to treatment
AU - Weijl, N. I.
AU - Van Der Harst, D.
AU - Brand, A.
AU - Kooy, Y.
AU - Van Luxemburg, S.
AU - Schroder, J.
AU - Lentjes, E.
AU - Van Rood, J. J.
AU - Cleton, F. J.
AU - Osanto, S.
PY - 1993/1/1
Y1 - 1993/1/1
N2 - Purpose: We investigated whether the association of interleukin-2 (IL-2) with hypothyroidism is related to the presence of thyroid autoantibodies, dose of IL-2, and clinical effectiveness of treatment, and reviewed the literature. Patients and Methods: Sixteen cancer patients were treated with high-dose recombinant, continuous infusion IL-2 (18 × 106 IU/m2/d) and lymphokine-activated killer (LAK) cells. One patient previously treated for a toxic goiter with radioactive iodine was analyzed separately. Thyroid function and levels of thyroid antibodies were determined regularly. Results: Seven of 15 patients (47%) became hypothyroid with high serum thyrotropin (TSH) levels within 60 to 120 days after the start of treatment; five responded favorably to treatment (one complete remission [CR], four partial remissions [PRs]), compared with none of the other eight patients. Two hypothyroid patients developed antimicrosomal antibodies (AMAs), one showed a further increase of antithyroglobulin antibodies (TgAbs), and six developed TgAbs. Only one of eight euthyroid patients developed slightly elevated TgAb levels. Development of hypothyroidism correlated significantly with a favorable response to treatment (r = .76, P = .001). The patient, treated with radioactive iodine, also became hypothyroid with high levels of TSH and development of AMAs and TgAbs. No difference was found between the hypothyroid and euthyroid patients in mean cumulative dose of IL-2 administered within the first 60 days or total treatment period, or with the relative dose-intensity. No other autoantibodies were found and patients had normal corticotropin (ACTH) ystimulation tests. Conclusion: The likelihood of developing (transient) hypothyroidism is higher in patients who respond to IL-2 treatment. The development of antithyroid antibodies suggests that IL-2 treatment triggers autoreactive B-cell clones or that cellular and/or cytokine-mediated thyroid destruction leads to activation of autoreactive B-cell clones.
AB - Purpose: We investigated whether the association of interleukin-2 (IL-2) with hypothyroidism is related to the presence of thyroid autoantibodies, dose of IL-2, and clinical effectiveness of treatment, and reviewed the literature. Patients and Methods: Sixteen cancer patients were treated with high-dose recombinant, continuous infusion IL-2 (18 × 106 IU/m2/d) and lymphokine-activated killer (LAK) cells. One patient previously treated for a toxic goiter with radioactive iodine was analyzed separately. Thyroid function and levels of thyroid antibodies were determined regularly. Results: Seven of 15 patients (47%) became hypothyroid with high serum thyrotropin (TSH) levels within 60 to 120 days after the start of treatment; five responded favorably to treatment (one complete remission [CR], four partial remissions [PRs]), compared with none of the other eight patients. Two hypothyroid patients developed antimicrosomal antibodies (AMAs), one showed a further increase of antithyroglobulin antibodies (TgAbs), and six developed TgAbs. Only one of eight euthyroid patients developed slightly elevated TgAb levels. Development of hypothyroidism correlated significantly with a favorable response to treatment (r = .76, P = .001). The patient, treated with radioactive iodine, also became hypothyroid with high levels of TSH and development of AMAs and TgAbs. No difference was found between the hypothyroid and euthyroid patients in mean cumulative dose of IL-2 administered within the first 60 days or total treatment period, or with the relative dose-intensity. No other autoantibodies were found and patients had normal corticotropin (ACTH) ystimulation tests. Conclusion: The likelihood of developing (transient) hypothyroidism is higher in patients who respond to IL-2 treatment. The development of antithyroid antibodies suggests that IL-2 treatment triggers autoreactive B-cell clones or that cellular and/or cytokine-mediated thyroid destruction leads to activation of autoreactive B-cell clones.
UR - https://www.scopus.com/pages/publications/0027245920
U2 - 10.1200/JCO.1993.11.7.1376
DO - 10.1200/JCO.1993.11.7.1376
M3 - Article
C2 - 8315436
AN - SCOPUS:0027245920
SN - 0732-183X
VL - 11
SP - 1376
EP - 1383
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 7
ER -