Ghosh Raisa, Auh Sungyoung, Gubbi Sriram, Veeraraghavan Padmasree, Cochran Craig, Shobab Leila, Urken Mark L, Burman Kenneth D, Wartofsky Leonard, Klubo-Gwiezdzinska Joanna
National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20814, USA.
Department of Endocrinology, MedStar Washington Hospital Center, Washington, DC, USA.
J Clin Endocrinol Metab. 2025 Apr 22;110(5):e1473-e1480. doi: 10.1210/clinem/dgae537.
Supraphysiologic T4 doses are used in intermediate- and high-risk patients with differentiated thyroid cancer (IR/HR-DTC) to suppress tumor progression by TSH. However, preclinical data suggest that T4 can also act as a growth stimulus for cancer, but there is no clinical evidence supporting this claim.
We analyzed the association between free T4 (FT4) and progression-free survival (PFS) in patients with IR/HR-DTC.
This longitudinal cohort study, approved by multi-institutional review board, included patients with IR/HR-DTC treated uniformly with total thyroidectomy, radioiodine, and TSH suppression therapy, with at least 3 TSH and FT4 values available. Association between FT4 and PFS at landmarks 6, 12, and 18 months was assessed by Kaplan-Meier survival curves, whereas competing risks were assessed through Cox proportional hazards model.
From 739 screened patients, 382 met the inclusion criteria and were characterized by a median age of 46 (34-59) years, 64.1% women, and treated with a median radioiodine dosage of 159 (110-410) mCi. During follow up of 7.1 (3.4-12.7) years, 34.6% experienced disease progression. Elevated FT4, observed in 29.3% of patients, was not associated with worse PFS (hazard ratio [HR], 0.9; CI, 0.54-1.5; P = .69), whereas age (HR, 1.02; CI, 1.004-1.04; P = .01), tumor size (HR, 1.15; CI, 1.04-1.28; P = .01) and metastases to the lateral neck lymph nodes (HR, 2.9; CI, 1.7-4.74; P < .001), bones (HR, 4.87; CI, 1.79-13.3; P = .002), and brain (HR, 5.56; CI; 2.54-12.2; P < .001) were associated with shorter PFS.
Contrary to preclinical evidence, elevated FT4 levels do not affect PFS in patients with IR/HR-DTC.
超生理剂量的甲状腺素（T4）用于中高危分化型甲状腺癌（IR/HR-DTC）患者，以通过促甲状腺激素（TSH）抑制肿瘤进展。然而，临床前数据表明T4也可作为癌症的生长刺激因素，但尚无临床证据支持这一说法。
我们分析了IR/HR-DTC患者游离甲状腺素（FT4）与无进展生存期（PFS）之间的关联。
这项纵向队列研究经多机构审查委员会批准，纳入接受全甲状腺切除术、放射性碘和TSH抑制治疗的IR/HR-DTC患者，至少有3个TSH和FT4值。通过Kaplan-Meier生存曲线评估FT4与6、12和18个月时间节点的PFS之间的关联，而通过Cox比例风险模型评估竞争风险。
在739名筛查患者中，382名符合纳入标准，中位年龄为46（34-59）岁，64.1%为女性，中位放射性碘剂量为159（110-410）mCi。在7.1（3.4-12.7）年的随访期间，34.6%的患者出现疾病进展。29.3%的患者FT4升高，这与较差的PFS无关（风险比[HR]，0.9；可信区间[CI]，0.54-1.5；P = 0.69），而年龄（HR，1.02；CI，1.004-1.04；P = 0.01）、肿瘤大小（HR，1.15；CI，1.04-1.28；P = 0.01）以及侧颈淋巴结转移（HR，2.9；CI，1.7-4.74；P < 0.001）、骨转移（HR，4.87；CI，1.79-13.3；P = 0.002）和脑转移（HR，5.56；CI；2.54-12.2；P < 0.001）与较短的PFS相关。
与临床前证据相反，FT4水平升高并不影响IR/HR-DTC患者的PFS。
