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PURPOSE: We aimed to investigate the influence of both hypothyroidism and thyroid-stimulating hormone (TSH) suppression on vascular inflammation, as assessed with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT). METHODS: Ten thyroid carcinoma patients underwent an 18F-FDG PET/CT during post-thyroidectomy hypothyroidism and during thyrotropin (TSH) suppression after 131I (radioiodine) ablation therapy. We analysed the 18F-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. RESULTS: In 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 = 2.9 mg/l and 4.8 mg/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 (TBRmaxp = 0.013, p = 0.016, p = 0.030 and p = 0.018 respectively). CONCLUSIONS: Arterial 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.
Asunto(s)
Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/terapia , Tirotropina/antagonistas & inhibidores , Adulto , Anciano , Arteritis , Proteína C-Reactiva/análisis , Femenino , Fluorodesoxiglucosa F18 , Humanos , Hipotiroidismo/complicaciones , Hipotiroidismo/diagnóstico por imagen , Hipotiroidismo/etiología , Inflamación/complicaciones , Radioisótopos de Yodo , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radiofármacos , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Tiroxina/uso terapéuticoRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0145049.].
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OBJECTIVE: Human brown adipose tissue (BAT) activity decreases with age and obesity. In addition to uncoupling protein 1 (UCP1), several genetic markers of BAT in humans have been published. However, the link between human BAT activity and genetic markers has been inadequately explored. METHODS: White adipose tissue (WAT) and BAT biopsies were obtained from 16 patients undergoing deep neck surgery. In vitro differentiated adipocytes were used to measure norepinephrine-stimulated mitochondrial uncoupling as a measure of in vitro BAT activity. Gene expression was determined in adipose tissue biopsies. RESULTS: Norepinephrine increased in vitro BAT activity in adipocytes derived from human BAT, and this increase was abolished by propranolol. Furthermore, in vitro BAT activity showed a negative correlation to age and BMI. UCP1 messenger RNA (mRNA) expression showed a positive correlation to in vitro BAT activity, while zinc finger protein of cerebellum 1 (ZIC1) mRNA showed a negative correlation to in vitro BAT activity. In human BAT biopsies, UCP1 mRNA showed negative correlations to age and BMI, while ZIC1 mRNA showed positive correlations to age and BMI. CONCLUSIONS: Differentiated adipocytes derived from human BAT maintain intrinsic characteristics of the donor. High ZIC1 mRNA does not necessarily reflect high BAT activity.
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Tejido Adiposo Pardo/metabolismo , Marcadores Genéticos/genética , Adulto , Anciano , Animales , Diferenciación Celular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
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.
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Tejido Adiposo Pardo/metabolismo , Termogénesis/efectos de los fármacos , Hormonas Tiroideas/farmacología , Neoplasias de la Tiroides/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hormonas Tiroideas/administración & dosificación , Hormonas Tiroideas/sangreRESUMEN
The 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.