ArticlesPrediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study
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
References (17)
Subclinical hyperthyroidism: just a low serum thyrotrophin concentration or something more?
N Engl J Med
(1994)- et al.
Applications of a new chemiluminometric thyrotropin assay to subnormal measurement
J Clin Endocrinol Metab
(1990) - et al.
The significance of TSH values measured in a sensitive assay in the follow-up of hyperthyroid patients treated with radioiodine
J Clin Endocrinol Metab
(1992) - et al.
Screening for thyroid disease in a primary care unit with a thyroid stimulating hormone assay with a low detection limit
BMJ
(1988) - et al.
Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom
Clin Endocrinol (Oxf)
(1991) - et al.
Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis
J Clin Endocrinol Metab
(1996) - et al.
Cardiac effects of long term thyrotropin suppressive therapy with levothyroxine
J Clin Endocrinol Metab
(1993) - et al.
Cardiac hypertrophy as a result of long-term thyroxine therapy and thyrotoxicosis
Heart
(1996)
Cited by (620)
The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis
2023, The Lancet Diabetes and EndocrinologyManagement of thyroid dysfunction and thyroid nodules in the ageing patient
2023, European Journal of Internal MedicineThe EANM guideline on radioiodine therapy of benign thyroid disease
2023, European Journal of Nuclear Medicine and Molecular ImagingAssociation of Thyroid-Stimulating Hormone With All-Cause Mortality: A 2-Sample Mendelian Randomization Study
2023, Journal of Clinical Endocrinology and MetabolismThyroid Dysfunction in Periand Postmenopausal Women- Cumulative Risks
2023, Deutsches Arzteblatt International