Characteristics of autoimmune thyroid disease occurring as a late complication of immune reconstitution in patients with advanced human immunodeficiency virus (HIV) disease
Abstract
Experimental evidence from animal models has provided a framework for our current understanding of autoimmune disease pathogenesis and supports the importance of genetic predisposition, molecular mimicry, and immune dysregulation. However, only recently has evidence emerged to support the role of immune dysregulation in human organ-specific autoimmune disease. In the current study of the "late" manifestation of autoimmune thyroid disease (AITD) in a cohort of human immunodeficiency virus (HIV)-positive patients following highly active antiretroviral therapy (HAART), we discuss how immune dysregulation and factors associated with the immunopathology of HIV infection fit the current understanding of autoimmunity and provide a plausible basis for our clinical observations. De novo diagnoses of thyroid disease were identified between 1996 and 2002 in 7 HIV treatment centers (5/7 centers completed the study). Patients were diagnosed as clinical case entities and not discovered through thyroid function test screening. Paired plasma specimens were used to demonstrate sequential rise in thyroid antibodies. Seventeen patients were diagnosed with AITD (median age, 38 yr; 65% were of black African or black Caribbean ethnicity; and 82% were female). The median duration of immune reconstitution was 17 months. Graves disease (GD) was diagnosed in 15 of 17 patients. One patient developed hashithyrotoxicosis with atypically raised C-reactive protein, and another developed hypothyroidism. One GD patient had associated secondary hypoadrenalism. The estimated combined prevalence of GD for 4 treatment centers for female patients was 7/234 and for males was 2/1289. The denominator numbers were matched controls, from 4 centers able to provide data, who commenced HAART during the same time (January 1996 to July 2002) and who did not develop clinical AITD. The mean baseline pre-HAART CD4 count was 67 cells/mL, and the mean increase from nadir to AITD presentation was 355 cells/mL. AITD patients were more likely than controls (95% confidence interval, chi-square test) to be severely compromised at baseline (as defined by a CD4 count < 200 cells/mL or the presence of an acquired immunodeficiency syndrome [AIDS]-defining diagnosis), and to experience greater CD4 increments following HAART. AITD may be a late manifestation of immune reconstitution in HIV-positive patients taking HAART, and immune dysregulation may be an important factor.
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In both alemtuzumab-induced TD and HIV/HAART patients, the commonest disorder is Graves' disease, followed by hypothyroidism and thyroiditis.
“In both alemtuzumab-induced TD and HIV/HAART patients, the commonest disorder is Graves' disease (GD), followed by hypothyroidism and thyroiditis; Graves' orbitopathy is observed in some GD patients.”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [15]
Among HIV patients, Graves' disease occurred 8-33 months (mean 17 months) after HAART initiation.
“Among HIV patients GD occurred 8-33 months (mean 17 months) after HAART initiation [15-21].”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [15]
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- Authors
- Chen, F., Day, S. L., Metcalfe, R. A., Sethi, G., Kapembwa, M. S., Brook, M. G., Churchill, D., de Ruiter, A., Robinson, S., Lacey, C. J., & Weetman, A. P.
- Affiliations
- St Thomas' Hospital (GB)
- Venue
- Medicine
- Published
- 2005-03
- Volume
- 84
- Issue
- 2
- Pages
- 98-106
- ISSN
- 0025-7974 (ISSN-L)
- OpenAlex
- W1989054797
- Cited by
- 142
- References
- 34
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 6 · 2019: 7 · 2018: 11 · 2017: 4 · 2016: 12 · 2015: 6 · 2014: 9 · 2013: 12 · 2012: 10
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
- Keywords
- autoimmune thyroid disease, Graves' disease, HIV infection, highly active antiretroviral therapy, immune reconstitution, immune dysregulation, thyroid autoantibodies, CD4 count, hypothyroidism, hyperthyroidism, C-reactive protein, autoimmune disease pathogenesis, molecular mimicry, genetic susceptibility, prevalence, women
- MeSH terms
- Adult, Autoantibodies, Female, Graves Disease, Humans, Male, Middle Aged, Receptors, Thyrotropin, Cohort Studies, HIV Infections, Leukocyte Common Antigens, CD4 Lymphocyte Count, Antiretroviral Therapy, Highly Active
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