Current issues of ACP Journal Club are published in Annals of Internal Medicine


Low thyrotropin levels predicted atrial fibrillation in the elderly

ACP J Club. 1995 Mar-April;122:47. doi:10.7326/ACPJC-1995-122-2-047

Source Citation

Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentration as a risk factor for atrial fibrillation in older persons. N Engl J Med. 1994 Nov 10;331:1249-52.



To determine whether a low serum thyrotropin level in adults ≥ 60 years of age is a risk factor for development of atrial fibrillation (AF).


10-year cohort study of participants in the original Framingham Heart Study.


Population-based study in Massachusetts.


2007 adults (59% women) aged ≥ 60 years at baseline assessment (1978 to 1980). Exclusion criteria were AF at baseline, a history of arrhythmia, concurrent clinical hyperthyroidism, or absence of follow-up data.

Assessment of risk factors

Serum samples were collected at baseline and were analyzed in 1990 and 1991 for serum thyrotropin. Participants were divided into 4 categories on the basis of thyrotropin level (≥ 0.1 mU/L [low], > 0.1 to 0.4 mU/L [slightly low], > 0.4 to 5.0 mU/L [normal], and > 5.0mU/L [high]). Other risk factors for AF were assessed (smoking, diabetes mellitus, hypertension, left ventricular hypertrophy, myocardial infarction, congestive heart failure, and heart murmur).

Main outcome measure

AF diagnosed by electrocardiography done at biennial examinations during the 10-year follow-up.

Main results

61 participants (3%) had low thyrotropin levels, 187 (9%) had slightly low levels, 1576 (79%) had normal levels, and 183 (9%) had high levels. During follow-up, 192 participants developed AF. The cumulative incidence of AF in 10 years was 28% in the low-level group, 16% in the slightly low-level group, 11% in the normal-level group and 15% in the high-level group. When adjusted for age, sex, and all risk factors, the relative risk (RR) for new AF in the low-level group compared with that in the normal-level group was 3.1 (95% CI 1.7 to 5.5, P < 0.001); for the slightly low-level group, the RR was 1.6 (CI 1.0 to 2.5, P = 0.05). The results were similar when participants who took thyroid hormones were excluded (RR for low levels 3.8, CI 1.7 to 8.3; P < 0.001, and RR for slightly low levels 1.6, CI 1.0 to 2.5, P = 0.04).


Low serum thyrotropin levels were independently associated with a 3-fold increase in the development of new atrial fibrillation in adults 60 years of age or older followed for 10 years.

Sources of funding: Department of Veterans Affairs, National Institutes of Health, and Boots Pharmaceuticals.

For article reprint: Dr. C.T. Sawin, Veterans Health Administration, Office of the Medical Inspector (IOMI), 810 Vermont Ave, NW, Washington, DC 20420, USA. FAX 202-273-9102.


In 1948, 5234 men and women enrolled in a study in Framingham, Massachusetts, to help define risk factors for cardiovascular disease. The Heart Study has also provided data on thyroid diseases, including nodules (1, 2); thyroid deficiency in elderly persons (3); and, most recently, low thyrotropin levels as a risk factor for AF. The authors lucidly describe the 10-year experience for this arrhythmia in 2007 of the original cohort participants.

After adjustment for AF risk factors, including age, sex, smoking, diabetes mellitus, hypertension, left ventricular hypertrophy, myocardial infarction, congestive heart failure, and heart murmur, low thyrotropin levels typical of subclinical hyperthyroidism were associated with a 3-fold increased risk for AF. Because hyperthyroidism is one of the most correctable causes of AF (4, 5), this study has important clinical ramifications.

Modification of risk factors to decrease the incidence of morbid events is a logical step. In this instance, the modification appears straightforward: Restore thyroid homeostasis to normal. For patients receiving thyroid replacements, sensitive thyrotropin assays and a wide spectrum of thyroxine doses make dose adjustments a precise and seemingly easy matter. Clinical experience, however, suggests that dose titration to normalize thyrotropin levels requires vigilance by the physician and considerable patience by the patient. Correcting endogenous hyperthyroidism is even more problematic. Treatment options, including thyroidectomy, radioiodine ablation, or antithyroid medications, are not trivial therapeutic steps for asymptomatic patients.

This study has 2 practical implications. In patients with suppressed thyrotropin levels receiving thyroxine supplementation, the dose should be reduced whenever possible. Patients with subclinical primary hyperthyroidism need conscientious follow-up to ensure prompt treatment when overt hyperthyroidism appears.

William J. Georgitis, MD
Fitzsimons Army Medical CenterAurora, Colorado, USA


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3. Sawin CT, Castelli WP, Hershman JM, McNamara P, Bacharach P. The aging thyroid. Thyroid deficiency in the Framingham Study. Arch Intern Med. 1985;145:1386-8.

4. Davidson E, Weinberger I, Rotenberg Z, Fuchs J, Agmon J. Atrial fibrillation. Cause and time of onset. Arch Intern Med. 1989;149:457-9.

5. Nakazawa HK, Sakurai K, Hamada N, Momotani N, Ito K. Management of atrial fibrillation in the post-thyrotoxic state. Am J Med. 1982;72:903-6.