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Anti TSH receptor antibodies (TSHrAb) are a family of antibodies with different activity, some of them stimulating thyroid function (TSAb), others with blocking properties (TBAb), it is a common finding that antibodies with different function might coexist in the same patient and can modulate the function of the thyroid. However, most of the labs routinely detect all antibodies binding to the TSH receptor (TRAb, i.e. TSH-receptor antibodies detected by binding assay without definition of functional property). Classical use of TSHr-Ab assay is in Graves’ disease where they are tested for diagnostic and prognostic issues; however, they can be used in specific settings of chronic autoimmune thyroiditis (CAT) as well. Aim of the present paper is to highlight these conditions where detection of TSHr-Ab can be of clinical relevance. Prevalence of TSHrAb is different in in the 2 main form of CAT, i.e. classical Hashimoto’s thyroiditis and in atrophic thyroiditis, where TBAb play a major role. Simultaneous presence of both TSAb and TBAb in the serum of the same patient might have clinical implication and cause the shift from hyperthyroidism to hypothyroidism and vice versa. Evaluation of TRAb is recommended in case of patients with Thyroid Associated Orbitopathy not associated with hyperthyroidism. At present, however, the most relevant recommendation for the use of TRAb assay is in patients with CAT secondary to a known agent; in particular, after treatment with alemtuzumab for multiple sclerosis. In conclusion, the routine use of anti-TSH receptor antibodies (either TRAb or TSAb/TBAb) assay cannot be suggested at the present for diagnosis/follow up of patients affected by CAT; there are, however, several conditions where their detection can be clinically relevant.

Nutraceuticals and functional foods are the main sources of antioxidants and have positive effects on health through regulation of the redox balance. Accordingly, they represent a useful nutritional source for the prevention of noncommunicable diseases (NCDs). Menopausal women have an increased risk of developing NCDs due to hormonal dysregulation and the ongoing aging process. Accordingly, a healthy lifestyle and good nutritional habits are of utmost importance in this population. Resveratrol (RSV) is a natural polyphenol, and it is used as a nutraceutical given its estrogenic, anti-inflammatory, and antioxidant properties. The aim of this study was to analyze the effects of RSV on the lymphocyte cytotoxicity in menopausal women. Lymphocytes from 13 healthy menopausal women (56.18 ± 4.24 years) were isolated, and then cocultured with hTERT-HME1, a breast cell line with a precancerous phenotype. The results showed that, when treated with RSV, lymphocytes significantly increased the TNF-α production (p < 0.001), the formation of immune synapses (p = 0.009), and the target cell lysis (p = 0.002). No effects were detected in the lymphocyte total antioxidant capacity. In conclusion, RSV might enhance the immune surveillance in menopausal women by increasing the cytotoxic activity of lymphocytes.

The efficacy of SARS-CoV-2 mRNA-based vaccines in preventing COVID-19 disease has been extensively demonstrated; however, it is of uttermost importance to acquire knowledge on the persistence of immune-protection both in terms of levels of neutralizing antibodies and specialized memory cells. This can provide important scientific basis for decisions on the need of additional vaccine doses and on when these should be administered thus resulting in an improvement in vaccination schedules. Here, we briefly report the changes in antibody levels and cellular immunity following BNT162b2 administration. We show an important fall in anti S1-Spike antibodies in BNT162b2 vaccinated subjects overtime, paralleled by a contextual consolidation of specific spike (S) T-cells, mainly of the CD8+ compartment. Contrariwise, CD4+ S-specific response shows a considerable interindividual variability. These data suggest that the well-known antibody drop in vaccinated subjects is replaced by memory cell consolidation that can protect from severe adverse effects of SARS-CoV-2 infection.

COVID-19 pandemic has hit people’s health, economy, and society worldwide. Great confidence in returning to normality has been placed in the vaccination campaign. The knowledge of individual immune profiles and the time required to achieve immunological protection is crucial to choose the best vaccination strategy. We compared anti-S1 antibody levels produced over time by BNT162b2 and AZD1222 vaccines and evaluated the induction of antigen-specific T-cells. A total of 2569 anti-SARS-CoV-2 IgG determination on dried blood spot samples were carried out, firstly in a cohort of 1181 individuals at random time-points, and subsequently, in an independent cohort of 88 vaccinated subjects, up to the seventeenth week from the first dose administration. Spike-specific T-cells were analysed in seronegative subjects between the two doses. AZD1222 induced lower anti-S1 IgG levels as compared to BNT162b2. Moreover, 40% of AZD1222 vaccinated subjects and 3% of BNT162b2 individuals resulted in seronegative during all the time-points, between the two doses. All these subjects developed antigen-specific T cells, already after the first dose. These results suggest that this test represents an excellent tool for a wide sero-surveillance. Both vaccines induce a favourable immune profile guaranteeing efficacy against severe adverse effects of SARS-CoV-2 infection, already after the first dose administration.

Radiological and endocrinological work up of adrenal neoplasms is aimed at distinguishing between frequent non-functioning adenomas and rare but very aggressive adrenocortical carcinoma (ACC). Relevant research has addressed the identification of molecular, genetic and hormonal markers that could have clinical significance for malignancy, as well as a prognostic value. Regarding endocrine aspects, attention has been paid to the pattern of steroid secretion that can be affected by altered steroidogenic pathway in ACC. The advent of mass spectrometry techniques has overcome many limitations usually associated with immunoassays, allowing the determination of both common and rarely measured steroids in a single analysis with high specificity and sensitivity. Indeed, mass spectrometry strategies may be able to identify an individualized steroid profile of ACC, allowing a rapid diagnosis and a specific follow-up. In this review, insights, strengths and limitations of mass spectrometry-based approaches in steroid profiling, as well as of immunoassay in steroid measurements, will be specifically discussed. Moreover, the latest findings on steroid profiling by mass spectrometry-based techniques, the most promising analytical tool, will be summarized to evaluate if steroid profiling might be the clue for solving the clinical dilemma in differentiating ACC from non-functioning adrenocortical adenomas (ACA).

Background: Neonatal thyrotropin (TSH) on dried blood spot (DBS), the most common screening strategy for primary congenital hypothyroidism (CH), is influenced by numerous factors that may hinder a true CH diagnosis. A second test can thus be performed to clarify the initial findings, although its application varies among screening programs. Objectives: The aim of this study was to evaluate the effect of maternal and neonatal factors on neonatal TSH levels and offer practical screening recommendations. Methods: We retrospectively analyzed screening data of 62,132 neonates born in Abruzzo, an Italian region considered mildly iodine deficient, between 2011 and 2016. We then performed a multiple linear regression to model the relationship between TSH (the dependent variable) and 13 independent variables extracted from blood collection cards. Results: Most neonates (53,551 of 62,132, 86%) had normal TSH and no clinical indications for a second screening. A minority (1,423, 2.3%) had elevated TSH in the initial DBS, which was confirmed in 97 cases (7%) on a second screen. The remaining neonates (6,594, 10.6%) had a normal initial TSH but underwent a second test in accordance with screening protocols, and were found to have delayed TSH elevation in 23 cases (0.4%). Those 120 newborns (97 + 23), considered highly suspicious for primary CH, were referred to a pediatrician for confirmatory testing and excluded from subsequent analysis of factors influencing TSH levels. Sex (β regression coefficient, β = 1.11 female to male, 95% CI 1.09, 1.12) and age at collection (β = 0.78 day 5 to days 2–3, 95% CI 0.74, 0.83) affected neonatal TSH, suggesting the utility of specific nomograms. In addition, prematurity (β = 0.85 term to preterm, 95% CI 0.80, 0.91), dopamine use (β = 0.71, 95% CI 0.62, 0.81), and birth weight (β = 1.40 normal vs. very low, 95% CI 1.05, 1.89) strongly influenced neonatal TSH. Conclusions: Neonatal TSH is influenced by several factors supporting the delineation of local sex- and age-adjusted TSH cutoffs, and the universal adoption of a second TSH test in neonates at risk of missed primary CH diagnosis.

The aim of this study was to analyse the health status of breast cancer survivors and the effects of 12 weeks of aerobic training. Twenty-three breast cancer survivors (51.71 ± 3.17 years) and 23 healthy women (50.73 ± 2.97 years) were investigated for body composition, daily physical activity, quality of life, salivary cortisol, and DHEA-S. Breast cancer survivors were then aerobically trained for 12 weeks. Breast cancer survivors have a worse psychophysical health than healthy women. Aerobic training increased salivary DHEA-S, aerobic fitness, self-reported health, and nocturnal sleeping time and reduced salivary cortisol in breast cancer survivors. Salivary cortisol variation correlated with change of sleeping time and self-reported health. Salivary DHEA-S correlated with change of self-reported physical pain and general health as well. Breast cancer survivors can live in a situation of continuous distress, requiring a multidisciplinary approach. Twelve weeks of aerobic training improve the psychophysical health of breast cancer survivors.

Summary Pregnancies complicated by diabetes have largely increased in number over the last 50 years. Pregnancy is characterized by a physiologic increase in insulin resistance, which, associated with increased oxidative stress and inflammations, could induce alterations of glucose metabolism and diabetes. If not optimally controlled, these conditions have a negative impact on maternal and foetal outcomes. To date, one can resort only to diet and lifestyle to treat obesity and insulin resistance during pregnancy, and insulin remains the only therapeutic option to manage diabetes during pregnancy. However, in the last years, in a variety of experimental models, inositol and antioxidants supplementation have shown insulin‐sensitizing, anti‐inflammatory, and antioxidant properties, which could be mediated by some possible complementary mechanism of action. Different isomers and multiple combinations of these compounds are presently available: Aim of the present review article is to examine the existing evidence in order to clarify and/or define the effects of different inositol‐ and antioxidant‐based supplements during pregnancy complicated by insulin resistance and/or by diabetes. This could help the clinician's evaluation and choice of the appropriate supplementation regimen.

Background: Menopause is associated with negative cardiovascular adaptations related to estrogen depletion, which could be counteracted by physical exercise (PhE). However, the impact of total adherence-rate (TA) to PhE and sedentary time (SedT) on cardiometabolic profile in this population has not been elucidated. Methods: For 13-weeks, 43 women (57.1 &plusmn, 4.7 years) participated in a 4-days-a-week moderate-intensity walking training. They underwent laboratory, anthropometric and echocardiographic assessment, before and after training (T0&ndash, T1). Spontaneous physical activity (PhA) was assessed with a portable multisensory device. The sample was divided according to TA to PhE program: &lt, 70% (n = 17) and &ge, 70% (n = 26). Results: TA &ge, 70% group experienced a significant T1 improvement of relative wall thickness (RWT), diastolic function, VO2max, cortisol, cortisol/dehydroandrostenedione-sulphate ratio and serum glucose. After adjusting for SedT and 10-min bouts of spontaneous moderate-to-vigorous PhA, TA &ge, 70% showed the most significant absolute change of RWT and diastolic function, body mass index, weight and cortisol. TA &ge, 70% was major predictor of RWT and cortisol improvement. Conclusions: In a group of untrained, postmenopausal women, a high TA to a 13-weeks aerobic PhE program confers a better improvement in cardiometabolic profile, regardless of SedT and PhA levels.

Severe forms of the Coronavirus disease 2019 (COVID-19) are characterized by an enhanced inflammatory syndrome called “cytokine storm” that produces an aberrant release of high amounts of cytokines, chemokines, and other proinflammatory mediators. The pathogenetic role of the “cytokine storm” has been confirmed by the efficacy of immunosuppressive drugs such as corticosteroids along with antiviral drugs in the treatment of the severe forms of this disease. Phenylmethimazole (C10) is a derivative of methimazole with anti-inflammatory properties. Studies performed both in vitro and in vivo have shown that C10 is able to block the production of multiple cytokines, chemokines, and other proinflammatory molecules involved in the pathogenesis of inflammation. Particularly, C10 is effective in reducing the increased secretion of cytokines in animal models of endotoxic shock. We hypothesize that these effects are not limited to the endotoxic shock, but can also be applied to any disease characterized by the presence of a “cytokine storm”. Therefore, C10 may be a potential drug to be used alternatively or in association with the corticosteroids or other immunosuppressive agents in the severe forms of COVID-19 as well as other viral diseases that induce a “cytokine storm”. Preclinical and clinical studies have to be performed to confirm this hypothesis.

[Purpose] The aims of this study were to verify the effects on upper limb circumferences and total body extracellular water of 10 weeks of Nordic Walking (NW) and Walking (W), both alone and combined with a series of exercises created for breast cancer survivors, the ISA method. [Subjects and Methods] Twenty breast cancer survivors were randomly assigned to 4 different training groups and evaluated for upper limb circumferences, total body and extracellular water. [Results] The breast cancer survivors who performed NW, alone and combined with the ISA method, and Walking combined with the ISA method (but not alone) showed significantly reduced arm and forearm circumferences homolateral to the surgical intervention. [Conclusion] For breast cancer survivors, NW, alone and combined with the ISA method, and Walking combined with the ISA method should be prescribed to prevent the onset and to treat light forms of upper limb lymphedema because Walking training practiced alone had no significant effect on upper limb circumference reduction.

Background Sedentarism is a risk factor for mortality that is independent of physical exercise. As indicated in the literature, there is negative compensation of non-exercise physical activity due to exercise training. The aim was to investigate potential predictor variables of physical activity compensation in post-menopausal women beginning aerobic physical exercise training. Methods One hundred and three post-menopausal women (mean age, 58.31±5.33 years) were eligible for the study. Metabolic markers were measured (plasma leptin, insulin, glucose), together with cardiovascular parameters and body composition. Daily physical activity was recorded objectively. Following baseline measurements, participants walked at moderate intensity on 4 days/week, for 13 weeks. Results Baseline mean intensity of daily physical activity and leptin-to-fat mass ratio (L/FMkg) were independently and negatively correlated with variations in non-exercise physical activity. High L/FMkg was associated with negative compensation of non-exercise physical activity due to aerobic physical exercise. The same was shown for participants starting their exercise training who showed high daily physical activity. Conclusions Knowledge of both L/FMkg and baseline spontaneous physical activity of participants in exercise training are important to programme physical exercise interventions and to prevent negative non-exercise physical activity compensation due to exercise training.

Background: The negative side effects of breast cancer treatments can include upper limb lymphoedema. The growing literature indicates that Nordic walking is an effective discipline against several disease symptoms. The aim of this study was to determine whether introduction to Nordic walking alone is effective against total body extracellular water and upper limb circumferences in breast cancer survivors compared to its combination with a series of specifically created exercises (i.e. the Isa method). Methods: 16 breast cancer survivors (49.09 ± 2.24 years) were recruited and randomly assigned to 1 of 2 different training groups. Results: 10 lessons on Nordic walking technique plus the Isa method significantly reduced both extracellular body water and the extracellular-to-total body water ratio (p = 0.01 for both), and also the circumference of the upper limb, (both relaxed arm and forearm circumferences) (p = 0.01 for all), whereas Nordic walking alone did not. Conclusions: Introduction to Nordic walking does not seem to affect lymphoedema in breast cancer survivors. This might be because novice Nordic Walkers do not adequately generate an effective muscular pump through coordination of the alternated bimanual open-close cycle. The Isa method appears to close this gap.

Graves’ disease is the most common cause of thyrotoxicosis in women of childbearing age. Approximately 1% of pregnant women been treated before, or are being treated during pregnancy for Graves’ hyperthyroidism. In pregnancy, as in not pregnant state, thyroid-stimulating hormone (TSH) receptor (TSHR) antibodies (TRAbs) are the pathogenetic hallmark of Graves’ disease. TRAbs are heterogeneous for molecular and functional properties and are subdivided into activating (TSAbs), blocking (TBAbs), or neutral (N-TRAbs) depending on their effect on TSHR. The typical clinical features of Graves’ disease (goiter, hyperthyroidism, ophthalmopathy, dermopathy) occur when TSAbs predominate. Graves’ disease shows some peculiarities in pregnancy. The TRAbs disturb the maternal as well as the fetal thyroid function given their ability to cross the placental barrier. The pregnancy-related immunosuppression reduces the levels of TRAbs in most cases although they persist in women with active disease as well as in women who received definitive therapy (radioiodine or surgery) before pregnancy. Changes of functional properties from stimulating to blocking the TSHR could occur during gestation. Drug therapy is the treatment of choice for hyperthyroidism during gestation. Antithyroid drugs also cross the placenta and therefore decrease both the maternal and the fetal thyroid hormone production. The management of Graves’ disease in pregnancy should be aimed at maintaining euthyroidism in the mother as well as in the fetus. Maternal and fetal thyroid dysfunction (hyperthyroidism as well as hypothyroidism) are in fact associated with several morbidities. Monitoring of the maternal thyroid function, TRAbs measurement, and fetal surveillance are the mainstay for the management of Graves’ disease in pregnancy. This review summarizes the biochemical, immunological, and therapeutic aspects of Graves’ disease in pregnancy focusing on the role of the TRAbs in maternal and fetal function.

Menopause is characterized by hormonal and metabolic changes. These are linked to increased risk of cardiovascular disease, for which low blood plasma levels of high density lipoprotein (HDL) cholesterol are an independent risk factor. The present study investigated variables linked with basal plasma HDL cholesterol levels and the effects of aerobic training, on their variations, in 40 postmenopausal women.We assessed body composition, dietary habits and maximal aerobic capacity of participants. Characteristics of daily physical activity and plasma lipoproteins were measured. The women walked on 4 days/week, for 14 weeks, at moderate intensity, and they were grouped according to the resulting tertiles of basal plasma HDL cholesterol levels.Logistic regression analysis showed that waist-to-hip ratio and number of daily bouts of moderate-intensity physical activity, held for at least 10 consecutive minutes (B10m/day), are predictive variables of basal plasma HDL cholesterol levels. After the training period, the first and second tertiles increased plasma HDL cholesterol levels, while the third tertile decreased plasma HDL cholesterol levels. The tertiles showed different remodelling of spontaneous physical activity: the third tertile reduced B10m/day, while the others did not.This study provides knowledge about the relationships of plasma HDL cholesterol levels with characteristics of physical activity. Furthermore, it shows that physical exercise engagement can result in negative compensation of spontaneous physical activity that could counteract or reduce the positive effects of the aerobic training on plasma HDL cholesterol levels.

The analysis of daily physical activity characteristics is an important starting point to favor the promotion of proper physical activity against obesity. The aim of our study was to characterize physical activity organization, among the different intensities and across age and ponderal status, to verify whether the normal-weight condition has the same physical activity characteristics across ages. We recruited 381 female participants; 100 were between 6 and 10 years old; 134 were between 35 and 54 years, and 147 were between 55 and 69 years. The body mass index of participants ranged from normal weight to obese. Daily physical activity was objectively recorded in the period between 15 June and 15 July, from 2011 to 2014. The effects of age, ponderal status, and their interaction on daily physical activity were studied. Normal-weight children (NW-C) have higher daily METs and more vigorous physical activity than other sub-samples, while overweight and obese children (OW-C, O-C) have the same daily physical activity characteristics as normal-weight adults and older adults (NW-A, NW-OA). In female population, the intensity of daily physical activity is a distinctive characteristic of NW-C, while time engaged in moderate physical activity is a distinctive characteristic for NW-A and NW-OA. As OW-C and O-C have the same physical activity characteristics as NW-A and NW-OA, it is suggested that an age-related approach in the field of physical activity promotion should be developed.

Background. About 10% of pregnancies are complicated by previously unknown impairment of glucose metabolism, which is defined as gestational diabetes. There are little data available on prevalence of thyroid disorders in patients affected by gestational diabetes, and about their postgestational thyroid function and autoimmunity. We therefore investigated pancreatic and thyroid autoimmunity in gestational diabetic patients and in women who had had a previous gestational diabetic pregnancy.Methods. We investigated 126 pregnant women at the time of a 100-g oral glucose tolerance test: 91 were classified as gestational diabetics, and 35 were negative (controls). We also studied 69 women who had delivered a baby 18–120 months prior to this investigation and who were classified at that time gestational diabetics (38 women) or normally pregnant (31 women; controls).Results. Our data show no differences for both thyroid function and prevalence of autoimmune disorders during pregnancy; however, a significant increase in thyroid autoimmunity was seen in women previously affected by gestational diabetes. This increased prevalence of thyroid autoimmunity was not associated with the development of impaired glucose metabolism after pregnancy.Conclusions. Our data suggest that maternal hyperglycemia is a risk factor for the development of thyroid autoimmunity, a conclusion that should now be confirmed in a larger cohort of patients.

Objective: Because physical exercise has been widely used for primary and secondary preventions of cardiometabolic diseases arising with menopause, the aim of our study was to determine whether participation in aerobic physical exercise is linked to the modification of spontaneous physical activity and whether this compensation affects aerobic trainingYrelated body adaptations. Methods: Both before and after a 13-week walking training program, 34 postmenopausal women (mean T SD age, 55.89 T 3.57 y) were analyzed for lipids, adipokines, glucose, and insulin plasma levels, as well as for body measures, heart rate and blood pressure at rest, maximal aerobic capacity, total daily energy expenditure, mean intensity of daily physical activities, and time and energy spent on physical activities with an intensity of more than three metabolic equivalents. Results: Aerobic training induced significant reductions in body mass, body mass index, heart rate, systolic blood pressure, basal cardiac double product, plasma glucose, leptin, and resistin. Aerobic fitness, the reserve of the cardiac double product, and the quantitative insulin sensitivity index were significantly improved. Cluster analysis of the variations in the total daily energy expenditure, the mean intensity of daily physical activities, and the time and energy spent on physical activities with an intensity of more than three metabolic equivalents identified two subgroups: one showed reduced spontaneous physical activity (GROUPj), whereas the other did not (GROUP+). The subgroups differed significantly only for plasma lipid variation. GROUP+ showed significantly reduced low-density lipoprotein cholesterol and total cholesterol, whereas GROUPj did not show significantly modified plasma lipids. Conclusions: In postmenopause, participation in a program of aerobic physical exercise can result in a reduction of spontaneous physical activity, which inhibits the positive effects of the aerobic exercise on plasma lipids and lipoproteins.

In subjects affected by trisomy 21 (Down syndrome), hypothyroidism is the most common endocrinological deficit. Plasma zinc levels, which are commonly detected below the normal range in Down patients, are related to some endocrinological and immunological functions; in fact, zinc deficiency has been shown to impair immune response and growth rate. Aims of this study were to evaluate (1) the role of zinc deficiency in subclinical hypothyroidism and (2) thyroid function changes in Down children cyclically supplemented with zinc sulfate. Inverse correlations have been observed between age and triiodotironine (T3) and between zinc and thyroid-stimulating hormone (TSH); higher TSH levels have been found in hypozincemic patients at the beginning of the study. After 6 mo of supplementation, an improvement of thyroid function (TSH levels: 3.96 +/- 1.84 vs 2.64 +/- 1.33 mUI/mL basally and after 6 mo, respectively) was observed in hypozincemic patients. In the second cycle of supplementation, a similar trend of TSH was observed. At the end of the study, TSH significantly decreased in treated hypozincemic subjects (4.48 +/- 1.93 vs 2.96 +/- 1.20 mUI/mL) and it was no longer different in comparison to normozincemic patients. We suggest zinc supplementation to the diet in hypozincemic Down children as a simple and useful therapeutic tool.

Purpose:High-intensity aerobic interval training (AIT) has been reported to be more effective than continuous aerobic training (CoAT) to improve metabolic health. The aim of our study was to investigate whether moderate-intensity AIT is more effective than CoAT on metabolic health when applied to a walking training program.Design/Methods:Thirty-two postmenopausal women (55.37 ± 3.46 years) were investigated for body composition, plasma glucose, insulin, lipids, adiponectin, HOMA-IR, HOMA-AD, aerobic fitness, dietary habits, and spontaneous physical activity, and randomly assigned to one of two different walking training programs: CoAT or AIT.Results:CoAT and AIT elicited the same physiological benefits, including: reduction of plasma glucose, insulin, HOMA-IR and HOMA-AD, and increase of plasma HDL-C, adiponectin, and aerobic fitness.Conclusions:An AIT scheme as part of an outdoor walking training program elicits the same physiological adaptations as a CoAT scheme, probably because walking does not promote exercise intensities that elicit greater effects.

Objective We hypothesized that physical exercise in postmenopausal women could interfere with the molecular interrelationship of the immune-endocrine system and be effective even in women in whom training determined a reduction of spontaneous physical activity (SPA). For this reason, we investigated the effects of an aerobic program on plasma dehydroepiandrosterone sulfate (DHEA-S) and cytokine levels in relationship to SPA modification. Methods Thirty-two postmenopausal women (mean [SD] age, 56.38 [4.33] y) were enrolled in the study. Inclusion criteria were as follows: age younger than 65 years, body mass index higher than 18.5 and lower than 35 kg/m2, no pharmacological treatments, and no history of chronic, cardiovascular, or orthopedic diseases. Before and after 3 months of walking training at moderate intensity (40-50 min, 4 d/wk), they were evaluated for SPA, body composition, energy intake, and levels of plasma cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-1α, IL-1β, IL-2, IL-8, and IL-10), C-reactive protein, DHEA-S, cortisol, and estrogen. Results At baseline, SPA did not correlate with either DHEA-S level or cytokine levels. There was negative correlation between DHEA-S and both TNF-α and IL-2. After the intervention program, 16 women showed increased SPA, and 16 women showed decreased SPA. Independent of these changes in SPA, both TNF-α levels and cortisol-to-DHEA-S ratio decreased, whereas DHEA-S levels increased. Conclusions In postmenopausal women, walking training, rather than SPA, influences DHEA-S and cytokine concentrations and their correlations, thus interfering with adrenal steroids and the inflammatory markers network. Physical exercise acts in parallel on menopausal neuroendocrine alterations and on the systemic inflammatory profile independent of SPA changes.

A functional thyroid-stimulating autoantibodies (TSAb) assay using a thyroid-stimulating hormone receptor chimera (Mc4) appears to be clinically more useful than the commonly used assay, a binding assay that measures all the antibodies binding to the thyroid-stimulating hormone receptor without functional discrimination, in diagnosing patient with Graves' disease (GD).The objective of the study was to investigate whether an Mc4 assay can predict relapse/remission of hyperthyroidism after antithyroid drug (ATD) treatment in patients with GD.An Mc4 assay was used to prospectively track TSAb activity in GD patients treated with ATD over a 5-yr period.GD patients from the Chieti University participated in this study.Interventions included the assessment of patients' sera using the Mc4 assay, the Mc4-derivative assay (Thyretain), and a human monoclonal thyroid-stimulating hormone receptor antibody, M22 assay.The Mc4 assay, a sensitive index of remission and recurrence, was used in this study.The TSAb levels significantly decreased only in the remitting group as evidenced by Mc4 assay values at the end of ATD (0.96 ± 1.47, 10.9 ± 26.6. and 24.7 ± 37.5 arbitrary units for the remitting, relapsing, and unsuspended therapy groups, respectively). Additional prognostic help was obtained by thyroid volume measurements at the end of treatment. Although not statistically significant, the Mc4 assay has a trend toward improved positive predictive value (95.4 vs. 84.2 or 87.5%), specificity (96.4 vs. 86.4 and 90.9%), and accuracy (87.3 vs. 83.3 and 80.9%) comparing the Mc4, Thyretain, and M22 assays, respectively. Thyretain has a trend toward improved negative predictive value (82.6 vs. 81.8 and 76.9%) and sensitivity (80 vs. 77.8 and 70%) comparing Thyretain, Mc4, and M22 assays, respectively.The Mc4 assay is a clinically useful index of remission and relapse in patients with GD. Larger studies are required to confirm these findings.

Stimulating thyrotropin receptor (TSHr) autoantibodies (TSAb) are the cause of hyperthyroidism in Graves' disease. In a patient's serum, TSAb can coexist with antagonist TSHr autoantibodies that block TSAb stimulatory activity (TSBAb); both can vary in amount and time.The objective of the study was to create a functional assay that detects only TSAb, thus having an increased accuracy for diagnosing Graves' disease.A TSHr chimera (Mc4) that retains an agonist-sensitive TSAb epitope but replaces a TSBAb epitope was stably transfected in cells to establish the Mc4 assay.The study was conducted at the Chieti University (Outpatient Endocrine Clinic) and the University of Pisa (the Department of Endocrinology).The assay was validated using sera from 170 individuals with Graves' disease, Hashimoto's thyroiditis, and nonautoimmune hyperthyroidism and normal subjects from Chieti University. A second blinded study evaluated sera from 175 patients with autoimmune thyroid disease (mainly Graves' disease) from the University of Pisa.Interventions included the assessment of patients' sera using human wild-type TSHr (WT-TSHr), Mc4 chimera, and binding (TRAb) assays.The Mc4 assay has the best accuracy for diagnosing Graves' disease.The Mc4 assay has a better diagnostic accuracy than WT-TSHr and second-generation TRAb assays. Indeed, the sensitivity of the WT-TSHr, TRAb, and Mc4 assays was 97.3, 86.5, and 100%, respectively, whereas the specificity was 93.1, 97, and 98.5%, respectively.The Mc4 assay is a functional assay with improved sensitivity and specificity for the detection of TSAb and is clinically useful in diagnosing Graves' disease.