Objective: Selenium (Se) in the form of selenocysteine is an essential component of the family of the detoxifying enzymes glutathione peroxidase (Gpx) and of the iodothyronine selenodeiodinases that catalyse the extrathyroidal production of tri-iodothyronine (T 3 ). Thus, Se deficiency may seriously influence the generation of free radicals, the conversion of thyroxine (T 4 ) to T 3 and the autoimmune process. Therefore, we performed a randomised, placebo-controlled prospective study to investigate the effects of Se treatment on patients with autoimmune thyroiditis (AIT). Design and methods: Sixty five patients aged 22-61 years (median age 48 years) with AIT were recruited into two groups. Group I (Gr I) ðn ¼ 34Þ was treated with selenomethionine (Seme) 200 mg, plus L-thyroxine (LT 4 ) to maintain TSH levels between 0.3-2.0 mU/l, whereas group II (Gr II) ðn ¼ 31Þ received LT 4 plus placebo over a period of 6 months. Moreover, the pharmacokinetics of Seme were studied in 10 patients and eight volunteers at baseline and 2 h, 4 h, 6 h and 24 h after oral administration of a 200 mg tablet of Seme. Finally, Se levels were measured at the end of the study in some patients of both groups and their results were correlated with thyroid hormone levels. Results: In the pharmacokinetics study, basal serum concentration of Se ð75^6 mg=lÞ was within the reference range (70 -125 mg/l), it promptly increased at 2 h, peaked at 4 h ð147^17 mg=l; P , 0:0001Þ and it was abundant in serum at 24 h. In Gr I, antibodies against thyroid peroxidase (anti-TPO) levels showed an overall decrease of 46% at 3 months (from 1875^1039 U=l to 1013^382 U=l; P , 0:0001) and of 55.5% at 6 months. In Gr II the overall decrease of anti-TPO amounted to 21% at 3 months and to 27% at 6 months (from 1758^917 U=l to 1284^410 U=l; P , 0:005). There were no significant changes of antibodies against thyroglobulin levels between the groups. At the end of this study Se levels were found to be statistically significantly increased in Gr I (n = 9/34) compared with Gr II ðn ¼ 11=31Þ ð97^8:4 vs 79^8; P , 0:01Þ but no correlation with thyroid hormone was found. Conclusions: Seme is proven to be rapidly absorbed by the gastrointestinal tract. It appears to be useful as adjunctive therapy with LT 4 in the treatment of AIT. The exact mechanism(s) is not very well determined, it might enhance the activity of detoxifying enzymes and enforce the defense against oxidative stress.
Objective: Thyroid function parameters have been associated with obesity, but associations with the type of adiposity have not been examined. We used ultrasound (US) to assess regional adiposity and investigated associations of thyroid function with parameters of central obesity. Design: Cross-sectional study. Methods: A total of 303 apparently healthy individuals (age 42.9G8.8, body mass index (BMI) 19.0-43.3, median 26.2 kg/m 2 , 181 women) were examined for indices of the metabolic syndrome. BMI, waist and hip circumference, abdominal subcutaneous fat (SF), and preperitoneal fat (PF) layer was estimated. TSH, free thyroxine (fT 4 ), triiodothyronine (T 3 ), thyroid autoantibodies, insulin, glucose, and lipid levels were measured. Subjects receiving T 4 (9.2%) were excluded. Results: SF and SF/PF ratio were inversely correlated with fT 4 levels (rZK0.169, PZ0.023, rZK0.193, PZ0.009 respectively). In multivariate analysis, fT 4 was a predictor of SF and SF/PF, independently of age, sex, and smoking. SF correlated with TSH levels (rZ0.149, PZ0.037). PF and SF were positively associated with T 3 levels (rZ0.245, PZ0.004 and rZ0.189, PZ0.019 respectively). T 3 levels were positively associated with BMI (rZ0.257, PZ0.0004), waist perimeter (rZ0.324, P!0.0001), and waist-to-hip ratio (WHR; rZ0.363, P!0.0001). The T 3 /fT 4 ratio was positively correlated with SF (rZ0.182, PZ0.028), WHR (rZ0.267, PZ0.0003), and BMI (rZ0.146, PZ0.043). Conclusions: Increasing SF accumulation as assessed by US is associated with lower fT 4 and higher TSH levels among euthyroid slightly overweight individuals. These associations indicate that subtle variation in thyroid function may participate in regional adiposity.
BackgroundThere have been increasing indications about an epigenetically-based elevated predisposition of assisted reproductive technology (ART) offspring to insulin resistance, which can lead to an unfavorable cardio-metabolic profile in adult life. However, the relevant long-term systematic molecular studies are limited, especially for the IntraCytoplasmic Sperm Injection (ICSI) method, introduced in 1992. In this study, we carefully defined a group of 42 prepubertal ICSI and 42 naturally conceived (NC) children. We assessed differences in their metabolic profile based on biochemical measurements, while, for a subgroup, plasma metabolomic analysis was also performed, investigating any relevant insulin resistance indices.Methods & ResultsAuxological and biochemical parameters of 42 6.8±2.1 yrs old ICSI-conceived and 42 age-matched controls were measured. Significant differences between the groups were determined using univariate and multivariate statistics, indicating low urea and low-grade inflammation markers (YKL-40, hsCRP) and high triiodothyronine (T3) in ICSI-children compared to controls. Moreover, plasma metabolomic analysis carried out for a subgroup of 10 ICSI- and 10 NC girls using Gas Chromatography-Mass Spectrometry (GC-MS) indicated clear differences between the two groups, characterized by 36 metabolites linked to obesity, insulin resistance and metabolic syndrome. Notably, the distinction between the two girl subgroups was accentuated when both their biochemical and metabolomic measurements were employed.ConclusionsThe present study contributes a large auxological and biochemical dataset of a well-defined group of pre-pubertal ICSI-conceived subjects to the research of the ART effect to the offspring's health. Moreover, it is the first time that the relevant usefulness of metabolomics was investigated. The acquired results are consistent with early insulin resistance in ICSI-offspring, paving the way for further systematic investigations. These data support that metabolomics may unravel metabolic differences before they become clinically or biochemically evident, underlining its utility in the ART research.
Brain-derived neurotrophic factor (BDNF) is an essential facilitator of neuronal plasticity. By counteracting the adverse effects of excessive stress-induced glucocorticoid signaling, BDNF has been implicated as a resilience factor to psychopathology caused by chronic stress. Insights into the effects of acute stress on peripheral BDNF levels in humans are inconclusive. The short-term interplay between BDNF and cortisol in response to acute psychosocial stress remains unexplored. Furthermore, it is unknown whether mental training that is effective at reducing cortisol reactivity can also influence BDNF during acute stress. In the current study, we investigated serum BDNF levels during an acute psychosocial stress paradigm, the Trier Social Stress Test (TSST), in 301 healthy participants (178 women, mean age = 40.65) recruited as part of the ReSource Project, a large-scale mental training study consisting of three distinct 3-month training modules. Using a cross-sectional study design, we first examined the relationship between BDNF and salivary cortisol in a control group with no mental training. Subsequent analyses focused on differences in BDNF stress levels between control and mental training groups. We show that serum BDNF is indeed stress-sensitive, characterized by a significant post-stress increase and subsequent decline to recovery. While respective increases in BDNF and cortisol were not associated, we found two indications for an antagonistic relationship. Higher BDNF peaks after stress were associated with steeper cortisol recovery. On the other hand, the magnitude of the cortisol stress response was linked to steeper BDNF recovery after stress. BDNF levels were not modulated by any of the mental training modules. Providing novel evidence for the dynamics of BDNF and cortisol during acute stress, our findings may further inform research on the physiological mechanisms involved in stress chronification and the associated health risks.
The increased low-density lipoprotein cholesterol (LDL-C) levels in hypothyroidism may enhance the formation of oxidized LDL (oxi-LDL) that may consequently generate foam cells by their uptake by the macrophages. The goal of this study was to investigate whether plasma circulating oxi-LDL levels are elevated in mild and in overt hypothyroidism, if the concentration of oxi-LDL is influenced in a short-term treatment period by thyroid hormone, and whether correlations exist between serum concentration of thyrotropin (TSH), thyroid hormone, and cholesterol. Thirty-nine patients with overt hypothyroidism (OH), 41 patients with mild thyroid failure (MTF), and 57 controls (CNTR) were investigated. Serum TSH concentrations were increased in OH (18 +/- 6 mU/L) and in MTF (6 +/- 2 mU/L), whereas in CNTR the levels were 1.6 +/- 0.3 mU/L. Plasma circulating levels of oxi-LDL were measured by a new enzyme-linked immunosorbent assay (ELISA) kit (normal range, 40-75 mU/L) and they were found statistically significantly increased in OH compared to MTF (86 +/- 16 mU/L vs. 73 +/- 13 mU/L; p < 0.01) and to CNTR (62 +/- 11 mU/L; p < 0.001). Smokers in all groups exhibited statistically significant higher plasma oxi-LDL levels compared to nonsmokers. The percentage of increase amounted to 17.7% in OH, to 9.8% in MTF, and to 8% in CNTR. Replacement treatment with levothyroxine over a period of 3 months in 12 of 39 patients with OH and in 14 of 41 patients with MTF resulted in a statistically significant decrease of oxi-LDL only in the OH group. Thus, plasma oxi-LDL decreased in OH from 82 +/- 12 mU/L to 73 +/- 10 mU/L (p < 0.05), to the upper normal level, and in MTF from 68 +/- 5 mU/L to 64 +/- 5 mU/L, respectively. In conclusion, we can state that circulating oxi-LDL levels are elevated in untreated overt hypothyroidism, they tend to be higher in mild thyroid failure, they are severely affected by smoking, however, they need a longer time course to decrease via thyroxine treatment.
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