Clinical Challenges of Thyroid Eye Disease in HIV-Positive Patients on Highly Active Antiretroviral Therapy

Edmunds, Matthew R.; Mellington, Faye; Ford, Rebecca; Torlińska, Barbara; Manavi, K; Boelaert, Kristien

doi:10.1210/jc.2014-3544

Cited by 9 publications

(10 citation statements)

References 34 publications

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“…[6][7][8] One recent analysis in the United Kingdom reported 11 cases of Graves' disease out of a cohort of 1,186 HIV-infected patients. 9 Notably, in our series the median time interval between initiation of cART and the diagnosis of G-IRD was 38.5 months, substantially greater than the interval described in the first reported cases of G-IRD (mean of 22 months). 10 In a more recent report, two patients developed G-IRD after being on cART for 12 and 28 months.…”

contrasting

confidence: 52%

Short Communication: Hyperthyroidism in Human Immunodeficiency Virus Patients on Combined Antiretroviral Therapy: Case Series and Literature Review

Hsu

Phadke

Nguyen

2016

AIDS Research and Human Retroviruses

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We describe an HIV-infected patient initiated on combined antiretroviral therapy (cART) who subsequently developed immune restoration disease (IRD) hyperthyroidism-this case represents one of five such patients seen at our center within the past year. Similar to previous reports of hyperthyroidism due to IRD, all of our patients experienced a rapid early recovery in total CD4 count, but developed symptoms of hyperthyroidism on average 3 years (38 months) after beginning cART, which represents a longer time frame than previously reported. Awareness and recognition of this potential complication of cART, which may occur years after treatment initiation, will allow patients with immune restorative hyperthyroidism to receive timely therapy and avoid the long-term complications associated with undiagnosed thyroid disease.

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contrasting

confidence: 52%

Short Communication: Hyperthyroidism in Human Immunodeficiency Virus Patients on Combined Antiretroviral Therapy: Case Series and Literature Review

Hsu

Phadke

Nguyen

2016

AIDS Research and Human Retroviruses

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“…It is characterized by lymphocytic infiltration of the extraocular muscles and orbital adipose tissue, orbital fibroblast proliferation and differentiation, deposition of hyaluronic acid and glycosaminoglycans, and de novo adipogenesis [7]. e pathogenesis of this condition is believed to be secondary to a complex interplay between genetic and lifestyle factors (e.g., cigarette smoking) leading to an inflammatory cascade, with involvement of autoantibodies such as TSH receptor (TSH-R) and insulin-like growth factor-1 (IGF-1) receptor [8].…”

Section: Discussionmentioning

confidence: 99%

“…TED has a spectrum of clinical manifestations and can range from mild disease to severe extraocular muscle dysfunction and vision loss due to exposure keratopathy or optic nerve compression [8]. ART treatment increases the CD4+ T-cell count in 2 phases: initial increase in the memory CD4+ T-cells that occurs in the first few months of therapy; and a slower and steady increase over many months to years, in the naive CD4+ T-cells, which originate from the thymus [9].…”

Section: Discussionmentioning

confidence: 99%

“…Another hypothesis for expansion of autoreactive T lymphocytes and their redistribution in IRIS is due to "molecular mimicry" due to homology between TSH-R and immunogenic HIV-related proteins [8]. Other predisposing factors associated with the development of IRIS include advanced immunodeficiency at baseline, more pronounced increase in CD4+ T lymphocytes, and genetic susceptibility [5].…”

Section: Discussionmentioning

confidence: 99%

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Thyroid Eye Disease due to Immune Reconstitution Inflammatory Syndrome as a Consequence of Antiretroviral Therapy in the Setting of AIDS

Nallu

Madhavan

Chirch

et al. 2020

Case Reports in Endocrinology

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We describe a case of worsening Graves’ orbitopathy due to immune reconstitution inflammatory syndrome (IRIS) in a 38-year-old HIV-infected male after beginning ART (antiretroviral therapy). Two years after initiation of ART, the patient developed symptoms of hyperthyroidism and thyroid eye disease (TED) or Graves’ orbitopathy (GO). Thyroid iodine uptake scan was consistent with Graves’ disease. The CT scan of the orbits revealed minimal right-sided proptosis, consistent with GO. He was treated with methimazole and a short course of high-dose prednisone for GO. Thyroid function tests normalized, and eye symptoms eventually stabilized. This case demonstrates the importance of awareness and early recognition of IRIS in its many forms, as it has significant therapeutic implications.

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“…Secondary thyroid autoimmunity and orbitopathy has also been described in other situations of immune reconstitution such as in HIV patients on highly active antiretroviral therapy [30][31][32] or following bone marrow transplantation [33]. Nevertheless alemtuzumab appears particularly prone to triggering this phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Immune reconstitution after alemtuzumab therapy for multiple sclerosis triggering Graves’ orbitopathy: a case series

Roos

Moran

Chatterjee

et al. 2018

Eye

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Alemtuzumab-a monoclonal antibody targeting the CD52 glycoprotein expressed by most mature leucocytes-effectively decreases relapse rate and disability progression in early, relapsing-remitting multiple sclerosis (MS). However, secondary autoimmune disorders complicate therapy in nearly 50% of treated patients, with Graves' disease being the most common. Rarely, thyroid eye disease (TED) ensues; only seven such cases have been reported. Our aim was to analyse the largest series of MS patients developing thyroid eye disease after alemtuzumab treatment. We performed a retrospective chart review of MS patients treated with alemtuzumab and subsequently identified by their treating physicians as having developed TED and referred to our ophthalmology service. As an original trial centre for alemtuzumab, our hospital has treated approximately 162 MS patients with this novel therapy. In total, 71 (44%) developed thyroid dysfunction, most of whom (87%) developed Graves' disease, with ten (16%) referred for ophthalmological evaluation. Two developed active orbitopathy following radioiodine treatment; one occurred after cessation of anti-thyroid drug treatment. Three developed sight-threatening disease requiring systemic immunosuppression, with one refractory to multiple immunosuppressants. The remaining patients were treated conservatively. TSH-receptor antibody (TRAb) levels were significantly raised in all cases, when ascertained. We report sight-threatening as well as mild TED in MS patients after treatment with alemtuzumab. Endocrine instability, radioiodine treatment and positive TRAb are all likely risk factors. The data support at least 6-monthly biochemical and clinical assessment with a low threshold for referral to an ophthalmologist, particularly for those with higher TRAb levels who may be at greater risk of orbitopathy.

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Clinical Challenges of Thyroid Eye Disease in HIV-Positive Patients on Highly Active Antiretroviral Therapy

Cited by 9 publications

References 34 publications

Short Communication: Hyperthyroidism in Human Immunodeficiency Virus Patients on Combined Antiretroviral Therapy: Case Series and Literature Review

Short Communication: Hyperthyroidism in Human Immunodeficiency Virus Patients on Combined Antiretroviral Therapy: Case Series and Literature Review

Thyroid Eye Disease due to Immune Reconstitution Inflammatory Syndrome as a Consequence of Antiretroviral Therapy in the Setting of AIDS

Immune reconstitution after alemtuzumab therapy for multiple sclerosis triggering Graves’ orbitopathy: a case series

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