Atkins M B, Mier J W, Parkinson D R, Gould J A, Berkman E M, Kaplan M M
Department of Medicine, New England Medical Center, Boston, MA 02111.
N Engl J Med. 1988 Jun 16;318(24):1557-63. doi: 10.1056/NEJM198806163182401.
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.
一名28岁男性曾接受白细胞介素-2和淋巴因子激活的杀伤细胞（LAK细胞）治疗转移性黑色素瘤，之后出现了甲状腺肿和甲状腺功能减退，这促使我们对接受该疗法的患者的甲状腺功能进行评估。34例接受白细胞介素-2和LAK细胞治疗的晚期肿瘤患者在治疗后至少随访了四周。7例患者（21%）有甲状腺功能减退的实验室证据，血清甲状腺素浓度降至正常以下（小于或等于35纳摩尔/升；正常为65至148），血清游离甲状腺素指数下降，血清促甲状腺素浓度在治疗后6至11周升高（峰值为7.2至166毫国际单位/升；正常为0.5至5.5）。2例患者在治疗前血清促甲状腺素水平就升高，治疗后进一步升高。2例患者的这些异常值在10个月内恢复正常。所有5例有症状的患者在治疗后血清抗微粒体抗体滴度处于临界值或升高；2例有抗甲状腺球蛋白血清抗体。7例甲状腺功能减退患者中有5例（71%）出现肿瘤消退迹象，但27例甲状腺功能正常的患者中只有5例（19%）出现肿瘤消退迹象（P<0.02）。11例仅接受白细胞介素-2治疗而未接受LAK细胞治疗的患者均未出现甲状腺功能减退。我们得出结论，白细胞介素-2和LAK细胞治疗可能通过加重已有的自身免疫性甲状腺炎而导致甲状腺功能减退，并且可能与良好的肿瘤反应相关。
