Frontiers of Hormone Research最新文献

Both prevalence and incidence of the metabolic syndrome is very high in women with polycystic ovary syndrome (PCOS). Obesity and visceral fat enlargement play a dominant role in determining the final phenotype of PCOS. Androgen excess and insulin resistance may be responsible for the development of all features of the metabolic syndrome. The major factors responsible for this association seem to be related to a triumvirate including androgen excess, insulin resistance and associated hyperinsulinemia, and obesity, particularly the abdominal-visceral phenotype. With respect to obesity, it can be suggested that the association may be bidirectional, in the sense that obesity can worsen the phenotype of PCOS when present and can also be responsible for the development of a secondary form of PCOS even in susceptible subjects. In spite of the strong association among a long list of cardiovascular risk factors, there is no evidence that women with PCOS may be affected by an increased risk for cardiovascular mortality. Future research should carry out a detailed investigation into the potential role of androgen excess in determining the insulin resistant state and, specifically, the very high risk of developing type 2 diabetes.

Parathyroid glands are the main regulator of body mineral metabolism through parathormone (PTH) actions on bone and kidney. Experimental evidence suggests that PTH may have non-classical target organs such as adipose tissue, arterial vascular wall, cardiac muscle cells, and adrenal cortex cells, where it may play a role in controlling body energy, blood pressure, and metabolism. Cardiometabolic features have been investigated in the wide spectrum of clinical parathyroid disorders, from hyperparathyroidism to pseudohypoparathyroidism and hypoparathyroidism. Indeed, in parathyroid disorders, besides altered PTH secretion, impaired serum calcium levels and vitamin D status occur. Both calcium and vitamin D have been shown to regulate metabolism and to be associated with cardiovascular diseases. However, despite the complexity of parathyroid disorders, features of metabolic syndrome, such as obesity, insulin resistance, and glucose intolerance, arterial blood hypertension, and dyslipidemia, are frequently diagnosed in primary and secondary hyperparathyroidism as well as in pseudohyperparathyroidism. Here, we reviewed the most consistent data highlighting challenges and providing clinical remarks.

Metabolic syndrome (MetS) and hypogonadism (HG) are frequently comorbid. In this review, we summarize interconnections between the construct of MetS and the presence of HG, as well as the effect of specific treatments for each condition on this association. Data from meta-analytic studies suggest a bidirectional pathogenic relationship. In fact, reduced T (-2.21 [-2.43 to -1.98] nmol/L) at baseline predicts incident MetS. On the other hand, MetS at study entry increases the risk of developing HG (OR 2.46 [1.77-3.42]). The bidirectional pathogenic link between MetS and HG is further confirmed by the fact that treating MetS with insulin sensitizer is associated with an increase in T. In addition, a huge effect on increasing T is found in obese men undergoing procedures for losing weight, with more dramatic results obtained after bariatric surgery than after low calorie diet (increase in T 8.73 [6.51-10.95] nmol/L and 2.87 [1.68-4.07] nmol/L, respectively, according to a recent meta-analysis). On the other hand, there is evidence of an improvement in several metabolic derangements characterizing MetS in subjects treated with T. However, the latter results are still not conclusive and need further evidence from randomized clinical trials.

There are very solid data to confirm that the vitamin D endocrine system is important not only for calcium transport or bone homeostasis but also for operational functions in most cells of the body. Preclinical studies convincingly demonstrated coherent actions of the vitamin D endocrine system on the proliferation/differentiation of most cells (and thus possibly on the evolution of cancer). The most plausible target tissues include skeletal and cardiac muscle, all immune cells, many cells involved in cardiovascular homeostasis, brain cells, and reproductive tissues. These data have been generated in models of (near) total absence of vitamin D action or when exposed to very high concentrations of the active hormone, 1,25-dihydroxyvitamin D or its analogs. In humans, observational data frequently demonstrate a link between poor vitamin D status and a large number of major human diseases such as cancer, muscle weakness and falls, infections or autoimmune diseases, hypertension and cardiovascular risks and events, obesity, diabetes and all aspects of the metabolic syndrome, and other health problems. Intervention studies so far have not convincingly demonstrated a positive effect on such extra-skeletal health outcomes. A very large number of ongoing studies (about 3,000), however, should help to clarify the role of vitamin D on the musculoskeletal system and on global health.

Vitamin D has been suggested as a protective compound for diabetes mellitus. Several mechanisms linking vitamin D to the regulation of the immune response support a role for vitamin D in the pathogenesis of autoimmune diabetes. Epidemiological evidence and observational studies suggesting that adequate vitamin D status is related to decreased risk of developing type 1 diabetes further corroborates this concept. However, only few and mostly underpowered randomized clinical trials have been conducted to test the effectiveness of vitamin D supplementation in autoimmune diabetes, with disappointing results. Similarly, recent evidence linking vitamin D action to insulin secretion and sensitivity led to the hypothesis that this compound may play a key role in the regulation of glucose homeostasis in both pre-diabetes and overt type 2 diabetes (T2D). However, the main clinical trials evaluating the efficacy of vitamin D supplementation for the control of glucose homeostasis in people at risk for or affected by T2D have yielded inconsistent results. The aim of this review is to summarize the rationale and results of randomized clinical trials testing vitamin D and its analogs in both autoimmune and T2D.

The number of requests for vitamin D metabolite measurements has increased dramatically over the past decade leading commercial laboratories to develop rapid high throughput assays. The measurement of 25-hydroxyvitamin D (25[OH]D) and to a lesser extent 1,25-dihydroxyvitamin D (1,25[OH]2D) dominates these requests, but requests for multiple metabolite measurements in the same sample are also increasing. The most commonly used methods include immunoassays and liquid chromatography/mass spectrometry (LC-MS). Each method has its advantages and disadvantages, but with improvements in technology, especially in LC-MS, this method is gaining ascendance due to its greater precision and flexibility. The use of standards from the National Institutes of Standards and Technology has substantially reduced the variability from laboratory to laboratory, thereby improving the reliability of these measurements. Although the current demand is for measurement of total vitamin D metabolite levels, these metabolites circulate in blood tightly bound to vitamin D binding protein (DBP) and albumin with less than 1% free. The free concentration may be a more accurate indicator of vitamin D status especially in individuals with DBP levels that deviate from the normal population. Thus, methods to measure the free concentration at least of 25(OH)D are becoming available and may supplement if not replace measurements of total levels.

The interplay between vitamin D and parathyroid hormone (PTH) represents one of the most important metabolic mechanisms of regulation of the calcium/phosphorus homeostasis. Secondary hyperparathyroidism is therefore a major complication that arises as a result of reduced vitamin D levels, both as primary 25-hydroxy-vitamin D (25[OH]D) and/or 1,25-dihydroxyvitamin D (1,25[OH]2D) reduction. Different metabolic pathways are involved, as well as target organs and tissues, with several clinical complications. The skeleton is primarily involved, but many other extra-skeletal organs expressing the vitamin D and/or PTH receptors may theoretically be affected by vitamin D inadequacy and secondary hyperparathyroidism. Mechanisms associated with low vitamin D (mostly, but not exclusively 1,25[OH]2D deficiency) and high serum PTH also intensify chronic kidney disease (CKD), with further consequences on the mineral metabolism system and development of skeletal and cardiovascular disease. Therapeutic intervention is primarily aimed at enhancing serum 25(OH)D levels and reducing secondary hyperparathyroidism, by employing different strategies and endpoints according to the clinical contest. This chapter reviews the current knowledge on the metabolic pathways involved in the vitamin D/PTH axis regulation in different clinical settings and gives an update on the recommended treatment strategies.

Cardiometabolic risk factors like abdominal obesity, hyperglycemia, low high-density lipoprotein (HDL) cholesterol, elevated triglycerides, and hypertension are defined as metabolic syndrome (MetS), which represents one of the most frequent endocrine disorders particularly in a society with increasing weight problems. As more and more evidence is accumulated that thyroid hormones affect components of the MetS, the present review aims to summarize the rapidly expanding knowledge on the pathophysiological interaction between thyroid hormone status and MetS. The review is based on a PubMed search for combinations of thyroid hormone action and MetS, blood pressure, hypertension, hyperlipidemia, cholesterol, HDL cholesterol, glucose, diabetes mellitus, body weight, or visceral fat. A special focus was given for manuscripts published after 2000 but we included seminal papers published before year 2000 as well.

The metabolic syndrome (MetS) is a term used to describe the constellation of cardiometabolic risk factors including central adiposity, dyslipidemia, insulin resistance, non-alcoholic fatty liver disease and arterial hypertension. Notably, a number of studies have shown high rates of testosterone (T) deficiency in men with MetS and type 2 diabetes mellitus (T2DM). Both hypogonadism and MetS confer increased health risk for morbidity and mortality as men with the MetS are at twice the risk for developing cardiovascular disease and at 5-fold higher risk for developing T2DM. Moreover, the inverse relationship between T and MetS is consistently observed across racial and ethnic groups. Thus, in the setting of growing obesity rates, this relationship between the reproductive endocrine axis and metabolism warrants renewed attention. This review specifically focuses on central hypogonadotrophic hypogonadism (CH) providing a concise overview of the metabolic implications of CH and identify the unanswered questions and future directions in this growing field.