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Bamini Gopinath, PhD; Gerald Liew, MBBS; Victoria M. Flood, PhD; Jie Jin Wang, PhD; Annette Kifley, PhD; Stephen R. Leeder, MD, PhD; Paul Mitchell, MD, PhD

Arch Intern Med. 2008;168(20):2283-2284.

A recent article¹ and editorial² in the Archives investigated the relationship between thyroid function, within the normal reference range and body weight gain. Fox et al¹ observed that change in serum thyrotropin concentration (TSH) was strongly and linearly associated with weight gain. The authors, however, did not account for diet and physical activity, covariates known to be strongly associated with weight change. We also examined the relationship between TSH within the reference range and weight change over a 5-year period, accounting also for baseline dietary parameters and reported physical activity.

Methods
The Blue Mountains Eye Study (BMES) is a population-based cohort study of age-related eye diseases and other health outcomes. Methods used to ascertain and survey this population were previously described.³ During 1992 though 1994, 3654 participants 49 years or older were examined (82.4% participation; BMES-1). Surviving baseline participants were invited to attend follow-up examinations after 5 years (1997-1999, BMES-2) and 10 years (2002-2004, BMES-3), at which 2334 (75.1% of survivors) and 1952 (75.6% of survivors) participants were reexamined, respectively. Of these, 926 participants were available for final analyses after exclusions (ie, data on missing covariates, use of thyroxine, or abnormal TSH level). Serum TSH concentration was measured in these subjects as previously described,⁴ and we used the same TSH reference range of 0.5 to 5.0 mIU/L as Fox et al. ¹ Change in serum TSH concentration was analyzed as a continuous variable or as quartiles.

Dietary data were assessed using a 145-item food frequency questionnaire.⁵ The physical activity questionnaire was based on the International Physical Activity Questionnaire.⁶ Total metabolic equivalents were calculated for each individual, based on their report of time spent performing moderate and/or vigorous activities.

Results
At follow-up, TSH ranged from –2.05 to 3.29 mIU/L in men and from –2.50 to 3.22 mIU/L in women. In women, weight increased by 0.8 kg for every 1-unit increase in TSH during the 5-year period (P = .01) after adjusting for age, baseline body weight (at BMES-2), and current smoking (Table). This association became stronger after further step-wise adjustment for physical activity and dietary covariates such as fat (P < .001) and carbohydrates (P = .002). Increasing TSH level (modeled as a continuous variable) during follow-up was associated with a 50% higher likelihood of weight gain of greater than 2 kg after adjusting for age, baseline body weight, and smoking in women (odds ratio, 1.50; 95% confidence interval, 1.10-2.05). This association persisted after further adjustment for physical activity and dietary covariates.

View this table: [in this window] [in a new window] [as a PowerPoint slide]   Table. Five-Year Weight Change in Relation to TSH and Sex in BMES Participants

Weight change at follow-up, however, was not associated with TSH in men (P = .92), either before or after adjusting for physical activity and diet (Table). Analyses by quartiles of TSH were also unrelated to weight change at follow-up either before or after multivariate adjustment.

Comment
We observed, in women but not in men, a strong positive association between TSH over time (within the reference range) and incident weight gain, which is in agreement with the findings of Fox et al¹ but of a lower magnitude. This association actually strengthened after we further adjusted for diet and physical activity. Since Fox et al¹ observed a smaller effect size in men compared with women, it is likely that we had insufficient study power to detect this association in men. We have shown that obesity was a significant predictor of incident overt hypothyroidism (unpublished data, 2008). Our study supports the findings of Fox et al¹ in providing evidence that the physiological mechanism of obesity may exert some influence on thyroid function and vice versa, as suggested by the editorial.²

In conclusion, our study provides additional support for the concept that modest changes in thyroid function may be a potential risk factor for the development of obesity, particularly in women.

AUTHOR INFORMATION
Correspondence: Dr Mitchell, Centre for Vision Research, University of Sydney, Westmead Hospital, Hawkesbury Road, Westmead, NSW 2145, Australia (paul_mitchell{at}wmi.usyd.edu.au).

Author Contributions: Study concept and design: Gopinath, Liew, and Mitchell. Acquisition of data: Mitchell. Analysis and interpretation of data: Gopinath, Flood, Wang, Kifley, and Leeder. Drafting of the manuscript: Gopinath. Critical revision of the manuscript for important intellectual content: Liew, Flood, Wang, Kifley, Leeder, and Mitchell. Statistical analysis: Kifley. Obtained funding: Mitchell. Administrative, technical, and material support: Gopinath, Liew, and Flood. Study supervision: Wang and Mitchell.

Financial Disclosure: None reported.

REFERENCES
1. Fox CS, Pencina MJ, D'Agostino RB; et al. Relations of thyroid function to body weight: cross-sectional and longitudinal observations in a community-based sample. Arch Intern Med. 2008;168(6):587-592. FREE FULL TEXT 2. Weiss RE, Brown RL. Doctor . . . could it be my thyroid? Arch Intern Med. 2008;168(6):568-569. FREE FULL TEXT 3. Attebo K, Mitchell P, Smith W. Visual acuity and the causes of visual loss in Australia: the Blue Mountains Eye Study. Ophthalmology. 1996;103(3):357-364. WEB OF SCIENCE | PUBMED 4. Empson M, Flood V, Ma G, Eastman CJ, Mitchell P. Prevalence of thyroid disease in an older Australian population. Intern Med J. 2007;37(7):448-455. FULL TEXT | WEB OF SCIENCE | PUBMED 5. Smith W, Mitchell P, Reay EM, Webb K, Harvey PW. Validity and reproducibility of a self-administered food frequency questionnaire in older people. Aust N Z J Public Health. 1998;22(4):456-463. WEB OF SCIENCE | PUBMED 6. Craig CL, Marshall AL, Sjostrom M; et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35(8):1381-1395. FULL TEXT | WEB OF SCIENCE | PUBMED

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