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

[This corrects the article DOI: 10.1371/journal.pone.0145049.]

TSH suppression aggravates arterial inflammation an F-18-FDG PET study in thyroid carcinoma patients

PurposeWe aimed to investigate the influence of both hypothyroidism and thyroid-stimulating hormone (TSH) suppression on vascular inflammation, as assessed with F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET)/computed tomography (CT).MethodsTen thyroid carcinoma patients underwent an F-18-FDG PET/CT during post-thyroidectomy hypothyroidism and during thyrotropin (TSH) suppression after I-131 (radioiodine) ablation therapy. We analysed the F-18-FDG uptake in the carotids, aortic arch, ascending, descending, and abdominal aorta to investigate the effects of thyroid hormone status on arterial inflammation. Target-to-background ratios (TBRs) corrected for blood pool activity were established for all arterial territories. Results were further compared to euthyroid historic control subjects.ResultsIn general, there was a trend towards higher vascular TBRs during TSH suppression than during hypothyroidism (TBRmax all vessels=1.6 and 1.8, respectively, p=0.058), suggesting a higher degree of arterial inflammation. In concurrence with this, we found increased C-reactive protein (CRP) levels after levothyroxine treatment (CRP=2.9mg/l and 4.8mg/l, p=0.005). An exploratory comparison with euthyroid controls showed significant higher TBRs during TSH suppression for the carotids, aortic arch, thoracic descending aorta, and when all vascular territories were combined (TBR(max)p=0.013, p=0.016, p=0.030 and p=0.018 respectively).ConclusionsArterial inflammation is increased during TSH suppression. This finding sheds new light on the underlying mechanism of the suspected increased risk of cardiovascular disease in patients with TSH suppression

The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity

SummaryThe interest in brown adipose tissue (BAT) as a target to combat metabolic disease has recently been renewed with the discovery of functional BAT in humans. In rodents, BAT can be activated by bile acids, which activate type 2 iodothyronine deiodinase (D2) in BAT via the G-coupled protein receptor TGR5, resulting in increased oxygen consumption and energy expenditure. Here we examined the effects of oral supplementation of the bile acid chenodeoxycholic acid (CDCA) on human BAT activity. Treatment of 12 healthy female subjects with CDCA for 2 days resulted in increased BAT activity. Whole-body energy expenditure was also increased upon CDCA treatment. In vitro treatment of primary human brown adipocytes derived with CDCA or specific TGR5 agonists increased mitochondrial uncoupling and D2 expression, an effect that was absent in human primary white adipocytes. These findings identify bile acids as a target to activate BAT in humans

Schematic representation of study measurements after total thyroidectomy in the Maastricht University Medical Centre.

<p>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.</p

BAT activity, BMR and NST before and after levothyroxine therapy.

<p>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 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145049#pone.0145049.g002" target="_blank">Fig 2D and 2E</a>. (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.</p

Consort 2010 flow chart.

<p>Consort 2010 flow chart.</p