CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Michael D. Gammage, MD, FRCP, FESC*,
Faizel Osman, MD, MRCP,
Michael C. Sheppard, PhD, FRCP and
Jayne A. Franklyn, MD, PhD, FRCP
* University Hospital Birmingham, Cardiology, Edgbaston, Birmingham, West Midlands B15 2TH, United Kingdom (Email: m.d.gammage{at}bham.ac.uk).
We thank Dr. Völzke for his comments on our recent publication describing the cardiovascular manifestations of hyperthyroidism before and after antithyroid therapy (1). This age- and gender-matched case-control study of a consecutive series of 393 subjects presenting with overt hyperthyroidism aimed to define the cardiovascular symptoms, signs, and dysrhythmias found in hyperthyroidism and to compare results with euthyroid control subjects. After a mean follow-up period of 5.5 years after presentation, 26 hyperthyroid subjects had died compared with 12 age- and gender-matched controls (p < 0.01). We state in our discussion that "the number of deaths remained too small to determine whether excess mortality [not a primary end point of our study] was specifically vascular in nature." We agree that the higher prevalence of smoking in our hyperthyroid subjects may be a confounder in terms of the mortality observed; however, there was no significant difference in prevalence of diabetes between subjects and controls. Whereas Dr. Völzke asserts that our hyperthyroid subjects may have been selected because they were seen in a university hospital setting, we consider this unlikely as our hospital serves as the general referral site for hyperthyroidism, rather than as a specialist referral center.
In summarizing previous reports examining the relationship between hyperthyroidism and mortality, Dr. Völzke failed to make the critical distinction between studies of overt hyperthyroidism and those examining subclinical hyperthyroidism (defined biochemically as low serum thyrotropin with normal circulating thyroid hormone concentrations). We have previously reported in 2 large cohort studies that overt hyperthyroidism is associated with excess all-cause and vascular mortality (2,3) findings in accord with a large cohort study in the U.S. (4) and together providing good evidence that the cardiovascular complications of overt thyroid hormone excess (1) translate into excess vascular mortality. Unsurprisingly, results are less clear-cut for subclinical hyperthyroidism, which represents a much lesser degree of thyroid hormone excess. Increasing evidence from several large studies supports a link between subclinical hyperthyroidism and atrial fibrillation (5–7). We have previously reported that a low serum thyrotropin result is, in turn, associated with increased mortality after follow-up of 10 years (8) however, a higher rate of coronary heart disease and all-cause mortality observed by Cappola et al. during follow-up of subclinical hyperthyroidism was not significant (5). Likewise, Walsh et al. (9) found no adverse outcomes in a prospective study of subclinical hyperthyroid subjects (9).
A very different study in subjects aged 73 to 94 years by van den Beld et al. (10)—incorrectly cited by Dr. Völzke as evidence against an association between subclinical hyperthyroidism and mortality—examined the relationship between circulating thyroid hormone concentrations and physical performance scores, other markers of muscle function, and bone density. That study revealed an association between higher serum T4 and reduced physical performance score. Gussekloo et al. (11) studied very elderly subjects from the Leiden cohort (85 to 89 years) and reported increased hazard ratios for mortality for increasing increments of serum-free T4, as well as reduced mortality associated with subclinical hypothyroidism, not hyperthyroidism as suggested by Dr. Völzke.
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References
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- Osman F, Franklyn JA, Holder RL, Sheppard MC, Gammage, MD. Cardiovascular manifestations of hyperthyroidism before and after antithyroid therapy: a matched case-control study J Am Coll Cardiol 2007;49:71-81.[Abstract/Free Full Text]
- Franklyn JA, Maisonneuve P, Sheppard MC, Betteridge J, Boyle P. Mortality after the treatment of hyperthyroidism with radioactive iodine N Engl J Med 1998;338:712-718.[Abstract/Free Full Text]
- Franklyn JA, Sheppard MC, Maisonneuve P. Thyroid function and mortality in patients treated for hyperthyroidism JAMA 2005;294:71-80.[Abstract/Free Full Text]
- Goldman MB, Monson RR, Maloof F. Cancer mortality in women with thyroid disease Cancer Res 1990;50:2283-2289.[Abstract/Free Full Text]
- Cappola AR, Fried LP, Arnold AM, et al. Thyroid status, cardiovascular risk, and mortality in older adults JAMA 2006;295:1033-1041.[Abstract/Free Full Text]
- Gammage MD, Parle JV, Holder RL, et al. Association between serum free T4 concentration and atrial fibrillation Arch Intern Med 2007In press.
- Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons N Engl J Med 1994;331:1249-1252.[Abstract/Free Full Text]
- Parle JV, Maisonneuve P, Sheppard MC, Boyle P, Franklyn JA. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study Lancet 2001;358:861-865.[CrossRef][ISI][Medline]
- Walsh JP, Bremner AP, Bulsara MK, et al. Subclinical thyroid dysfunction and blood pressure: a community-based study Clin Endocrinol (Oxf) 2006;65:486-491.[CrossRef][Medline]
- van den Beld AW, Visser TJ, Feelders RA, Grobbee DE, Lamberts SW. Thyroid hormone concentrations, disease, physical function, and mortality in elderly men J Clin Endocrinol Metab 2005;90:6403-6409.[Abstract/Free Full Text]
- Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frolich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age JAMA 2004;292:2591-2599.[Abstract/Free Full Text]
Related articles in JACC:
- Hyperthyroidism and Mortality
- Henry Völzke
JACC 2007 49: 2228-2229.
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