Thyroid response to cold activation of brown adipose tissue in Greenlanders and Danes

INTRODUCTION: Brown adipose tissue (BAT) thermogenesis is mediated by sympathetic nervous system activation and enhanced by thyroid hormones via upregulation of uncoupling protein 1. Studying thyroid hormone response to cooling in populations with habitual cold exposure may give new insights to the role of thyroid hormones in non-shivering thermogenesis. METHODS: Twenty-one participants (11 Greenlanders, 10 Danes) underwent a cross-over protocol with experimental sessions of cooling and thermal comfort, followed by [18F]FDG positron emission tomography/computed tomography scans. Serial blood samples were collected to assess thyrotropin (TSH), total triiodothyronine (TT3), total thyroxine (TT4), and thyroglobulin (Tg) before, during, and after cooling. RESULTS: Cooling induced an increase in TSH (Danes: 0.24 mIU/L, P < .001; Greenlanders: 0.15 mIU/L, P = .009). TT3 also increased in response to cooling (Danes: 0.15 nmol/L, Greenlanders: 0.09 nmol/L, Pboth < .001). Greenlanders had lower TSH and higher TT3 levels compared to Danes (baseline 0.27 nmol/L, P = .009) with an attenuated TT3 response to cooling (-0.07 nmol/L, P = .009). The T3/T4 ratio was elevated during cold exposure compared to thermoneutral conditions in both Danes (P < .001) and Greenlanders (P = .022), and Greenlanders had consistently higher T3/T4 ratios compared to Danes (baseline, P = .001; after cooling, P = .023). Finally, Tg levels were higher in participants with low- compared to high-BAT volume (7.27 µg/L, P = .008). CONCLUSION: Serial measurements of thyroid hormones and thyroglobulin with gold-standard detection of BAT activity documented distinct thyroid responses to cooling. The findings suggested a physiological preparedness to acute cold exposure in individuals with cold adaptation, irrespective of origin.