Background A new harmful respiratory disease, called COVID-19 emerged in China in December 2019 due to the infection of a novel coronavirus, called SARS-Coronavirus 2 (SARS-CoV-2), which belongs to the betacoronavirus genus, including SARS-CoV-1 and MERS-CoV. SARS-CoV-2 shares almost 80% of the genome with SARS-CoV-1 and 50% with MERS-CoV. Moreover, SARS-CoV-2 proteins share a high degree of homology (approximately 95%) with SARS-CoV-1 proteins. Hence, the mechanisms of SARS-Cov-1 and SARS-Cov-2 infection are similar and occur via binding to ACE2 protein, which is widely distributed in the human body, with a predominant expression in endocrine tissues including testis, thyroid, adrenal and pituitary. Purpose On the basis of expression pattern of the ACE2 protein among different tissues, similarity between SARS-Cov-1 and SARS-Cov-2 and the pathophysiology of COVID-19 disease, we aimed at discussing, after almost one-year pandemic, about the relationships between COVID-19 infection and the endocrine system. First, we discussed the potential effect of hormones on the susceptibility to COVID-19 infection; second, we examined the evidences regarding the effect of COVID-19 on the endocrine system. When data were available, a comparative discussion between SARS and COVID-19 effects was also performed. Methods A comprehensive literature search within Pubmed was performed. This review has been conducted according to the PRISMA statements. Results Among 450, 100 articles were selected. Tissue and vascular damages have been shown on thyroid, adrenal, testis and pituitary glands, with multiple alterations of endocrine function. Conclusion Hormones may affect patient susceptibility to COVID-19 infection but evidences regarding therapeutic implication of these findings are still missing. SARS and COVID-19 may affect endocrine glands and their dense vascularization, impairing endocrine system function. A possible damage of endocrine system in COVID-19 patients should be investigated in both COVID-19 acute phase and recovery to identify both early and late endocrine complications that may be important for patient’s prognosis and well-being after COVID-19 infection.

Obesity is strongly associated with chronic low-grade inflammation. Obese patients have an increased risk to develop thyroid autoimmunity and to became hypothyroid, suggesting a pathogenetic link between obesity, inflammation and autoimmunity. Moreover, type 2 diabetes and dyslipidemia, also characterized by low-grade inflammation, were recently associated with more aggressive forms of Graves’ ophthalmopathy. The association between obesity and autoimmune thyroid disorders may also go in the opposite direction, as treating autoimmune hyper and hypothyroidism can lead to weight gain. In addition, restoration of euthyroidism by L-T4 replacement therapy is more challenging in obese athyreotic patients, as it is difficult to maintain thyrotropin stimulation hormone (TSH) values within the normal range. Intriguingly, pro-inflammatory cytokines decrease in obese patients after bariatric surgery along with TSH levels. Moreover, the risk of thyroid cancer is increased in patients with thyroid autoimmune disorders, and is also related to the degree of obesity and inflammation. Molecular studies have shown a relationship between the low-grade inflammation of obesity and the activity of intracellular multiprotein complexes typical of immune cells (inflammasomes). We will now highlight some clinical implications of inflammasome activation in the relationship between obesity and thyroid disease.

Background Although calcitonin (Ctn) measurement is recognized as the most accurate diagnostic test for medullary thyroid carcinoma (MTC), its routine execution is not universally accepted for several reasons, including the lack of recommendations for managing indeterminate Ctn values (ICV); such as 10-to-100 pg/mL. This study aimed to gather data on 1) the frequency of ICV among patients undergoing Ctn test and 2) the MTC rate among patients with ICV. Methods This review was conducted according to the Meta-analyses Of Observational Studies in Epidemiology guidelines. PubMed and Cochrane databases were searched, with no language restrictions. The final search was completed on January 2023. Then, quality assessment and proportion meta-analyses were performed. Results The online search retrieved 233 articles and 15 were included for quantitative analysis. The risk of bias was low. The number of patients undergone Ctn testing was 29,533. The pooled percentage of those with ICV was 1.7% (95% confidence interval [CI]:1.2–2.3). The pooled proportion of MTC incidence among patients with ICV was 9.6% (95% CI:5–14.1). Heterogeneity was explained by the covariates of Ctn assay sensitivity and the resection rate. The subgroup with Ctn 10–20 pg/mL showed a significantly lower MTC rate than the subgroup with Ctn 20–100 pg/mL. Conclusions The percentage of ICV among patients with thyroid nodules who underwent Ctn testing is negligible. The rate of MTC in patients with ICV cannot be overlooked. Among the ICV intervals, the risk of MTC increases significantly when Ctn is above 20 pg/mL.