Caetano Celina, Pico Paola Tabaro, Singh Charan, Tendler Beatriz, Malchoff Diana M, Malchoff Carl D
Neag Comprehensive Cancer Center, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
Department of Radiology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
J Endocr Soc. 2022 Sep 13;6(11):bvac140. doi: 10.1210/jendso/bvac140. eCollection 2022 Oct 11.
The conventional treatment of nonmedullary thyroid carcinoma (NMTC) includes surgical resection, thyrotropin (TSH) suppression, and 131-iodine. Some patients develop persistent/recurrent metastatic disease requiring expensive alternative therapies, such as external radiation and multikinase inhibitors, which may have clinically significant side effects. Recent in vitro studies, in vivo studies in animals, and association studies in humans suggest that metformin, an inexpensive medication with a modest side effect profile, may help prevent or treat NMTC. No interventional trials analyzing the effect of metformin have been performed in humans.
We hypothesize that metformin administration will decrease serum thyroglobulin concentration (Tg), a surrogate marker for NMTC burden.
This retrospective institutional review board-approved study included 10 patients with persistent/recurrent NMTC who had exhausted conventional therapies including total thyroidectomy and 131-iodine. Five had detectable disease on computed tomography imaging. All had biochemical evidence of NMTC with Tg > 2.0 ng/mL with nondetectable serum thyroglobulin antibody concentrations. Five elected to have metformin treatment at doses varying from 500 to 2000 mg/day for 2 to 5 months. The remaining 5 served as untreated controls. Statistical significance was determined by the Mann-Whitney test.
Tg decreased (mean decrease = 21.7 ± 8.4%) in all 5 patients receiving metformin and increased (mean increase = 16.6 ± 12.1%) in all 5 controls ( < .01). TSH did not change significantly in either group.
In summary, metformin caused a TSH-independent Tg decrease in patients with persistent/recurrent NMTC. More extensive studies are required to determine if metformin slows NMTC progression.
非髓样甲状腺癌（NMTC）的传统治疗方法包括手术切除、促甲状腺激素（TSH）抑制和碘-131治疗。一些患者会出现持续性/复发性转移性疾病，需要昂贵的替代疗法，如外部放疗和多激酶抑制剂，这些疗法可能会产生具有临床意义的副作用。最近的体外研究、动物体内研究以及人体关联研究表明，二甲双胍这种价格低廉且副作用较小的药物，可能有助于预防或治疗NMTC。目前尚未在人体中进行分析二甲双胍疗效的干预性试验。
我们假设给予二甲双胍会降低血清甲状腺球蛋白浓度（Tg），这是NMTC负荷的替代标志物。
这项经机构审查委员会批准的回顾性研究纳入了10例持续性/复发性NMTC患者，这些患者已用尽包括全甲状腺切除和碘-131治疗在内的传统疗法。5例患者在计算机断层扫描成像上可检测到疾病。所有患者均有NMTC的生化证据，血清甲状腺球蛋白（Tg）>2.0 ng/mL，血清甲状腺球蛋白抗体浓度不可检测。5例患者选择接受二甲双胍治疗，剂量为500至2000 mg/天，持续2至5个月。其余5例作为未治疗的对照。采用曼-惠特尼检验确定统计学意义。
所有5例接受二甲双胍治疗的患者Tg均下降（平均下降=21.7±8.4%），而所有5例对照患者的Tg均升高（平均升高=16.6±12.1%）（P<0.01）。两组患者的TSH均无显著变化。
总之，二甲双胍使持续性/复发性NMTC患者的Tg在不依赖TSH的情况下下降。需要进行更广泛的研究来确定二甲双胍是否能减缓NMTC的进展。
