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This version published online on September 12, 2006
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2006-1402
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*Smoking
*Smoking and Youth

Submitted on July 3, 2006
Accepted on September 5, 2006

Influences of age, gender, smoking and family history on autoimmune thyroid disease phenotype

N. Manji, J. D. Carr-Smith, K. Boelaert, A. Allahabadia, M. Armitage, V. K. Chatterjee, J. H. Lazarus, S. H.S. Pearce, B. Vaidya, S. C. Gough, and J. A. Franklyn*

Division of Medical Sciences, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TH, UK; Northern General Hospital, Sheffield S5 7AU, UK; Royal Bournemouth Hospital, Bournemouth BH7 7DW, UK; #University of Cambridge, Addenbrookes Hospital, Cambridge CB2 2QQ, UK; Centre for Endocrine and Diabetes Sciences, Cardiff University, Cardiff, UK; The Medical School, Newcastle-upon-Tyne, Newcastle NE2 4HH; Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK

* To whom correspondence should be addressed. E-mail: j.a.franklyn{at}bham.ac.uk.

Context Both genetic and environmental factors contribute to susceptibility to Graves' disease (GD) and Hashimoto's thyroiditis (HT), as well as to disease manifestations. Objective To define how endogenous/environmental factors contribute to variation in phenotype.

Design/Setting. Multicenter cohort study.

Patients/Outcome measures We prospectively collected clinical/biochemical data as part of the protocol for a UK 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 between 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.




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