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Lookup NU author(s): Professor Simon PearceORCiD, Dr Bijayeswar Vaidya
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Context: Both genetic and environmental factors contribute to susceptibility to Graves' disease (GD) and Hashimoto's thyroiditis (HT), as well as disease manifestations. Objective: The objective of the study was to define how endogenous/environmental factors contribute to variation in phenotype. Design/Setting: This was a multicenter cohort study. Patients/Outcome Measures: We prospectively collected clinical/ biochemical data as part of the protocol for a United Kingdom DNA collection for GD and HT. We investigated, in 2805 Caucasian subjects, whether age at diagnosis, gender, family history (FH), smoking history, and presence of goiter influenced disease manifestations. Results: For 2405 subjects with GD, the presence of goiter was independently associated with disease severity (serum free T4 at diagnosis) (P < 0.001). Free T4 (P < 0.05) and current smoking (P < 0.001) were both independent predictors of the presence of ophthalmopathy. Approximately half of those with GD (47.4% of females, 40.0% of males) and HT (n = 400) (56.4% of females, 51.7% of males) reported a FH of thyroid dysfunction. In GD, a FH of hyperthyroidism in any relative was more frequent than hypothyroidism (30.1 vs. 24.4% in affected females, P < 0.001). In HT, a FH of hypothyroidism was more common than hyperthyroidism (42.1 vs. 22.8% in affected females, P < 0.001). For GD (P < 0.001) and HT (P < 0.05), a FH was more common in maternal than paternal relatives. The reporting of a parent with thyroid dysfunction (hyper or hypo) was associated with lower median age at diagnosis of both GD (mother with hyperthyroidism, P < 0.001) and HT (father with hypothyroidism, P < 0.05). In GD and HT, there was an inverse relationship between the number of relatives with thyroid dysfunction and age at diagnosis (P < 0.01). Conclusions: Marked associations among age at diagnosis, disease severity, goiter, ophthalmopathy, smoking, and FH provide evidence for interactions between genetic and environmental/endogenous factors; understanding these may allow preventive measures or better tailoring of therapies. Copyright © 2006 by The Endocrine Society.
Author(s): Manji N, Carr-Smith JD, Boelaert K, Allahabadia A, Armitage M, Chatterjee VK, Lazarus JH, Pearce SHS, Vaidya B, Gough SC, Franklyn JA
Publication type: Article
Publication status: Published
Journal: Journal of Clinical Endocrinology and Metabolism
Year: 2006
Volume: 91
Issue: 12
Pages: 4873-4880
ISSN (print): 0021-972X
ISSN (electronic): 1945-7197
Publisher: The Endocrine Society
URL: http://dx.doi.org/10.1210/jc.2006-1402
DOI: 10.1210/jc.2006-1402
PubMed id: 16968788
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