Endocrine Reviews

Steroid biosynthesis and metabolism is reflected by the serum steroid metabolome and, in even more detail, by the 24-hour urine steroid metabolome, which can provide unique insights into alterations of steroid flow and output indicative of underlying conditions. Mass spectrometry-based steroid metabolome profiling has allowed for the identification of unique multi-steroid signatures associated with disorders of steroid biosynthesis and metabolism that can be used for personalized approaches to diagnosis, differential diagnosis and prognostic prediction...

Recent, rapid changes in the treatment of type 1 diabetes have allowed for commercialization of an "artificial pancreas" which is better described as a closed-loop controller of insulin delivery. This review presents the current state of closed-loop control systems and expected future developments with a discussion of the human factor issues in allowing automation of glucose control. The goal of these systems is to minimize or prevent both short and long-term complications from diabetes and to decrease the daily burden of managing diabetes...

While bariatric surgery was developed primarily to treat morbid obesity, evidence from the earliest clinical observations to the most recent clinical trials is consistently demonstrates that these procedures have substantial effects on glucose metabolism. A large base of research indicates that bariatric surgeries such as Roux-en-Y-gastric bypass (RYGB), vertical sleeve gastrectomy (VSG), and biliopancreatic diversion (BPD) improve diabetes in most patients, with effects frequently evident prior to substantial weight reduction...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Parathyroid hormone (PTH) is an important regulator of calcium and phosphate homeostasis and bone remodeling. PTH is metabolized into PTH fragments which are measured to a different extent by PTH assays of different generations. This is due to differences in fragments recognized and lack of assay standardization. PTH is measured in the workup of several conditions and clinical guidelines provide recommendations concerning these measurements. This review provides an overview of the impact of differences between PTH assays, when applying distinct clinical guidelines for primary and secondary hyperparathyroidism and perioperative use of PTH measurements...

The gut microbiome is now considered as an organ contributing to the regulation of host metabolism. Since the finding of the existence of a relationship between the gut microbiome and specific diseases, numerous studies have also deciphered molecular mechanisms explaining how gut bacteria dialogue with host cells and eventually shape metabolism. Both metagenomic and metabolomic analyses have contributed to the discovery of bacterial-derived metabolites acting on host cells. In this review, we examine the molecular mechanisms by which bacterial metabolites are acting as paracrine or endocrine factors thereby regulating host metabolism...

This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic gastroenteropathy, which encompasses all the gastrointestinal manifestations of diabetes mellitus (DM). Up to 50% of patients with type 1 and 2 DM and suboptimal glycemic control have delayed gastric emptying (GE), which can be documented with scintigraphy, 13 C-breath tests, or a wireless motility capsule; the remainder have normal or rapid GE. Many patients with delayed GE are asymptomatic; others have dyspepsia (i...

All mammalian uteri contain glands in the endometrium that develop only or primarily after birth. Gland development or adenogenesis in the postnatal uterus is intrinsically regulated by proliferation, cell-cell interactions, growth factors and their inhibitors as well as transcription factors including forkhead box A2 (FOXA2) and estrogen receptor alpha (ESR1). Extrinsic factors regulating adenogenesis originate from other organs including the ovary, pituitary, and mammary gland. The infertility and recurrent pregnancy loss observed in uterine gland knockout sheep and mouse models support a primary role for secretions and products of the glands in pregnancy success...

The Glycation Gap (GGap) and the similar Hemoglobin Glycation Index (HGI) define consistent differences between glycated hemoglobin and actual glycemia derived from fructosamine or mean blood glucose respectively. Such a disparity may be found in a substantial proportion of people with diabetes, being > than 1 unit of glycated HbA1c% or 7.2 mmol/mol in almost 40% of estimations. In this review we define these indices, explain how they can be calculated and that they are not spurious, being consistent in individuals over time...

Thyroid plays a crucial and pervasive role in physiology (metabolism, thermogenesis and immunity, among others) and its aging and related changes in thyroid hormones production contribute to the common occurrence of thyroid diseases in elderly and to age-associated changes in other organs and systems. We address the complexity of thyroid aging following the basic suggestions of Geroscience. This integrative new perspective identifies few basic molecular mechanisms or "pillars" (inflammation, adaptation to stress, loss of proteostasis, stem cell exhaustion, metabolism derangement, macromolecular damage, and epigenetic modifications) as a unifying conceptual framework to understand the aging process and age-associated diseases...

Sex steroid estrogens, androgens, and progesterone, produced by the gonads which have long been considered as endocrine glands, are implicated in sexual differentiation, puberty, and reproduction. However, the impact of sexual hormones goes beyond these effects through their role on energy metabolism. Indeed, sexual hormones are important physiological regulators of glucose homeostasis and, in particular of the entero-insular axis. In this review, we describe the roles of estrogens, androgens, and progesterone on glucose homeostasis, through their effects on pancreatic alpha and beta-cells as well as on entero-endocrine L-cells and their implication in hormonal biosynthesis and secretion...

Type 2 diabetic patients are at high risk for macrovascular complications, which represent the major cause of mortality. Despite effective treatment of established cardiovascular (CV) risk factors (dyslipidemia, hypertension, procoagulant state), there remains a significant amount of unexplained cardiovascular risk. Insulin resistance is associated with a cluster of cardiometabolic risk factors known collectively as the insulin resistance (metabolic) syndrome (IRS). Considerable evidence, reviewed herein, suggests that insulin resistance and the IRS contribute to this unexplained cardiovascular risk in type 2 diabetic patients...

The presence of adipocytes in mammalian bone marrow (BM) has been recognized histologically for decades, yet, until recently, these cells have received little attention from the research community. Advancements in mouse transgenics and imaging methods, particularly in the last ten years, have permitted more detailed examinations of marrow adipocytes than ever before and yielded data that show these cells are critical regulators of the BM microenvironment and whole body metabolism. Indeed, marrow adipocytes are anatomically and functionally separate from brown, beige, and classical white adipocytes...

The liver is a dynamic organ that plays critical roles in many physiological processes, including the regulation of systemic glucose and lipid metabolism. Dysfunctional hepatic lipid metabolism is a cause of non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disorder worldwide, and is closely associated with insulin resistance and type 2 diabetes. Through the use of advanced mass spectrometry 'omics' approaches and detailed experimentation in cells, mice and humans, we now understand that the liver secretes a wide array of proteins, metabolites and non-coding RNAs (miRNAs) and that many of these secreted factors exert powerful effects on metabolic processes both in the liver and in peripheral tissues...

The role of chronic inflammation in the pathogenesis of type 2 diabetes mellitus and associated complications is now well established. Therapeutic interventions counteracting metabolic inflammation improve insulin secretion and action and glucose control and may prevent long-term complications. Thus, a number of anti-inflammatory drugs approved for the treatment of other inflammatory conditions are evaluated in patients with metabolic syndrome. Most advanced are clinical studies with IL-1 antagonists showing improved β-cell function and glycemia and prevention of cardiovascular diseases and heart failure...

Thyroid hormone (TH) molecules enter cells via membrane transporters and, depending on the cell type, can be activated (i.e., T4 to T3 conversion) or inactivated (i.e., T3 to 3,3'-diiodo-l-thyronine or T4 to reverse T3 conversion). These reactions are catalyzed by the deiodinases. The biologically active hormone, T3, eventually binds to intracellular TH receptors (TRs), TRα and TRβ, and initiate TH signaling, that is, regulation of target genes and other metabolic pathways. At least three families of transmembrane transporters, MCT, OATP, and LAT, facilitate the entry of TH into cells, which follow the gradient of free hormone between the extracellular fluid and the cytoplasm...

Glucose homeostasis requires an organism to rapidly respond to changes in plasma glucose concentrations. Iatrogenic hypoglycemia as a result of treatment with insulin or sulfonylureas is the most common cause of hypoglycemia in humans and is generally only seen in patients with diabetes who take these medications. The first response to a fall in glucose is the detection of impending hypoglycemia by hypoglycemia-detecting sensors, including glucose-sensing neurons in the hypothalamus and other regions. This detection is then linked to a series of neural and hormonal responses that serve to prevent the fall in blood glucose and restore euglycemia...

The number of patients surviving ≥5 years after initial cancer diagnosis has significantly increased during the last decades due to considerable improvements in the treatment of many cancer entities. A negative consequence of this is that the emergence of long-term sequelae and endocrine disorders account for a high proportion of these. These late effects can occur decades after cancer treatment and affect up to 50% of childhood cancer survivors. Multiple predisposing factors for endocrine late effects have been identified, including radiation, sex, and age at the time of diagnosis...

Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. The underlying pathologic mechanisms in the intracavitary endometrium and extra-uterine endometriotic tissue involve defectively programmed endometrial mesenchymal progenitor/stem cells...