Subclinical Thyroid Disease Associated With Increased Mortality in the Elderly

Both subclinical hypothyroidism and subclinical hyperthyroidism are associated with increased mortality in the elderly, according to a new study. Additionally, a threshold thyroid-stimulating hormone value (>6.35 mIU/L) exists for increased mortality in subclinical hypothyroidism but not in subclinical hyperthyroidism.

The researchers performed a retrospective cohort study with a review of a computerized database of a large healthcare organization. They included in the analysis patients aged >65 years evaluated from 2002-2012 with documented normal free T4 values. The investigators excluded all cases of known thyroid disease or cases in which thyroid medications were dispensed. They performed analysis only on individuals treated for hyperthyroidism or hypothyroidism during the follow-up period.
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The researchers divided subjects 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). They compared all-cause mortality hazard ratio (HR) among the 3 groups, and a subanalysis according to thyroid-stimulating hormone values was performed in those with subclinical hypothyroidism and subclinical hyperthyroidism.

They performed a final analysis on 17440 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 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 >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.

“The major importance of our study is that it provides data on the future risk of all-cause mortality in a large cohort of subjects aged 65 years or more followed up in the community setting and defines the thyroid-stimulating hormone cutoff associated with significantly increased mortality in those with subclinical hypothyroidism,” the researchers concluded, noting the effect of treatment of subclinical hypothyroidism and subclinical hyperthyroidism in this age group should be evaluated in a prospective study.

-Mike Bederka

Reference:
Grossman A, Weiss A, Koren-Morag N, et al. Subclinical thyroid disease and mortality in the elderly: a retrospective cohort study. Am J Med. 2016 Apr;129(4):423-30.