Studies of Benign and Malignant Thyroid Disease

左旋甲状腺素抑制促甲状腺激素(通常被称为促甲状腺激素，或TSH)用于治疗中高风险分化型甲状腺癌(DTC)以降低进展和死亡的可能性是基于相互矛盾的证据。 我们的目标是检查一组中高危DTC患者，以评估促甲状腺激素抑制与无进展生存期(PFS)和总生存期的关系。 这项队列研究使用了多中心数据库分析，包括来自第三转诊中心和当地诊所的患者，平均(SD)为7.2(5.8)年。纳入1979年1月1日至2015年3月1日期间接受全甲状腺切除和放射性碘治疗的DTC患者。在1012名患者中，145名患者因缺乏纵向促甲状腺激素测定而被排除在外。 这些患者接受左旋甲状腺素治疗，以靶向促甲状腺激素抑制，并根据促甲状腺激素目标的改变调整剂量。 主要的预后指标是总存活率和PFS。使用COX比例风险模型评估年龄、性别、肿瘤大小、组织学、淋巴结和远处转移在1.5、3.0和5.0年标志性事件中的作用。根据每个标志物前的平均促甲状腺激素评分将患者分为3组：(1)促甲状腺激素抑制组，(2)促甲状腺激素中度抑制或低正常组，(3)促甲状腺激素低-正常或升高组。 867例患者(女性557例，64.2%；平均SD年龄48.5~16.5岁)接受151(30~1600)mCI放射性碘治疗，293例(33.8%)观察到疾病进展，34例(3.9%)死亡，因此本研究在死亡事件方面力度不足。在具有里程碑意义的1.5年(P=.41)、3.0年(P=.51)和5.0年(P=.64)，促甲状腺激素抑制与PFS的改善无关。在1.5岁和3.0岁时，年龄(危险比HR，1.06；95%CI，1.03-1.08和HR，1.05；95%CI，1.01-1.08)、侧颈淋巴结转移(HR，4.64；95%CI，2.00-10.70和HR，4.02；95%CI，1.56-10.40)和远处转移(HR，7.54；95%CI，3.46-16.50和HR，7.10；95%可信区间(95%CI，2.77~18.20)与随后的进展时间独立相关，而在5.0年，侧颈淋巴结转移(HR，3.7；95%CI，1.16~11.90)和低分化组织学(HR，71.8；95%CI，9.80~526.00)患者的PFS较短。 中高危DTC患者可能无法从促甲状腺激素抑制中受益。这项研究为随机试验提供了理由。

Suppression of thyrotropin (often referred to as thyroid-stimulating hormone, or TSH) with levothyroxine used in management of intermediate- and high-risk differentiated thyroid cancer (DTC) to reduce the likelihood of progression and death is based on conflicting evidence. Our goal was to examine a cohort of patients with intermediate- and high-risk DTC to assess the association of thyrotropin suppression with progression-free survival (PFS) and overall survival. This cohort study used a multicenter database analysis including patients from tertiary referral centers and local clinics followed up for a mean (SD) of 7.2 (5.8) years. Patients with DTC treated uniformly with total thyroidectomy and radioactive iodine between January 1, 1979, and March 1, 2015, were included. Among the 1012 patients, 145 patients were excluded due to the lack of longitudinal thyrotropin measurements. The patients were exposed to levothyroxine therapy to target thyrotropin suppression with dose adjustments based on changing thyrotropin goal. The primary outcome measures were overall survival and PFS. A Cox proportional hazards model was used to assess the contribution of age, sex, tumor size, histology, and lymph node and distant metastases at landmarks 1.5, 3.0, and 5.0 years. The patients were divided into 3 groups based on mean thyrotropin score before each landmark: (1) suppressed thyrotropin, (2) moderately suppressed or low-normal thyrotropin, and (3) low-normal or elevated thyrotropin. Among 867 patients (557 64.2% female; mean SD age, 48.5 16.5 years) treated with a median (range) cumulative dose of 151 (30-1600) mCi radioactive iodine, disease progression was observed in 293 patients (33.8%), and 34 patients (3.9%) died; thus, the study was underpowered in death events. Thyrotropin suppression was not associated with improved PFS at landmarks 1.5 (P = .41), 3.0 (P = .51), and 5.0 (P = .64) years. At 1.5 and 3.0 years, older age (hazard ratio HR, 1.06; 95% CI, 1.03-1.08 and HR, 1.05; 95% CI, 1.01-1.08, respectively), lateral neck lymph node metastases (HR, 4.64; 95% CI, 2.00-10.70 and HR, 4.02; 95% CI, 1.56-10.40, respectively), and distant metastases (HR, 7.54; 95% CI, 3.46-16.50 and HR, 7.10; 95% CI, 2.77-18.20, respectively) were independently associated with subsequent time to progression, while at 5.0 years, PFS was shorter for patients with lateral neck lymph node metastases (HR, 3.70; 95% CI, 1.16-11.90) and poorly differentiated histology (HR, 71.80; 95% CI, 9.80-526.00). Patients with intermediate- and high-risk DTC might not benefit from thyrotropin suppression. This study provides the justification for a randomized trial.