Purpose It is well established that thyroiditis and other thyroid disorders can be induced by COVID-19 infection, but there is limited information about the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We report two cases of thyrotoxicosis following SARS-CoV-2 vaccine. Methods and results Two young health care peoples (wife and husband) received a first dose of SARS-CoV-2 vaccine, and few weeks later developed clinical manifestations of thyroid hyperactivity, with increased thyroid hormone levels on thyroid function tests, suppressed thyroid-stimulating hormone and negative antithyroid antibodies, despite being healthy before vaccination. They were diagnosed at the 4th week after first dose of SARS-Cov-2 vaccine as silent thyroiditis and followed without treatment, since their symptoms were not severe. At the 6th week, the patients became wholly asymptomatic and their thyroid function returned to normal. Conclusions Thyrotoxicosis can occur after SARS-CoV-2 vaccination probably related to silent thyroiditis.

Context The definition of familial non medullary thyroid cancer (FNMTC), as presence of the disease in two or more first degree relatives, is controversial due to the high probability to observe a sporadic association when only two members are affected. Objective To evaluate the role of age at diagnosis in differentiating the true cases of FNMTC. Design, Setting, Participants, and Main Outcome From a group of 721 papillary thyroid cancer (PTC), 95 familial PTC (FPTC) patients with two first degree relatives, have been identified. They were split in two groups: Group 1 consisting of both the proband and the affected relative with age at diagnosis ≤ 45 years; Group 2 consisting of proband and/or affected family member with age at diagnosis >45 years. The clinical-pathological features and outcome of both FPTC groups were compared with 626 sporadic PTC patients (SPTC). Results FPTC patients with age at diagnosis ≤ 45yrs, compared to the matched group of sporadic PTCs, had more frequently multifocal, bilateral and extrathyroidal extension of tumor and showed worse outcome. No differences were found between FPTC and SPTC patients with age >45yrs. At multivariate analysis, distant metastases, ATA risk and FPTC ≤ 45yrs were independent predictors of outcome. Conclusions Based on the observation that PTC is more aggressive when the diagnosis is made in two family members, both with age <45yrs, we suggest that definition of FPTC in kindreds with 2 affected members should take into account also the age at diagnosis, as key element of familial cancer.

The incidence of thyroid cancer (TC) in Italy is one of the highest in Europe, and the reason for this is unclear. The intra-country heterogeneity of TC incidence suggests the possibility of an overdiagnosis phenomenon, although environmental factors cannot be excluded. The aim of our study is to evaluate the TC incidence trend in southern Tuscany, Italy, an area with particular geological characteristics, where the pollution and subsequent deterioration of various environmental matrices with potentially toxic elements (heavy metals) introduced from either geological or anthropogenic (human activities) sources are documented. The Tuscany cancer registry (ISPRO) provided us with the number of cases and EU standardized incidence rates (IR) of TC patients for all three provinces of southeast Tuscany (Siena, Grosseto, Arezzo) during the period of 2013–2016. In addition, we examined the histological records of 226 TC patients. We observed that the TC incidence rates for both sexes observed in Grosseto Province were significantly higher than those observed in the other two provinces. The increase was mostly due to the papillary (PTC) histotype (92% of cases), which presented aggressive variants in 37% of PTCs and tumor diameters more than 1 cm in 71.3% of cases. We demonstrated a high incidence of TC in Grosseto province, especially among male patients, that could be influenced by the presence of environmental heavy metal pollution.

Fine-needle aspiration cytology (FNAC) is the gold standard to diagnose thyroid nodules but fails in discriminating the nature of indeterminate lesions. Molecular testing can improve the diagnosis of these nodules and next-generation sequencing (NGS) can be used to test many genes simultaneously. Assess the performance of an NGS 17-gene panel on thyroid indeterminate FNAC. One hundred five indeterminate FNACs, 30.5% high-risk (TIR3B) and 69.5% low-risk (TIR3A), were analyzed by NGS. For TIR3A, the rate of mutated samples was 10.9%, significantly lower (p = 0.0001) compared to TIR3B (63.6%). Twenty-two mutated and fourteen non-mutated samples were submitted to surgery. At histology, the overall malignancy was 85.7% in the indeterminate group that had a positive molecular test and 13.3% in the mutation-negative (p = 0.01). The 17-gene panel had a sensitivity of 90%, specificity of 87%, positive predictive value (PPV) of 91%, and negative predictive value (NPV) of 87%. We reported the utility of Ultrasound Malignancy Risk Stratification of Thyroid Nodules in Adults (EU-TIRADS) in selecting indeterminate nodules for molecular analysis, showing a significant correlation between US score and mutation (p = 0.004). The performance of a 17-gene panel based on NGS technology is promising, allowing the selection of indeterminate nodules to submit to surgery with a great specificity and PPV.

Purpose: Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase initially described for its role during pregnancy. PAPPA regulates IGF ligands 1 (IGF1) bioavailability through the degradation of IGF-binding protein 4 (IGFBP4). After the cleavage of IGFBP4, free IGF1 is able to bind IGF1 receptors (IGF1R) triggering the downstream signaling. Recently, PAPPA expression has been linked with development of several cancers. No data have been published on thyroid cancer, yet. Methods: We evaluated PAPPA, insulin-like growth factor (IGF1), IGF1 receptors (IGF1R) and IGF-binding protein 4 (IGFBP4) mRNA expression levels in a “Surgical series” of 94 thyroid nodules (64 cancers, 16 follicular adenomas and 14 hyperplastic nodules) and in a “Cytological series” of 80 nodules from 74 patients underwent to fine-needle aspiration cytology (FNAC). In tissues, PAPPA was also evaluated by western blot. Results: We found that PAPPA expression was increased in thyroid cancer specimen at mRNA and protein levels and that, adenomas and hyperplastic nodules had an expression similar to normal tissues. When applied on thyroid cytologies, PAPPA expression was able to discriminate benign from malignant nodules contributing to pre-surgical classification of the nodules. We calculated a cut-off with a good specificity (91%) which reached 100% when combined with molecular biology. Conclusion: These results show that PAPPA could represent a promising diagnostic marker for differentiated thyroid cancer.

Background: Tyrosine kinase inhibitors (TKIs) have improved progression-free survival in patients with advanced thyroid cancer. So far, few studies have investigated the efficacy of TKIs in a second-line setting. The purpose of our study was to explore the salvage therapy efficacy in patients with advanced thyroid cancer. Methods: We retrospectively evaluated 63 patients with progressive advanced thyroid carcinoma treated with TKIs divided into a Study group (23 patients) treated with salvage therapy, and a Control group (40 patients) treated with only one TKI. Results: Similar clinical benefits (stable disease + partial response) and progression free survival between the first and the second line TKI were observed in the Study group (p > 0.99 and p = 0.5, respectively). Median overall survival (OS) was 67.7 months in the Study group and 22.6 months in the Control group (HR 2.46; 95% CI 1.34–4.52, p = 0.004). After stratifying the whole population by age (<65 and ≥65 years), OS was significantly different (p < 0.001) with the best survival curve in younger patients, treated with salvage therapy and the worst in older subjects, treated with only one TKI. Conclusions: Salvage therapy showed a significant improvement of OS in patients with advanced thyroid cancer who experienced disease progression during prior TKI therapies.