Unusual evolution from overt autoimmune hypothyroidism to hyperthyroidism after IFN-α therapy for chronic hepatitis.

A 41-year-old women was submitted to interferon-alpha (IFN-α) treatment for chronic hepatitis C (CHC). Serum thyroid hormone (TH), and thyroid ultrasonography (US) were normal and anti-thyroid autoantibodies (ATA) undetectable before starting IFN-α therapy. After two months, the patient developed overt hypothyroidism (TSH: 140 mU/I; FT4: 1.38 pg/ml; FT3: 0.89 pg/ml) and positive serum ATA (TPOAb: 416 U/ml; TgAb: 1/25600), with intense hypoechogenicity at thyroid US, suggestive of hypothyroid Hashimoto’s thyroiditis. She was submitted to L-thyroxine therapy (75 g/day): 2 months later, the patient noticed symptoms suggestive of mild thyrotoxicosis confirmed by suppressed TSH and slight increased serum TH. L-T4 therapy was temporary withdrawn, but, after 2 months, mild thyrotoxicosis was still present (TSH: 0.003 mU/I; FT4: 18.4 pg/ml; FT3: 6.6 pg/ml) and TSH receptor auto antibodies (TRAb) were detected (11.9 U/l). Thyroid color flow doppler sonography displayed diffuse hypoechogenicity with increased parenchymal blood flow, a diffuse radionuclide distribution and increased radioiodine uptake were detected at 99mTc-thyroid scintiscan and at 131I uptake, respectively: these findings excluded destructive thyrotoxicosis and were suggestive of autoimmune hyperthyroidism. IFN-α treatment was withdrawn and β-block therapy was started; 2 months later, overt hyperthyroidism was confirmed and the patient was eventually treated with anti-thyroid drugs. Thyroid dysfunctions (mostly transient) may often be induced by IFN-α therapy by different mechanisms, including induction/exacerbation of thyroid autoimmunity. In this rare case exacerbation of thyroid autoimmunity followed a functional bi-phasic pattern leading to long-lasting Graves disease.