Correlation between serum anti-TSH receptor autoantibodies (TRAbs) and the clinical feature of Graves’ orbitopathy

Nicolì, Francesca; Lanzolla, Giulia; Mantuano, Michele; Ionni, Ilaria; Mazzi, Barbara; Leo, Marenza; Sframeli, Angela Tindara; Posarelli, Chiara; Maglionico, Maria Novella; Figus, Michele; Nardi, Marco; Marcocci, Claudio; Marinò, Michele

doi:10.1007/s40618-020-01353-y

Cited by 48 publications

(38 citation statements)

References 37 publications

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“…Dragan et al [ 31 ] argued that the TRAb measurement is an excellent tool for assessing the prognosis and evaluating the response of active GO to treatment [ 32 , 33 ]. The results of the present study corroborate the close correlation between CAS and TRAb [ 34 ].…”

Section: Discussionsupporting

confidence: 90%

Steroid-Resistant Graves’ Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience

Pérez-Moreiras¹,

Varela-Agra²,

Prada-Sánchez³

et al. 2021

JCM

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This study aimed to assess the effectiveness and safety of tocilizumab use for the treatment of active steroid-resistant Graves’ orbitopathy (GO). A retrospective longitudinal study was conducted by reviewing the medical records at a single center between November 2009 and December 2018. A total of 114 patients with steroid-resistant Graves’ orbitopathy were examined and treated with tocilizumab, of which 54 adults met the inclusion criteria. No concomitant medication for the treatment of orbitopathy was used. The main primary outcomes included changes from baseline in the Clinical Activity Score (CAS) and thyrotropin receptor antibody (TRAb) levels throughout therapy with tocilizumab. The absolute responses to treatment were defined as the achievement of CAS ≤ 1 and TRAb ≤ 10 U/L. A composite ophthalmic score including CAS, proptosis, eyelid retraction, and diplopia was used to evaluate individual improvement in GO. Adverse drug reactions were also assessed. Analysis of the patient’s CAS and TRAb levels showed meaningful reductions during tocilizumab treatment. Differences between values at baseline and subsequent time points were statistically significant (p < 0.001 for all comparisons). The absolute CAS response (CAS = 0 or 1) was achieved in 74% (37/50) of patients after the fourth dose of tocilizumab (at week 16), with a TRAb response being achieved in 55% (23/42) of patients. The relative CAS response (reduction ≥ 2 points) was achieved in 90.9% of patients (40/44) after the first dose of tocilizumab (at week 4). Measurements of proptosis (reduction ≥ 2 mm in 78% of patients, 42/54) and eyelid retraction (reduction ≥ 2 mm in 75%, 33/44), and the prevalence of diplopia (improvement in 68%, 19/28) were significantly reduced after the last dose of tocilizumab (p < 0.001 for all comparisons). GO improved in 98% (53/54) of patients when at least two criteria of the composite evaluation were required. Four patients exhibited disease recurrence, defined as an increase in CAS of ≥2 points in the six months following the date of inactivation. Most adverse drug reactions were mild or moderate in severity. In conclusion, our data suggest that a course of at least 4 months (one monthly dose) of tocilizumab therapy provides a significant benefit to patients with active moderate-to-severe steroid-resistant GO.

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Section: Discussionsupporting

confidence: 90%

Steroid-Resistant Graves’ Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience

Pérez-Moreiras¹,

Varela-Agra²,

Prada-Sánchez³

et al. 2021

JCM

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“…TRAbs are the only specific biomarker for Graves' disease and GO (3). TRAb levels correlate with the Clinical Activity Score (4,43). TRAbs with stimulating activities in a recently developed bioassay tested positive in 150/155 patients with Graves' disease (97%) and 148/155 of those with GO (95%), their levels were 3-fold higher in patients with GO than in those without GO, and strongly correlated with GO activity and severity (76).…”

Section: Tsh-receptor Antibody Levelsmentioning

confidence: 99%

“…Most patients affected with GO are hyperthyroid (1), but a substantial proportion, ranging from 0.2 to 11% in different studies (35,(39)(40)(41), are euthyroid or subclinical/overt hypothyroid. TSH-receptor antibodies (TRAbs) are the ultimate responsible for hyperthyroidism due to Graves' disease (42), but they also strongly correlate with the clinical activity and severity of GO (3,4,43). But, in a series of 700 unselected patients with chronic autoimmune thyroiditis, overt GO was present in 44 (6%): among them TRAb bioassay for stimulating activities tested positive in 30/44 (68%) patients with GO vs. 36/656 (5.5%, p <0.001) patients without GO (44).…”

Section: Relation With Thyroid Dysfunctionmentioning

confidence: 99%

“…• TRAb levels are higher in patients with GO than in those without GO (76) • TRAb levels correlate with GO activity and severity (4,43,76),…”

Section: Radioiodine Treatmentmentioning

confidence: 99%

“…The close link of GO with thyroid autoimmune disorders, mainly Graves' disease, underpin the hypothesis that GO is triggered by immune reactions against one or more antigens shared by thyroid and orbit. The thyrotropin (TSH) receptor is the most likely culprit, supporting an important role of TSH receptor antibodies (TRAbs) in the pathogenesis and course not only of thyroid disease, but also of orbital disease (3,4). The insulin-like growth factor-1 (IGF-1) receptor seems also to be involved, which may explain the recent promising results obtained by treating patients with active, moderate-to-severe GO with an IGF-1 receptor antagonist monoclonal antibody, teprotumumab (5,6).…”

Section: Introductionmentioning

confidence: 99%

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Epidemiology, Natural History, Risk Factors, and Prevention of Graves’ Orbitopathy

et al. 2020

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GO is the most frequent extrathyroidal manifestation of Graves’ disease, although it may rarely occur in euthyroid/hypothyroid patients with chronic autoimmune thyroiditis. It is a relatively infrequent disorder, and men tend to have more severe ocular involvement at an older age. The prevalence of GO is lower than in the past among patients with recent onset Graves’ hyperthyroidism, and moderate-to-severe forms requiring aggressive treatments are no more than 5–6% of all cases of GO. After an initial inflammatory (active) phase and a phase of stabilization (plateau phase), GO tends to improve and eventually inactivates (inactive or burnt-out phase). Minimal-to-mild GO often remits spontaneously, but complete restitutio ad integrum almost never occurs when GO is more than mild. Several risk factors contribute to its development on a yet undefined genetic background. Cigarette smoking is the most important of them. Early diagnosis, control and removal of modifiable risk factors, early treatment of mild forms of GO may effectively limit the risk of progression to more severe forms, which have a profound and dramatic impact on the quality of life of affected individuals, and remain a therapeutic challenge, often requiring long-lasting and multiple medical and surgical therapies.

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Application of Multiparameter Quantitative Magnetic Resonance Imaging in the Evaluation of Graves' Ophthalmopathy

Luo

Feng

et al. 2023

Magnetic Resonance Imaging

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BackgroundAssessment of the activity of Graves' ophthalmopathy (GO) is difficult. Existing methods need improvement.PurposeInvestigate the application of multiparametric magnetic resonance imaging (MRI) in GO.Study TypeRetrospective.PopulationA total of 235 GO patients (age: 38.8 ± 13.4 years; 90 male; 96 active patients).Field Strength/SequenceShort‐tau inversion recovery (STIR) fast spin echo, multiecho spin echo T2 mapping and 3D T1‐weighted fast field echo sequences at 3.0 T.AssessmentTwo physicians assessed the mean and maximum signal intensity ratio of extraocular muscles to white matter (SIR), T2 relaxation time (T2RT), extraocular muscle area (EMA), fat fraction (FF), retrobulbar fat volume (RFV), and extraocular muscle volume (EMV). Clinical activity score (CAS) ≧ 3 was in active stage.Statistical TestsThe optimal cut‐off point of diagnostic efficacy was selected using receiver operating characteristic (ROC) curve analysis and evaluated using area under the curve (AUC), compared using Student's t test, analysis of variance or Kruskal–Wallis H test. The correlation used Pearson correlation analysis. The discriminant equation used a binary logistic regression analysis. P < 0.05 was considered statistically significant.ResultsThe SIRmean, SIRmax, T2RTmean, T2RTmax, EMA, and EMV in active GO patients were significantly higher than those in inactive and were positively correlated with CAS (r = 0.276, 0.228, 0.438, 0.388, 0.502, and 0333, respectively). The FFmax of active patients was significantly lower than that of inactive patients and was negatively correlated with CAS (r = −0.44). Logistic regression analysis indicated that T2RTmean was independently associated with GO active periods and had good diagnostic performance (area under ROC curve = 0.736, sensitivity 70.7%, specificity 69.3%). T2RTmean ≧ 74.295 could be a diagnostic cut‐off for judging GO activity (sensitivity 55.3%).ConclusionSIR, T2RT, EMV, and FF can quantitatively assess the activity and severity of GO and can potentially provide a basis for clinical judgment and selection of treatment options.Evidence Level4.Technical EfficacyStage 2.

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Correlation between serum anti-TSH receptor autoantibodies (TRAbs) and the clinical feature of Graves’ orbitopathy

Cited by 48 publications

References 37 publications

Steroid-Resistant Graves’ Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience

Steroid-Resistant Graves’ Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience

Epidemiology, Natural History, Risk Factors, and Prevention of Graves’ Orbitopathy

Application of Multiparameter Quantitative Magnetic Resonance Imaging in the Evaluation of Graves' Ophthalmopathy

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