Hypothyroidism Limits Adaptation to Cold Environments

Nancy A. Melville

April 25, 2019

Patients with overt and even subclinical hypothyroidism show reductions in energy expenditure that can affect sensitivity to cold, but successful treatment to normalize thyroid hormone levels reverses the overriding process of cold-induced thermogenesis, new research shows.

"We...speculate that hypothyroidism limits the adaptation to environmental cold exposure in humans," say Claudia Irene Maushart, University Hospital Basel, Switzerland, and colleagues in their article published in the April issue of in Thyroid.

"Our study is the first to investigate the effect on cold-induced thermogenesis in a large group of people, initially with mild to moderate hypothyroidism and after restoration of euthyroidism," senior author Matthias Johannes Betz, MD, Department of Endocrinology, Diabetes, and Metabolism, also at University Hospital Basel, told Medscape Medical News.

"Taken together, this study shows that even moderate levels of hypothyroidism reduce cold-induced thermogenesis in humans and that sufficient replacement of thyroid hormone restores it."

Study Details

While physical activity and basal metabolic rate make up most of the total energy expenditure of the body, cold-induced thermogenesis (also known as "adaptive thermogenesis") is another influential factor that helps maintain the body's core temperature by activating adipocytes, contributing to total energy expenditure.

Studies in mice have shown thyroid hormones can affect cold-induced thermogenesis; however, research in humans has been conflicting.

The current study involved 42 patients with subclinical or overt hypothyroidism, defined as thyrotropin (TSH) levels > 4.5 mIU/L or free thyroxine (fT4) levels < 10 pmol/L, and for whom thyroid hormone replacement was clinically indicated.

Those who were obese (body mass index [BMI] > 30 kg/m2), had uncontrolled diabetes, or had received glucocorticoids were excluded.

Participants were enrolled within 2 weeks of diagnosis, and replacement therapy with levothyroxine was started, as indicated by the treating physician.

Energy expenditure was measured noninvasively by indirect calorimetry for 30 minutes with a ventilated hood calorimeter while study participants were exposed to warm conditions.

Thereafter, a mild cold stimulus of 90 minutes' duration was applied with a water-circulating cooling system placed on their midsection. The temperature of the water was continuously reduced to a minimal temperature of 14ºC. During the last 30 minutes of cold exposure, energy expenditure was measured again.

"All patients tolerated the cooling procedure well and care was taken to avoid shivering," the authors write.

The same tests were performed at least 3 months after sufficient thyroid hormone replacement had been reached.

Energy Expenditure Increases After Thyroid Hormone Replacement

Among the 33 patients who completed the study, energy expenditure during the warm exposures increased from a median of 1330 kcal/24 hours at baseline to a median of 1442 kcal/24 hours in the normal thyroid state (+8.5%; P = .0002).

Even greater energy expenditure increases were seen during mild cold exposure, from 1399 kcal/24 hours to 1610 kcal/24 hours (+15%; P < .0001).

The authors calculated cold-induced thermogenesis (defined as the difference between energy expenditure during mildly cold and warm conditions) and they found that cold-induced thermogenesis increased by 102%, from a median of 55 kcal/24 hours at baseline to a median of 111 kcal/24 hours after normal thyroid levels were reached (P = .011).

The findings indicate that "cold-induced thermogenesis is reduced in spontaneously hypothyroid patients and substitution of T4 in a dose to restore euthyroid thyroid levels significantly increases cold-induced thermogenesis," they note.

In addition, they investigated the known influence of seasonal changes in outdoor temperatures on cold-induced thermogenesis and assessed mean outdoor temperatures during the preceding 30 days of each visit.

Those results showed a significant association between outdoor temperatures and cold-induced thermogenesis (P = .001). 

Finally, serum fT4 levels at each visit likewise were associated with cold-induced thermogenesis (P = .021).

The combination of cold and warm outdoor temperatures, along with association with free T4, account for as much as 75% of the variation of cold-induced thermogenesis, the authors explain.

Nevertheless they stress that it will be "important to continue research in this field as many patients being treated for hypothyroidism still do not recover fully to their baseline well-being."

The study was funded by a Young Independent Investigator grant from the Goldschmidt-Jacobson Foundation, University of Basel, and Swiss National Science Foundation.

Thyroid. 2019;29:493-501. Abstract

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