**3.6 Viruses**

Many viruses affect the thyroid gland some of which associated with presence of thyroid autoantibodies i.e. congenital rubella, hepatitis C virus, subacute thyroiditis. But these are not appearing to be associated with development or progression of GD [34]. However, the potential influence of various common infections (such as Epstein–Barr virus and influenza virus) on the epigenetic characteristics of a variety of susceptibility genes remains a major hypothesis for the etiology of GD.

### **3.7 Iodine and related drugs**

Iodine and iodine-containing drugs, such as amiodaroneand iodine-containing contrast media, precipitate GD or its recurrence in a genetically susceptible individual which may be due to presence of some cryptic epitope on Thyroglobulin antibodies [35, 36]. Amiodarone is an iodinated derivative of benzofuran used in tachyarrhythmias. Each molecule of amiodarone contains two iodine atoms, which constitute 37.5% of its mass and its metabolism results in the daily release of approximately 6 mg of free iodine into the circulation which is 20–40 times higher than the daily iodine intake. Amiodarone can cause hypothyroidism or thyrotoxicosis by various mechanisms depending on duration of therapy, autoimmunity and other characteristics [36].

## **3.8 Drugs**

Various drugs can cause supression of TSH by their direct cytotoxic effect on thyroid follicular cells. Interferon and ribaverin used in the treatment of HCV disease can aggravate hyperthyroidism associated with GD. Highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infection Alemtuzumab humanized anti-CD52 monoclonal antibody, Ipilimumab is a monoclonal antibody against CTLA4, Nivolumab and pembrolizumab antibodies against programmed death protein 1 (PD1) can also precipitate hyperthyroidism by immune mechanisms [37–41].
