Jury Still Out on Whether to Treat Subclinical Hypothyroidism in Elderly

Nancy A. Melville

December 13, 2019

Elderly patients with overt hypothyroidism show a significantly increased risk of all-cause, but not cardiovascular, death in a new meta-analysis; the risk does not extend to subclinical hypothyroidism, however, say the authors.

"In accordance with guidelines, our findings imply that individuals with subclinical hypothyroidism — those who have milder thyroid dysfunction — may not benefit from being treated with synthetic thyroid hormone," coauthor Kashif M. Munir, MD, said in a press statement from the Endocrine Society.

"However, treatment should be considered in individuals diagnosed with hypothyroidism, given increased all-cause mortality," added Munir, associate professor in the division of endocrinology, diabetes, and nutrition at the University of Maryland School of Medicine, Baltimore.

The researchers also acknowledge, however, that "owing to the between-study heterogeneity" observed among the trials included in their meta-analysis, the results "should be interpreted cautiously, and further prospective large-scale high-quality studies are necessary to confirm our findings.

The work was published online December 12 in the Journal of Clinical Endocrinology & Metabolism by Tou-Yuan Tsai, MD, of Dalin Tzu Chi Hospital, Chiayi, Taiwan, and colleagues.

First Meta-Analysis of Mortality Risk With Hypothyroidism in the Elderly

Hypothyroidism is known to increase the risk of cardiac and all-cause mortality in the general population, however, the elderly tend to have less severe clinical responses and most current guidelines therefore only recommend routine treatment if elderly patients are symptomatic or at increased vascular risk.

However, research on the effects of hypothyroidism in the elderly is inconsistent and there have been no previous meta-analyses specifically assessing the link between hypothyroidism and mortality in the elderly, representing a "knowledge gap," say Tsai and coauthors.

"Our meta-analysis is the first to evaluate and confirm the association between hypothyroidism and mortality, specifically focusing on an older population," coauthor Carol Chiung-Hui Peng, MD, also of the University of Maryland, told Medscape Medical News.

For the analysis, Tsai and colleagues evaluated data from 27 cohort studies involving hypothyroidism and all-cause and/or cardiovascular mortality in the elderly population (aged 60 years and older).

Among the more than 1 million participants in the studies, those with hypothyroidism had a higher risk of all-cause mortality compared to those with normal thyroid function (pooled relative risk (RR), 1.26).

Looking at cardiovascular death specifically, however, the relative risk was not significantly different between those with and without hypothyroidism (pooled RR, 1.10; 95% CI, 0.84 - 1.43).

"It was a surprise that we didn't see higher cardiovascular mortality in this meta-analysis," Peng said.

"There were two recently published meta-analyses, focusing on the general population, showing that both overt hypothyroidism and subclinical hypothyroidism were linked to higher all-cause (as well as) cardiovascular mortality," she added.

In subgroup analyses of several recent studies, Tsai and colleagues found the elevated risk of all-cause mortality remained higher with overt hypothyroidism, defined as having decreased free thyroxine (FT4) and elevated thyroid-stimulating hormone (TSH) (pooled RR, 1.10; P = .03). The difference was not significant among those with subclinical hypothyroidism, defined as having a normal FT4 but elevated TSH (pooled RR, 1.14; P = .23).

The subanalysis also showed some geographical differences. The higher risk of all-cause mortality was only noted in studies involving patients from North America and Asia, but not in those from Europe and Oceania.

In addition, the differences in all-cause mortality were not observed in studies including patients aged 80 and older.

Geographic Differences Could Reflect Differing Iodine Intake

Peng noted that the differences in geographic regions could reflect variations in iodine intake in various countries.

"This finding may be related to higher than required iodine intake in the United States and Asia, although there are still different levels of iodine intake within the country," she noted.

"The hypothesis is supported by a recent large observational study in the United States, which showed that a population with high iodine intake was associated with significantly higher all-cause and cardiovascular mortalities," said Peng.

She added that several underlying mechanisms of hypothyroidism could affect mortality in elderly and younger patients alike.

"Hypothyroidism results in a generalized slowing of metabolic processes that affect different systems, such as neurologic, cardiovascular, hematologic, gastrointestinal, musculoskeletal, hematologic, and the skin system," she said. "The dysregulation of various systems may be associated with higher all-cause mortality, not only in the general population but also in the older population."

Further Study to Determine Effect of Subclincal Hypothyroidism on Mortality

The authors note that with significant between-study heterogeneity, more studies are needed to draw more definitive conclusions, particularly in terms of subclinical hypothyroidism.

"The heterogeneity of the studies that evaluated the association between subclinical hypothyroidism and mortality remained high [and] the definition of subclinical hypothyroidism also differed among studies," they write.

"This heterogeneity and inconsistency may have biased the results and contributed to a nonsignificant association between subclinical hypothyroidism and mortality, which prevents drawing a definite conclusion on this issue."

"Further studies are still needed to accurately determine the effect of subclinical hypothyroidism on mortality," they conclude.

J Clin Endocrinol Metab. Published online December 12, 2019. Abstract

For more diabetes and endocrinology news, follow us on Twitter and Facebook.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.