Analytical Performance And Clinical Utility Of Thyroid F

甲状腺疾病是最常见的内分泌异常，据估计，在美国，每年约有2000万张左旋甲状腺素处方分配给约1.8%的人口。因此，最佳使用有效的实验室测试来评估甲状腺状况在医学上和经济上都很重要。在一项多机构合作研究中，我们继续评估甲状腺功能测试的性能，以监测甲状腺激素治疗抑制乳头状甲状腺癌和/或滤泡性甲状腺癌的潜在临床效用。以抑制血清促甲状腺激素(TSH)为目标的长期甲状腺激素治疗传统上用于高分化甲状腺癌的治疗。然而，通过随机对照试验对甲状腺激素抑制治疗的效果进行正式验证尚缺乏。此外，低环境浓度的TSH对人类甲状腺肿瘤发生的影响尚不清楚。我们从文献中确定了28项临床试验，这些试验涉及1934年至2001年期间甲状腺激素抑制疗法在甲状腺癌患者中的应用。应用Likert量表，17项“可解释的”研究中有15项显示了甲状腺激素抑制治疗对甲状腺癌预后的“可能的”或“可疑的”有益效果。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项有资格进行荟萃分析的研究。这10项研究代表了总共4174名患者，其中2880名(69%)据报道正在接受甲状腺激素抑制治疗。Meta分析显示，接受甲状腺激素抑制治疗的患者发生主要不良临床事件的风险降低(相对风险0.73，可信区间0.60~0.88，p<0.05)。因此，尽管长期服用甲状腺激素有已知的不良反应，但对于甲状腺癌患者来说，使用这些激素进行抑制治疗是合理的。高灵敏度的TSH检测需要能够检测到非常低的TSH水平(至少低于0.10mU/L，可能低于0.01mU/L)，以评估这些患者是否接受甲状腺激素抑制治疗。 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获得性的极端变化对接受甲状腺激素抑制治疗的甲状腺癌患者的血脂、脂蛋白、载脂蛋白以及止血的影响。在这些患者接受扫描前、扫描时和扫描后，评估甲状腺功能测试、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，因为众所周知，甲状腺功能减退与血脂升高和动脉粥样硬化血栓事件的发生率增加有关。

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.