Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin.
OBJECTIVE
To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C.


BACKGROUND
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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Unidade de Tireóide, Laboratório de Endocrinologia Celular e Molecular, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. deboraseguro@hotmail.com
Debora Lucia Seguro
DL
Danilovic
Maria Cassia
MC
Mendes-Correa
Maria Cristina
MC
Chammas
Heverton
H
Zambrini
Suemi
S
Marui
D000328:Adult; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D013960:Thyroid Function Tests; D013963:Thyroid Hormones / Q000097:blood* / Q000276:immunology; D013966:Thyroiditis / Q000097:blood / Q000139:chemically induced* / Q000000981:diagnostic imaging; D013967:Thyroiditis, Autoimmune / Q000097:blood / Q000139:chemically induced / Q000000981:diagnostic imaging; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography
D000998:Antiviral Agents; D016898:Interferon-alpha; D013963:Thyroid Hormones; D012254:Ribavirin