Sartore-Bianchi Andrea, Soriani Alessandra, Mattioni Raffaella, Vaglio Augusto, Buzio Carlo, Porta Camillo
Medical Oncology, I.R.C.C.S. San Matteo University Hospital, I-27100 Pavia, Italy.
Oncol Rep. 2004 Oct;12(4):855-9.
The incidence of thyroid function changes among renal cell carcinoma (RCC) patients treated with high-dose IL-2 plus IFN-alpha ranges from 9 to 59%, independently of the administration route (i.v. or s.c.) of IL-2. Although several studies demonstrated a correlation between high-dose IL-2/IFN-alpha regimens and autoimmune thyroid disease, only very limited data are available when low doses of IL-2 plus IFN-alpha are used. We prospectively studied thyroid function in 52 patients with metastatic RCC undergoing immunotherapy with low-dose IL-2 + IFN-alpha. All patients received treatment cycles consisting of both s.c. IL-2 and i.m. IFN-alpha for 4 consecutive weeks; cycles were repeated at 4-month intervals in all patients, irrespectively of their response. Thyroid stimulating hormone (TSH), 3,3',5-triiodo-L-thyronine (T3), thyroxine (T4), human anti-thyroglobulin antibodies (hTg-Ab) and human anti-thyroid peroxidase antibodies (hTPO-Ab) were assayed in all patients before and after each of the first 3 cycles. None of the patients showed clinical signs of dysthyroidism, nor required replacement or suppressive treatment on thyroid function; specifically, no statistically significant differences were found when the median pre- and post-treatment TSH, T3, T4, hTg-Ab and hTPO-Ab levels of each cycle were compared. The median TSH values after the 3 cycles were, respectively, 1.06 [Inter Quartile Range (IQR) 0.58-1.51], 1.21 (IQR 0.58-1.51) and 1.05 micro U/ml (IQR 0.67-1.73). As for thyroid hormones, median values after each of the 3 cycles were: 1.38 (IQR 1.19-1.50), 1.46 (IQR 1.17-1.66) and 1.36 (IQR 1.16-1.46) ng/ml for T3, and 8.74 (IQR 7.26-9.45), 8.67 (IQR 7.12-9.18) and 8.40 (IQR 7.12-9.33) micro g/dl for T4. These data show that a regimen of low-dose IL-2 plus IFN-alpha does not seem to affect thyroid function, neither inducing signs or symptoms of dysthyroidism, nor by causing major biochemical changes in TSH and thyroid hormone levels, or an increase in thyroid-specific auto-antibodies.
接受高剂量白细胞介素-2（IL-2）加α干扰素治疗的肾细胞癌（RCC）患者中，甲状腺功能改变的发生率在9%至59%之间，与IL-2的给药途径（静脉注射或皮下注射）无关。尽管多项研究表明高剂量IL-2/α干扰素方案与自身免疫性甲状腺疾病之间存在关联，但使用低剂量IL-2加α干扰素时，仅有非常有限的数据。我们前瞻性地研究了52例接受低剂量IL-2 +α干扰素免疫治疗的转移性RCC患者的甲状腺功能。所有患者均接受连续4周的皮下注射IL-2和肌肉注射α干扰素组成的治疗周期；所有患者均每隔4个月重复治疗周期，无论其反应如何。在最初3个周期的每个周期前后，对所有患者检测促甲状腺激素（TSH）、3,3',5-三碘-L-甲状腺原氨酸（T3）、甲状腺素（T4）、人抗甲状腺球蛋白抗体（hTg-Ab）和人抗甲状腺过氧化物酶抗体（hTPO-Ab）。没有患者出现甲状腺功能障碍的临床体征，也无需进行甲状腺功能的替代或抑制治疗；具体而言，比较每个周期治疗前和治疗后TSH、T3、T4、hTg-Ab和hTPO-Ab水平的中位数时，未发现统计学上的显著差异。3个周期后的TSH中位数分别为1.06 [四分位间距（IQR）0.58 - 1.51]、1.21（IQR 0.58 - 1.51）和1.05微单位/毫升（IQR 0.67 - 1.73）。至于甲状腺激素，3个周期中每个周期后的中位数分别为：T3为1.38（IQR 1.19 - 1.50）、1.46（IQR 1.17 - 1.66）和1.36（IQR 1.16 - 1.46）纳克/毫升，T�为8.74（IQR 7.26 - 9.45）、8.67（IQR 7.12 - 9.18）和8.40（IQR 7.12 - 9.33）微克/分升。这些数据表明，低剂量IL-2加α干扰素方案似乎不会影响甲状腺功能，既不会诱发甲状腺功能障碍的体征或症状，也不会导致TSH和甲状腺激素水平出现重大生化变化，或甲状腺特异性自身抗体增加。
