Introduction—heterogeneity in clinical outcomes and survival was observed in patients with papillary thyroid cancer (PTC) and distant metastases. Here, we investigated the effect of distant metastases sites on survival in PTC patients. Methods—patients with a diagnosis of PTC and known metastases were identified using the Surveillance, Epidemiology, and End Results database (1975–2016). Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on thyroid cancer-specific survival (TCSS) and overall survival (OS). Results—from 89,694 PTC patients, 1819 (2%) developed distant metastasis at the initial diagnosis, of whom 26.3% presented with the multiple-organ disease. The most common metastatic sites were lung (53.4%), followed by bone (28.1%), liver (8.3%), and brain (4.7%). In metastatic patients, thyroid cancer-specific death accounted for 73.2%. Kaplan–Meier curves showed decreased OS in patients with metastases to the brain (median OS = 5 months) and liver (median OS = 6 months) compared to lung (median OS = 10 months) and bone (median OS = 23 months). Moreover, multiple organ metastasis had a higher mortality rate (67.4%) compared to single organ metastasis (51.2%, p < 0.001). Using multivariate analysis, risk factors that significantly influence TCSS and OS were male gender (HR = 1.86, 95% CI = 1.17–2.94, p < 0.001, and HR = 1.90, 95% CI = 1.40–2.57, p = 0.009), higher tumor grade (HR = 7.31, 95% CI = 2.13–25.0, p < 0.001 and HR = 4.76, 95% CI = 3.93–5.76, p < 0.001), multiple organ involvement (HR = 6.52, 95% CI = 1.50–28.39, p = 0.026 and HR = 5.08, 95% CI = 1.21–21.30, p = 0.013), and brain metastasis (HR = 1.82, 95% CI = 1.15–2.89, p < 0.001 and HR = 4.21, 95% CI = 2.20–8.07, p = 0.010). Conclusion—the pattern of distant metastatic organ involvement was associated with variability in OS in PTC. Multi-organ metastasis and brain involvement are associated with lower survival rates in PTC. Knowledge of the patterns of distant metastasis is crucial to personalize the treatment and follow-up strategies.

An association between the BRAF^V600E mutation and the clinicopathological progression of papillary thyroid microcarcinoma (PTMC) has been suggested. We aimed to summarize the relevant literature and determine the predictive value of BRAF^V600E mutation in predicting clinical outcomes and risk stratification in patients with PTMC. A systematic search using PubMed, Cochrane, and Embase up to February 2020 was performed. A total of 33 studies met the inclusion criteria, resulting in a pool of 8838 patients, of whom 5043 (57.1%) patients were positive for BRAF^V600E mutation. Tumors with positive BRAF^V600E mutation had a higher tendency for multifocality (RR = 1.09, 95%CI = 1.03–1.16), extrathyroidal extension (RR = 1.79, 95%CI = 1.37–2.32), and lymph node metastasis (RR = 1.43, 95%CI = 1.19–1.71). Patients with BRAF^V600E mutation were at increased risk of disease recurrence (RR = 1.90, 95%CI = 1.43–2.53). PTMC in patients positive for the BRAF^V600E mutation is more aggressive than wild-type BRAF PTMC. Since BRAF-mutated PTMC is generally more resistant to radioiodine treatment, patients with BRAF^V600E-mutated PTMC may require earlier management, such as a minimally invasive ablative intervention. Conservative management by active surveillance may be suitable for patients with wild-type BRAF^V600E PTMC.

Thyroid nodules can be classified as benign, malignant, or indeterminate, the latter of which make up 10–30% of nodules. Radiofrequency ablation (RFA) has become an attractive and promising therapy for the treatment of benign thyroid nodules. However, few studies have investigated the safety and efficacy of RFA for the management of indeterminate thyroid nodules. In this study, 178 patients with thyroid nodules diagnosed as benign (Bethesda II) or indeterminate (Bethesda III/IV) by preoperative cytopathological analysis were included. Patients in the benign and indeterminate cohorts had similar thyroid nodule volume reduction rates at 65.60% and 64.20%, respectively (p = 0.68). The two groups had similar nodular regrowth rates, at 11.2% for benign nodules and 9.40% for indeterminate nodules (p = 0.72). A total of three cases of transient dysphonia were reported. RFA of indeterminate thyroid nodules was comparable to that of benign thyroid nodules in all parameters of interest, including volume reduction rate. To our best knowledge, our work is the first North American analysis comparing benign and indeterminate thyroid nodules and suggests RFA to be a promising modality for the management of indeterminate thyroid nodules.

Hashimoto’s thyroiditis (HT) (autoimmune thyroiditis) is a clinicopathological entity associated with chronic lymphocytic infiltration resulting in hypothyroidism. HT is a double-edged sword that increases the risk of papillary thyroid cancer (PTC), yet it serves as a protective factor for PTC progression. BRAF mutation in PTCs is associated with rapid cell growth, aggressive tumor characteristics, and higher mortality rates. Here, we aimed to analyze the influence of HT in patients with PTCs and its effect on lymph node metastasis (LNM) in BRAF mutant tumors. Adults diagnosed with PTC between 2008 and January 2021 were retrospectively included. A total of 427 patients, 128 of whom had underlying HT, were included. The HT group had significantly higher rates of microcarcinoma (49.2% vs. 37.5%, p = 0.025) and less lateral LNM (8.6% vs. 17.1%, p = 0.024). Interestingly, BRAF-mutated PTCs were found to have significantly less overall LNM (20.9% vs. 51%, p = 0.001), central LNM (25.6% vs. 45.1%, p = 0.040) and lateral LNM (9.3% vs. 29.4%, p = 0.010) in patients with HT when compared to those without underlying HT. HT was found to be an independent protective predictor of overall and lateral LNM. Altogether, HT was able to neutralize the effect of BRAF mutation and was determined to be an independent protective factor against LNM. Specifically, our work may influence treatment-aggressiveness decision making for endocrinologists, oncologists and surgeons alike.

Papillary thyroid carcinomas (PTCs) account for most endocrine tumors; however, screening and diagnosing the recurrence of PTC remains a clinical challenge. Using microRNA sequencing (miR-seq) to explore miRNA expression profiles in PTC tissues and adjacent normal tissues, we aimed to determine which miRNAs may be associated with PTC recurrence and metastasis. Public databases such as TCGA and GEO were utilized for data sourcing and external validation, respectively, and miR-seq results were validated using quantitative real-time PCR (qRT-PCR). We found miR-145 to be significantly downregulated in tumor tissues and blood. Deregulation was significantly related to clinicopathological features of PTC patients including tumor size, lymph node metastasis, TNM stage, and recurrence. In silico data analysis showed that miR-145 can negatively regulate multiple genes in the TC signaling pathway and was associated with cell apoptosis, proliferation, stem cell differentiation, angiogenesis, and metastasis. Taken together, the current study suggests that miR-145 may be a biomarker for PTC recurrence. Further mechanistic studies are required to uncover its cellular roles in this regard.

Background: Parathyroidectomy is the definitive cure for patients with primary hyperparathyroidism (pHPT) and has an annual prevalence of 0.2–1% in the United States. Some patients with mild disease are medically managed effectively using calcium-lowering medications and drugs against complications such as osteoporosis; however, many maintain a persistently high calcium level that negatively impacts their skeletal, renal, and psychogenic systems over the long term. This meta-analysis aims to compare the outcomes of medical management versus parathyroidectomy in patients with mild pHPT. Study Design: This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed, Embase, and Web of Science by two teams of investigators. Analysis was run using R packages. Results: A total of 12 publications including seven randomized control, two prospective, and three retrospective trials with a total of 1346 patients were included for analysis. The average follow-up for all patients was 41 ± 23.8 months. Demographics, pre-treatment calcium, PTH, and bone mineral density (BMD) were similar between the medical (N = 632) and surgical (N = 714) cohorts. Post-treatment calcium and PTH levels were significantly higher in the medical cohort (10.46 vs. 9.39, p < 0.01), (106.14 vs. 43.25, p = 0.001), respectively. Interestingly, the post-treatment PTH in the medical cohort increased when compared to pre-treatment (83.84 to 106.14). Patients in the medical cohort had lower BMD in lumbar (0.48 g/cm²; OR = 0.42, 95% CI = 0.21, 0.83), femoral (0.48; OR = 0.42, 95% CI = 0.29, 0.61), and hip (0.61; OR = 0.33, 95% CI = 0.13, 0.85). Incidences of fracture, nephrolithiasis, cardiovascular death, or overall mortality were not significantly different between the cohorts. Conclusions: The present study is the most comprehensive meta-analysis on mild pHPT to date. Our findings reflect that parathyroidectomy is the superior option in the treatment of mild pHPT patients as opposed to medical management.