Multiple changes in thyroid function in patients with chronic active HCV hepatitis treated with recombinant interferon-alpha

Objective Recombinant human interferon-alpha (r-IFN-alpha) is often successfully used in the treatment of patients with chronic viral hepatitis B and C. Thyroid dysfunction has been reported to occur with variable frequency during r-IFN-alpha therapy especially in patients with preexisting thyroid autoimmunity. We have prospectively evaluated the effect of r-IFN-alpha on various aspects of thyroid function in patients with HCV chronic hepatitis. Design Thirty-two patients with HCV chronic active hepatitis were studied prospectively before and during r-IFN-alpha therapy. Serum TSH, FT4, FT3, and thyroid receptor (TSR) and thyroid peroxidase (TPO) antibodies, and the iodide-perchlorate discharge test (I-C104) to detect subtle defects in the thyroid organication of iodide were carried out during the study. Thyroid radioactive iodine uptakes (RAIU) were obtained in patients who developed thyrotoxicosis. Results All patients were clinically and biochemically euthyroid prior to r-IFN-alpha therapy with negative I-C104 discharge tests. Four patients became thyrotoxic, 3 secondary to destructive or inflammatory thyroiditis with a low thyroid RAIU, and 1 patient developed hypothyroidism. The I-C104 discharge test became positive in 7 of the 32 patients studied prospectively; 5 of these patients did not develop other evidence of thyroid dysfunction and did not have positive TPO antibodies. In these 5 patients the test became negative after r-IFN-alpha was discontinued. Appropriate therapy of the patients with thyrotoxicosis (methylprednisolone for 3 patients with destructive thyroiditis and methimazole for 1 patient with hyperthyroidism) or with hypothyroidism (L-thyroxine) was successful. Conclusions Thyroid dysfunction, especially destructive or silent thyroiditis resulting in thyrotoxicosis, is not infrequently observed in patients receiving r-IFN-alpha therapy for chronic active hepatitis. Although underlying autoimmune thyroid disease appears to predispose patients to develop thyroid dysfunction, other patients become thyrotoxic or hypothyroid in the absence of baseline positive TPO-Ab. Subtle defects in the thyroidal organisation of iodine as determined by the I-C104 discharge test, in the absence of autoimmune thyroid disease, was observed in 5 patients who remained euthyroid, suggesting that r-IFN-alpha directly reduces the intrathyroidal organisation of iodine.