Analytical Performance And Clinical Utility Of Thyroid F

甲状腺 F 的分析性能和临床实用性

• 批准号: 6675221
• 负责人: Gyorgy Csako
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6675221
• 关键词: cancer prevention; clinical trials; diagnosis design /evaluation; diagnostic tests; hormone regulation /control mechanism; hormone therapy; human subject; human therapy evaluation; meta analysis; neoplasm /cancer therapy; patient oriented research; thyroid function; thyroid neoplasm; thyroxine

Thyroid diseases represent the most common endocrine abnormalities and it has been estimated that about 20 million levothyroxine prescriptions are dispensed to about 1.8% of the population in the United States annually. Optimal use of valid laboratory tests for the assessment of thyroid status is thus important both medically and economically. In a multi-institute collaborative study, we continued to assess the performance of thyroid function tests for monitoring and the potential clinical utility of thyroid hormone therapy for suppressing papillary and/or follicular thyroid cancer. Long-term thyroid hormone therapy aiming at the suppression of serum thyrotropin (TSH) has been traditionally used in the management of well-differentiated thyroid cancer. However, formal validation of the effects of thyroid hormone suppression therapy through randomized controlled trials is lacking. Additionally, the effect of TSH at low ambient concentrations upon human thyroid tumorigenesis remains unclear. We identified 28 clinical trials from the literature that dealt with the use of thyroid hormone suppression therapy in patients with thyroid cancer between 1934 and 2001. Applying a likert scale, 15 of the17 "interpretable" studies showed either a "likely" or "questionable" beneficial effect of thyroid hormone suppression therapy on the outcome of thyroid cancer. We quantitatively evaluated the effect of thyroid hormone suppression therapy on the likelihood of major adverse clinical events (disease progression/recurrence and death) in a cumulative thyroid cancer cohort from 10 studies that qualified for meta-analysis. The 10 studies represented a combined total of 4,174 patients of whom 2,880 (69%) were reported as being on thyroid hormone suppression therapy. According to meta-analysis, the group of these patients with thyroid hormone suppression therapy had a decreased risk of major adverse clinical events (relative risk 0.73, confidence interval 0.60-0.88, p less than 0.05). Thus, despite the known adverse effects of long-term administration of thyroid hormones, suppression therapy with these hormones is justified in patients with thyroid cancer. High-sensitivity TSH assays that are capable of detecting very low TSH levels (at least less than 0.10 mU/L and, possibly, less than 0.01 mU/L) are needed to assess the adequacy of thyroid hormone suppression therapy in these patients. In another collaborative project, we analyzed the results of a pilot trial that evaluated the effects of extreme changes in thyroid hormone availability on serum lipids, lipoproteins, apolipoproteins, and on the hemostasis in thyroid cancer patients receiving thyroid hormone suppression therapy. Thyroid function tests, serum lipid parameters (with special respect to lipoprotein[a]) and various hemostatic parameters were assessed before, at, and after the time these patients were undergoing scanning. Better understanding of the relationship between thyroid hormones and the lipid and hemostatic system is important because hypothyroidism is known to be associated with elevated serum lipids and increased incidence of atherothrombotic events.

甲状腺疾病代表最常见的内分泌异常，据估计，在美国每年约有2000万张左甲状腺素处方被分配给约1.8%的人口。因此，最佳使用有效的实验室检查评估甲状腺状态是重要的医学和经济。在一项多机构合作研究中，我们继续评估甲状腺功能检测用于监测的性能以及甲状腺激素治疗抑制乳头状和/或滤泡性甲状腺癌的潜在临床效用。长期的甲状腺激素治疗，旨在抑制血清促甲状腺激素（TSH）的传统已被用于高分化甲状腺癌的管理。然而，缺乏通过随机对照试验对甲状腺激素抑制治疗效果的正式验证。此外，TSH在低环境浓度下对人类甲状腺肿瘤发生的影响仍不清楚。我们从1934年至2001年间涉及甲状腺癌患者使用甲状腺激素抑制治疗的文献中确定了28项临床试验。应用李克特量表，17项“可解释”的研究中有15项显示甲状腺激素抑制治疗对甲状腺癌预后的有益作用“可能”或“可疑”。我们定量评估了甲状腺激素抑制治疗对累积甲状腺癌队列中主要不良临床事件（疾病进展/复发和死亡）可能性的影响，这些研究来自10项符合荟萃分析条件的研究。这10项研究共涉及4，174例患者，其中2，880例（69%）报告为接受甲状腺激素抑制治疗。根据荟萃分析，接受甲状腺激素抑制治疗的患者组发生主要不良临床事件的风险降低（相对风险0.73，置信区间0.60-0.88，p <0.05）。因此，尽管已知长期服用甲状腺激素会产生不良反应，但在甲状腺癌患者中使用这些激素进行抑制治疗是合理的。需要能够检测非常低的TSH水平（至少低于0.10 mU/L，可能低于0.01 mU/L）的高灵敏度TSH测定来评估这些患者的甲状腺激素抑制治疗的充分性。 在另一个合作项目中，我们分析了一项试点试验的结果，该试验评估了甲状腺激素可用性的极端变化对血脂、脂蛋白、载脂蛋白以及接受甲状腺激素抑制治疗的甲状腺癌患者止血的影响。在这些患者接受扫描之前、之中和之后，评估甲状腺功能检查、血脂参数（特别是脂蛋白[a]）和各种止血参数。更好地了解甲状腺激素与脂质和止血系统之间的关系是很重要的，因为已知甲状腺功能减退症与血脂升高和动脉粥样硬化血栓事件发生率增加有关。