Resolution of Hypothyroidism Restores Cold-Induced Thermogenesis in Humans

Abstract

Background: Hypothyroidism is a frequent endocrine disorder with common symptoms of increased cold sensitivity and unintended weight gain, indicating changes in energy expenditure (EE) and response to cold exposure. Thyroid hormones (TH) play an important role for proper function of brown adipose tissue (BAT) and cold-induced thermogenesis (CIT) in rodents, but the role of hypothyroidism on CIT in humans is uncertain. Methods: This was a prospective observational study. Forty-two patients presenting with subclinical or overt hypothyroidism in whom TH replacement was planned were recruited. Thirty-three patients completed the study. Thermogenesis was measured by indirect calorimetry during warm conditions and after a mild cold stimulus of 90 minutes, both during the hypothyroid state and after at least three months of sufficient TH replacement. CIT was determined as the difference between EE during mildly cold and warm conditions. The primary endpoint was the change of CIT between the hypothyroid and euthyroid state. Results: EE during warm conditions increased from a median of 1330 (interquartile range [IQR] 1251–1433) kcal/24 hours in the hypothyroid state to a median of 1442 (IQR 1294–1579) kcal/24 hours in the euthyroid state (+8.5%; p = 0.0002). EE during mild cold exposure increased from 1399 (IQR 1346–1571) kcal/24 hours to 1610 (IQR 1455–1674) kcal/24 hours (+15%; p < 0.0001). The median CIT was 55 (IQR 1–128) kcal/24 hours at the baseline visit, after restoration of euthyroidism CIT increased by 102% to a median of 111 (IQR 15.5–200) kcal/24 hours ( p = 0.011). Serum levels of free thyroxine at the respective visit and mean outdoor temperature during the preceeding 30 days were significantly associated with CIT ( p = 0.021 and p = 0.001, respectively). Conclusion: Restoring euthyroidism significantly increases CIT in hypothyroid humans.

Free Thyroxine Levels are Associated with Cold Induced Thermogenesis in Healthy Euthyroid Individuals

“…Previously, we and others were able to demonstrate that REE is reduced in hypothyroidism and that restoring euthyroidism normalizes REE in humans (17,28). Here, higher levels of free T4 within the reference range did not lead to higher REE at room temperature in euthyroid individuals, which is in line with a recent study in a larger cohort (29).…”

“…Importantly, the main stimulus of CIT in adult humans appears to be cool environmental temperatures ( 21 , 35 , 36 ). Previously, we could demonstrate that in hypothyroid individuals the effect of environmental temperatures on CIT seems to be abrogated ( 17 ). Therefore, we would like to speculate that thyroid hormones facilitate the dynamic adaptations to cool temperatures also in humans.…”

“…Recently, we demonstrated that CIT is reduced in hypothyroid individuals and can be restored by sufficient thyroid hormone replacement ( 17 ). In the present study, we investigated whether levels of thyroid hormones within the reference range in healthy, euthyroid individuals are connected to EE at warm and cold temperatures.…”

Thermogenesis in Adipose Tissue Activated by Thyroid Hormone

“…TH plays a critical role in thermogenic response to the cold. TH replacement in hypothyroid patients significantly increases energy expenditure at room temperature and even more during mild cold exposure [87]. However, a study with thyroid cancer patients undergoing thyroidectomy showed that TH replacement did not consistently increase energy expenditure [88], possibly due to suppression of catecholamine synthesis and adrenergic response in the hyperthyroid state [88,89].…”

Climate Change and Obesity

“…Thyroid hormone regulates the basal metabolic rate and energy expenditure. Cold-induced thermogenesis is higher in euthyroid compared to hypothyroid individuals 39 .…”