The association between subclinical hypothyroidism and hyperthyroidism and mortality in the elderly is poorly defined. This study was designed to evaluate the association between subclinical hypothyroidism and subclinical hyperthyroidism and mortality in the elderly and to define the thyroid-stimulating hormone values associated with excess mortality in the elderly.
Methods
We performed a retrospective cohort study with a review of a computerized database of a large health care organization. Patients aged more than 65 years evaluated in the years 2002 to 2012 with documented normal free T4 values were included in the analysis. All cases of known thyroid disease or cases in which thyroid medications were dispensed were excluded. Analysis was performed only on individuals who were not treated for hyperthyroidism or hypothyroidism during the follow-up period. Subjects were divided into 3 groups based on thyroid-stimulating hormone values: normal (normal thyroid-stimulating hormone), subclinical hypothyroidism (thyroid-stimulating hormone >4.2 mIU/L), and subclinical hyperthyroidism (thyroid-stimulating hormone <0.35 mIU/L). All-cause mortality hazard ratio (HR) was compared among the 3 groups, and a subanalysis according to thyroid-stimulating hormone values was performed in those with subclinical hypothyroidism and subclinical hyperthyroidism.
Results
A final analysis was performed on 17,440 individuals with subclinical thyroid disease (538 with subclinical hyperthyroidism [3.1%], 1956 with subclinical hypothyroidism [11.2%], 14,946 normal cases [85.7%], average age of 83 years, 10,289 were women) who were followed up for 10 years. Both subclinical hypothyroidism (HR, 1.75; confidence interval [CI], 1.63-1.88) and subclinical hyperthyroidism (HR, 2.33; CI, 2.08-2.63) were associated with significantly increased mortality, and this association persisted on multivariate analysis (subclinical hypothyroidism HR, 1.68; CI, 1.56-1.8, subclinical hyperthyroidism HR, 1.93; CI, 1.7-2.17). Crude mortality was elevated at 1, 2, and 5 years, but this association seemed to decrease as time from initial analysis increased (most significant association at 1 year). Thyroid-stimulating hormone values greater than 6.38 mIU/L were associated with the highest mortality in those with subclinical hypothyroidism after multivariate adjustment (HR, 1.708; CI, 1.38-2.12), whereas in subclinical hyperthyroidism, no threshold for increased mortality was identified. Mortality was higher.
Conclusions
Both subclinical hypothyroidism and subclinical hyperthyroidism are associated with increased mortality in the elderly. A threshold thyroid-stimulating hormone value (>6.35 mIU/L) exists for increased mortality in subclinical hypothyroidism, but not in subclinical hyperthyroidism.
The association between subclinical hypothyroidism and mortality is well established in young individuals. Yet, in individuals aged more than 65 years, the association between subclinical hypothyroidism and ischemic heart disease or mortality is far less convincing. Several studies failed to find any association between subclinical hypothyroidism and mortality in this population, whereas others found an association at thyroid-stimulating hormone values greater than 10mIU/L. In addition, it has been suggested that hypothyroidism may be associated with decreased mortality in those aged more than 85 years irrespective of baseline morbidity, although this has not been substantiated regarding subclinical hypothyroidism. All of the studies evaluating the association between subclinical hypothyroidism and mortality did not evaluate cause-specific mortality, but rather all-cause mortality. Because of the lack of large-scale studies in the elderly, the association between subclinical hypothyroidism and mortality in this population is less clear, and this is particularly true at thyroid-stimulating hormone values less than 10 mIU/L.
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-Alon Grossman, MD, MHA, Avraham Weiss, MD, Nira Koren-Morag, PhD, Ilan Shimon, MD, Yichayaou Beloosesky, MD, Joseph Meyerovitch, MD
This article originally appeared in the April 2016 issue of The American Journal of Medicine.
