Graves' disease following immune reconstitution or immunomodulatory treatment: should we manage it any differently?

Weetman, Anthony P.

doi:10.1111/cen.12427

Cited by 41 publications

(24 citation statements)

References 32 publications

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“…[2][3][4][5] Secondary autoimmune disorders develop as the lymphocyte count recovers, at a frequency between 20% and 34%. [7][8][9]18 . Graves' disease as a result of alemtuzumab was first reported in 1999 10 and is reported to occur as high as 22% of patients on alemtuzumab, with 23% reverting spontaneously to euthyroid states.…”

Section: Discussionmentioning

confidence: 99%

“…Graves' disease as a result of alemtuzumab was first reported in 1999 10 and is reported to occur as high as 22% of patients on alemtuzumab, with 23% reverting spontaneously to euthyroid states. 18 The mechanism behind thyroid autoimmunity secondary to alemtuzumab is thought to be due to the loss of selftolerance during the homeostatic proliferation of T-cells after significant lymphopaenia. 10 The development of Graves' disease is more common in smokers and those with a family history but does not appear to be influenced by treatment dose, frequency or interval of alemtuzumab.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ocular Findings in Alemtuzumab (Campath-1H)-induced Thyroid Eye Disease

Trinh¹,

Haridas²,

Sullivan³

2016

Ophthalmic Plastic &Amp; Reconstructive Surgery

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Alemtuzumab (Campath-1H) is a humanized anti-CD52 monoclonal antibody used in the treatment of multiple sclerosis (MS). Studies demonstrate significant reduction in relapse risk and the risk of accumulating sustained disability. Adverse events include infusion-associated reactions, infections, and secondary autoimmunity. Systemic thyroid disease is the most common secondary autoimmune event and affects up to approximately 30% of treated patients. This is the first description of the ocular findings and management in a case of thyroid eye disease (Graves' Ophthalmopathy [GO]) following alemtuzumab therapy. The ocular disease was managed conservatively while the systemic Graves' was managed with thyroidectomy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ocular Findings in Alemtuzumab (Campath-1H)-induced Thyroid Eye Disease

Trinh¹,

Haridas²,

Sullivan³

2016

Ophthalmic Plastic &Amp; Reconstructive Surgery

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“…In most cases, the hyperthyroidism is manageable and, depending on the underlying condition, it is not an indication to discontinue the immunomodulatory therapy that precipitated it. Although initial reports suggested that definitive therapy was warranted in these patients, additional experience now suggests that they can be managed similarly to patients with "spontaneous" GD [163]. However, as the immunological "insult" may be transient in these cases, a reasonable approach is to treat with ATD until circulating TSH-R-Ab become undetectable.…”

Section: Immune Reconstitutionmentioning

confidence: 99%

2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism

Kahaly¹,

Bartalena²,

Hegedüs³

et al. 2018

Eur Thyroid J

684

650

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Graves’ disease (GD) is a systemic autoimmune disorder characterized by the infiltration of thyroid antigen-specific T cells into thyroid-stimulating hormone receptor (TSH-R)-expressing tissues. Stimulatory autoantibodies (Ab) in GD activate the TSH-R leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with biochemically confirmed thyrotoxicosis, positive TSH-R-Ab, a hypervascular and hypoechoic thyroid gland (ultrasound), and associated orbitopathy. In GD, measurement of TSH-R-Ab is recommended for an accurate diagnosis/differential diagnosis, prior to stopping antithyroid drug (ATD) treatment and during pregnancy. Graves’ hyperthyroidism is treated by decreasing thyroid hormone synthesis with the use of ATD, or by reducing the amount of thyroid tissue with radioactive iodine (RAI) treatment or total thyroidectomy. Patients with newly diagnosed Graves’ hyperthyroidism are usually medically treated for 12–18 months with methimazole (MMI) as the preferred drug. In children with GD, a 24- to 36-month course of MMI is recommended. Patients with persistently high TSH-R-Ab at 12–18 months can continue MMI treatment, repeating the TSH-R-Ab measurement after an additional 12 months, or opt for therapy with RAI or thyroidectomy. Women treated with MMI should be switched to propylthiouracil when planning pregnancy and during the first trimester of pregnancy. If a patient relapses after completing a course of ATD, definitive treatment is recommended; however, continued long-term low-dose MMI can be considered. Thyroidectomy should be performed by an experienced high-volume thyroid surgeon. RAI is contraindicated in Graves’ patients with active/severe orbitopathy, and steroid prophylaxis is warranted in Graves’ patients with mild/active orbitopathy receiving RAI.

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“…22 Medical therapy of conventional GD with thionamides is almost always effective initially but relapse of GD is reported in up to 42% of patients treated with thionamides alone. 23 In contrast, Crossbun et al reported that only 28% of patients with AITD GD required radioactive iodine (RAI) due to failure of medical treatment.…”

Section: Treatment Of Alemtuzumab Induced Thyrotoxicosis In Major Trialsmentioning

confidence: 99%

“…In other words, 76.8% of the patients with GD due to AITD in CAMMS223 did not require RAI or thyroidectomy. 18,22 It is not described in detail when RAI or thyroidectomies were done, or whether it was due to failure of medical treatment or physician and patient preference.…”

Section: Treatment Of Alemtuzumab Induced Thyrotoxicosis In Major Trialsmentioning

confidence: 99%

Alemtuzumab Induced Thyroid Disease in Multiple Sclerosis: A Review and Approach to Management

Mahzari

Arnaout

Freedman

2015

Can. J. Neurol. Sci.

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Alemtuzumab, an anti-CD52 monoclonal antibody, was recently approved for treatment of MS in Canada, having shown to significantly reduce relapses and disability in patients, particularly those who relapsed despite first line treatment. Offsetting its benefit however, is the development of novel secondary autoimmune disease, particularly affecting the thyroid gland in up to 36% of patients. The incidence of Alemtuzumab induced thyroid dysfunction (AITD) will likely rise as alemtuzumab becomes more widely used for treating MS. We review the clinical and investigational cues that help delineate the aetiology and management of thyrotoxicosis and hypothyroidism in ATID. AITD can be easily managed and we present a simple approach for its evaluation and management by neurologists that should be implemented prior to considering a referral to an internist or endocrinologist for further opinion or treatment.RÉSUMÉ: Maladie thyroïdienne induite par l'alemtuzumab dans la sclérose en plaques: revue et traitement. L'alemtuzumab, un anticorps monoclonal dirigé contre CD52, a récemment été approuvé pour le traitement de la sclérose en plaques (SP) au Canada. Les études ont démontré qu'il diminuait significativement les rechutes et l'invalidité chez les patients, particulièrement chez ceux qui avaient eu des rechutes malgré le traitement de première intention. Cependant, l'apparition d'une nouvelle maladie auto-immune secondaire à ce traitement, touchant la glande tyroïde chez 36% des patients, en amoindrit les bénéfices. L'incidence de la dysfonction thyroïdienne induite par l'alemtuzumab (DTIA) augmentera vraisemblablement à mesure que l'alemtuzumab sera plus fréquemment prescrit pour traiter la SP. Nous revoyons les indices cliniques et biochimiques qui aident à définir l'étiologie et le traitement de la thyrotoxicose et de l'hypothyroïdie dans la DTIA. La DTIA peut être traitée facilement et nous présentons une approche simple de son évaluation et son traitement par des neurologues. Cette approche devrait être utilisée avant d'envisager de référer le patient à un interniste ou à un endocrinologue pour connaître son opinion ou pour prescrire un traitement.

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Graves' disease following immune reconstitution or immunomodulatory treatment: should we manage it any differently?

Cited by 41 publications

References 32 publications

Ocular Findings in Alemtuzumab (Campath-1H)-induced Thyroid Eye Disease

Ocular Findings in Alemtuzumab (Campath-1H)-induced Thyroid Eye Disease

2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism

Alemtuzumab Induced Thyroid Disease in Multiple Sclerosis: A Review and Approach to Management

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