Recent data indicates an increasing incidence of thyroid cancer not accompanied by a proportional increase in mortality, suggesting overdiagnosis, which may represent a big public health problem, ...particularly where resources are scarce. This article aims to describe and evaluate the procedures related to investigation of thyroid nodules and treatment and follow-up of thyroid cancer and the costs for the Brazilian public health system between 2008 and 2015.
Data on procedures related to investigation of thyroid nodules and treatment/follow-up of thyroid cancer between 2008 and 2015 in Brazil were collected from the Department of Informatics of the Brazilian Unified Health System (Datasus) website.
A statistically significant increase in the use of procedures related to thyroid nodules investigation and thyroid cancer treatment and follow-up was observed in Brazil, though a reduction was noted for procedures related to the treatment of more aggressive thyroid cancer, such as total thyroidectomy with neck dissection and higher radioiodine activities such as 200 and 250 milicuries (mCi). The procedures related to thyroid nodules investigation costs increased by 91% for thyroid ultrasound (p = 0.0003) and 128% in thyroid nodule biopsy (p < 0.001). Costs related to treatment and follow-up related-procedures increased by 120%.
The increase in the incidence of thyroid cancer in Brazil is directly associated with an increased use of diagnostic tools for thyroid nodules, which leads to an upsurge in thyroid cancer treatment and followup-related procedures. These data suggest that substantial resources are being used for diagnosis, treatment and follow-up of a potentially indolent condition.
There is a concern regarding the use of iodinated contrast agents (ICA) for chest and neck computed tomography (CT) to localize metastatases in patients with differentiated thyroid cancer (DTC). This ...is because the iodine in ICA can compete with (131)I and interfere with subsequent whole scans or radioactive iodine treatment. The required period for patients to eliminate the excess iodine is not clear. Therefore, knowing the period for iodine levels to return to baseline after the injection of ICA would permit a more reliable indication of CT for DTC patients. The most widely used marker to assess the plasmatic iodine pool is the urinary iodine (UI) concentration, which can be collected over a period of 24 hours (24U) or as a single-spot urinary sample (sU). As 24U collections are more difficult to perform, sU samples are preferable. It has not been established, however, if the measurement of iodine in sU is accurate for situations of excess iodine.
We evaluated 25 patients with DTC who received ICA to perform chest or neck CT. They collected 24U and sU urinary samples before the CT scan and 1 week and 1, 2, and 3 months after the test. UI was quantified by a semiautomated colorimetric method.
Baseline median UI levels were 21.8 μg/dL for 24U and 26 μg/dL for sU. One week after ICA, UI median levels were very high for all patients, 800 μg/dL. One month after ICA, however, UI median levels returned to baseline in all patients, 19.0 μg/dL for 24U and 20 μg/dL for sU. Although the values of median UI obtained from sU and 24U samples were signicantly different, we observed a significant correlation between samples collected in 24U and sU in all evaluated periods.
One month is required for UI to return to its baseline value after the use of ICA and for patients (after total thyroidectomy and radioiodine therapy) to eliminate the excess of iodine. In addition, sU samples, although not statistically similar to 24U values, can be used as a good marker to evaluate patients suspected of contamination with iodine.
Purpose
The aims of this study were to assess the role of an in-house competitive thyroglobulin assay (Tg-c) in the follow-up of metastatic differentiated thyroid carcinoma (DTC) patients who ...presented underestimated Tg measurements by immunometric assays (Tg-IMA) and to compare the results with IMA and LC-MS/MS Tg methods.
Methods
This prospective study included 40 patients. Twenty-one with metastatic disease: 14 had Tg-IMA levels inappropriately low or undetectable (eight patients with positive and six with borderline TgAb) and seven had high Tg-IMA levels. Nineteen had an excellent response to therapy. The competitive assay employs a polyclonal antibody produced in rabbits immunized with human Tg, Tg labeled with biotin, and for the solid phase separation, a monoclonal anti-rabbit IgG antibody adsorbed to microtiter plates.
Results
All 14 patients with structural disease and underestimated levels of Tg-IMA presented detectable Tg-c levels. The median Tg-c level in the group with positive TgAb was 183 µg/L (range: 22–710 µg/L), and 58 µg/L (range 23–148 µg/L) in the borderline TgAb group. The levels of Tg-LC-MS/MS were detectable in some patients (range < 0.5–18 µg/L). All seven patients with high Tg-IMA presented also high levels of Tg-c. Only 2/19 patients with excellent response had Tg-c levels above the functional sensitivity.
Conclusions
The competitive assay was able to detect Tg in all patients, even in the presence of serum TgAb, and may be an option in patients with underestimated Tg-IMA and relevant structural disease.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The risk of malignancy and diagnostic accuracy of fine-needle aspiration biopsy (FNAB) of thyroid nodules (TN) with diameters ≥ 3-4 cm remains controversial. However, some groups have indicated ...surgical treatment in these patients regardless of the FNAB results. We aimed to evaluate the diagnostic accuracy of the FNAB in systematically resected ≥4 cm TN and if the risk of malignancy is higher in these patients.
We retrospectively evaluated 138 patients (142 nodules) with TN with diameters ≥4 cm who underwent thyroidectomy.
The FNAB results were nondiagnostic/unsatisfactory (ND/UNS) in 2.1% of the cases and benign in 51.4%. They indicated atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in 23.9% of cases, follicular neoplasia/suspicious for a follicular neoplasm (FN/SFN) in 9.2%, suspicion of malignancy (SUS) in 8.5%, and malignant in 4.9%. The histopathological analysis after thyroidectomy revealed a thyroid cancer rate of 100% in the FNABs classified as malignant, 33.3% in SUS cases, 7.7% in FN/SFN, 17.6% in AUS/FLUS, and 4.1% in benign FNABs. None of the ND/UNS FNABs were malignant. The global malignancy diagnosis was 14.8% (n = 21). However, the rate of false negatives for FNAB was low (4.1%).
We showed that the risk of malignancy in nodules with diameters ≥4 cm was higher compared to the risk of thyroid cancer in TN in general. However, we found a low rate of false-negative cytological results; therefore, our data do not justify the orientation of routine resection for these larger nodules.
The presence of thyroglobulin (Tg) in needle washouts of fine needle aspiration biopsy (Tg-FNAB) in neck lymph nodes (LNs) suspected of metastasis has become a cornerstone in the follow-up of ...patients with papillary thyroid carcinoma (PTC). However, there are limited data regarding the measurement of anti-Tg antibodies in these washouts (TgAb-FNAB), and it is not clear whether these antibodies interfere with the assessment of Tg-FNAB or whether there are other factors that would more consistently justify the finding of low Tg-FNAB in metastatic LNs.
We investigated 232 FNAB samples obtained from suspicious neck LNs of 144 PTC patients. These samples were divided according to the patient's serum TgAb status: sTgAb- (n = 203 samples) and sTgAb+ (n = 29). The TgAb-FNAB levels were measured using two different assays. Tg-FNAB was also measured using two assays when low levels (< 10 ng/mL) were identified in the first assay of the metastatic LNs from the sTgAb+ samples.
The TgAb-FNAB results were negative in both assays in all samples. Low levels of Tg-FNAB were identified in 11/16 of the metastatic LNs of the sTgAb+ patients and 16/63 of the sTgAb- patients (p < 0.05) using assay 1. The measurement of the Tg-FNAB levels using assay 2 indicated additional metastases in 5 LNs of the sTgAb+ patients.
Factors other than the presence of TgAb-FNAB may contribute to the higher number of metastatic LNs with undetectable Tg-FNAB in the sTgAb+ group. In addition, the measurement of Tg-FNAB using different assays was useful to enhance the diagnosis of metastatic LNs, particularly when cytological and Tg-FNAB results are discordant.
Summary
Objective
Staging systems applied to medullary thyroid cancer (MTC) rely on initial clinical and pathological features and do not consider the response to treatment. To determine whether MTC ...staging can be improved by incorporating the first postoperative calcitonin measurement.
Patients and measurements
Eighty‐five patients being monitored for MTC (median follow‐up 5 years) were retrospectively classified according to both the American Joint Committee on Cancer (AJCC) and the proposed combined risk stratification system (low, intermediate and high risk), which incorporates the first postoperative calcitonin measurement, using the outcomes no evidence of disease (NED), biochemical evidence of disease, structurally identifiable disease and death.
Results
Ninety per cent of AJCC I patients were classified as NED at final follow‐up. When we added a postoperative calcitonin measurement, 95% low‐risk patients were classified as NED at final follow‐up. AJCC stages I and IV were associated, respectively, with no occurrence and a high rate (63%) of structurally identifiable disease. Stages II and III yielded similar predictions of structurally identifiable disease, 13% and 14%, respectively. When we included the postoperative calcitonin level, the patients with structural evidence of disease included none from the low‐risk group, 10% from the intermediate group and 63% from the high‐risk group. The proportion of variance explained analysis (PVE) was better for the combined risk stratification system (54%) than for the AJCC system alone (32%).
Conclusion
Including the first postoperative calcitonin measurement with the anatomical staging system can better predict the clinical outcome of patients with MTC and refine the follow‐up of these patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To evaluate the clinical utility of 18F-FDG PET/CT in patients with high-risk DTC.
Single-center retrospective study with 74 patients with high-risk differentiated thyroid cancer (DTC), classified in ...4 groups. Group 1: patients with positive sTg or TgAb, subdivided in Group 1A: negative RxWBS and no foci of metastases identified at conventional image (n = 9); Group 1B: RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level (n = 13); Group 2: patients with histological findings of aggressive DTC variants (n = 21) and Group 3: patients with positive RxWBS (n = 31).
18F-FDG PET/CT identified undifferentiated lesions and helped restage the disease in groups 1B and 2. The scan helped guide clinical judgment in 9/13 (69%) patients of group 1B, 10/21 (48%) patients of group 2 and 2/31 (6%) patients of group 3. There was no clinical benefit associated with group 1A. 18F-FDG PET/CT was associated with progressive disease.
18F-FDG PET/CT is a useful tool in the follow-up of patients with high-risk DTC, mainly in the group of RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level and in those with aggressive DTC variants. Additionally, this study showed that 18F-FDG PET/CT was associated with progression and helped display undifferentiated lesions guiding clinical assessments regarding surgeries or expectant treatments.
Serum calcitonin (sCT) is the main tumor marker for medullary thyroid cancer (MTC), but it has certain limitations. Various sCT assays may have important intra-assay or interassay variation and may ...yield different and sometimes conflicting results. A pentagastrin- or calcium-stimulation calcitonin (CT) test may be desirable in some situations. Alternatively, or in the absence of the stimulation test, mRNA detection offers the advantages of being more comfortable and less invasive; it only requires blood collection and has no side effects. The objective of this study was to investigate the applicability of measuring calcitonin-related polypeptide alpha (CALCA) gene transcripts (CT-CALCA and calcitonin gene-related peptide CGRP-CALCA) in patients with MTC and in relatives diagnosed with a RET mutation and to test mRNA as an alternative diagnostic tool for the calcitonin-stimulation test.
Twenty-three healthy controls and 26 individuals evaluated for MTC were selected, including patients with sporadic or hereditary MTC and RET mutation-carrying relatives. For molecular analysis, RNA was extracted from peripheral blood, followed by cDNA synthesis using 3.5 μg of total RNA. Quantitative real-time polymerase chain reaction (RT-qPCR) was performed with SYBR Green and 200 nM of each primer for the two specific mRNA targets (CT-CALCA or CGRP-CALCA) and normalized with the ribosomal protein S8 as the reference gene.
We detected CALCA transcripts in the blood samples and observed a positive correlation between them (r=0.946, p<0.0001). Both mRNAs also correlated with sCT (CT-CALCA, r=0.713, p<0.0001; CGRP-CALCA, r=0.714, p<0.0001). The relative expression of CT-CALCA and CGRP-CALCA presented higher clinical sensitivity (86.67 and 100, respectively), specificity (97.06 and 97.06), positive predictive value (92.86 and 93.75), and negative predictive value (94.29 and 100), than did sCT (73.33, 82.35, 64.71, and 87.50, respectively). In addition, the CALCA transcript measurement mirrored the response to the pentagastrin test.
We demonstrate that the measurement of CALCA gene transcripts in the bloodstream is feasible and may refine the management of patients with MTC and RET mutation-carrying relatives. We propose considering the application of this diagnostic tool as an alternative to the calcitonin-stimulation test.
To investigate whether circulating thyroglobulin (Tg) messenger ribonucleic acid (mRNA) and sodium/iodide symporter (NIS) mRNA transcripts in peripheral blood are valuable in the follow-up of ...patients with thyroid cancer, we developed highly sensitive nested Tg and NIS mRNA detection assays and compared their accuracy with serum thyroglobulin (sTg) and whole body scan with 131I during the monitoring of 34 patients with well differentiated thyroid carcinoma who had undergone total thyroidectomy (17 of 34 also submitted to thyroid ablation with radioiodine) and were taking T4. Circulating Tg mRNA was found in 13 of 34 patients, 5 of 13 with detectable and 8 of 13 with undetectable sTg. From these 8 patients with undetectable Tg, 6 showed no cervical radioiodine uptake, and 3 presented proven metastatic disease (2 of them positive for antithyroglobulin antibodies). NIS mRNA was detected in 11 of 34 patients, but its measurement did not improve the ability to detect patients with metastases. Overall, identification of metastatic thyroid cancer was better associated with Tg mRNA than with NIS mRNA, sTg, or whole body scan (83% vs. 16.6% vs. 50% vs. 50%; P < 0.001). These data showed that circulating Tg mRNA is not only a more sensitive marker of residual thyroid tissue or thyroid cancer than sTg, particularly in patients during T4 therapy and with positive antithyroglobulin antibodies, but also was more sensitive than NIS mRNA in all patients.
Objectives: To prospectively evaluate the outcome of patients with low-risk papillary thyroid carcinoma treated with total thyroidectomy (TT) who did not undergo radioiodine remnant ablation (RRA). ...Study Design: We prospectively followed up 57 patients; 3 months after TT, thyroglobulin (Tg) assessment and neck ultrasonography (US) were performed while patients were taking L-T4, presenting suppressed TSH. Six months after TT, patients underwent stimulated Tg testing and whole-body scan (WBS) after recombinant TSH (rhTSH). Then, 18 months after TT, the patients were evaluated by neck US and Tg under TSH between 0.5 and 2.0 mIU/ml. Two years after TT, we performed another rhTSH assessment, measuring Tg and making a WBS. The patients were then annually monitored with neck US and Tg measurement under TSH between 0.5 and 2.0 mIU/l for 36-84 months. Results: Neck US of all patients, 3 months after TT, presented no evidence of abnormal residual tissues or metastatic lymph nodes (negative neck US); at this time, the mean Tg level was 0.42 ng/ml. Six months after surgery, after rhTSH, the mean thyroid bed uptake was 1.82%, and Tg levels ranged from 0.10 to 22.30 ng/ml (mean, 2.89 ng/ml). The patients were followed up without any sign of recurrence (negative neck US and stable or decreasing Tg levels). During the ongoing follow-up, the Tg trend was stable or decreasing, independently of the initial suppressed or stimulated Tg level, or WBS uptake. Conclusions: In patients with low-risk differentiated thyroid cancer, who were operated by TT and who did not undergo RRA, an excellent response to treatment may be confirmed by annual neck US and Tg trend.
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