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Thyroid hormones are essential for normal skeletal development and normal bone metabolism in adults but can have detrimental effects on bone structures in states of thyroid dysfunction. Untreated severe hyperthyroidism influences the degree of bone mass and increases the probability of high bone turnover osteoporosis. Subclinical hyperthyroidism, defined as low thyrotropin (TSH) and free hormones within the reference range, is a subtler disease, often asymptomatic, and the diagnosis is incidentally made during screening exams. However, more recent data suggest that this clinical condition may affect bone metabolism resulting in decreased bone mineral density (BMD) and increased risk of fracture, particularly in postmenopausal women. The main causes of exogenous subclinical hyperthyroidism are inappropriate replacement dose of thyroxin and TSH suppressive L-thyroxine doses in the therapy of benign thyroid nodules and thyroid carcinoma. Available data similarly suggest that a long-term TSH suppressive dose of thyroxin may decrease BMD and may induce an increased risk of fracture. These effects are particularly observed in postmenopausal women but are less evident in premenopausal women. Overt hypothyroidism is known to lower bone turnover by reducing both osteoclastic bone resorption and osteoblastic activity. These changes in bone metabolism would result in an increase in bone mineralization. At the moment, there are no clear data that demonstrate any relationship between BMD in adults and hypothyroidism. Despite these clinical evidences, the cellular and molecular actions of thyroid hormones on bone structures are not complete clear.

PurposePolycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age and is characterized by ovulatory dysfunction and/or androgen excess or polycystic ovaries. Women with PCOS present a number of systemic symptoms in addition to those related to the reproductive system. It has been associated with functional derangements in adipose tissue, metabolic syndrome, type 2 diabetes, and an increased risk of cardiovascular disease (CVD).MethodsA detailed literature search on Pubmed was done for articles about PCOS, adipokines, insulinresistance, and metabolic syndrome. Original articles, reviews, and meta-analysis were included.ResultsPCOS women are prone to visceral fat hypertrophy in the presence of androgen excess and the presence of these conditions is related to insulin resistance and worsens the PCO phenotype. Disturbed secretion of many adipocyte-derived substances (adipokines) is associated with chronic low-grade inflammation and contributes to insulin resistance. Abdominal obesity and insulin resistance stimulate ovarian and adrenal androgen production, and may further increase abdominal obesity and inflammation, thus creating a vicious cycle.ConclusionThe high prevalence of metabolic disorders mainly related to insulin resistance and CVD risk factors in women with PCOS highlight the need for early lifestyle changes for reducing metabolic risks in these patients.

Aging of the vascular system is associated with deep changes of the structural proprieties of the arterial wall. Arterial hypertension, diabetes mellitus, and chronic kidney disease are the major determinants for the loss of elasticity and reduced compliance of vascular wall. Arterial stiffness is a key parameter for assessing the elasticity of the arterial wall and can be easily evaluated with non-invasive methods, such as pulse wave velocity. Early assessment of vessel stiffness is critical because its alteration can precede clinical manifestation of cardiovascular disease. Although there is no specific pharmacological target for arterial stiffness, the treatment of its risk factors helps to improve the elasticity of the arterial wall.

Purpose To review the literature on thyroid function and thyroid disorders during pregnancy. Methods A detailed literature research on MEDLINE, Cochrane library, EMBASE, NLH, ClinicalTrials.gov, and Google Scholar databases was done up to January 2018 with restriction to English language about articles regarding thyroid diseases and pregnancy. Results Thyroid hormone deficiencies are known to be detrimental for the development of the fetus. In particular, the function of the central nervous system might be impaired, causing low intelligence quotient, and mental retardation. Overt and subclinical dysfunctions of the thyroid disease should be treated appropriately in pregnancy, aiming to maintain euthyroidism. Thyroxine (T4) replacement therapy should reduce thyrotropin (TSH) concentration to the recently suggested fixed upper limits of 2.5 mU/l (first and second trimester) and 3.0 mU/l (third trimester). Overt hyperthyroidism during pregnancy is relatively uncommon but needs prompt treatment due to the increased risk of preterm delivery, congenital malformations, and fetal death. The use of antithyroid drug (methimazole, propylthiouracil, carbimazole) is the first choice for treating overt hyperthyroidism, although they are not free of side effects. Subclinical hyperthyroidism tends to be asymptomatic and no pharmacological treatment is usually needed. Gestational transient hyperthyroidism is a self-limited non-autoimmune form of hyperthyroidism with negative antibody against TSH receptors, that is related to hCG-induced thyroid hormone secretion. The vast majority of these patients does not require antithyroid therapy, although administration of low doses of β-blocker may by useful in very symptomatic patients. Conclusions Normal maternal thyroid function is essential in pregnancy to avoid adverse maternal and fetal outcomes.

Adipose-derived stem cells (ADSCs) represent one of the cellular populations resident in adipose tissue. They can be recruited under certain stimuli and committed to become preadipocytes, and then mature adipocytes. Controlling stem cell differentiation towards the adipogenic phenotype could have a great impact on future drug development aimed at counteracting fat depots. Stem cell commitment can be influenced by different molecules, such as melatonin, which we have previously shown to be an osteogenic inducer. Here, we aimed at evaluating the effects elicited by melatonin, even in the presence of vitamin D, on ADSC adipogenesis assessed in a specific medium. The transcription of specific adipogenesis orchestrating genes, such as aP2, peroxisome proliferator-activated receptor γ (PPAR-γ), and that of adipocyte-specific genes, including lipoprotein lipase (LPL) and acyl-CoA thioesterase 2 (ACOT2), was significantly inhibited in cells that had been treated in the presence of melatonin and vitamin D, alone or in combination. Protein content and lipid accumulation confirmed a reduction in adipogenesis in ADSCs that had been grown in adipogenic conditions, but in the presence of melatonin and/or vitamin D. Our findings indicate the role of melatonin and vitamin D in deciding stem cell fate, and disclose novel therapeutic approaches against fat depots.

Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their microenvironment, also known as niche. The stem cell niche is regulated by complex interactions between multiple cell types. When transplanted in a specific area, ADSCs can secrete several immunomodulatory factors. At the same time, a tumor microenvironment can influence stem cell behavior, modulating proliferation and their ability to differentiate into a specific phenotype. Whitin this context, we exposed ADSCs to plasma samples derived from human patients diagnosed with prostate cancer (PC), or precancerous lesions (PL), or benign prostatic hyperplasia (BPH) for 4, 7 or 10 days. We then analyzed the expression of main stemness-related markers and cell-cycle regulators. We also measured cytokine production and polyamine secretion in culture medium and evaluated cell morphology and collagen production by confocal microscopy. The results obtained from this study show significant changes in the morphology of ADSCs exposed to plasma samples, especially in the presence of prostate cancer plasma, suggesting important implications in the use of ADSCs for the development of new treatments and application in regenerative medicine.

Growth differentiation factor 15 (GDF15) is a stress-response cytokine, which exerts different actions in physiological and pathological conditions. Thyroid disorders are common in the general population and their role on GDF15 levels has not been sufficiently addressed. Serum levels of GDF-15 and thyroid function were assessed in a large sample from the SardiNIA cohort (n = 4413). We further collected antibodies against thyroperoxidase and anti-thyroglobulin in all participants. Thyroid function correlated with GDF15. Specifically, after adjusting for covariates, thyrotropin had a positive association with GDF15, while free thyroxine was negatively correlated. We also found that subjects with circulating antibodies against thyroperoxidase had lower GDF15 levels. The reduced level of the thyroid hormone can cause a decreased metabolic activity and higher cell stress response, which, in turn, increases the production of GDF-15 as a defense mechanism. The association between antibodies against thyroperoxidase and GDF15 deserves additional study to elucidate the pathophysiologic relationship.

Diabetes mellitus and heart failure are two diseases that are commonly found together, in particular in older patients. High blood glucose has a detrimental effect on the cardiovascular system, and worse glycemic control contributes to the onset and the recrudesce of heart failure. Therefore, any specific treatment aimed to reduce glycated hemoglobin may, in turn, have a beneficial effect on heart failure. Sodium-glucose cotransporter-2 inhibitors have been initially developed for the treatment of type 2 diabetes mellitus, and their significant action is to increase glycosuria, which in turn causes a reduction in glucose blood level and contributes to the reduction of cardiovascular risk. However, recent clinical trials have progressively demonstrated that the glycosuric effect of the sodium-glucose cotransporter-2 inhibitors also have a diuretic effect, which is a crucial target in the management of patients with heart failure. Additional studies also documented that sodium-glucose cotransporter-2 inhibitors improve the therapeutical management of heart failure, independently by the glycemic control and, therefore, by the presence of diabetes mellitus. In this review, we analyzed studies and trials demonstrating the efficacy of sodium-glucose cotransporter-2 inhibitors in treating chronic and acute heart failure.

AimsPrevious cross-sectional observation identified arterial aging, indexed as pulse-wave velocity (PWV), as a key determinant of the simultaneous multiple organ damage (heart, carotid artery, and kidney). The aim of the present cohort study is to investigate trajectories of repeated measures of PWV and traditional CV risk factors in subjects who eventually presented clinical evidence of multiple organ damage in the SardiNIA study.Methods and resultsOrgan damage was measured in the heart (left ventricular hypertrophy, LVH), the common carotid artery (intima–media thickness > 0.9 mm and/or plaque), and the kidney (eGFR < 60 ml/min/1.73 m2) of 2130 men and women of a broad age range participating the SardiNIA study. SHATS was defined as the simultaneous occurrence of all the three-organ damages. Trajectory in traditional CV risk factors and PWV was analyzed retrospectively (four observations over 9 years) according to the number of organ damage (from 0 to 3). Compared to subjects with no organ damage, after controlling for traditional CV risk factors, each 1 m/s increase in baseline PWV was accompanied by a 93% higher odds of developing SHATS; and each 1 cm/s (0.01 m/s) annual increase in PWV by a 31% greater odds of developing SHATS.ConclusionsArterial stiffness, a proxy of arterial aging that can be measured clinically as PWV, is an integrated predictive marker of multiple age-associated organ damage recognized as clinical diseases.

Obesity is a complex worldwide disease, characterized by an abnormal or excessive fat accumulation. The onset of this pathology is generally linked to a complex network of interactions among genetic and environmental factors, aging, lifestyle, and diets. During adipogenesis, several regulatory mechanisms and transcription factors are involved. As fat cells grow, adipose tissue becomes increasingly large and dysfunctional, losing its endocrine function, secreting pro-inflammatory cytokines, and recruiting infiltrating macrophages. This long-term low-grade systemic inflammation results in insulin resistance in peripheral tissues. In this review we describe the main mechanisms involved in adipogenesis, from a physiological condition to obesity. Current therapeutic strategies for the management of obesity and the related metabolic syndrome are also reported.