Thyroid dysfunction can predict response to immunotherapy with interleukin-2 and interferon-2α

Reid, I.; Sharpe, I.; McDevitt, Jennifer; Maxwell, W.M.C.; Emmons, Racine R.; Tanner, W. A.; Monson, J. R. T.

doi:10.1038/bjc.1991.426

Cited by 32 publications

(8 citation statements)

References 11 publications

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“…Thyroid dysfunction was not associated with the response of chronic hepatitis C to IFN-a therapy in the present study; in contrast a positive relationship between the appearance of thyroid dysfunction and the response to IFN-a therapy was observed in previous studies (7,34,35). However, all those previous studies did not evaluate the pretreatment serum HCV RNA levels.…”

Section: Discussioncontrasting

confidence: 54%

Virologic factors related to interferon-alpha-induced thyroid dysfunction in patients with chronic hepatitis C

Chuang

et al. 2000

European Journal of Endocrinology

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Objective: Hepatitis C virus (HCV), being reported to be associated with a high prevalence of serological markers of autoimmunity in HCV-infected patients, and possibly sharing partial sequences in amino acid segments with thyroid tissue antigens, may be associated with interferon-a (IFN-a)-induced thyroid dysfunction in chronic hepatitis C patients. We conducted this study to clarify the issue. Design and Methods: One hundred and fifty chronic hepatitis C patients with normal baseline thyroid function were treated with IFN-a 2a, 2b and n1 (3-6 million Units three times weekly for 24 weeks). Pretreatment sera were tested for HCV genotype and HCV RNA levels. Serum thyrotropin, total thyroxine and free thyroxine index were performed every 4 weeks for 24 weeks followed by every 8 weeks for another 24 weeks. Results: Twenty-one (14.0%) patients developed early thyroid dysfunction (abnormal thyroid function during the first 3 months of therapy). Female gender, lower HCV RNA levels, IFN-a n1 and a lower IFN-a dose were significantly associated with early thyroid dysfunction. On multivariate analysis, gender, IFN-a preparation and HCV RNA levels were the significant factors associated with early thyroid dysfunction. Seven (4.7%) patients developed thyroid dysfunction during the second 3 months of IFN-a therapy. Taken together, 18.7% patients developed thyroid dysfunction. Female, mixed HCV genotype infection and lower HCV RNA levels were significantly associated with thyroid dysfunction. However, only gender remained significantly associated with IFN-a-induced thyroid dysfunction in multivariate analysis. Conclusions:The virologic features of HCV may be associated with thyroid dysfunction in chronic hepatitis C patients treated with IFN-a. Nevertheless, gender still plays the most important role in IFN-a-induced thyroid dysfunction.

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Section: Discussioncontrasting

confidence: 54%

Virologic factors related to interferon-alpha-induced thyroid dysfunction in patients with chronic hepatitis C

Chuang

et al. 2000

European Journal of Endocrinology

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“…[29][30][31] In our patients, the presence of thyroid dysfunction did not lead to changes in the dose or therapy withdrawal.…”

Section: Discussionmentioning

confidence: 99%

Virus C genotype predisposes to primary hypothyroidism during interferon-α treatment for chronic hepatitis C

Pavan¹,

Pavin²,

Gonçales³

et al. 2011

Braz J Infect Dis

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Objective: The treatment of the chronic hepatitis C (HCV) with α-interferon is associated with thyroid dysfunction (TD). The aim of this study was to evaluate thyroid function outcome among patients with chronic HCV under treatment with conventional interferon (IFN) or peguilated interferon (PEG-IFN) in association with ribavirin. Patients and Methods: We studied 293 patients with chronic HCV, submitted to drug therapy for 24 or 48 weeks. Initially, we evaluated FT4, TSH, TPOAb, TgAb, and continued to monitor FT4 and TSH every three months during therapy and six months thereafter. Results: At baseline, TD prevalence was 6.82% (n = 20); 6.14% hypothyroidism; 0.68% hyperthyroidism. TPOAb was present in 5.46% of euthyroid patients. Out of 273 euthyroid patients at baseline, 19% developed TD: 17.2% hypothyroidism; 1.8% hyperthyroidism; 5.1% destructive thyroiditis (DT). 90% of TPOAb-positive patients at baseline developed hypothyroidism vs 14.5% of TPOAb-negative patients (p < 0.001). On average, TD occurred after 25.8 ± 15.5 weeks of treatment. 87.2% of patients who developed hypothyroidism did so during the first therapeutic cycle (p = 0.004; OR = 3.52; 95% CI = 1.36-9.65). Patients infected with genotype 1 virus were 2.13 times more likely to develop hypothyroidism (p = 0.036; 95% CI = 1.04-4.38). Hypothyroid and DT patients presented higher TSH levels before-treatment than patients who had remained euthyroid (p < 0.001; p = 0.002, respectively). DT patients presented lower qALT (p = 0.012) than euthyroid patients. Conclusion: Hypothyroidism was the most frequent TD, especially during the first cycle of α-interferon. Genotype 1 virus was associated with a risk two times higher for developing the illness. There was no need to interrupt or to change HCV treatment. Therefore, approximately 34% of TD was transient.

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“…Some authors have suggested that patients who develop thyroid autoimmunity in relation to IFN-α treatment, or to combined therapy with interleukin-2 (IL-2) and IFN-α, have a better clinical response of the underlying disease [106,107], but this was not confirmed by other studies [18,41,91,92]. Recently, a correlation between the degree of autoimmune disease and improved prognosis in metastatic renal cancer has been reported, suggesting that autoimmunity while on cytokine therapy may mark a breach of immune tolerance in patients with cancer [108].…”

Section: Type I Ifn Therapy and Incident Thyroid Abnormalitiesmentioning

confidence: 99%

Thyroid autoimmunity and dysfunction associated with type I interferon therapy

Monzani

Caraccio

Dardano

et al. 2004

Clinical and Experimental Medicine

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Type I interferons are currently used for the treatment of chronic viral hepatitis, multiple sclerosis and several hematological and solid tumors. Side effects are not uncommon, and include multiple alterations in thyroid function, some of which are unrelated to autoimmunity. Review of the literature revealed an overall mean prevalence of incident thyroid dysfunction of 6.2%, hypothyroidism occurring more frequently (3.9%) than hyperthyroidism (2.3%). Destructive thyroiditis characterized by early transient thyrotoxicosis followed by hypothyroidism has also been described. Thyroid dysfunction was mainly subclinical, and spontaneous resolution occurred in almost 60% of patients with or without withdrawal of interferon. Risk factors for developing thyroid abnormalities were female sex and the presence of pre-existing autoimmune thyroiditis. Whether prolonged interferon therapy will increase the likelihood of experiencing thyroid dysfunction, as well as the relationship between incident thyroid autoimmunity and the efficacy of interferon therapy, are still open questions. Although the most-likely explanation for thyroid disease occurring with type I interferon therapy remains an autoimmune reaction or immune system dysregulation, a direct inhibitory effect on thyrocytes may be presumed in patients who developed hypothyroidism without autoimmunity. However, the mechanisms of thyroid damage induced by type I interferons have not yet been clarified in detail. We recommend routine evaluation of serum thyroid-stimulating hormone during interferon therapy. A systematic thyroid assessment is useful only for those patients with pre-existing thyroiditis or incident dysfunction. Although discontinuation of interferon therapy is seldom required, it may be necessary in patients who develop Graves' disease and overt hyperthyroidism.

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Thyroid dysfunction can predict response to immunotherapy with interleukin-2 and interferon-2α

Cited by 32 publications

References 11 publications

Virologic factors related to interferon-alpha-induced thyroid dysfunction in patients with chronic hepatitis C

Virologic factors related to interferon-alpha-induced thyroid dysfunction in patients with chronic hepatitis C

Virus C genotype predisposes to primary hypothyroidism during interferon-α treatment for chronic hepatitis C

Thyroid autoimmunity and dysfunction associated with type I interferon therapy

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