Interferons and the thyroid
Interferon-alpha (IFNa) is used for the treatment of various disorders, including chronic hepatitis C virus (HCV) infection and certain malignancies. One of the commonest side effects of IFNa therapy is thyroiditis, with up to 40% of HCV patients on IFNa developing clinical or subclinical disease. In some cases interferon induced thyroiditis (IIT) may cause complications such as atrial fibrillation resulting in discontinuation of therapy. IIT can manifest clinically as thyrotoxicosis or hypothyroidism. Both thyrotoxicosis and hypothyroidism can present as autoimmune thyroid disease or non-autoimmune. The commonest etiology of IIT presenting with hypothyroidism is Hashimotos thyroiditis, and less commonly non-autoimmune hypothyroidism. Thyrotoxic IIT can be caused by destructive thyroiditis or Graves disease. While the epidemiology and clinical presentation of IIT have been well characterized the mechanisms causing IIT are still poorly understood. Several risk factors for IIT have been identified including genetic predisposition and the presence of thyroid antibodies prior to initiation of IFNa therapy. It is likely that the hepatitis C virus (HCV) itself plays a role in the disease. Indeed, new data from our lab show that HCV can bind to thyroid cells and induce cytokine production. Both immune and thyroid-toxic effects of IFNa contribute to the etiology of IIT. Immune effects of IFNa include increased expression of HLA class I molecules, inducing Th1 responses, and activation of lymphocytes, macrophages and NK cells. Thyroid toxic effects of IFNa include induction of thyroid specific protein expression, activation of heat shock proteins, and induction of thyroid cell death by necrosis. Early detection and therapy of this condition are important in order to avoid complications of thyroid disease such as cardiac arrhythmias.