(engl. Graves’ Orbitopathy [GO], Thyroid Eye Disease [TED])

Abstract Background: The current standard of care for moderate to severe thyroid eye disease (TED) is intravenous methylprednisolone (IVMP), though alternative immunosuppressive options are emerging. In a recent randomized trial, Tocilizumab (TCZ), an anti-IL-6 receptor antibody, demonstrated improved efficacy for corticosteroid-resistant TED compared to placebo. Clinical response to TCZ retreatment, however, has not been previously reported. Clinical case: A 64-year old man presented with progressive diplopia, eyelid retraction and edema and retrobulbar pain. Initial labs revealed TSH 0.221 uIU/mL, free thyroxine (FT4) 1.11 ng/dL, total T3 172 ng/dL and a thyroid stimulating immunoglobulin (TSI) index of 329 (normal < 140). The patient was a former cigarette smoker who had recently transitioned to e-cigarettes. He was treated with 12 weeks of IVMP with improvement in ocular redness and swelling. Three months following completion of treatment, he presented with worsening left sided proptosis, restrictive strabismus, and compressive optic neuropathy (CON) evidenced by deteriorating central acuity and color vision. He underwent urgent surgical decompression for CON with full restoration of visual acuity. He then received a second 12-week course of IVMP with concomitant orbital radiation. Of note, his hyperthyroidism was well controlled with methimazole. Two months after his second IVMP course, he had a third flare of ophthalmic symptoms. He was then treated with TCZ 8 mg/kg (800mg) IV monthly for six months. The patient’s Clinical Activity Score (CAS) improved from 4 to 2 and TSI index decreased from 610 to 92 (normal). He had significant improvement in periorbital edema, caruncle/plica swelling, and conjunctival injection. However, ten months following completion of the TCZ course he again complained of worsening diplopia and left proptosis. Of note, relapse of his TED symptoms was preceded by an increase in TSI from 92 to 300 two months prior. Orbital CT demonstrated progression of left orbitopathy and increased orbital apex crowding. Following these CT findings he was restarted on TCZ, of which he has now completed 5 additional infusions. His CAS has improved from 3 to 2 and TSI index has decreased from 284 to 100. Conclusion: This is the first reported case of response to successive courses of TCZ in relapsing, severe, corticosteroid-resistant TED. TCZ can be an effective option for refractory TED though retreatment may be necessary for recurrent inflammation. Further study of TCZ is required to determine its role in relapsing TED and the optimal duration of therapy needed. References: Perez-Moreiras et al., 2018. Efficacy of Tocilizumab in patients with moderate to severe corticosteroid resistant Graves’ orbitopathy: a randomized controlled trial. Am J Ophthalmol 195:181

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A Case of Thyroid Eye Disease Revealed During Secondary Adrenal Insufficiency

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1858 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A910-A910

Author(s):

Amira Ibrahim ◽

Victoria Loseva

Keyword(s):

Adrenal Insufficiency ◽

Extraocular Muscle ◽

Early Recognition ◽

Thyroid Eye Disease ◽

Eye Disease ◽

Secondary Adrenal Insufficiency ◽

Movement Restriction ◽

Free T4 ◽

Muscle Movement ◽

Graves Orbitopathy

Abstract Introduction: Thyroid eye disease (TED) or Graves’ orbitopathy (GO) is an autoimmune disease of the retro-orbital tissues. GO is mostly associated with hyperthyroidism in 90% of patients; however, it may coexist with hypothyroid conditions in 5% of cases. Clinical Case: A 56-year-old male with a past medical history of autoimmune diseases including hypothyroidism and Ulcerative Colitis on chronic steroid therapy presented to the emergency department with nausea, fatigue, weight loss, and muscle weakness. The patient stated that his glucocorticoids were abruptly discontinued a month prior to his current presentation. On examination, vitals were stable. The patient was somnolent with a depressed mood. He had bilateral periorbital edema and bilateral eyeball protrusion, left more pronounced than right. Extraocular muscle movement revealed a delay in the lateral movement of the left eye causing double vision on exam. He had no starring look or lid lag. The thyroid gland was normal in size and contour. Initial Laboratories revealed a white blood cell count of 6.7 K/mcL (4-10 K/mcL) with 18% eosinophil count (0-5%). Cortisol at 8 AM was 2.9 mcg/dL (4.3 -22.4 mcg/dl). The patient was managed for secondary adrenal insufficiency and restarted immediately on Prednisone. A review of a recent CT scan of the head revealed bilateral proptosis with no signs of compressing lesions. Further thyroid studies revealed TSH of 2.9 mcIU/mL (0.3-3.7 mcIU/mL), free T4 of 0.8 ng/dL (0.75-2.0 ng/dL), free T3 of 1.6 ng/dL (2.4-4.2 ng/dL), TPO antibodies <0.3 IU/mL (0.0-9.0 IU/mL) and TSH receptor antibodies 0.90 IU/L (reference range <1.75 IU/L). The patient was then diagnosed with Hypothyroid Grave’s ophthalmopathy with negative antibodies given the evidence of proptosis on CT and exam revealing extraocular muscle movement restriction causing diplopia. The patient had a unique presentation of TED with hypothyroidism and asymmetric ophthalmic signs that were only manifested after the patient discontinued the prednisone and therefore unmasking the underlying disorder. Fortunately, in June of 2020, the US Food and Drug Administration (FDA) approved Teprotumumab (an insulin-like growth factor 1 [IGF-1] receptor inhibitor) for the treatment of Graves’ orbitopathy based on the findings from two 24-week trials comparing teprotumumab with placebo in 171 patients with active, moderate-to-severe orbitopathy. (1) Our patient was started on Levothyroxine along with Prednisone and referred for ophthalmology evaluation for possible qualification for Teprotumumab treatment. Conclusion: Clinician awareness of the unusual presentations of TED would allow for early recognition and prevention of progression, especially with the recently approved treatment modality. References: (1) Teprotumumab for Thyroid-Associated Ophthalmopathy. Smith TJ Et al. N Engl J Med. 2017;376(18):1748.

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Gender differences in clinical presentation and prognosis of thyroid eye disease

European Journal of Ophthalmology ◽

10.1177/1120672120964112 ◽

2020 ◽

pp. 112067212096411

Author(s):

Ofira Zloto ◽

Oded Sagiv ◽

Ayelet Priel ◽

Tali Cukierman-Yaffe ◽

Amir Tirosh ◽

...

Keyword(s):

Quality Of Life ◽

Thyroid Eye Disease ◽

Eye Disease ◽

Clinical Activity ◽

Life Questionnaire ◽

Men And Women ◽

Graves Orbitopathy ◽

Eye Examination ◽

Active Disease

Objective: To examine the clinical differences in manifestation, treatment, and prognosis of thyroid-eye-disease (TED) between men and women. Methods: This is a longitudinal cohort study. Men and women, who diagnosed with TED and treated at a multidisciplinary TED clinic, were compared regarding differences in demographics, eye examination, disease activity, and quality of life evaluation. Results: TED was diagnosed in 132 patients during the study period, and they included 38 men (28.78%) and 94 women (71.21%). There were six men and 20 women with active disease (Clinical-Activity-Score (CAS) ⩾ 3) during the entire follow-up period ( p < 0.01). The mean time from TED diagnosis to CAS ⩾ 3 was 4.50 years for men and 2.35 years for women ( p = 0.05). There were no significant differences in mean total Graves’ Orbitopathy-Quality-of-Life questionnaire (GO-QOL) score. However, mean GO-QOL subtotal score of external appearance of women was significantly lower compare to men in the first and last visit ( p = 0.04, 0.03, respectively). Conclusion: Active disease was more common in women and the time-from-diagnosis of TED to CAS ⩾ 3 was shorter among women. Moreover, the appearance QOL score of women was poorer. These findings should be taken into consideration when planning the timing of treatment and when choosing the best treatment for TED patients.

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Graves' Orbitopathy: Improving Outcomes for Thyroid Eye Disease—The Amsterdam Declaration

Thyroid ◽

10.1089/thy.2010.1619 ◽

2010 ◽

Vol 20 (3) ◽

pp. 351-352 ◽

Cited By ~ 4

Keyword(s):

Thyroid Eye Disease ◽

Eye Disease ◽

Graves Orbitopathy

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

Case Reports in Endocrinology ◽

10.1155/2020/1728423 ◽

2020 ◽

Vol 2020 ◽

pp. 1-3 ◽

Cited By ~ 2

Author(s):

Ravali Nallu ◽

Parvathy Madhavan ◽

Lisa Chirch ◽

Pooja Luthra

Keyword(s):

Antiretroviral Therapy ◽

Immune Reconstitution Inflammatory Syndrome ◽

Immune Reconstitution ◽

Early Recognition ◽

Thyroid Eye Disease ◽

Eye Disease ◽

High Dose ◽

Thyroid Function Tests ◽

Graves Orbitopathy ◽

Inflammatory Syndrome

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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Targeting TSH and IGF-1 Receptors to Treat Thyroid Eye Disease

European Thyroid Journal ◽

10.1159/000511538 ◽

2020 ◽

Vol 9 (Suppl. 1) ◽

pp. 59-65

Author(s):

Susanne Neumann ◽

Christine C. Krieger ◽

Marvin C. Gershengorn

Keyword(s):

Thyroid Stimulating Hormone ◽

Thyroid Eye Disease ◽

Therapeutic Interventions ◽

Eye Disease ◽

Thyroid Cells ◽

Hormone Synthesis ◽

Dependent Component ◽

Graves Orbitopathy ◽

Blocking Antibodies ◽

Orbital Fibroblasts

Graves’ disease (GD) is an autoimmune disease caused in part by thyroid-stimulating antibodies (TSAbs) that activate the thyroid-stimulating hormone receptor (TSHR). In Graves’ hyperthyroidism (GH), TSAbs cause persistent stimulation of thyroid cells leading to continuous thyroid hormone synthesis and secretion. Thyroid eye disease (TED), also called Graves’ orbitopathy, is an orbital manifestation of GD. We review the important roles of the TSHR and the insulin-like growth factor 1 receptor (IGF-1R) in the pathogenesis of TED and discuss a model of TSHR/IGF-1R crosstalk that considers two pathways initiated by TSAb activation of TSHR in the eye, an IGF-1R-independent and an IGF-1R-dependent signaling pathway leading to hyaluronan (HA) secretion in orbital fibroblasts. We discuss current and future therapeutic approaches targeting the IGF-1R and TSHR. Teprotumumab, a human monoclonal anti-IGF-1R-blocking antibody, has been approved as an effective treatment in patients with TED. However, as the TSHR seems to be the primary target for TSAbs in patients with GD, future therapeutic interventions directly targeting the TSHR, e.g. blocking antibodies and small molecule antagonists, are being developed and have the advantage to inhibit the IGF-1R-independent as well as the IGF-1R-dependent component of TSAb-induced HA secretion. Antigen-specific immunotherapies using TSHR peptides to reduce serum TSHR antibodies are being developed also. These TSHR-targeted strategies also have the potential to treat both GH and TED with the same drug. We propose that combination therapy targeting TSHR and IGF-1R may be an effective and better tolerated treatment strategy for TED.

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The patient experience of services for thyroid eye disease in the United Kingdom: results of a nationwide survey

Acta Endocrinologica ◽

10.1530/eje-09-0383 ◽

2009 ◽

Vol 161 (3) ◽

pp. 483-487 ◽

Cited By ~ 22

Author(s):

Stephanie Estcourt ◽

Janis Hickey ◽

Petros Perros ◽

Colin Dayan ◽

Bijay Vaidya

Keyword(s):

Nationwide Survey ◽

Postal Questionnaire ◽

Thyroid Eye Disease ◽

Eye Disease ◽

The United Kingdom ◽

Multidisciplinary Clinic ◽

Graves Orbitopathy ◽

Charitable Trust ◽

The Uk ◽

European Group

BackgroundA recent consensus statement from the European Group on Graves' Orbitopathy recommends referring all patients with thyroid eye disease (TED), except the mildest cases, to a specialist multidisciplinary clinic.ObjectiveTo study the patients' experiences of accessing services for the treatment of TED in the UK.MethodsA postal questionnaire survey of 395 members of two patients support organisations for TED in the UK, the TED Charitable Trust and the British Thyroid Foundation.ResultsThe response rate was 67%. The majority of responders were females (91%) and aged above 45 (74%). There were delays in the diagnosis and referral. In 26% of responders, the time lapsed from the first symptoms to the diagnosis of TED for over 12 months. There was a wide variation in the type of clinic and healthcare professionals involved in the treatment of TED. Only 25% of the responders attended a specialist TED clinic. Out of these, 33% waited over 6 months from the first consultation with a doctor to being seen at a specialist TED clinic. Only 56% of responders were satisfied with the treatment they received for TED. More responders who had attended a specialist TED clinic were satisfied with the treatment than those who had not attended a specialist clinic (67 vs 52%, P<0.05).ConclusionOnly a minority of patients with TED are treated at a specialist TED clinic in the UK. Those patients who are treated at a specialist TED clinic are more likely to be satisfied with the treatment.

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Hashimoto’s Thyroiditis Associated Thyroid Eye Disease:A Success Story of Teprotumumab

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1905 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A932-A932

Author(s):

Issra Jamal

Keyword(s):

Hashimoto’S Thyroiditis ◽

Thyroid Eye Disease ◽

Hashimoto's Thyroiditis ◽

Eye Disease ◽

Fat Pad ◽

Inferior Rectus ◽

Thyroid Associated Ophthalmopathy ◽

History Of ◽

Graves Orbitopathy ◽

The Right

Abstract Background: Thyroid-associated eye disease is more common in patients with Graves’ disease. However, patients with Hashimoto’s may also be affected by thyroid-associated eye disease in up to 6% of patients. Clinical Case: 44 year old female patient with history of Hashimoto’s thyroiditis presented to the clinic for her hypothyroidism and evaluation of thyroid eye disease. The patient was experiencing episodes of bilateral and unilateral inflammation of her eyes described as redness, dryness, bulging of the eyes. She was evaluated by ophthalmology and was diagnosed with thyroid eye disease and was prescribed a course of steroids with partial improvement of the symptoms. Orbital MRI was ordered and it showed symmetrical enlargement of the inferior rectus muscles bellies bilaterally with the left being slightly more enlarged than the right, retro orbital fat pad was grossly inflamed. TPO was elevated,TSI and TRAb were negative. Patient continued to have frequent flare ups with suboptimal response to steroid therapy. A discussion about starting Teprotumumab was made due to lack of optimal response to steroids and worsening of her symptoms and therapy was started. Patient did develop significant hyperglycemia, but she did not have recurrent flare ups. Studies have found that Thyroid-associated eye disease was present in up to (6%) of Hashimoto’s thyroiditis patients, those with thyroid-associated eye disease tended to be older, have a longer duration of Hashimoto’s thyroiditis, heavy smokers, and were less likely to present with another associated autoimmune disease. TSAb was positive in 5.5% in the patients with Hashimoto’s and thyroid-associated eye disease. Teprotumumab ([IGF-1] receptor inhibitor) was approved for the treatment of Graves’ orbitopathy by the (FDA) in 2020. Conclusion: Hashimoto’s thyroiditis associated thyroid eye disease is a rare clinical presentation. Teprotumumab is a new FDA approved treatment for thyroid eye disease that was successful in treating the symptoms and prevented flare ups in this patient. Careful monitoring of side effects is recommended. References: Kahaly GJ et al Thyroid stimulating antibodies are highly prevalent in Hashimoto’s thyroiditis and associated orbitopathy. J Clin Endocrinol Metab. March 10, 2016\Krassas GE, Wiersinga WM. - Thyroid eye disease: current concepts and the EUGOGO perspective. Thyroid International. 2005;4:3–4. Teprotumumab for Thyroid-Associated Ophthalmopathy. Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS SO N Engl J Med. 2017;376(18):1748.

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