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Department of Ophthalmology, University Hospital Essen, Essen, Germany
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Background: Selenium (Se) is of importance for regular functioning of the immune system and thyroid gland, and may have a health effect in mild Graves' ophthalmopathy (GO). Objective: As the Se status declines in inflammation, we analyzed whether GO activity or severity affects the Se status of patients. Methods: Serum Se and selenoprotein P (SePP) concentrations were retrospectively determined in 84 consecutive GO patients before treatment and compared to their clinical activity score (CAS) and severity of eye changes (NOSPECS) status, and to the concentrations of autoantibodies targeting the TSH receptor (TRAK) or the IGF1 receptor (IGF1R-aAB). Results: Serum Se and SePP were linearly associated, indicating a suboptimal Se status of our patients. In comparison to data from other European cohorts, the majority of GO patients had a relatively poor Se status ([Se] ± SD; 70.0 ± 23.8 µg/l), below the threshold needed for full expression of selenoproteins. TRAK were inversely associated with Se concentrations, while IGF1R-aAB titers were not associated with Se. Neither Se nor SePP concentrations differed between GO patients with severe versus mild or active versus inactive disease, or showed significant associations with the CAS or NOSPECS values. Conclusion: GO patients are at risk of a low Se status, yet disease severity or activity does not seem to affect Se or SePP concentrations directly. However, as the retrospective nature of the analysis does not allow conclusions on a potential causative role of Se on Graves' disease or GO risk, these results neither support nor discourage adjuvant Se supplementation attempts.
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Introduction: Injection of 3-iodothyronamine into experimental animals profoundly affects their metabolism and body temperature. As 3-iodothyronamine is rapidly acetylated in vivo after injection, it was hypothesized that the metabolites N- or O-acetyl-3-iodothyronamines could constitute the active hormones. Methods: Adult male mice were injected once daily with one of the metabolites (5 mg/kg body weight intraperitoneally dissolved in 60% DMSO in PBS) or solvent. Metabolism was monitored by indirect calorimetry, body temperature by infrared thermography, and body composition by nuclear magnetic resonance analysis. Signaling activities in brown fat or liver were assessed by studying target gene transcription by qPCR including uncoupling protein 1 or deiodinase type 1 or 2, and Western blot. Results: The markers of metabolism, body composition, or temperature tested were similar in the mice injected with solvent and those injected with one of the acetylated 3-iodothyronamines. Conclusions: In our experimental setup, N- and O-acetyl-3-iodothyronamine do not constitute compounds contributing to the metabolic or temperature effects described for 3-iodothyronamine. The acetylation of 3-iodothyronamine observed in vivo may thus rather serve degradation and elimination purposes.
Center of Brain, Behavior and Metabolism (CBBM)/Medizinische Klinik I, University of Lübeck, Lübeck, Germany
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Center of Brain, Behavior and Metabolism (CBBM)/Medizinische Klinik I, University of Lübeck, Lübeck, Germany
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Institute for Experimental Endocrinology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
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Objectives: Thyronamines are decarboxylated and deiodinated metabolites of thyroid hormones (THs). Of all possible thyronamine variants, only 3-iodothyronamine (3-T<sub>1</sub>AM) and iodine-free thyronamine (T<sub>0</sub>AM) have been detected in vivo. While intensive research has been done on the (patho-)physiological action of 3-T<sub>1</sub>AM, the role of T<sub>0</sub>AM has been studied less intensively. Study Design: We determined whether a single pharmacological dose (50 mg/kg, i.p.) or repeated administration (5 mg/kg/day, i.p., for 7 days) of T<sub>0</sub>AM affects metabolism, cardiovascular function, or thermoregulation in male C57BL/6J mice. Since selenium (Se) is important for proper TH function and Se metabolism is affected by TH, we additionally analyzed Se concentrations in liver, serum, and kidney using total reflection X-ray analysis. Results: A single injection of T<sub>0</sub>AM had no effect on heart rate, temperature, or activity as assessed by radio telemetry. Likewise, daily administration of T<sub>0</sub>AM did not alter body weight, food or water intake, heart rate, blood pressure, brown adipose tissue thermogenesis, or body temperature, and no significant differences in hepatic glycogen content or mRNA expression of genes involved in cardiovascular function or metabolic control were determined. Also, the X-ray analysis of Se concentrations revealed no significant changes. However, hepatic T<sub>0</sub>AM was significantly increased in the treated animals. Conclusions: In summary, our data demonstrate that T<sub>0</sub>AM elicits no obvious metabolic, cardiovascular, or thermoregulatory activities in mice. As T<sub>0</sub>AM does also not interfere with TH or Se metabolism, we conclude that the deiodination of 3-T<sub>1</sub>AM to T<sub>0</sub>AM constitutes an efficient inactivation mechanism, terminating the actions of the more powerful precursor.
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Background: Several studies have suggested that selenium may influence the natural history of autoimmune thyroiditis (AIT). Recently, IFNγ-inducible chemokines (CXCL-9, -10 and -11) were shown to be elevated in AIT patients. Objective: This prospective, randomized, controlled study was conducted to evaluate the effect of two doses of selenomethionine (Semet; 80 or 160 µg/day) versus placebo in euthyroid women with AIT, in terms of reduction of anti-thyroid antibodies, CXCL-9, -10 and -11 and improvement of thyroid echogenicity, over 12 months. Patients and Methods: Sixty patients, aged 21-65 years, were equally randomized into 3 groups: placebo, 80 µg/day of Semet (80-Semet) or 160 µg/day of Semet (160-Semet). Results: Anti-thyroperoxidase antibody (TPOAb) levels remained unaffected by Semet supplementation; anti-thyroglobulin antibody levels showed a significant reduction in the 160-Semet and the placebo group at 12 months. No significant change in thyroid echogenicity, thyroid volume and quality of life was observed within and between the groups. Subclinical hypothyroidism was diagnosed in 2 patients of the placebo group versus 1 patient in each Semet group. Serum CXCL-9 and -10 were significantly reduced in both Semet groups at 6 and 12 months, while they remained unchanged or increased in the placebo group. CXCL-11, TNFα and IFNγ showed a transient decrease at 6 months in both Semet groups but returned nearly to the basal levels at 12 months. Conclusions: Semet supplementation had no positive effect on thyroid echogenicity or TPOAb in our patients. However, we observed a Semet-dependent downregulation of the IFNγ-inducible chemokines, especially CXCL-9 and -10, which may serve as helpful biomarkers in future selenium supplementation trials.
Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Institute of Clinical Medicine, Faculty of Health and Clinical Sciences, Copenhagen University, Copenhagen, Denmark
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QualityMetric Inc, Johnston, Lincoln, Rhode Island, USA
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Internal Medicine Research Unit, University Hospital of Southern Jutland, Aabenraa, Denmark
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Institute of Clinical Medicine, Faculty of Health and Clinical Sciences, Copenhagen University, Copenhagen, Denmark
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Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Purpose
We investigated whether selenium supplementation improves quality-of-life (QoL) in patients with autoimmune thyroiditis (ID:NCT02013479).
Methods
We included 412 patients ≥18 years with serum thyroid peroxidase antibody (TPOAb) level ≥100 IU/mL in a multicentre double-blinded randomised clinical trial. The patients were allocated 1:1 to daily supplementation with either 200 μg selenium as selenium-enriched yeast or matching placebo tablets for 12 months, as add-on to levothyroxine (LT4) treatment. QoL, assessed by the Thyroid-related Patient-Reported-Outcome questionnaire (ThyPRO-39), was measured at baseline, after 6 weeks, and after 3, 6, 12, and 18 months.
Results
In total, 332 patients (81%) completed the intervention period, of whom 82% were women. Although QoL improved during the trial, no difference in any of the ThyPRO-39 scales was found between the selenium group and the placebo group after 12 months of intervention. In addition, employing linear mixed model regression no difference between the two groups was observed in the ThyPRO-39 composite score (28.8 (95% CI: 24.5–33.6) and 28.0 (24.5–33.1), respectively; P = 0.602). Stratifying the patients according to duration of the disease at inclusion, ThyPRO-39 composite score, TPOAb level, or selenium status at baseline did not significantly change the results. TPOAb levels after 12 months of intervention were lower in the selenium group than in the placebo group (1995 (95% CI: 1512–2512) vs 2344 kIU/L (1862–2951); P = 0.016) but did not influence LT4 dosage or free triiodothyronine–free thyroxine ratio.
Conclusion
In hypothyroid patients on LT4 therapy due to autoimmune thyroiditis, daily supplementation with 200 μg selenium or placebo for 12 months improved QoL to the same extent.
