Temporal relationship between the appearance of thyroid autoantibodies and development of destructive thyroiditis in patients undergoing treatment with two different type-1 interferons for HCV-related chronic hepatitis: A prospective study

Abstract

In this prospective study we performed repeated evaluations of thyroid status in patients undergoing treatment with different preparations of recombinant interferons (IFNs), in order to identify early markers of thyroid dysfunction. Moreover, we aimed to investigate whether the development of thyroid dysfunction was related to the appearance of thyroid autoimmunity. Our study included 51 consecutive patients without pre-existing thyroid disease, admitted to our hospital for Hepatitis C virus (HCV)-related chronic hepatitis. Thirty-six patients (Gr. A) were treated with IFN-alpha 2b plus ribavirin (RIBA), whereas 15 patients (Gr. B) underwent treatment with IFN-alphacon-1 (CIFN) plus RIBA. Thyroid autoimmunity and function were prospectively evaluated before, every month during treatment and for 6 months after IFN withdrawal. At study entry, all patients were euthyroid and negative for thyroid autoantibodies. In Gr. A, 10 patients developed thyroid autoimmunity after a median period of 3 months (range: 1-6) treatment with IFN-alpha+RIBA. At the time of appearance of thyroid autoantibodies, 4 patients developed destructive thyrotoxicosis (overt in one case, subclinical in 3 cases), while other 4 patients showed a high reduction of serum TSH levels (median decrease: -75.7%, range: -61.9- -84.2), which reached the low values of normal range. After a median period of 2 months (range: 1-3) from these biochemical abnormalities, 6 patients continuing antiviral treatment developed hypothyroidism (overt in 3 cases and subclinical in the other 3). In Gr. B, 5 patients developed thyroid autoimmunity after a median period of 3 months (range: 2-10) of treatment with CIFN+RIBA. Soon after the appearance of thyroid autoantibodies, all patients developed an overt thyrotoxicosis (with hyperthyroidism in 2 cases). Antiviral treatment was discontinued in all 5 cases. Thereafter, thyroid function recovered spontaneously without significant modifications of serum TGAb and TPOAb levels until the end of the study. In conclusion our prospective study demonstrated that: 1) the appearance of thyroid autoantibodies during treatment with IFN was accompanied in most cases by the occurrence of a destructive process in the thyroid gland; 2) The clinical expression of destructive thyroiditis was more evident in patients treated with CIFN than that in patients treated with IFN; 3) The thyroid clinical outcome of these patients was strictly correlated to the continuation of cytokine treatment.

The presence of thyroid peroxidase antibody of IgG2 subclass is a risk factor for thyroid dysfunction in chronic hepatitis C patients

“…We observed similar trends between TD and euthyroid patients. Previous reports showed that the incidence of TAs in HCV-infected patients ranged from 10 to 45% (21,22,23). These observed differences might be related to geographical distribution, genetic variability, and environmental factors (24).…”

Interferon-α-induced hyperthyroidism: a three-stage evolution from silent thyroiditis towards Graves’ disease

“…We can only speculate about the mechanism of action of IFN-a in this process and this is of interest as IFNmediated thyroid disease could constitute a model for human autoimmunity (13). With regard to the destructive phase of the disease, evidence has accumulated in favor of an autoimmune process, as it was demonstrated that production of thyroid autoantibodies preceded thyroid dysfunction (14) and, indeed, this phase looks like postpartum thyroiditis (15) and silent thyroiditis. Moreover, Graves' disease occurring after biphasic thyroiditis does not seem to be specific to IFN-a, as several case reports have described it after subacute thyroiditis (16), postpartum thyroiditis (17,18) or spontaneous thyroiditis (16) or even after treatment of euthyroid goiter by 131 I (19).…”

The clinical and physiological spectrum of interferon-alpha induced thyroiditis: Toward a new classification

“…In addition, a subset of these patients may progress to permanent hypothyroidism, usually accompanied by the development of TAb's suggesting an underlying autoimmune thyroiditis. 16 Alternatively, the hypothyroidism may be due to a direct toxic effect of IFN␣ on the thyroid.…”

“…1A) Previous studies have shown how IIT can cause serious complications of hyper-or hypo-thyroidism. 13,[16][17][18]37,39 Therefore, careful screening of all patients before, during, and after IFN␣ treatment is recommended. Since many symptoms of thyroid dysfunction could be attributed to HCV infection, clinicians should routinely look for signs of thyroid dysfunction such as tachycardia or bradycardia, sweating, heat or cold intolerance, unexpected weight loss or weight gain, and extreme fatigue and weakness.…”

“…14 Thyroid abnormalities following interferon therapy have also been described in children receiving interferon for hepatitis C infection. 15 Some of these complications of IFN␣ therapy, especially thyrotoxicosis, can be severe and may interfere with adequate interferon therapy in patients with hepatitis C. 13,[16][17][18] Moreover, because the symptoms of hypothyroidismsuch as fatigue, hair loss, myalgia, and weight gain-may be attributable to hepatitis C or IFN␣ therapy, 8 the diagnosis of hypothyroidism in these patients may be delayed. This delay may lead to development of further complications.…”