[Dysthyroidism in patients treated with interferon alpha]

In addition to their initially recognized antiviral activity, interferons are known to have a number of effects on the immune system. The role of alpha-interferon (alpha-IFN) has been evaluated in 8 studies, including 573 patients, aimed at determining the prevalence, clinical course and predictive factors of autoimmune dysthyroidism in patients treated with alpha-IFN. Two major categories of patients were treated with alpha-IFN: those with cancer and those with chronic viral hepatitis. Two types of interferon were used: human leukocyte IFN and recombinant IFN. Among the 542 patients in which thyroid function was evaluated, 47 (8.7%) had clinical or biological dysthyroidism: hypothyroidism in 25 (53%), hyperthyroidism in 13 (28%) and biphasic hyper-hypothyroidism in 9 (19%). The delay to onset was known in 44 patients (mean 9 months, range 1.5 to 23 months). Dysthyroidism was temporary in certain patients and did not require treatment, but antithyroid drugs were required in others. The prevalence of antithyroglobulin and/or antimicrosomal antibodies varied from 0 to 20% (mean 13.7%). The prevalence of antithyroid stimulating hormone receptor antibodies appeared to be lower than that of antithyroid antibodies. The pathogenic mechanism of dysthyroidism in patients given alpha-IFN remains unknown, but could result from the induction of antithyroid antibodies or an increase in pre-existing levels. Abherent expression of HLA-DR antigens on the surface of the thyrocytes has been proposed as a possible factor, although gamma-IFN and not alpha-IFN leads to the expression of class II antigens. It has also been shown that alpha-IFN induces the expression of class I antigens on thyrocytes, indicating that the observed dysthyroidism might result from an over-expression of class I antigens which would facilitate direct activation of cytotoxic T cells. In summary, alpha-IFN can induce dysthyroidism in about 1 out of 10 patients, probably by the induction or stimulation of autoimmune phenomena. The positive predictive value of antithyroid antibodies is modest, about 60%, but the negative predictive value is high at 93%. Thyroid function should be monitored closely in patients given alpha-interferon.