Primary Hypothyroidism Associated With Interferon Therapy of Breast Cancer

Is, Fentiman; Thomas, B.S.; Balkwill, Frances R.; Rubens, Robert; Hayward, J. L.

doi:10.1016/s0140-6736(85)92475-4

Cited by 148 publications

(53 citation statements)

References 6 publications

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“…8 Standard or PEG-IFN-α may lead to influenza-like symptoms at the onset of treatment, as well as psychiatric, hematologic (neutropenia and thrombocytopenia) 10,11 and thyroid dysfunction. 12 As referred by Sachithanandan et al, 13 thyropathies affect 26.3% of HCV treated patients. The association with RBV usually induces hemolytic anemia, with no additional risk of thyropathy.…”

Section: Discussionmentioning

confidence: 92%

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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Section: Discussionmentioning

confidence: 92%

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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“…8 The association between IFN␣ and thyroid disease was recognized as early as 1985 in patients treated with IFN␣ for carcinoid tumors and breast cancer. 9,10 Since then, numerous studies have reported a high incidence of thyroid disease in patients treated with IFN␣. 11,12 Prospective studies have shown that up to 15% of patients with hepatitis C receiving IFN␣ developed clinical thyroid disease, 13 and up to 40% developed thyroid antibodies.…”

mentioning

confidence: 99%

The clinical and physiological spectrum of interferon‐alpha induced thyroiditis

et al. 2006

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Interferon-alpha (IFN␣) is a major treatment modality for several malignant and nonmalignant diseases, especially hepatitis C. Prospective studies have shown that up to 15% of patients with hepatitis C receiving IFN␣ develop clinical thyroid disease, and up to 40% were reported to develop thyroid antibodies. Some of these complications may result in discontinuation of interferon therapy. Thus, interferon induced thyroiditis (IIT) is a major clinical problem for patients receiving interferon therapy. IIT can be classified as autoimmune type and non-autoimmune type. I nterferons were discovered in the 1950Јs and were immediately recognized for their ability to render cells resistant to virus infection. 1 Interferons have been classified into two major groups, type I interferons and type II interferons, based on their capacity to bind to common receptor types. Type I interferons bind to a type I interferon receptor and include interferon-␣, interferon-␤, interferon-, and interferon-. 2 Type II interferons bind to a distinct type II receptor and include interferon-␥. 2 In addition to their antiviral properties, interferons have immunomodulatory, antiangiogenic, antiproliferative and antitumor activity, and act as important regulators of growth and differentiation. 3 Interferons work by directly binding to either type I or type II receptors. The cytoplasmic domains of the transmembrane glycoproteins are associated with members of the JAK family of kinases. They activate various signaling pathways, including the JAK-STAT pathway, the Crk-pathway, the IRS signaling pathway, and the MAP kinase pathway, which leads to signal transduction and subsequent activation or repression of specific genes. 3,4 More than twenty interferon-induced proteins have been identified. 5 Interferon-alpha (IFN␣) was the first cytokine to be reproduced by recombinant DNA technology and has emerged as a major therapeutic modality for several malignant and nonmalignant diseases. Among the diseases treated by IFN␣ are melanoma, renal cell carcinoma, hairy cell leukemia, Kaposi's sarcoma, and hepatitis B and C. 5 However, the most common prescription for IFN␣

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“…Thyroid dysfunction during interferon alpha is also quite common. Hypothyroidism was initially described as a side effect of interferon alpha therapy in patients receiving long-term interferon alpha treatment for breast cancer (Fentiman et al 1985). Thyroid effects of interferon alpha have been classified as autoimmune and nonautoimmune, mostly based on the presence or absence of markers of thyroid autoimmunity such as serum thyroid peroxidase and / or thyroglobulin antibodies (Mandac et al 2006).…”

Section: Interferon Alphamentioning

confidence: 99%