Frequency and characteristics of TBII‐seronegative patients in a population with untreated Graves’ hyperthyroidism: a prospective study

Vos, Xander G; Smit, Natalie; Endert, E.; Tijssen, Jan G.P.; Wiersinga, Wilmar M.

doi:10.1111/j.1365-2265.2008.03192.x

Cited by 117 publications

(35 citation statements)

References 35 publications

(60 reference statements)

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“…We also observed a decrease in the clinical severity of Graves' hyperthyroidism with age as evident from the fall in the HSS score. There was furthermore a shift toward smaller goiter size in elderly patients, a finding again explainable from the direct relationship between TBII and goiter size (10). Other studies also reported a lower frequency of symptoms and signs in elderly Graves' hyperthyroidism patients (notably less heat tolerance, less perspiration, less irritability, and less often increased appetite, tachycardia and goiter), although weight loss and atrial fibrillation are more common in old age (20)(21)(22).…”

Section: Discussionmentioning

confidence: 77%

“…The mechanism behind less severe Graves' hyperthyroidism in the older age groups is incompletely understood. Less severe Graves' hyperthyroidism is due to lower levels of thyrotropin-binding inhibitory immunoglobulin (TBII) (10). Furthermore, it has been shown that advancing age is associated with a decreased experience of selfreported stress (pleasant and unpleasant life events) (11).…”

Section: Introductionmentioning

confidence: 99%

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Age and stress as determinants of the severity of hyperthyroidism caused by Graves' disease in newly diagnosed patients

Vos

Smit

Endert

et al. 2009

European Journal of Endocrinology

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Objective: The evidence that stress may provoke Graves' hyperthyroidism in genetically susceptible subjects is substantial. Whether exposure to stress is related to the severity of thyrotoxicosis has not been studied. Advancing age is associated with not only less severe Graves' hyperthyroidism but also self-reported stress. We tested the hypothesis whether advancing age is associated with less exposure to stress, resulting in a lower immunological response, and less severe Graves' hyperthyroidism. Design: Cross-sectional multicenter study. Patients: Two hundred and sixty-three consecutive untreated patients with a first episode of Graves' hyperthyroidism were included. The severity of Graves' hyperthyroidism was evaluated biochemically (freeT 4 -index and freeT 3 -index, thyrotropin-binding inhibitory immunoglobulin (TBII)) and clinically by the hyperthyroid symptom scale score (HSS score). Stress exposure was quantitated by three questionnaires. Results: Advancing age was associated with less severe Graves' hyperthyroidism, both biochemically by lower serum freeT 3 -index and freeT 4 -index (P!0.01), lower serum TBII (PZ0.05), and clinically by lower HSS scores (PZ0.04) and smaller goiter size (P!0.01). FreeT 3 -index and freeT 4 -index were directly associated with HSS scores (P!0.01). Stress scores were associated with HSS scores (P!0.01) but not with biochemical severity of Graves' hyperthyroidism. Advancing age was associated with lower scores for stress exposure. Multivariate regression analysis showed that HSS score was independently related to the tendency to report negative feelings (P!0.01) but not to other stress scores and also not to age. Conclusion: Advancing age is associated with less exposure to stress, lower serum TBII and less severe clinical and biochemical Graves' hyperthyroidism. Because no direct relationship exists between stress exposure and TBII or freeT 3 -index and freeT 4 -index, we reject our hypothesis that less stress is causally related to biochemically less severe Graves' hyperthyroidism in old age. HSS score is primarily determined by negative feelings and not by age.

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Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Age and stress as determinants of the severity of hyperthyroidism caused by Graves' disease in newly diagnosed patients

Vos

Smit

Endert

et al. 2009

European Journal of Endocrinology

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“…Through first-, second-, and third-generation modification, TBII has been modified to enhance its diagnostic sensitivity and specificity for Graves' disease (GD). [6][7][8] Classical TBII assays are limited by their inability to discriminate between thyroid-stimulating antibodies (TSAbs) and thyroid-blocking antibodies (TBAbs). However, the most newly developed thirdgeneration TBII assay inhibits binding of a labeled TSAb (monoclonal Ab clone #M22) rather than labeled TSH to the TSH receptor 9,10 This results in enhanced sensitivity and specificity vs earlier assays using radiolabeled TSH.…”

Section: Introductionmentioning

confidence: 99%

Relevance of TSH-receptor antibody levels in predicting disease course in Graves’ orbitopathy: comparison of the third-generation TBII assay and Mc4-TSI bioassay

Jang

Shin

Lee

et al. 2013

Eye

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Aims To investigate if TSH-receptor antibody (TRAb) levels measured in early Graves' orbitopathy (GO) stages are predictive of clinical disease course beyond 1 year after initial GO diagnosis and to compare performance of two newly developed TRAb assays (third-generation thyrotropin-binding inhibitor immunoglobulin (TBII) assay vs Mc4-thyroid-stimulating immunoglobulin (TSI) bioassay) in predicting disease course. Methods Newly diagnosed, untreated GO patients whose duration of ocular symptoms was less than 6 months were included. One year after initial diagnosis, all patients were classified as presenting either a mild (Group 1) or severe course (Group 2) according to their clinical manifestations. The measurements of two TRAb assays at initial GO diagnosis were used for analysis. Results Data from 112 patients were available for analysis. Seventy-three patients (65.2%) were designated as Group 1, and 39 patients (34.8%) as Group 2. Patients with higher initial TRAb levels demonstrated a higher risk of severe disease course upon multiple regression analysis (Po0.01). The cutoff values for the prediction of severe course of the third-generation TBII and Mc4-TSI assays were 10.67 IU/l and 555.10%, respectively, with assay specificities of 84.9 and 89.0%. The TBII assay predictive power

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“…It might be that advancing age is associated with greater concern on the significance of symptoms and on health in general, leading to earlier consultation. Longer duration of symptoms until diagnosis was associated with greater goiter size, which can be understood from the longer exposure time to TBII in view of the thyroid growth promoting effect of TBII (13,14). Longer duration of symptoms was also related to higher TPO-Ab concentrations, tentatively explained from epitope spreading after the initial immune reaction against the TSH receptor (15).…”

Section: Discussionmentioning

confidence: 99%

Variation in phenotypic appearance of Graves' disease: effect of genetic anticipation and duration of complaints

Vos¹,

Smit²,

Endert

et al. 2009

European Journal of Endocrinology

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Objective: Both genetic and environmental factors contribute to susceptibility of Graves' disease. In this study, we evaluated whether the duration of symptoms or a positive family history of autoimmune thyroid disease (AITD) are related to specific phenotypes in patients with a first episode of Graves' hyperthyroidism (GH). Design: Cross-sectional multicentre observational study. Patients: Two hundred and sixty-three consecutive untreated patients (mean age (GS.D.) 42.6G12.4 years; range 16-79 years) with a first episode of GH were included. Biochemical and clinical severity of GH was evaluated. Participants were asked to complete questionnaires about environmental factors (smoking behavior, use of estrogens, stress etc.), the duration of symptoms (interval between start of symptoms and date of referral) and family history for AITD. We ascertained the autoimmune nature of thyroid disease in affected relatives. Family history scores (FHS; high score indicating a close genetic relationship and/or a large number of affected relatives) were calculated for patients with a positive family history for AITD. Results: The peak incidence for the diagnosis of GH was 2-3 months after onset of symptoms (32% of patients). Duration of symptoms was negatively associated with age (P for trendZ0.04). A positive family history for AITD was present in 42.6% of patients. Patients with the highest FHS were more often male (PZ0.01) while age at onset was lower (PZ0.02) compared to patients with a lower FHS. Among patient groups with different FHS, no differences were found in exposure to environmental factors, nor in clinical or biochemical severity of hyperthyroidism. Conclusion: Our study does not support the hypothesis that a short duration of thyrotoxic symptoms until diagnosis is related to more severe hyperthyroidism in Graves' disease. We have found supporting evidence for the existence of genetic anticipation in Graves' disease by means of a lower age of onset in the group with the highest FHS.

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Frequency and characteristics of TBII‐seronegative patients in a population with untreated Graves’ hyperthyroidism: a prospective study

Cited by 117 publications

References 35 publications

Age and stress as determinants of the severity of hyperthyroidism caused by Graves' disease in newly diagnosed patients

Age and stress as determinants of the severity of hyperthyroidism caused by Graves' disease in newly diagnosed patients

Relevance of TSH-receptor antibody levels in predicting disease course in Graves’ orbitopathy: comparison of the third-generation TBII assay and Mc4-TSI bioassay

Variation in phenotypic appearance of Graves' disease: effect of genetic anticipation and duration of complaints

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