Table 2.

Details of clinical trials investigating effect of Thyroid Axis on energy expenditure/BAT activity.

Authors	Agent	Study Design	Dose	Population	Duration	Measurement of EE/BAT Activity	EffectEE/BAT	Key Findings
Broeders, E. P. M. et al. (29)	Levothyroxine (synthetic thyroid hormone (T4)) and cold exposure.	Longitudinal study.	137.75 ± 23.75 µg/day	10 patients (8 females/2 males) with well-differentiated thyroid carcinoma eligible for surgical treatment and radioactive iodine ablation therapy.	2 conditions: 4-6 months with administration of Levothyroxine (subclinical hyperthyroid state) and measurement 6-8 weeks after surgical removal of the thyroid gland (hypothyroid state).	EE measured by indirect calorimetry. BAT activity measured using FDG-PET/CT analysis.	↑/↑	Significant increase in RMR after treatment in the hyperthyroid state (BMR: 3.8 ± 0.5 kJ/min vs. 4.4 ± 0.6 kJ/min, p = 0.012). NST increased from 15 ± 10% to 25 ± 6% (p = 0.009). Mean BAT activity increased in the subclinical hyperthyroid state (SUV of 4.0 ± 2.9 vs. 2.4 ± 1.8, p = 0.039). Mean Tsk significantly lower in hypothyroid state. High levels of thyroid hormone are associated with a higher level of cold activated BAT.
Heinen, C. A. et al. (30)	TRH or placebo and cold exposure.	Randomized, double-blind, placebo controlled, cross-over.	400µg TRH or 2 mL saline and Mild cold exposure (17°C ± 1°C), or placebo.	16 healthy lean men.	2 scans: 1-3 weeks apart.	BAT activity was measured as standardized FDG uptake and glucose metabolic rate (MRglu) measured using dynamic PET/CT imaging. Measurement of EE not specified.	↔/↔	Experiment #1 at room temp: no significant changes in BAT activity. Experiment #2 at mild cold exposure: BAT glucose uptake visibly higher in 4/9 subjects after TRH compared to placebo. Overall effect is an increase in BAT glucose uptake.

EE, energy expenditure; BMR, basal metabolic rate; NST, non-shivering thermogenesis; BAT, brown adipose tissue; SUV, standard uptake value; Tsk, skin temperature; TRH.