Reviews & Analysis

Disorders of sex development (DSDs) are congenital conditions in which chromosomal, gonadal or anatomical sex is atypical. In this Review, the authors outline the complex network of gene regulation that is required for gonadal development. They then describe gene mutations that perturb the delicate balance of the network and lead to DSDs. Finally, the authors discuss management of patients with DSDs.

The diagnosis and monitoring of osteoporosis have been improved by the development of new methods for undertaking skeletal assessment. A number of imaging methods exist and all have advantages and disadvantages. In this Review, the use of different quantitative skeletal assessment tools and techniques for imaging bone structure are discussed. The advantages and disadvantages of each method are examined and the feasibility of using these techniques in both clinical and research settings is considered.

Primary aldosteronism is determined by deregulated aldosterone production from the adrenal glands and both sporadic and genetic forms exist. Mutations in the GIRK4 potassium channel are associated with both sporadic aldosterone-producing adenomas and familial hyperaldosteronism type III. This Review highlights the pathophysiological role of GIRK4 in sporadic and genetic hyperaldosteronism and discusses the molecular alterations associated with channel dysfunction.

Low circulating levels of vitamin D metabolites were found to be associated with development of microalbuminuria in patients with type 1 diabetes mellitus from the DCCT/EDIC study. Could interventions aimed at improving vitamin D levels be a new option for the prevention of diabetic kidney disease?

A joint task force of the American Association of Clinical Endocrinologists and the American Thyroid Association has produced updated clinical guidelines for the diagnosis and treatment of hypothyroidism in adults. The new guidelines include 52 evidence-based best practice recommendations to help clinicians provide optimal care for patients with hypothyroidism.

A large Danish study overturns the concept that postmenopausal hormone replacement therapy increases the risk of experiencing cardiovascular events. Indeed, the study shows that such therapy decreases the risk of myocardial infarction by ∼50% and mortality by ∼40%. So what is the truth?

Total thyroidectomy and subsequent radioiodine ablation improve the outcome of patients with thyroid tumours measuring >1 cm. Best practice guidelines should serve as a basis for clinical decision making in stage I thyroid cancer; however, Haymart et al. report that soft factors, unrelated to clinical presentation, affect the rate of radioiodine ablation.

Advances in understanding of B-lymphocyte maturation and immune tolerance are yielding new insight into the influence of gonadal steroids on the humoral immune system. Kovacs and colleagues examine how oestrogens and androgens directly and indirectly modulate B-lymphocyte development and function, focusing on B lymphopoiesis, elimination of autoreactive B-cell clones, and generation of high-affinity, class-switched, immunoglobulin-producing B cells.

Vagus-nerve signalling regulates immune activation and metabolic homeostasis. Dysregulation of metabolism and immune function in obesity results in chronic inflammation associated with insulin resistance and type 2 diabetes mellitus. In this Review, exploiting the vagus-nerve-mediated inflammatory reflex in the treatment of obesity-related disorders is discussed.

A variety of gastrointestinal disorders, including Crohn's disease, ulcerative colitis and coeliac disease, are recognized risk factors for osteoporosis and osteoporotic fractures. A recent study suggests that individuals with irritable bowel syndrome might also be at increased risk of osteoporosis and osteoporosis-related fractures.

The worldwide increase in obesity has been driven by global trade liberalization, economic growth and rapid urbanization. Owing to the scope and complexity of the obesity epidemic, prevention strategies and policies across multiple levels are needed in order to have a measurable effect. Although many putative causes of the obesity epidemic exist, in this Review the effect of globalization on global trends in obesity prevalence is discussed and population-based interventions from several countries are reviewed. The authors make broad policy recommendations for obesity and chronic disease prevention at the global population level.

The weight of evidence indicates that bisphenol A (BPA), a widespread endocrine disruptor, might be an important risk factor for obesity and metabolic disorders. An epidemiological study shows an association between urinary BPA levels and increased body mass in children and adolescents.

Individuals with obesity who undergo bariatric surgery are much less likely to develop type 2 diabetes mellitus than are those receiving routine care, new findings reveal. Intriguingly, baseline data on surrogate measures of insulin resistance rather than BMI were predictive of the preventive effect of surgery on type 2 diabetes mellitus.

Urban traffic is a major source of ambient air pollution and induces oxidative stress, systemic inflammation and cardiovascular disease. A recent study shows that the risk of death from diabetes mellitus is increased in individuals exposed to high levels of traffic-related air pollution.

Controlled clinical trials have demonstrated a substantial reduction in all long-term complications of type 1 diabetes mellitus (T1DM) if an HbA_1c level of <7% is achieved. Long-acting insulin analogues have now been developed; however, their role in the intensive therapy of patients with T1DM is debatable.

Osteocalcin is a vitamin-K-dependent bone matrix protein that has been linked to glucose metabolism in mice. This finding presents a new paradigm for understanding the role of the skeleton and energy metabolism. This Review highlights the unique species-specific features of osteocalcin and the evidence for its role in energy metabolism in humans.

People with or who are at risk of developing type 2 diabetes mellitus (T2DM) could prevent or reduce T2DM-related complications through physical activity. A new study shows the effects of physical activity on mortality in T2DM and another compares the effects of aerobic exercise, weight training or a combined programme on risk of T2DM.

A growing body of research is examining the potential health implications of menopausal vasomotor symptoms. A recent study found that vasomotor symptoms are associated with increased insulin resistance in middle-aged women undergoing the menopausal transition.

A recent meta-analysis provides robust data on the weight gain that is likely to be experienced by individuals who give up smoking. Weight gain 1 year after quitting was 4–5 kg; therefore, is weight gain following smoking cessation of sufficient importance to affect approaches to and success of smoking cessation?

In African countries, just as in developed nations, data now show that maternal obesity is associated with an increased risk of neonatal death. Additional consequences of maternal obesity on child health, such as reduced breastfeeding duration and an increased risk of child obesity, will probably soon become evident.