Objective Thyroid-stimulating hormone (TSH) is a growth factor affecting initiation or progression of papillary thyroid cancer (PTC), which supports TSH suppressive therapy in PTC patients. In patients with papillary thyroid microcarcinoma (PTMC) during active surveillance, however, the association between serum TSH level and growth of PTMC has not been demonstrated. Patients We analyzed 127 PTMCs in 126 patients under active surveillance with serial serum TSH measurement and ultrasonography. Design The patients were categorized into highest, middle, and lowest time-weighted average of TSH (TW-TSH) group. PTMC progression was defined as volume increase by 50% or more compared to starting point. Kaplan-Meier survival analysis according to TW-TSH groups and Cox proportional hazard modeling was performed. We identified the cut-off point for TSH level using maximally selected log-rank statistics. Results During a median follow-up of 26 months, PTMC progression was detected in 28 (19.8%) patients. Compared to the lowest TW-TSH group, the adjusted HR (95% CI, P-value) for PTMC progression in the highest TW-TSH group was significantly higher [3.55 (1.22-10.28); P = 0.020] while that in middle TW-TSH group was not [1.52 (0.46-5.08); P = 0.489]. The cut-off point of serum TSH level for PTMC progression was 2.50 mU/L. Conclusions Sustained elevation of serum TSH level during active surveillance is associated with PTMC progression. Maintaining low-normal TSH range by levothyroxine (LT4) treatment during active surveillance of PTMC might be considered with future studies.

Kim WG, et al. Endocrinol Metab. 2017 Mar;32(1):106-114. https://doi.org/10.3803/EnM.2017.32.1.106

Context: Detection of the BRAF V600E mutation in fine-needle aspiration cytology (FNAC) specimens may increase the value of FNAC. Objective: The objectives of the study was to compare the diagnostic performance of BRAF assays that differ in sensitivity and to examine the associations between the BRAF V600E mutation status and the clinicopathological features in papillary thyroid carcinoma (PTC). Design and Setting: Three molecular assays were performed in all subjects and compared with regard to FNAC and histology results. Participants: We evaluated 4585 consecutive patients who were found to have malignant or indeterminate thyroid nodules by ultrasonography. Outcome Measures: All FNAC samples were tested for the BRAF V600E mutation using conventional Sanger sequencing, dual-priming oligonucleotide-PCR, and mutant enrichment with 3′-modified oligonucleotide (MEMO) sequencing. Results: The detection sensitivities of the three molecular assays for the BRAF V600E mutation were 20, 2, and 0.1%, respectively. Compared with conventional Sanger sequencing (n = 673), dual-priming oligonucleotide-PCR and MEMO sequencing detected more tumors with the BRAF V600E mutation (n = 919 and n = 1044, respectively), especially tumors with a benign, indeterminate, or nondiagnostic cytology. All BRAF-positive tumors that were histologically examined were shown to be PTC, regardless of cytology results. The clinical sensitivities of the three assays for detecting PTC were 54.8, 74.4, and 79.7%, respectively. BRAF V600E mutations in microcarcinomas (≤10 mm) were detected more efficiently as the detection sensitivity of the assay increased (P < 0.001). Tumor size correlated significantly with multifocality, extrathyroidal extension, and lymph node metastasis (P = 0.003, P < 0.001 and P < 0.001, respectively), but the BRAF V600E mutation status was not associated with any of those features. Conclusion: Highly sensitive and specific molecular assays such as MEMO sequencing are optimal for detecting the BRAF mutations in thyroid FNAC because these techniques can detect PTC that might be missed by cytology or less sensitive molecular assays.

Background: Concern regarding the health-related quality of life (HRQOL) of long-term survivors of thyroid cancer has risen due to the rapid increase in the incidence of thyroid cancer, which generally has an excellent prognosis. The aim of this study was to evaluate the status of HRQOL in disease-free survivors of differentiated thyroid carcinoma (DTC) and to evaluate the important determinants of HRQOL. Methods: This was a cross-sectional study in which we interviewed consecutive disease-free survivors of DTC. Three different validated questionnaires ("EORTC QLQ-C30" for various functional domains, the "brief fatigue inventory (BFI)" and the "hospital anxiety and depression scale" (HADS)) were used. Data from a large, population based survey of 1,000 people were used as a control. Results: The response rate for the questionnaires was 78.9% (316/401). Disease-free survivors of DTC showed a decreased HRQOL in all five functional domains (physical, role, cognitive, emotional, and social) on the EORTC QLQ-C30 compared with controls (P < 0.01). BFI and HADS-anxiety scores also showed greater distress in disease-free survivors of DTC than in controls (P < 0.05). A multiple regression analysis for the determinants of HRQOL showed that the HADS-anxiety, HADS-depression, and BFI scores were the most significant components of decreased HRQOL. Conclusions: Although disease-free survivors of DTC are expected to have disease-specific survival comparable to the general population, they experience a significantly decreased HRQOL. Anxiety, depression, and fatigue were the major determinants of the decreased HRQOL. Supportive psychological care should be integrated into the management of long-term survivors of DTC.