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2020 Feb 14


Early diagnosis of medullary thyroid cancer: Are calcitonin stimulation tests still indicated in the era of highly sensitive calcitonin immunoassays?



Background Measurements of basal(b) calcitonin(CT) and calcium(Ca)-stimulated CT(Ca-sCT) levels are performed to identify medullary thyroid cancer(MTC) at an early stage when used as part of the diagnostic workup of thyroid nodules(CT-screening).Novel immunochemiluminometric assays (highly sensitive and specific for monomeric CT) have been introduced over the past decade.No prospectively generated data have so far become available to answer the frequently raised question as to whether Ca-sCT in contrast to bCT alone is helpful and therefore still indicated for the early detection of MTC. Methods Ca-stimulation tests were performed in 149 consecutive patients with thyroid nodules and elevated bCT.Regardless of Ca-sCT levels,all patients had an operation applying a uniform surgical protocol,including thyroidectomy and systematic lymph node surgery.Recently published sex-specific cut-off levels for the differentiation of MTC and other C-cell pathologies were used to compare the diagnostic performance of bCT or Ca-sCT alone and in combination using receiver-operating characteristic(ROC) analysis.Additionally,CT cut-off levels to predict lateral lymph node metastasis were evaluated for bCT compared to Ca-sCT.Follow-up for all patients was documented and correlated with initial CT levels. Results MTC was identified in 76(50.1%) patients,in 21/76(27.6%) with lymph node and in 4(5.3%) with distant metastasis.Using predefined cut-off levels,patients could effectively be subdivided into a group above the cut-off level with definitive diagnosis of MTC(100%) and below with a significant overlap of C-cell hyperplasia and MTC(all classified as pT1a;males:19/58[37.5%],females:7/41[17.1%]).The areas under the ROC curve(AUC) were excellent for the diagnosis of MTC in all tests.Determination of bCT proved to be superior for both diagnosing MTC in males(AUC bCT:0.894;AUC Ca-sCT:0.849) and females(bCT:0.935;Ca-sCT:0.868) and also for diagnosing lymph node metastasis in the lateral compartment(males:bCT:0.925;Ca-sCT:0.810; females:bCT:0.797;Ca-sCT:0.674).Combining both tests did not improve diagnostic accuracy.Using a cut-off level of>85pg/ml for females and>100pg/ml for males,the sensitivity for diagnosing lateral neck lymph node metastasis was 100%.Below these cut-off levels,no patient showed persistent or recurrent disease. Conclusion Predefined sex-specific bCT cut-off levels are helpful for the early detection of MTC and for predicting lateral neck lymph node metastasis.Ca-sCT did not improve preoperative diagnostics.bCT levels>43pg/ml and>100pg/ml for males and of >23pg/ml and >85pg/ml for females are relevant for advising patients and planning the extent of surgery.