Eustatia-Rutten C F A, Smit J W A, Romijn J A, van der Kleij-Corssmit E P M, Pereira A M, Stokkel M P, Kievit J
Department of Endocrinology, Leiden University Medical Centre, Leiden, The Netherlands.
Clin Endocrinol (Oxf). 2004 Jul;61(1):61-74. doi: 10.1111/j.1365-2265.2004.02060.x.
To investigate to what extent thyroid remnant ablation and withdrawal from thyroxine are required to achieve sufficient accuracy of serum thyroglobulin (Tg) measurements as an indicator of tumour recurrence in the follow-up of patients with differentiated thyroid carcinoma.
We conducted a meta-analysis of the literature from 1975 to 2003 on serum Tg measurements in the follow-up of differentiated thyroid carcinoma. In a computer-based search, we initially found 915 articles that were finally narrowed down to 120. These 120 papers were subjected to strict in/and exclusion criteria, leaving 46 articles (totalling 9094 patients). Data from these articles were extracted in a structured fashion and were grouped according to initial therapy, TSH status, Tg assay method and definition of a 'gold standard'. Original 2 x 2 tables were pooled by summary receiver operating characteristic curve analysis (sROCa), best estimates of sensitivity and specificity being obtained by the combination of sROCa and Mantel-Haenszel odds ratios.
Despite considerable differences between series in laboratory and clinical methodology, we consistently found higher specificity for Tg measurements after thyroid remnant ablation than after surgery alone. Highest pooled sensitivity 0.961 +/- 0.013 (SE) was found for immunometric assay (IMA) after thyroid remnant ablation and thyroid hormone withdrawal, at a specificity of 0.947 +/- 0.007. Pooled sensitivity decreased significantly if ablated patients were tested while on thyroid hormone (0.778 +/- 0.023, at a specificity of 0.977 +/- 0.005). Significantly decreased pooled specificity was found in patients who did not undergo remnant ablation (sensitivity 0.972 +/- 0.023, at a specificity of 0.759 +/- 0.028). If recombinant human TSH (rhTSH) stimulation was used as a substitute for thyroxine withdrawal, sensitivity remained high (0.925 +/- 0.018) while specificity decreased to 0.880 +/- 0.013. In all analyses, specificity of Tg would decrease when unspecified activity in the thyroid region at scintigraphy was considered benign, whereas sensitivity decreased when such activity was considered malignant.
This study confirms that the best accuracy of Tg-guided follow-up in patients treated for differentiated thyroid carcinoma is obtained if treatment includes remnant ablation, and Tg testing is performed while off thyroxine.
探讨在分化型甲状腺癌患者随访中，为使血清甲状腺球蛋白（Tg）测量作为肿瘤复发指标达到足够的准确性，甲状腺残留组织消融及停用甲状腺素的必要性。
我们对1975年至2003年有关分化型甲状腺癌随访中血清Tg测量的文献进行了荟萃分析。通过计算机检索，最初找到915篇文章，最终筛选至120篇。这120篇论文接受了严格的纳入和排除标准，最终留下46篇文章（共9094例患者）。从这些文章中以结构化方式提取数据，并根据初始治疗、促甲状腺激素（TSH）状态、Tg检测方法及“金标准”定义进行分组。通过汇总受试者工作特征曲线分析（sROCa）合并原始的2×2列联表，通过sROCa与Mantel-Haenszel比值比相结合获得敏感性和特异性的最佳估计值。
尽管各研究系列在实验室和临床方法上存在显著差异，但我们始终发现甲状腺残留组织消融后Tg测量的特异性高于单纯手术后。甲状腺残留组织消融及停用甲状腺激素后，免疫测定法（IMA）的汇总敏感性最高为(0.961\pm0.013)（标准误），特异性为(0.947\pm0.007)。如果在服用甲状腺激素时对接受消融治疗的患者进行检测，汇总敏感性显著降低（(0.778\pm0.023)，特异性为(0.977\pm0.005)）。未进行残留组织消融的患者汇总特异性显著降低（敏感性(0.972\pm0.023)，特异性为(0.759\pm0.028)）。如果使用重组人促甲状腺激素（rhTSH）刺激替代停用甲状腺素，敏感性仍较高（(0.925\pm0.018)），而特异性降至(0.880\pm0.013)。在所有分析中，当甲状腺闪烁显像中甲状腺区域未明确的活性被视为良性时，Tg的特异性会降低，而当这种活性被视为恶性时，敏感性会降低。
本研究证实，对于接受分化型甲状腺癌治疗的患者，若治疗包括残留组织消融且在停用甲状腺素时进行Tg检测，则Tg引导的随访准确性最佳。
