Both environmental and genetic triggers factor into the etiology of autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT). Although the exact pathogenesis and causative interaction between environment and genes are unknown, GD and HT share similar immune-mediated mechanisms of disease. They both are characterized by the production of thyroid autoantibodies and by thyroidal lymphocytic infiltration, despite being clinically distinct entities with thyrotoxicosis in GD and hypothyroidism in HT. Family and population studies confirm the strong genetic influence and inheritability in the development of AITD. AITD susceptibility genes can be categorized as either thyroid specific (Tg, TSHR) or immune-modulating (FOXP3, CD25, CD40, CTLA-4, HLA), with HLA-DR3 carrying the highest risk. Of the AITD susceptibility genes, FOXP3 and CD25 play critical roles in the establishment of peripheral tolerance while CD40, CTLA-4, and the HLA genes are pivotal for T lymphocyte activation and antigen presentation. Polymorphisms in these immune-modulating genes, in particular, significantly contribute to the predisposition for GD, HT and, unsurprisingly, other autoimmune diseases. Emerging evidence suggests that single nucleotide polymorphisms (SNPs) in the immunoregulatory genes may functionally hinder the proper development of central and peripheral tolerance and alter T cell interactions with antigen presenting cells (APCs) in the immunological synapse. Thus, susceptibility genes for AITD contribute directly to the key mechanism underlying the development of organ-specific autoimmunity, namely the breakdown in self-tolerance. Here we review the major immune-modulating genes that are associated with AITD and their potential functional effects on thyroidal immune dysregulation.

Diabetes and hepatitis C infection are both prevalent diseases worldwide, and are associated with increased morbidity and mortality. Most studies, but not all, have shown that patients with chronic hepatitis C are more prone to develop type 2 diabetes (T2D) compared to healthy controls, as well as when compared to patients with other liver diseases, including hepatitis B. Furthermore, epidemiological studies have revealed that patients with T2D may also be at higher risk for worse outcomes of their hepatitis C infection, including reduced rate of sustained virological response, progression to fibrosis and cirrhosis, and higher risk for development of hepatocellular carcinoma. Moreover, hepatitis C infection and mainly its treatment, interferon α, can trigger the development of type 1 diabetes. In this review, we discuss the existing data on this two-way association between diabetes and hepatitis C infection with emphasis on possible mechanisms. It remains to be determined whether the new curative therapies for chronic hepatitis C will improve outcomes in diabetic hepatitis C patients, and conversely whether treatment with Metformin will reduce complications from hepatitis C virus infection. We propose an algorithm for diabetes screening and follow-up in hepatitis C patients.

Context Hyperglycemic emergencies such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) and new-onset diabetes mellitus (DM) have been reported in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Hyperglycemia is a predictor of poor prognosis in COVID-19 disease. Objectives The objective of this work is to describe a case series of HHS and/or DKA likely triggered by the COVID-19 vaccine. The aim is to alert physicians of the potential hyperglycemic complications from the COVID-19 vaccination and to provide further insight into the underlying mechanism of the bidirectional relationship between SARS-CoV-2 and DM. Case description All 3 patients developed HHS and/or DKA within 2-10 days of the COVID-19 vaccination. PCR testing for SARS-CoV-2 was negative and other clinical precipitating factors were excluded. Two patients had a history of type 2 DM (T2DM) with pre-admission HbA1c levels of 7.0-7.5% while one patient was newly diagnosed with T2DM during the hospitalization. They were each treated with insulin infusion and were discharged on subcutaneous insulin therapy. Due to the rapid resolution of the hyperglycemia, insulin was discontinued in all patients within 8 weeks and they remain well-controlled on oral DM medications. Conclusion Severe hyperglycemia including HHS and DKA may be triggered by COVID-19 vaccination. Early evaluation and screening of patients with hyperglycemic symptoms after COVID-19 vaccination is recommended. The vaccine-induced hyperglycemia may provide further insight into the underlying pathogenesis caused by the SARS-CoV-2 infection itself. The underlying robust inflammatory response and “cytokine storm” may be the primary precipitant.

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