Review Articles

Down syndrome can be associated with major impairments in skeletal maturation and bone mass accrual, which increases the risk of fragility fractures. Here, the authors outline various endocrine and metabolic factors that could contribute to suboptimal bone health in children and adolescents with Down syndrome, review indications and limitations of bone density measurement in children and discuss available therapeutic strategies to improve bone health in such patients.

Until recently, weight loss has been viewed as the principal determinant of success in obesity reduction. This Review details a growing body of evidence that links adoption of a healthy lifestyle (but minimal or no weight loss) with appreciable reductions in obesity, in particular abdominal obesity, and related cardiometabolic risk.

Glucose control does not have a clear cardiovascular benefit in people with established, long-duration diabetes mellitus; however, it reduces the risk of diabetes-related eye disease and kidney disease, myocardial infarction and mortality in those with recent-onset diabetes mellitus. Here, the author discusses the relationship between blood glucose level and cardiovascular disease and compares the cardiovascular effects of various glucose-lowering drugs and strategies.

Sleep curtailment, which has become a common behavior in modern society, and sleep disorders, such as obstructive sleep apnea, might have detrimental effects on endocrine functions and glucose metabolism. This review discusses the role of sleep loss and poor-quality sleep in the development of obesity and diabetes mellitus, and highlights the importance of screening for sleep problems in patients with endocrine and metabolic disorders.

Carcinoid tumors are characterized by their ability to secrete hormones, such as serotonin, tachykinins and other mediators that might contribute to carcinoid syndrome. The authors of this Review describe the incidence and prevalence of carcinoid tumor related fibrosis, which is a major complication of this syndrome, and explore the role of potential causative agents.

Incretin-based drugs have several advantages over commonly used antidiabetic agents, including a glucose-dependent mechanism of action and no risk of weight gain. However, their long-term efficacy, safety and durability are yet to be established. This Review summarizes the available data on the mechanisms of action of currently used and emerging incretin-based agents.

Obesity is associated with a systemic, chronic, inflammatory response that involves the production of various cytokines, such as tumor necrosis factor and interleukins. Several interleukins, in particular IL-6 and IL-1, have been suggested to contribute to the development of insulin resistance and type 2 diabetes mellitus, by acting both on insulin signaling pathways and on pancreatic beta and alpha cells. This article provides insights into the latest findings regarding the role of these interleukins in the pathology and physiology of obesity-related insulin resistance and type 2 diabetes mellitus.

Trans fatty acids, which are largely consumed from partially hydrogenated vegetable oils, adversely affect circulating lipid and lipoprotein levels and endothelial function, trigger systemic inflammation, and might increase visceral adiposity, body weight, and insulin resistance. The authors provide an overview of these adverse effects and their relationships with clinical endpoints, with a focus on potential effects on insulin resistance and diabetes.

Chronic hyperglycemia in diabetes mellitus can lead to erythropoietic stress and subsequent anemia, which might contribute to diabetes-related complications. The authors of this Review discuss the various causes of diabetes-related anemia and current guidelines on its correction, and emphasize the role of screening and monitoring for this preventable condition in patients with diabetes mellitus.

Innate immunity and inflammatory mediators have been suggested to have a much broader role in type 1 diabetes mellitus than initially assumed. Inflammation might contribute to early induction and amplification of the immune assault against pancreatic β-cells and, at later stages, to the stabilization and maintenance of insulitis. This review summarizes the latest findings that demonstrate the role of inflammation in the different phases of the course of type 1 diabetes mellitus.

Studies of common genetic variants have yielded new insights into the actions of thyroid hormones and highlighted the importance of local regulation of thyroid hormones in tissues. The authors describe genetic polymorphisms that are related to the thyroid hormone pathway and discuss the influence of these polymorphisms on various biological systems.

The discovery of human embryonic stem cells raised hopes that cell-based therapies would soon become widely available. However, ethical concerns have limited their clinical use. An alternative approach is to reprogram adult somatic cells to a pluripotent state. The pros and cons of generating pluripotent stem cells for clinical applications are discussed.

The rapid obesity surge in industrialized countries is attributed to genetic susceptibility and environmental factors; however, the primary defects that lead to obesity are still largely unknown. This Review summarizes our current knowledge about the neuronal populations and intracellular signaling molecules that are involved in maintaining normal body weight.

Diabetic dyslipidemia, characterized by low HDL cholesterol level and high levels of triglyceride and small dense, LDL cholesterol, greatly increases the risk of cardiovascular disease. Given the complexity of the dyslipidemic profile, multiple agents are often required to achieve therapeutic goals. This Review discusses the use of various pharmacological agents as well as lifestyle changes for the treatment of dyslipidemia in diabetes mellitus.

Abnormalities in hypothalamic–pituitary axis function frequently occur in cancer survivors following prophylactic or therapeutic cranial irradiation. Growth hormone deficiency is particularly prevalent, even after low radiation doses. The author of this Review provides an overview of the epidemiology and pathophysiology of radiation-induced hypopituitarism and describes strategies for effective diagnosis and patient care.

Hyperinsulinemic hypoglycemia is a consequence of inappropriate and unregulated secretion of insulin by pancreatic β-cells. This Review provides an overview of the known genetic and nonhereditary causes and various clinical presentations of this condition, and discusses how advances in imaging and laparoscopic surgery have transformed its clinical management.

From middle-age onwards, men experience a characteristic decline in circulating total and free testosterone levels. These hormonal changes are associated with negative health outcomes, although the direction of causation is still uncertain. This Review discusses risk factors associated with age-related androgen deficiency, therapeutic approaches and possible preventive measures.

The passage of thyroid hormones from the maternal circulation to the fetal circulation is important for normal fetal development. This Review discusses the changes in maternal and fetal thyroid hormone levels during pregnancy and the factors modulating transplacental thyroid hormone supply to the fetus, as well as pathological situations in which the placenta cannot optimize fetal thyroid hormone levels.

Calcitonin is produced by the parafollicular C cells and represents the classical clinical marker for medullary thyroid carcinoma. Here, the authors describe how measurement of basal and stimulated serum calcitonin levels can be used for screening, differential diagnosis, prognostic assessment, and follow-up monitoring in patients with medullary thyroid carcinoma.

In addition to well-characterized hepatic effects, a large body of evidence now suggests that chronic infection with hepatitis C virus (HCV) can lead to endocrine dysfunction. The authors of this Review evaluate the data supporting a link between hepatitis C virus infection and the endocrine system, and discuss potential pathophysiological mechanisms.