Phenotypes of Interferon-α-Induced Thyroid Dysfunction among Patients Treated for Hepatitis C Are Associated with Pretreatment Serum TSH and Female Sex
Abstract
CONTEXT: Thyroid dysfunction is a common complication of interferon-α (IFNα) therapy, with many phenotypic patterns and the potential for significant morbidity. OBJECTIVE: Our objective was to gain mechanistic insight and predict clinical presentations by determining the risk factors for distinct subtypes of IFNα-induced thyroid dysfunction. DESIGN: ACHIEVE-1, a randomized trial conducted from 2005-2009, compared long-acting preparations of IFNα in 1323 patients with hepatitis C, genotype 1. SETTING: A total of 149 outpatient clinics in North America, Europe, and Australia participated. PATIENTS: We studied 1233 patients who were euthyroid at baseline. This population is 60% male and 82% Caucasian. INTERVENTIONS: Patients were treated with pegylated IFNα2a weekly or albumin-IFNα2b every 2 wk for 48 wk. Serum TSH and free T(4) were measured before therapy and 12 or more times over 60 weeks. MAIN OUTCOME MEASURES: Thyroid dysfunction was defined as a TSH outside the normal range during the course of therapy. Low serum TSH indicated thyrotoxicosis, elevated TSH indicated hypothyroidism, and both abnormalities occurred in biphasic thyroiditis. RESULTS: Of previously euthyroid patients, 16.7% developed abnormal TSH values during therapy, including 24 with TSH below 0.1 mU/liter, 69 with TSH over 5.5 mU/liter, and 76 with biphasic thyroiditis. Biphasic thyroiditis was over 8-fold more common among women than men using multivariate logistic regression analysis [odds ratio (OR) = 8.4; 95% confidence interval (CI) = 4.5-15.8]. Thyrotoxicosis was most strongly associated with a lower pretreatment TSH (OR = 4.1 per -1 mU/liter decline; 95% CI = 1.9-9), whereas hypothyroidism was strongly associated with higher pretreatment TSH (OR = 3.9 per 1 mU/liter increase; 95% CI = 3-5.2). CONCLUSIONS: Biphasic thyroiditis is common among women treated for hepatitis C with IFNα. Lower and higher pretreatment serum TSH are associated with greater likelihood of thyrotoxicosis and hypothyroidism, respectively. Antithyroid antibody levels were not available for the cohort, and thus we cannot clarify the role of pretreatment thyroid autoimmunity as a risk factor. Our results do show that readily identifiable patient characteristics are risk factors for specific patterns of IFN-induced thyroid dysfunction. These findings suggest that distinct mechanisms may underlie subtypes of thyroid dysfunction associated with immune-modulatory therapy for hepatitis C.
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A recent study including 1233 patients who were euthyroid at baseline found that 79 (6.4%) patients developed a biphasic thyroiditis and an additional 57 (4.6%) patients developed a suppressed TSH value.
“A recent study including 1233 patients who were euthyroid at baseline found that 79 (6.4%) patients developed a biphasic thyroiditis and an additional 57 (4.6%) patients developed a suppressed TSH value (638).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [638]
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“6%) patients developed a suppressed TSH value (638).”
BackgroundBurch, H. B. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1901214 · Cited by 164 · see citing works
- Authors
- Mammen, J. S., Ghazarian, S. R., Pulkstenis, E., Subramanian, G. M., Rosen, A., & Ladenson, P. W.
- Affiliations
- Department of Medicine (J.S.M., P.W.L.), Division of Endocrinology
- Department of Pediatrics (S.R.G.), Baltimore, Maryland 21224
- Human Genome Sciences (United States) (US)
- Gilead Sciences (United States) (US)
- Johns Hopkins University (US)
- Corresponding author
- Mammen, Jennifer S.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-09-01
- Volume
- 97
- Issue
- 9
- Pages
- 3270-3276
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1985279004
- Cited by
- 16
- References
- 26
- Citations by year
- 2023: 1 · 2022: 1 · 2019: 2 · 2017: 1 · 2016: 3 · 2014: 2 · 2013: 5 · 2012: 1
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Johns Hopkins University
- Walton Family Foundation
- National Institute of Diabetes and Digestive and Kidney Diseases (K23DK095954)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- interferon-alpha, hepatitis C, thyroid dysfunction, thyrotoxicosis, hypothyroidism, thyroid-stimulating hormone, sex differences, female sex, peginterferon alfa-2a, risk factors, genotype 1, free thyroxine
- MeSH terms
- Adult, Antiviral Agents, Delayed-Action Preparations, Female, Hepatitis C, Humans, Hypothyroidism, Male, Middle Aged, Phenotype, Risk Factors, Sex Characteristics, Thyroid Diseases, Thyroiditis, Thyrotoxicosis, Thyrotropin, Thyroxine, Cohort Studies, Multivariate Analysis, Logistic Models, Treatment Outcome, Interferon-alpha, Risk Assessment
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