Clinical challenges of thyroid eye disease in HIV-positive patients on highly active antiretroviral therapy
Abstract
BACKGROUND: Graves' disease (GD) as an immune reconstitution inflammatory syndrome during highly active antiretroviral therapy (HAART) for HIV has previously been reported. However, clinical challenges associated with HIV in the context of thyroid eye disease (TED) are not as well-characterized. OBJECTIVE: To determine the frequency of coexisting HIV and TED, describe TED presentation and course in the context of HIV, and evaluate management difficulties as well as potential solutions. METHODS: Cross-sectional study of all patients with coexisting GD and HIV at University Hospitals Birmingham (2003-2014). Retrospective case note review to identify TED with particular reference to HAART regimen, CD4+ T-cell count, HIV viral load, and TED activity and severity. RESULTS: Of 783 subjects with GD and 1186 with HIV, 11 were identified with both GD and HIV. Of these, three had clinical features of TED; each was of Afro-Caribbean origin, was in their fourth decade, and initially presented with undetectable CD4 T cells and high HIV viral loads. All went on to develop GD >3 years after commencing HAART, with normal CD4 count and undetectable viral load at the time of GD diagnosis. The full spectrum of TED was represented, with two subjects requiring orbital decompression surgery. DISCUSSION: TED in the context of HIV is uncommon. Many challenges exist in such patients, particularly HAART drug interactions with antithyroid and immunosuppressant medications. To better understand TED in HIV and to counsel patients with this copathology most effectively, future multicenter surveillance is required.
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A GO-focused cross-sectional study identified 3/11 (27%) patients with HIV/HAART-induced Graves' disease developing Graves' orbitopathy.
“A GO-focused cross-sectional study identified 3/11 (27%) patients with HIV/HAART-induced GD developing GO, characterized by different EUGOGO severity: 1 mild, 1 moderate-severe, 1 sight threatening [89].”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [89]
The clinical management of Graves' orbitopathy in HIV patients involves additional challenges, since HAART conflicts with antithyroid drugs, immunosuppressive treatments and analgesics for orbital decompression surgery often used in Graves' orbitopathy treatment.
“The clinical management of GO in HIV patients involves additional challenges, since HAART conflicts with ATD, immunosuppressive treatments and analgesics for orbital decompression surgery often used in GO treatment [89].”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [89]
Cites
(1958) · Journal of the American Pharmaceutical Association (Scientific ed ) · doi:10.1002/jps.3030470133 · Cited by 2,491 · see citing works
Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO
Bartalena, L., Baldeschi, L., Dickinson, A. J., Eckstein, A. K., Kendall‐Taylor, P., Marcocci, C., Mourits, M. P., Perros, P., Boboridis, K. G., Boschi, A., et al. (2008) · European Journal of Endocrinology · doi:10.1530/eje-07-0666 · Cited by 793 · see citing works
Müller, M. C. M., Wandel, S., Colebunders, R., Attia, S. L., Furrer, H., & Egger, M. (2010) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(10)70026-8 · Cited by 749 · see citing works
Immune Reconstitution Inflammatory Syndrome
Shelburne, S. A., Hamill, R. J., Rodriguez‐Barradas, M. C., Greenberg, S. B., Atmar, R. L., Musher, D. M., Gathe, J., Visnegarwala, F., & Trautner, B. W. (2002) · Medicine · doi:10.1097/00005792-200205000-00005 · Cited by 654 · see citing works
Pathogenesis of Graves' Ophthalmopathy
Epstein, F. H., Bahn, R. S., & Heufelder, A. E. (1993) · New England Journal of Medicine · doi:10.1056/nejm199311113292007 · Cited by 610 · see citing works
Bartalena, L., Baldeschi, L., Dickinson, A. J., Eckstein, A., Kendall-Taylor, P., Marcocci, C., Mourits, M. P., Perros, P., Boboridis, K., Boschi, A., et al. (2008) · Thyroid · doi:10.1089/thy.2007.0315 · Cited by 406 · see citing works
Zandman‐Goddard, G., & Shoenfeld, Y. (2002) · Autoimmunity Reviews · doi:10.1016/s1568-9972(02)00086-1 · Cited by 382 · see citing works
Tanda, M. L., Piantanida, E., Liparulo, L., Veronesi, G., Lai, A., Sassi, L., Pariani, N., Gallo, D., Azzolini, C., Ferrario, M., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3873 · Cited by 328 · see citing works
Extrathyroidal manifestations of Graves’ disease: a 2014 update
Bartalena, L., & Fatourechi, V. (2014) · Journal of Endocrinological Investigation · doi:10.1007/s40618-014-0097-2 · Cited by 280 · see citing works
Effect of Abnormal Thyroid Function on the Severity of Graves' Ophthalmopathy
Prummel, M. F. (1990) · Archives of Internal Medicine · doi:10.1001/archinte.1990.00390170124027 · Cited by 238 · see citing works
Boelaert, K., Torlinska, B., Holder, R. L., & Franklyn, J. A. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2495 · Cited by 196 · see citing works
Self-citationEvaluating Graves’ Orbitopathy
Dolman, P. J. (2012) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2011.11.007 · Cited by 182 · see citing works
Foisy, M., Yakiwchuk, E., Chiu, I., & Singh, A. (2008) · HIV Medicine · doi:10.1111/j.1468-1293.2008.00579.x · Cited by 174 · see citing works
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., et al. (2005) · Medicine · doi:10.1097/01.md.0000159082.45703.90 · Cited by 142 · see citing works
Highly Active Antiretroviral Therapy
Sendi, P., Palmer, A. J., Gafni, A., & Battegay, M. (2001) · PharmacoEconomics · doi:10.2165/00019053-200119070-00001 · Cited by 142 · see citing works
Jubault, V., Penfornis, A., Schillo, F., Hoen, B., Izembart, M., Timsit, J., Kazatchkine, M. D., Gilquin, J., & Viard, J. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.11.6988 · Cited by 135 · see citing works
Thyroid Function Abnormalities in HIV-Infected Patients
Mayer, K. H., Hoffmann, C. J., & Brown, T. T. (2007) · Clinical Infectious Diseases · doi:10.1086/519978 · Cited by 131 · see citing works
Madeddu, G., Spanu, A., Chessa, F., Calia, G. M., Lovigu, C., Solinas, P., Mannazzu, M., Falchi, A., Mura, M. S., & Madeddu, G. (2006) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2006.02472.x · Cited by 97 · see citing works
Immune reconstitution syndrome and the thyroid
Weetman, A. (2009) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2009.07.003 · Cited by 87 · see citing works
Delayed occurrence of Graves' disease after immune restoration with HAART
Gilquin, J., Viard, J.-P., Jubault, V., Sert, C., & Kazatchkine, M. D. (1998) · The Lancet · doi:10.1016/s0140-6736(05)60398-4 · Cited by 86 · see citing works
Sereti, I., Sarlis, N. J., Oral, E. A., Turner, M. L. C., & Mican, J. M. (2001) · AIDS · doi:10.1097/00002030-200101050-00026 · Cited by 64 · see citing works
French, M. A., Lewin, S. R., Dykstra, C., Krueger, R., Price, P., & Leedman, P. J. (2004) · AIDS Research and Human Retroviruses · doi:10.1089/088922204773004879 · Cited by 59 · see citing works
Orbital Infections in Patients with Human Immunodeficiency Virus Infection
Kronish, J. W., Johnson, T. E., Gilberg, S. M., et al. (1996) · Ophthalmology · doi:10.1016/s0161-6420(96)30479-x · Cited by 58 · see citing works
Knysz, B., Bolanowski, M., Klimczak, M., Gladysz, A., & Zwolinska, K. (2006) · Viral Immunology · doi:10.1089/vim.2006.19.102 · Cited by 58 · see citing works
Graves disease: an increasingly recognized immune reconstitution syndrome
Crum, N. F., Ganesan, A., Johns, S. T., & Wallace, M. R. (2006) · AIDS · doi:10.1097/01.aids.0000196173.42680.5f · Cited by 57 · see citing works
Weetman, A. P. (2014) · Clinical Endocrinology · doi:10.1111/cen.12427 · Cited by 46 · see citing works
Moss, J. A. (2013) · PubMed · Cited by 45 · see citing works
Rasul, S., Delapenha, R., Farhat, F., Gajjala, J., & Zahra, S. M. (2011) · AIDS Research and Treatment · doi:10.1155/2011/743597 · Cited by 40 · see citing works
Autoimmune Diabetes in HIV-Infected Patients on Highly Active Antiretroviral Therapy
Takarabe, D., Rokukawa, Y., Takahashi, Y., Goto, A., Takaichi, M., Okamoto, M., Tsujimoto, T., Noto, H., Kishimoto, M., Kaburagi, Y., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0055 · Cited by 40 · see citing works
Graves' disease during immune reconstitution in HIV-infected patients treated with HAART
Vos, F. J., PIETERS, G. F. F. M., Keuter, M., & van de Ven, A. (2005) · Scandinavian Journal of Infectious Diseases · doi:10.1080/00365540500348960 · Cited by 29 · see citing works
Sheikh, V., DerSimonian, R., Richterman, A. G., Porter, B. O., Natarajan, V., Burbelo, P. D., Rupert, A. W., Santich, B. H., Kardava, L., Mican, J. M., et al. (2013) · AIDS · doi:10.1097/qad.0000000000000006 · Cited by 29 · see citing works
Is IGF-I Receptor a Target for Autoantibody Generation in Graves' Disease?
Smith, T. J. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-1004 · Cited by 28 · see citing works
Clinical Hyperthyroidism in Chinese Patients with Stable HIV Disease
Wong, K.-H., Chow, W. S., & Lee, S. S. (2004) · Clinical Infectious Diseases · doi:10.1086/424749 · Cited by 15 · see citing works
Brown, J. D., Kangwanprasert, M., Tice, A. D., & Melish, J. S. (2007) · PubMed · Cited by 15 · see citing works
Višković, K., Stemberger, L., Brnić, Z., & Begovać, J. (2013) · PubMed · Cited by 9 · see citing works
Mingote, E., Urrutia, A., Viteri, A., Faingold, C., & Musso, C. (2013) · World Journal of AIDS · doi:10.4236/wja.2013.33024 · Cited by 4 · see citing works
Two endocrine diseases in one case of immune reconstitution inflammatory syndrome
Ferreira, M. A., Carvalho, A., Silva, S. V., França, M., & Borges, F. (2014) · HIV & AIDS Review · doi:10.1016/j.hivar.2014.02.001 · Cited by 3 · see citing works
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Muller, I., Moran, C., Lecumberri, B., Decallonne, B., Robertson, N., Jones, J., & Dayan, C. M. (2019) · European Thyroid Journal · doi:10.1159/000500881 · Cited by 78 · see citing works
- Authors
- Edmunds, M. R., Mellington, F., Ford, R. L., Torlinska, B., Manavi, K., & Boelaert, K.
- Affiliations
- Birmingham City Hospital (GB)
- University Hospitals Birmingham NHS Foundation Trust (GB)
- University of Birmingham (GB)
- Corresponding author
- Edmunds, Matthew R.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-03
- Volume
- 100
- Issue
- 3
- Pages
- 779-787
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2143201885
- Cited by
- 14
- References
- 37
- Citations by year
- 2026: 1 · 2025: 4 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2016: 2
- FWCI
- 0.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Ophthalmology and Eye Disorders
- Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Keywords
- Graves' ophthalmopathy, Graves' disease, HIV, highly active antiretroviral therapy, immune reconstitution inflammatory syndrome, orbital decompression, CD4 count, HIV viral load
- MeSH terms
- Adult, Cross-Sectional Studies, Female, HIV Seropositivity, Humans, Male, HIV-1, Antiretroviral Therapy, Highly Active, Graves Ophthalmopathy
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