Interferon alfa hypothyroidism

Since the first reports of hypothyroidism, a number of studies have reported the occurrence of thyroid dysfunction in patients receiving aldesleukin alone or in combination with LAK cells, interferon alfa, interferon gamma, or tumor necrosis factor alfa (SED-13, 1104 6). Symptoms were usually observed after 2-4 months of treatment (7-9), and mostly consisted of moderate hypothyroidism, which resolved after immunotherapy withdrawal or thyroxine treatment (9,10). Patients treated with aldesleukin plus interferon alfa more commonly developed biphasic thyroiditis with subsequent hypothyroidism or hyperthyroidism (10-13). 

Since the original 1988 report of hypothyroidism in patients with breast cancer receiving leukocyte-derived interferon alfa (498), numerous investigators have provided clear clinical and biological data on thyroid disorders induced by different forms of interferon in patients with various diseases (499,500-503). Two of these reports also mentioned associated adverse effects that developed concomitantly, namely myelosuppression and severe proximal myopathy (Hoffmann s syndrome). 

The spectrum of interferon alfa-induced thyroid disorders ranges from asymptomatic appearance or increase in antithyroid autoantibody titers to moderate or severe clinical features of hypothyroidism, hyperthyroidism, and acute biphasic thyroiditis. Antithyroid hormone antibodies have also been found in one patient, and this could have been the cause of erroneously raised thyroid hormone concentrations (504). 

Hypothyroidism occurs more often than hyperthyroidism, and spontaneous resolution is expected in almost 60% of patients with or without interferon alfa withdrawal. Finally, female sex and the presence of baseline thyroid autoimmunity were confirmed to be the most significant risk factors. The mechanisms of interferon alfa-induced thyroid dysfunction are not yet fully clarified. Although an autoimmune reaction or immune dys-regulation are the most likely mechanisms, a direct inhibitory effect of interferon alfa on thyrocytes should be considered in patients without thyroid antibodies. 

The clinical, biochemical, and thyroid imaging characteristics of thyrotoxicosis resulting from interferon alfa treatment have been retrospectively analysed from data on 10 of 321 patients with chronic hepatitis (75 with chronic hepatitis B and 246 with chronic hepatitis C) who developed biochemical thyrotoxicosis (161). Seven patients had symptomatic disorders, but none had ocular symptoms or a palpable goiter. Six had features of Graves disease that required interferon alfa withdrawal in four and prolonged treatment with antithyroid drugs in all six. Three presented with transient thyrotoxicosis that subsequently progressed to hypothyroidism and required interferon withdrawal in one and thyroxine treatment in aU three. 

The occurrence of thyroid dysfunction in 72 patients treated with interferon alfa plus ribavirin (1.0-1.2 g/day) has been compared with that of 75 age- and sex-matched patients treated with interferon alfa alone for chronic hepatitis C (177). Of the former, 42 patients, and of the latter, 40 patients had received previous treatment with interferon alfa alone. There was no difference in the rate of thjroid autoimmunity (antithyroglobuUn, antithjroid peroxidase, and thyroid-stimulating hormone receptor antibodies) between the two groups, but the patients who received interferon alfa plus ribavirin developed subclinical or overt hypothyroidism more often (15 versus 4%). Similarly, the incidence of hypothjroidism increased to 19% in patients who underwent a second treatment with interferon alfa plus ribavirin compared with 4.8% after the first treatment with interferon alfa alone, while the incidence remained essentially the same in patients who had two consecutive treatments with interferon alfa alone... 

Two studies have provided insights into the incidence and risk factors of the immune-mediated comphcations of interferon alfa in patients with chronic myeloid leukemia. In the first study, 13 of 46 patients had autoimmune manifestations consisting of a combination of autoimmune thyroiditis in four, a direct antiglobulin test without hemolysis in eight, cryoagglutinins in one, Raynaud s phenomenon in two, and chronic autoimmune hepatitis in one (343). Overall, six patients had chnically symptomatic manifestations after a median of 15 months of treatment. In the second study, there were autoimmune diseases in seven of 76 patients after a median of 19 months of treatment, including hypothyroidism in one, immune-mediated hemolysis in two, systemic lupus erythematosus in two, Raynaud s phenomenon in one, and mixed connective tissue disease in one (344). In... 

Interferon alfa-2b can cause both hyperthyroidism and hypothyroidism, the commonest cause being thyroiditis. Seven women and four men developed thyroiditis over 30 months while using peginterferon alfa-2b and ribavirin for hepatitis [48 ]. The average time to the development of thyroid disease was 10 weeks and the duration of the disease was 9 weeks. All eventually recovered normal biochemical thyroid function, although two required short-term supplementation. 

Endocrine disorders Peginterferon alfa-2b causes or aggravates hypothyroidism and hyperthyroidism. Flyperglycemia has been observed in patients treated with peginterferon alfa-2b. Diabetes mellitus has been observed in patients treated with alpha interferons. 

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