CLINICS 2011;66(10):1757-1763 CLINICAL SCIENCE DOI:10.1590/S1807-59322011001000014 Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin Debora Lucia Seguro Danilovic,I Maria Cassia Mendes-Correa,II Maria Cristina Chammas,III Heverton Zambrini,II Suemi MaruiI I Unidade de Tireo´ ide - Laborato´ rio de Endocrinologia Celular e Molecular - LIM 25 - Faculdade de Medicina da Universidade de S a˜o Paulo, S a˜o Paulo, SP, Brazil. II Disciplina de Mole´ stias Infecciosas, Hospital das Clı´nicas da Faculdade de Medicina da Universidade de S a˜o Paulo, S a˜o Paulo, SP, Brazil. III Disciplina de Radiologia, Hospital das Clı´nicas da Faculdade de Medicina da Universidade de Sa˜ o Paulo, Sa˜ o Paulo, SP, Brazil. OBJECTIVE: To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C. INTRODUCTION: Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis. METHODS: We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy. RESULTS: Of the patients in our study, 54% had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH) levels remained stable. A total of 19% of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16% had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11% remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns. DISCUSSION: Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis. CONCLUSION: Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels), which occur despite stable free T4 and TSH levels. A thyroid hormonal evaluation, including the analysis of the free T4, TSH, and antithyroid antibody levels, should be mandatory before therapy, and an early re-evaluation within three months of treatment is necessary as an appropriate follow-up. KEYWORDS: Thyroid hormones; Hepatitis C; Interferon-induced thyroiditis; Destructive thyroiditis; Thyroid ultrasonography. Danilovic DLS, Mendes-Correa MC, Chammas MC, Zambrini H, Marui S. Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin. Clinics. 2011;66(10):1757-1763. Received for publication on March 29, 2011; First review completed on May 16, 2011; Accepted for publication on July 4, 2011 E-mail: deboraseguro@hotmail.com Tel.: 55-11-95177498 INTRODUCTION Hepatitis C is a disease that is disseminated worldwide, and chronic infections affect up to 80% of the infected Copyright 2011 CLINICS – This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non- commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. No potential conflict of interest was reported. subjects.1 Consequently, interferon-alpha (IFNa) therapy has frequently been used. IFNa is one of a group of cytokines with antiviral, antiproliferative, and immunomo- dulatory properties. In cases of hepatitis C, the presence of moderate to severe necroinflammatory activity and/or moderate to severe fibrosis (as assessed by a liver biopsy) represent formal indications of IFNa use. The drug is available in both conventional and pegylated forms and is frequently used in association with ribavirin, another antiviral drug.2,3 The treatment is continuous and lasts from 6 to 12 months, and retreatment can be necessary. 1757