Background: The extent of thyroidectomy in patients with differentiated thyroid cancer (DTC) remains controversial. The aim of this study was to identify how surgical technique and postoperative treatments influence survival and locoregional recurrence in DTC. Methods: A nested case-control study was conducted in a cohort of 5123 patients diagnosed with DTC in Sweden between 1958 and 1987. One matched control subject was selected randomly for each patient who died from DTC. Details regarding surgery and postoperative treatments were obtained from medical records. The effect of treatment on survival was estimated by conditional logistic regression. Results: Patients not treated surgically had a poorer prognosis, but the risk of death from DTC was not affected by the choice of surgical technique. The extent of surgery influenced survival only in patients with TNM stage III disease. Locoregional recurrence resulted in a fivefold increased risk of death. Postoperative treatment was not associated with improved survival. Conclusion: In operated patients, the most important prognostic factor was complete removal of the tumour. The extent of removal of remaining thyroid tissue was of prognostic importance in stage III disease only. Adjuvant postoperative treatment did not influence the prognosis favourably.

Introduction: To minimize recurrence risk in differentiated thyroid cancer (DTC), TSH is usually lifelong suppressed with levothyroxine. A common consequence of this treatment is subclinical hyperthyroidism which can induce cardiovascular disease (CV). This study's aim was to compare CV incidence in DTC patients with the general population in Sweden.Materials and methods: All Swedish patients diagnosed with DTC in 1987–2013 were included in the cohort study. Lifelong TSH suppression treatment was assumed to be administered to patients in compliance with prevalent national guidelines. Patients were followed from 1 year after DTC diagnosis until December 31, 2014, death, or migration. The event of interest was hospitalization due to any of the following diseases: atrial fibrillation (AF), cerebrovascular disease, cerebral infarction, ischemic heart disease, ischemic heart attack, and heart failure. Standardized incidence ratios (SIRs) were calculated to compare CV incidence between DTC patients and the general population.Results: The cohort consisted of 6900 patients with DTC. Hospitalization was increased among DTC patients for AF (SIR 1.66, CI 95% 1.41–1.94), and women faced increased hospitalization for cerebrovascular disease (SIR 1.20 CI 95% 1.04–1.38). Regarding the remaining CV diseases, no consistent difference in SIR between the groups was observed.Conclusion: Compared to the general population, DTC patients have a higher incidence in AF, and female face a slightly higher incidence in cerebrovascular disease. However, there was no difference in hospitalization for other studied CV diseases between DTC patients and the general population.

Papillary thyroid cancer (PTC) and poorly differentiated thyroid cancer (PDTC) are treated with radioiodine to reduce recurrence and to treat the spread of disease. Adequate iodine accumulation in cancer tissue, iodine avidity, is important for treatment effect. This study investigated which clinical and histological tumour characteristics correlate with avidity. To quantify avidity in cancer tissue, tracer amounts of iodine-131 were given to 45 patients with cytologically confirmed thyroid cancer. At pathology grossing, representative samples of tumour and lymph nodes were taken and subjected to radioactivity quantification ex vivo to determine avidity. Afterwards, samples underwent extended pathology work-up and analysis. We found that tumoural Tg expression and Ki-67 index were correlated with avidity, whereas tumour size and pT stage were not. The histological variant of thyroid cancer was also correlated with iodine avidity. Variants associated with worse clinical prognoses displayed lower avidity than variants with better prognoses. This work provides new information on which tumours have low iodine avidity. Lower avidity in aggressive histological PTC variants may explain their overall poorer prognoses. Our findings also suggest that radioiodine dosage could be adapted to Tg expression, Ki-67 index or histological variant instead of pT stage, potentially improving the efficacy of radioiodine therapy.

Background: Despite a good prognosis, survivors of differentiated thyroid cancer (DTC) may have reduced health-related quality of life (HRQOL) many years after treatment, and it is unclear how suppression of thyroid-stimulating hormone (TSH) may contribute to HRQOL. This study investigated changes in HRQOL in the 5 years following DTC treatment, the association between HRQOL and TSH suppression, and how HRQOL compares to the general population. Methods: In this nationwide prospective cohort study, 487 patients with DTC were identified between 2012 and 2017 from all Swedish hospitals treating patients with DTC. Patients treated with total thyroidectomy and planned for radioiodine answered the Swedish version of the Short Form-36 Health Survey (SF-36) and a study specific questionnaire at treatment and after 1, 3, and 5 years. Summary measures for physical and mental QOL were derived from the SF-36, and TSH values were collected from patient records. To study changes in HRQOL over time, linear mixed models were fitted on multiply imputed data, with all patients and measurement points included in the model. Results: In total, 351 patients consented to participate in the study. In the 5 years following DTC treatment, physical QOL did not change significantly with time, while mental QOL improved by on average 0.61 ( p < 0.001) per year. TSH levels were not predictive of either physical or mental QOL, or their change over time. At 5 years, there was a significant difference in physical and mental QOL compared with the Swedish general population, but effect sizes were small (Cohen’s d = 0.29 and −0.21, respectively). The SF-36 domains general health, vitality, social functioning, and mental health were lower at 5 years compared with the general population (difference 8.7–13.3), and these differences were clinically significant. Conclusions: The mental component of HRQOL improves over time following DTC treatment. HRQOL in patients with DTC is not explained by TSH suppression. Although overall differences in physical and mental HRQOL compared with the general population were small 5 years after treatment, several specific psychosocial HRQOL domains were clinically meaningfully reduced. Psychosocial health issues should be screened for during DTC follow-up.

Papillary thyroid carcinoma (PTC) is the most common form of well-differentiated thyroid cancer (WDTC) and generally has a favorable prognosis. However, subsets of these tumors can metastasize, leading to aggressive disease progression and poorer clinical outcomes. Radioactive iodine (RAI) therapy is routinely given in the adjuvant setting following thyroidectomy and lymph node dissection for WDTC. Nevertheless, its therapeutic efficacy is limited to tumors with high iodine avidity. Early post-surgical classification of thyroid cancers as either iodine-avid or refractory is crucial for enabling more personalized and effective treatment strategies. In this study, we aimed to identify transcriptomic determinants associated with RAI refractoriness (RAI-R) to improve prognostication. We collected clinicopathologic data and conducted RNA-seq on 36 tissue samples (18 high-avidity and 18 low-avidity), each uniquely characterized by ex vivo iodine concentration measurements taken directly from surgical specimens. Whole-transcriptomic analysis identified 63 differentially expressed genes, with six ( S100A4 , CRTC2 , ANO1 , WWTR1 , DEPTOR , MT1G ) showing consistent deregulation. The expression of ANO1, an established iodine transporter at the apical membrane of the thyroid follicular cells, correlated significantly with iodine avidity ( r = 0.54). Validation via RT-qPCR confirmed differential expression trends. Gene ontology and pathway enrichment analyses highlighted thyroid hormone synthesis, PI3K-AKT, and MAPK signaling pathways as key regulators of RAI avidity. A refined multivariate predictive model incorporating ANO1 mRNA expression, histological subtypes, and sample type demonstrated strong predictive performance (adjusted R ² = 0.55). These findings suggest ANO1 as a promising biomarker for predicting iodine avidity in thyroid cancer.