Low 'normal' free T3 thyroid hormone predicts death in older patients even without overt hypothyroid

Low free T3 thyroid hormone (triiodothyronine, FT3), even without overt hypothyroid and still within most 'normal' reference ranges, predicts death from cardiovascular disease and all causes in people over 65 according to a study just published in The Journal of Clinical Endocrinology & Metabolism. The authors state:

"Several alterations in thyroid function test (TFT) results have been associated with mortality in elderly patients...Our aim was to investigate the relationship between TFT results and all-cause and cardiovascular (CV) mortality in aged hospitalized patients."

They measured TSH, free T4, and free T3 (FT3) for 404 patients aged >65 years admitted to the Hospital General, Segovia, Spain for any reason in 2005 and followed the outcomes for seven years, correlating the total survival times, number of deaths, and all-cause and CV mortality with the thyroid function test (TFT) values. The data showed that functionally low free T3 was strongly associated with mortality:

"During the study, 323 patients (80%) died. Kaplan-Meier analysis showed that median survival time for all-cause mortality was significantly lower in patients in the first tertile of serum FT3, in the first tertile of TSH, and in the first tertile of serum free T4 concentrations. Multivariate adjusted Cox regression analysis showed that the history of cancer (hazard ratio, 1.60), age (1.03), and FT3 levels (0.72) were significant factors related to all-cause mortality. The cause of death was known in 202 patients. Of this group, 61 patients (30.2%) died of CV disease. Patients in the first tertile of TSH and FT3 exhibited a significant higher mortality due to CV disease. In the adjusted Cox regression analysis, FT3 was a significant predictor of CV mortality (0.76)."

Medscape Family Medicine quotes from the study:

"Median survival time for all-cause mortality was 3.0, 13.0, and 19.0 months for patients belonging to the first (<3.18 pmol/L), second (3.18> to <3.96 pmol/L), and third (>3.96 pmol/L) tertiles of free T3, respectively (P < .001)."

In the US we use pg/mL to measure free T3. In this study the lowest survival time was associated with less than 3.18 pmol/L which converts to less than 2.1 pg/mL. In my practice I use 3.0-4.5 pg/mL as the desired functional reference range; 2.1 pg/mL is within the 'normal' range of most labs. Medscape also quotes the authors:

"Our results clearly show a significant relationship between TFT results and mortality in aged hospitalized patients not only during hospitalization but also long term after hospital discharge," say Dr. Iglesias and colleagues... The study "confirms this association between low free-T3 levels and all-cause and CV mortality being the most important predictor of 7-year CV mortality in octogenarian patients, even more than age.""

Clinical note: Practitioners should consider not only the effects of suboptimal free T3, but also be diligent in investigating the underlying causes that are making it low. The authors conclude:

"Alterations in TFT results during hospitalization are associated with long-term mortality in elderly patients. In particular, low FT3 levels are significantly related to all-cause and CV mortality."