Elsevier

The Lancet

Volume 358, Issue 9285, 15 September 2001, Pages 861-865
The Lancet

Articles
Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study

https://doi.org/10.1016/S0140-6736(01)06067-6Get rights and content

Summary

Background

Low serum thyrotropin, in combination with normal concentrations of circulating thyroid hormones, is common, especially in elderly people and in individuals with a history of thyroid disease. We aimed to assess the long-term effects of subclinical hyperthyroidism on mortality.

Methods

We did a population-based study of mortality in a cohort of 1191 individuals not on thyroxine or antithyroid medication. All participants were aged 60 years or older. We measured concentration of thyrotropin in serum at baseline in 1988–89. We recorded vital status on June 1, 1999, and ascertained causes of death for those who had died. We compared data for causes of death with age-specific, sex specific, and year-specific data for England and Wales. We also compared mortality within the cohort according to initial thyrotropin measurement.

Results

During 9733 person-years of follow-up, 509 of 1191 people died, the expected number of deaths being 496 (standardised mortality ratio [SMR] 1·0, 95% Cl 0·9–1·1). Mortality from all causes was significantly increased at 2 (SMR 2·1), 3 (2·1), 4 (1·7), and 5 (1·8) years after first measurement in those with low serum thyrotropin (n = 71). These increases were largely accounted for by significant increases in mortality due to circulatory diseases (SMR 2·1, 2·2, 1·9, 2·0, at years 2, 3, 4, and 5 respectively). Increases in mortality from all causes in years 2–5 were higher in patients with low serum thyrotropin than in the rest of the cohort (hazard ratios for years 2, 3, 4, and 5 were 2·1, 2·2, 1·8, and 1·8, respectively). This result reflects an increase in mortality from circulatory diseases (hazard ratios at years 2, 3, 4, and 5 were 2·3, 2·6, 2·3, 2·3), and specifically from cardiovascular diseases (hazard ratios at years 2, 3, 4, and 5 were 3·3, 3·0, 2·3, 2·2).

Interpretation

A single measurement of low serum thyrotropin in individuals aged 60 years or older is associated with increased mortality from all causes, and in particular mortality due to circulatory and cardiovascular diseases.

Introduction

The widespread availability of sensitive assays for the measurement of thyrotropin in serum has led to recognition that concentrations of serum thyrotropin are often low in patients with apparently normal thyroid function. This knowledge has resulted in the description of a condition termed subclinical hyperthyroidism, which is defined as a reduction in serum thyrotropin in association with normal concentrations of the circulating thyroid hormones thyroxine and tri-iodothyronine.1 The condition is common in people taking thyroxine replacement therapy, in those with goitre, and after treatment of hyperthyroidism;2, 3 in these situations low serum thyrotropin is thought to suggest mild thyroid hormone excess.

Subclinical hyperthyroidism is common, with estimates of prevalence in iodine-replete areas varying from 3·9% in adults of all ages (thyrotropin ≤0·2 mU/L)4 to 5·9% in those aged 60 years and older (%≤0·5 mU/L);5 prevalence might be even higher than average in areas of iodine deficiency. Although subclinical hyperthyroidism is common, the clinical importance of these biochemical abnormalities is unclear. There is debate about the potential adverse effect of subclinical hyperthyroidism on bone metabolism and on the cardiovascular system.1 Results of studies showing a reduction in bone mineral density associated with thyrotropin-suppressive doses of thyroxine6 have led to concern about later risk of osteoporotic fracture, and effects of thyroxine treatment on indices of cardiovascular function7, 8 have raised doubts about long-term circulatory morbidity and mortality.

Results of a large study9 of patients aged 60 years and older, forming part of the Framingham population, showed that people with suppressed serum thyrotropin (≤0·1 mU/L) had a relative risk for development of atrial fibrillation of 3·1 (95% CI 1·7–5·5) compared with those with normal serum thyrotropin concentrations, lending support to the view that mild thyroid hormone excess might result in long-term vascular morbidity. That study did not, however, examine the association of concentrations of serum thyrotropin with mortality, and the study population was heterogeneous in that some of those with low serum thyrotropin were taking thyroxine therapy whereas others were not. Our aim was to investigate the relation between serum thyrotropin and mortality from all causes, and due to circulatory diseases in elderly people.

Section snippets

Participants

We enrolled 1209 individuals who were registered with one primary care practice in Birmingham, UK. We originally recruited people for a study of the prevalence of abnormalities of thyrotropin in a population-based cohort; characteristics of the cohort (table 1) and results are described elsewhere.5 Briefly, all individuals were living in the community at the time of recruitment and were aged 60 years or older on June 1, 1988. We excluded patients who were being prescribed thyroxine or

Results

Of 1191 individuals, 71 (6%) had serum thyrotropin concentrations below the normal range (including 20 with undetectable serum thyrotropin of < 0·1 mU/L) and 94 (8%) above the normal range (table 1). Of those with abnormal thyrotropin concentrations, one had overt hyperthyroidism (low thyrotropin and high free thyroxine) and was put on antithyroid medication at the start of the study, and 18 had overt hypothyroidism (high thyrotropin and low free thyroxine) and began thyroxine replacement

Discussion

Our results show an increase in mortality from all causes and from circulatory diseases in individuals with subclinical hyperthyroidism. Patients with a low serum thyrotropin at the start of our study were at a clear survival disadvantage during the first 5 years of follow-up. Significant increases in mortality in individuals with low thyrotropin at the start of the study were no longer present at the end of follow-up, however. This finding is expected, since whatever the initial concentration

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