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

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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.

Section: Methodsmentioning

confidence: 99%

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

Vos¹,

Smit²,

Endert

et al. 2009

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“…But this study did not reveal any effect of stress on biological parameters. In other words, stress can directly influence the clinical expression of the disease (49). However, one may argue that a statistically significant association between severity of stress and severity of biochemical hyperthyroidism is not necessarily expected because two major determinants of the latter are thyroid size and concentrations of TSH receptor-stimulating autoantibodies.…”

Section: Stress and Clinical Expression Of Graves' Diseasementioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Role of emotional stress in the pathophysiology of Graves' disease

Falgarone¹,

Heshmati²,

Cohen³

et al. 2013

The role of stress in the pathophysiology of Graves' disease is suggested by several clinical observations, by recent advances in immunology and by better understanding of autoimmune diseases which provides new insights into potential effects of stress hormones on T helper cell imbalance involved in the pathogenesis of autoimmune diseases. Stress management should therefore be an important part of the treatment of Graves' disease, as stress reduction may improve the effect of therapy. However, this field still requires interventional data to support stress management in the treatment of Graves' disease. European Journal of Endocrinology 168 R13-R18

“…Participants were asked to complete questionnaires asking about smoking habits and stress at the time of diagnosis as published previously (7,10). Smoking habits were assessed as current smokers, ex-smokers, and never smokers.…”

Section: Patientsmentioning

confidence: 99%

Genotypes in relation to phenotypic appearance and exposure to environmental factors in Graves' hyperthyroidism

Vos

Endert

Tijssen

et al. 2012

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Background: Genetic polymorphisms and environmental factors are both involved in the pathogenesis of Graves' disease, but their interaction and effect on Graves' phenotypes have scarcely been investigated. Objective: To test the hypothesis that subjects with susceptibility genotypes develop more severe Graves' hyperthyroidism at a younger age and after less exposure to environmental factors, with attention to gender differences. Study design: A prospective observational multicenter study in 205 adult Caucasian patients with untreated first episode of Graves' hyperthyroidism. Methods: Evaluation of genotypes (HLA DRB1*03, DQA1*05, DQB1*02; CTLA4 49A/G, CT60 A/G; PTPN22 C/T) in relation to phenotypes (age, sex, severity (clinical, biochemical, and immunological)) of hyperthyroidism and environmental factors (smoking, stress questionnaires). Results: G-alleles in CTLA4 single nucleotide polymorphisms were dose-dependently associated with younger age at the time of diagnosis and less exposure to daily hassles. In gender-specific analysis, this association is enhanced in men and attenuated in women. Males (but not females) in HLA linkage disequilibrium had more severe (biochemical and immunological) hyperthyroidism and a tendency to younger age at diagnosis, compared with those not in linkage disequilibrium. Conclusion: Graves' hyperthyroidism occurs at a younger age with less exposure to environmental factors in subjects carrying susceptibility genotypes. The impact of genotypes seems to be greater in males than in females.