Elevated free T4 predicts death in older men

SAN FRANCISCO – Higher free thyroxine levels may predict all-cause mortality in older men who do not have thyroid disease, researchers from Perth, Australia, have found.

From 2001 to 2004, they checked levels of thyroid hormones in 3,888 community-dwelling men in Perth 70-89 years old and free of thyroid disease, then followed them for a mean of 6.4 years; 837 (22%) died through 2010.

Men who died had baseline thyroid-stimulating hormone (TSH) levels comparable to those who did not (2.4 vs. 2.3 mIU/L), but significantly higher mean baseline free thyroxine (FT4) levels (16.2 vs. 15.8 pmol/L).

After adjustment for age, smoking, body mass index, waist-to-hip ratio, creatinine, hypertension, diabetes, dyslipidemia, and cardiovascular disease, higher baseline FT4 levels – of at least 17.32 pmol/L – increased the risk of all-cause mortality significantly, by 21%. Baseline TSH levels did not predict mortality.

The finding has "made us think much more carefully about thyroid hormone. This is observational data, and we need to look at it a bit more thoroughly, but it’s certainly shifted us away from thinking that if a man’s [TSH] level is good," there’s nothing to worry about, said lead investigator Dr. Bu Yeap, an endocrinologist and professor at the University of Western Australia, Fremantle.

"The point for physicians might be that if they see someone in clinic with a normal TSH, and a free T4 that’s in the high end of the normal range, that should be a trigger to look very carefully at that man’s underlying health and see if there are any risk factors for cardiovascular disease or any other ill health that can be carefully addressed and managed. The standard workup" now probably doesn’t always include FT4, Dr. Yeap said at the Endocrine Society’s annual meeting.

"Others have published studies saying there’s actually no mortality association with free T4. I think we are seeing this now because we have a large cohort of men and a large number of deaths, so we have a better chance of seeing an association if it’s present," Dr. Yeap said.

It’s unknown for now what the men died of. "We are still cleaning the data for the cause-specific mortality," he said.

Even so, the relationship still held true when men with subclinical hyper- or hypothyroidism were excluded from the analysis; higher baseline FT4 remained independently associated with all-cause mortality in 3,445 euthyroid men (adjusted HR, 1.21).

Free T4 "may be a biomarker. It may be a contributing factor. If it’s a contributing factor, it’s probably that the body is seeing a marginal excess of thyroid hormone for a long period of time. We know that excess thyroid hormone is bad for the cardiovascular system; having more free T4 may actually be deleterious to other body systems, as well," Dr. Yeap said.

The men were members of the Health in Men Study, an ongoing observational study of older men in Western Australia.

Dr. Yeap and the other investigators had no disclosures. Foundations and the Australian government funded the work.

aotto@frontlinemedcom.com

SAN FRANCISCO – Higher free thyroxine levels may predict all-cause mortality in older men who do not have thyroid disease, researchers from Perth, Australia, have found.

From 2001 to 2004, they checked levels of thyroid hormones in 3,888 community-dwelling men in Perth 70-89 years old and free of thyroid disease, then followed them for a mean of 6.4 years; 837 (22%) died through 2010.

Men who died had baseline thyroid-stimulating hormone (TSH) levels comparable to those who did not (2.4 vs. 2.3 mIU/L), but significantly higher mean baseline free thyroxine (FT4) levels (16.2 vs. 15.8 pmol/L).

After adjustment for age, smoking, body mass index, waist-to-hip ratio, creatinine, hypertension, diabetes, dyslipidemia, and cardiovascular disease, higher baseline FT4 levels – of at least 17.32 pmol/L – increased the risk of all-cause mortality significantly, by 21%. Baseline TSH levels did not predict mortality.

The finding has "made us think much more carefully about thyroid hormone. This is observational data, and we need to look at it a bit more thoroughly, but it’s certainly shifted us away from thinking that if a man’s [TSH] level is good," there’s nothing to worry about, said lead investigator Dr. Bu Yeap, an endocrinologist and professor at the University of Western Australia, Fremantle.

"The point for physicians might be that if they see someone in clinic with a normal TSH, and a free T4 that’s in the high end of the normal range, that should be a trigger to look very carefully at that man’s underlying health and see if there are any risk factors for cardiovascular disease or any other ill health that can be carefully addressed and managed. The standard workup" now probably doesn’t always include FT4, Dr. Yeap said at the Endocrine Society’s annual meeting.

"Others have published studies saying there’s actually no mortality association with free T4. I think we are seeing this now because we have a large cohort of men and a large number of deaths, so we have a better chance of seeing an association if it’s present," Dr. Yeap said.

It’s unknown for now what the men died of. "We are still cleaning the data for the cause-specific mortality," he said.

Even so, the relationship still held true when men with subclinical hyper- or hypothyroidism were excluded from the analysis; higher baseline FT4 remained independently associated with all-cause mortality in 3,445 euthyroid men (adjusted HR, 1.21).

Free T4 "may be a biomarker. It may be a contributing factor. If it’s a contributing factor, it’s probably that the body is seeing a marginal excess of thyroid hormone for a long period of time. We know that excess thyroid hormone is bad for the cardiovascular system; having more free T4 may actually be deleterious to other body systems, as well," Dr. Yeap said.

The men were members of the Health in Men Study, an ongoing observational study of older men in Western Australia.

Dr. Yeap and the other investigators had no disclosures. Foundations and the Australian government funded the work.

aotto@frontlinemedcom.com

SAN FRANCISCO – Higher free thyroxine levels may predict all-cause mortality in older men who do not have thyroid disease, researchers from Perth, Australia, have found.

From 2001 to 2004, they checked levels of thyroid hormones in 3,888 community-dwelling men in Perth 70-89 years old and free of thyroid disease, then followed them for a mean of 6.4 years; 837 (22%) died through 2010.

Men who died had baseline thyroid-stimulating hormone (TSH) levels comparable to those who did not (2.4 vs. 2.3 mIU/L), but significantly higher mean baseline free thyroxine (FT4) levels (16.2 vs. 15.8 pmol/L).

After adjustment for age, smoking, body mass index, waist-to-hip ratio, creatinine, hypertension, diabetes, dyslipidemia, and cardiovascular disease, higher baseline FT4 levels – of at least 17.32 pmol/L – increased the risk of all-cause mortality significantly, by 21%. Baseline TSH levels did not predict mortality.

The finding has "made us think much more carefully about thyroid hormone. This is observational data, and we need to look at it a bit more thoroughly, but it’s certainly shifted us away from thinking that if a man’s [TSH] level is good," there’s nothing to worry about, said lead investigator Dr. Bu Yeap, an endocrinologist and professor at the University of Western Australia, Fremantle.

"The point for physicians might be that if they see someone in clinic with a normal TSH, and a free T4 that’s in the high end of the normal range, that should be a trigger to look very carefully at that man’s underlying health and see if there are any risk factors for cardiovascular disease or any other ill health that can be carefully addressed and managed. The standard workup" now probably doesn’t always include FT4, Dr. Yeap said at the Endocrine Society’s annual meeting.

"Others have published studies saying there’s actually no mortality association with free T4. I think we are seeing this now because we have a large cohort of men and a large number of deaths, so we have a better chance of seeing an association if it’s present," Dr. Yeap said.

It’s unknown for now what the men died of. "We are still cleaning the data for the cause-specific mortality," he said.

Even so, the relationship still held true when men with subclinical hyper- or hypothyroidism were excluded from the analysis; higher baseline FT4 remained independently associated with all-cause mortality in 3,445 euthyroid men (adjusted HR, 1.21).

Free T4 "may be a biomarker. It may be a contributing factor. If it’s a contributing factor, it’s probably that the body is seeing a marginal excess of thyroid hormone for a long period of time. We know that excess thyroid hormone is bad for the cardiovascular system; having more free T4 may actually be deleterious to other body systems, as well," Dr. Yeap said.

The men were members of the Health in Men Study, an ongoing observational study of older men in Western Australia.

Dr. Yeap and the other investigators had no disclosures. Foundations and the Australian government funded the work.

aotto@frontlinemedcom.com