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Thyroid hormone (TH) is an important regulator of mammalian metabolism and facilitates cold induced thermogenesis (CIT) in brown adipose tissue (BAT). Profound hypothyroidism or hyperthyroidism lead to alterations in BAT function and CIT. In euthyroid humans the inter-individual variation of thyroid hormones is relatively large. Therefore, we investigated whether levels of free thyroxine (T4) or free triiodothyronine (T3) are positively associated with CIT in euthyroid individuals. We performed an observational study in 79 healthy, euthyroid volunteers (mean age 25.6 years, mean BMI 23.0 kg · m-2). Resting energy expenditure (REE) was measured by indirect calorimetry during warm conditions (EEwarm) and after a mild cold stimulus of two hours (EEcold). CIT was calculated as the difference between EEcold and EEwarm. BAT activity was assessed by 18F-FDG-PET after a mild cold stimulus in a subset of 26 participants. EEcold and CIT were significantly related to levels of free T4 (R2 = 0.11, p=0.0025 and R2 = 0.13, p=0.0011, respectively) but not to free T3 and TSH. Cold induced BAT activity was also associated with levels of free T4 (R2 = 0.21, p=0.018). CIT was approximately fourfold higher in participants in the highest tertile of free T4 as compared to the lowest tertile. Additionally, free T4 was weakly, albeit significantly associated with outdoor temperature seven days prior to the respective study visit (R2 = 0.06, p=0.037). These finding suggests that variations in thyroid hormone levels within the euthyroid range are related to the capability to adapt to cool temperatures and affect energy balance. Keywords: brown adipose tissue; cold adaptation; cold induced thermogenesis; energy expenditure; thyroid hormone; thyroxine.

BACKGROUND: Positron emission tomography (PET) is increasingly applied for in vivo brown adipose tissue (BAT) research in healthy volunteers. To limit the radiation exposure, the injected $^{18}$F-FDG tracer dose should be as low as possible. With simultaneous PET/MR imaging, the radiation exposure due to computed tomography (CT) can be avoided, but more importantly, the PET acquisition time can often be increased to match the more extensive magnetic resonance (MR) imaging protocol. The potential gain in detected coincidence counts, due to the longer acquisition time, can then be applied to decrease the injected tracer dose. The aim of this study was to investigate the minimal $^{18}$F-FDG dose for a 10-min time-of-flight (TOF) PET/MR acquisition that would still allow accurate quantification of supraclavicular BAT volume and activity. METHODS: Twenty datasets from 13 volunteers were retrospectively included from a prospective clinical study. PET emission datasets were modified to simulate step-wise reductions of the original 75 MBq injected dose. The resulting PET images were visually and quantitatively assessed and compared to a 4-min reference scan. For the visual assessment, the image quality and artifacts were scored using a 5-point and a 3-point Likert scale. For the quantitative analysis, image noise and artifacts, BAT metabolic activity, BAT metabolic volume (BMV), and total BAT glycolysis (TBG) were investigated. RESULTS: The visual assessment showed still good image quality for the 35%, 30%, and 25% activity reconstructions with no artifacts. Quantitatively, the background noise was similar to the reference for the 35% and 30% activity reconstructions and the artifacts started to increase significantly in the 25% and lower activity reconstructions. There was no significant difference in supraclavicular BAT metabolic activity, BMV, and TBG between the reference and the 35% to 20% activity reconstructions. CONCLUSIONS: This study indicates that when the PET