Interferon alfa thyroid antibodies

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). 

After 6 months of treatment, 12% of patients with chronic hepatitis C had thyroid disorders, compared with 3% of patients with chronic hepatitis B. This study also suggested a possible relation between low free triiodothyronine serum concentrations before treatment and the subsequent occurrence of thyroid dysfunction. After a follow-up of 6 months after the end of interferon alfa treatment, 60% of affected patients with chronic hepatitis C still had persistent thyroid dysfunction all had been positive for thyroid peroxidase antibodies before treatment. Long-term surveillance is therefore needed in these patients. 

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. 

In addition to the underlying disease, there are many potential susceptibility factors (499,519). There is as yet no definitive evidence that age, sex, dose, and duration of treatment play an important role in the development of thyroid disorders. However, patients with previous thyroid abnormalities are predisposed to develop more severe thyroid disease (SEDA-20, 328). The incidence of thyroid disease was not different between natural and recombinant interferon alfa. Although this should be taken into account, a previous familial or personal history of thyroid disease was generally not considered a major risk factor. Finally, only pre-treatment positivity or the development of thyroid antibodies during treatment seem to be strongly associated with the occurrence of thyroid dysfunction. 

Of 62 initially autoantibody-negative patients treated with interferon alfa for chronic hepatitis C for a mean of 8 months, three developed antibodies to 21b-hydroxylase, a sensitive assay of adrenocortical autoimmunity (528). However, there were no cases of Addison s disease or subclinical adrenal insufficiency. This study suggested that the adrenal cortex is another potential target organ of autoimmune effects of interferon alfa, along with thyroid and pancreatic islet cells. 

Possible mechanisms need to be clarified. Since thyroid autoantibodies are detected in most patients who develop thyroid disorders, the induction or exacerbation of preexisting latent thyroid autoimmunity is the most attractive hypothesis. This is in accordance with the relatively frequent occurrence of other autoantibodies or clinical autoimmune disorders in patients who develop thyroid disorders (168). However, 20-30% of patients who develop thyroid diseases have no thyroid antibodies, and it is thus not yet proven that autoimmunity is the universal or primary mechanism. In fact, there were subtle and reversible defects in the intrathjroidal organification of iodine in 22% of antithyroid antibody-negative patients treated with interferon alfa (169). In addition, the acute systemic administration of interferon alfa in volunteers or chronic hepatitis patients reduces TSH concentrations (SED-13,1093) (170), and in vitro studies have suggested that interferon alfa directly inhibits thyrocyte function (SED-13, 1093) (171). Finally, the thyroid autoantibody... 

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... 

Type I diabetes mellitus and thyroid disease reportedly develop in 0.08-2.6% and 10-15% of patients treated with combined interferon alfa- -ribavirin for chronic hepatitis C but rarely coexist however, both conditions have been reported in a 33-year-old woman [50 ]. In another case, a 55-year-old woman developed type 1 diabetes and had a recurrence of Graves disease during treatment with peginterferon alfa -I- ribavirin for chronic hepatitis C [51 ]. There were serum anti-glutamic acid decarboxylase antibodies and the authors suggested that she had autoimmune polyglandular syndrome type III. 

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