Thyroid Hormone Activates Brown Adipose Tissue and Increases Non-Shivering Thermogenesis--A Cohort Study in a Group of Thyroid Carcinoma Patients

Evie P M Broeders, Guy H E J Vijgen, Bas Havekes, Nicole D Bouvy, Felix M Mottaghy, Marleen Kars, Nicolaas C Schaper, Patrick Schrauwen, Boudewijn Brans, Wouter D van Marken Lichtenbelt, Evie P M Broeders, Guy H E J Vijgen, Bas Havekes, Nicole D Bouvy, Felix M Mottaghy, Marleen Kars, Nicolaas C Schaper, Patrick Schrauwen, Boudewijn Brans, Wouter D van Marken Lichtenbelt

Abstract

Background/objectives: Thyroid hormone receptors are present on brown adipose tissue (BAT), indicating a role for thyroid hormone in the regulation of BAT activation. The objective of this study was to examine the effect of thyroid hormone withdrawal followed by thyroid hormone in TSH-suppressive dosages, on energy expenditure and brown adipose tissue activity.

Subjects/methods: This study was a longitudinal study in an academic center, with a follow-up period of 6 months. Ten patients with well-differentiated thyroid carcinoma eligible for surgical treatment and subsequent radioactive iodine ablation therapy were studied in a hypothyroid state after thyroidectomy and in a subclinical hyperthyroid state (TSH-suppression according to treatment protocol). Paired two-tailed t-tests and linear regression analyses were used.

Results: Basal metabolic rate (BMR) was significantly higher after treatment with synthetic thyroid hormone (levothyroxine) than in the hypothyroid state (BMR 3.8 ± 0.5 kJ/min versus 4.4 ± 0.6 kJ/min, P = 0.012), and non-shivering thermogenesis (NST) significantly increased from 15 ± 10% to 25 ± 6% (P = 0.009). Mean BAT activity was significantly higher in the subclinical hyperthyroid state than in the hypothyroid state (BAT standard uptake value (SUVMean) 4.0 ± 2.9 versus 2.4 ± 1.8, P = 0.039).

Conclusions: Our study shows that higher levels of thyroid hormone are associated with a higher level of cold-activated BAT.

Trial registration: ClinicalTrials.gov NCT02499471.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Consort 2010 flow chart.
Fig 1. Consort 2010 flow chart.
Fig 2. Schematic representation of study measurements…
Fig 2. Schematic representation of study measurements after total thyroidectomy in the Maastricht University Medical Centre.
Blue arrows indicate moment of study measurements. FT4 indicates free thyroxine, TSH indicates thyroid-stimulating hormone, levothyroxine treatment indicates pharmacological levothyroxine suppletion that suppresses endogenous TSH. I131 indicates radioactive iodine, used for radioactive ablation therapy of thyroid gland remnants after thyroid gland resection for well-differentiated thyroid carcinoma. I124 indicates a proton-rich isotope of iodine used as a radiochemical for determination of thyroid gland remnants after thyroid gland resection for well-differentiated thyroid carcinoma.
Fig 3. BAT activity, BMR and NST…
Fig 3. BAT activity, BMR and NST before and after levothyroxine therapy.
Brown adipose tissue (BAT) activity before and after levothyroxine substitution therapy. (A) Basal metabolic rate (BMR) in joules per minute. (B) Non-shivering thermogenesis (NST) before and after levothyroxine replacement therapy. (C) BAT activity in Mean Standard Uptake Values (SUV mean) before and after levothyroxine therapy. Subject indicated with X is also depicted in Fig 2D and 2E. (D) Transversal CT (top) and PET/CT fusion (bottom) slice of the supraclavicular region demonstrating 18F-FDG-uptake in BAT locations (white arrows) after cold exposure in hypothyroid state. (E) Transversal CT (top) and PET/CT fusion (bottom) slice of the supraclavicular region demonstrating 18F-FDG-uptake in BAT locations (white arrows) after cold exposure in subclinical hyperthyroid state.

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