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.

Objective Coronavirus disease-2019 (COVID-19) causes acute respiratory distress syndrome. Patients with adrenal insufficiency (AI) may develop severe complications due to this infection and should undergo COVID-19 vaccination; however, there is no consensus about the management of their replacement therapy. The aim of our study was to evaluate the tolerability and need for glucocorticoid dose adjustment related to COVID-19 mRNA vaccines in a cohort of patients with AI. Design and methods We prospectively administered to 88 patients (51 M/37 F; mean age: 62.3 ± 16 years), with AI (28 primary and 60 secondary AI), a questionnaire about the occurrence, severity and duration of the side effects and the need for glucocorticoid dose adjustment within 1 week after the first and the second dose of COVID-19 mRNA vaccines (Pfizer–BioNTech and Moderna). Results Side effects of mild to moderate severity occurred in about 70% of patients after both vaccine doses. The most common adverse events were pain at the injection site, fatigue, fever and flu-like symptoms. The occurrence and severity of the side effects were not correlated to gender, type of AI and mRNA vaccine, but their total number was higher after the second vaccine dose. Doubling the oral glucocorticoid dose was needed in up to 8% of patients, especially after the second vaccine dose, but no parenteral administration was required. Conclusions COVID-19 mRNA vaccines were well tolerated in patients with AI. Side effects were similar to those observed in the general population, and increasing glucocorticoid replacement therapy before vaccine administration was not needed.

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.

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