Autoimmune thyroid disease associated with interferon therapy occurs in 2.7 to 10% of patients and at a median time of 17-weeks (range 4 weeks–23 months) after beginning interferon therapy. Destructive thyroiditis, Graves’ Hyperthyroidism and autoimmune (often subclinical) hypothyroidism have been described, the latter occurring in 87% of cases and persisting in >50% of interferon-treated patients. Graves’ Hyperthyroidism is the more common form of thyrotoxicosis, occuring in 2/3 of cases whereas destructive thyroiditis occurs in 1/3. Thyroid replacement or anti-thyroid therapy are indicated in autoimmune hypo- and hyperthyroidism, respectively, with continuation of interferon. However, in destructive thyroiditis, cessation of interferon may be temporarily necessary. Little is known about the development of the extremes of autoimmune thyroid disease activated by the undesirable immunomodulatory effects of interferon treatment, especially within a single patient, as reported below.
A 60-year old man with no prior history of thyroid disease received 48-week pegylated interferon and ribavirin therapy for chronic HCV with achievement of sustained virological response. Six months into treatment, he reported fatigue, weight gain and slowed cognition. Examination was normal. Serum TSH was 58.8mIU/L [0.27 – 4.2], fT4 11.1 pmol/L [12 – 25], and fT3 4.2 pmol/L [2.5 - 6.0] with elevated anti-TPO (983 IU/mL, <35) and anti-TG (733 U/mL, <80) antibodies. He was commenced on thyroxine 100mcg daily with initial clinical and biochemical resolution but developed symptoms of hyperthyroidism with weight loss and tremor 14-months later. Serum TSH was <0.02 mIU/L, fT4 54.3 pmol/L, fT3 20.2 pmol/L, with an elevated TRAb of 4.0 U/L (<1.0), anti-TPO (1,163 IU/mL) and anti-TG (114 U/mL) antibodies. Technetium scan confirmed Graves’ Disease with bilateral diffuse increased tracer uptake (5.9%, 0.5 – 3.5%). The patient was commenced on carbimazole 15mg daily for 6-months. He self-ceased therapy with serendipitous clinical and biochemical remission (TSH 3.84 mIU/L, fT4 17 pmol/L, fT3 4.5 pmol/L, anti-TPO 383 IU/mL, anti-TG 23 U/mL, TRAb <1U/L).
This case should heighten the clinical awareness regarding the possible development of thyroid dysfunction closely in patients both during and following completion of interferon treatment. The frequency and period of follow-up are not clearly established and the presentation of thyroid dysfunction may be variable.