Review Articles in 2012

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.

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.

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.

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.

Pregnancy has a considerable effect on maternal thyroid function. In this Review, the pros and cons of universal screening for thyroid disease during pregnancy versus targeted case finding are discussed and the changes in thyroid function that occur during pregnancy are detailed. Accordingly, best-practice guidance for thyroid function testing and treatment of hypothyroidism, hyperthyroidism and thyroid autoimmune disease during pregnancy are provided. In addition, an algorithm for diagnosing, monitoring and treating women who develop postpartum thyroiditis is provided.

Experimental and animal data suggest that maternal obesity adversely affects offspring health, but effects in humans are less clear. This Review evaluates the evidence for a causal effect of maternal increased adiposity and gestational weight gain on perinatal and long-term offspring outcomes in humans and explores the possible contribution of epigenetic modifications.

Normal gestation is characterized by dramatic changes in a number of endocrine systems and particularly by activation of the renin–angiotensin–aldosterone system and the hypothalamic–pituitary–adrenal axis. This Review provides an overview of adrenal steroid metabolism during pregnancy, focusing on diagnosis and treatment of the most common fetal and maternal adrenal disorders.

Pregnant women with type 1 diabetes mellitus have an increased risk of adverse pregnancy outcomes. This Review discusses the importance of preconception counselling and careful monitoring of glucose levels, and describes the use of insulin analogues to maintain tight glycaemic control from pregnancy planning through to breastfeeding.

In this Review, the possibilities for utilizing GLP-1 receptor agonists in individualized treatment for type 2 diabetes mellitus are discussed. The currently available compounds are evaluated in terms of their efficacy, duration of action and adverse effects. The feasibility of selecting a treatment option on the basis of an individual's clinical parameters and requirements is also touched upon.

Clinical assessment of the hypothalamic–pituitary–adrenal axis relies on measuring total serum cortisol levels. However, most circulating cortisol is bound to carrier proteins and only free cortisol is biologically available. This Review examines factors that regulate peripheral and tissue glucocorticoid bioavailability and highlights specific clinical indications for the measurement of bioavailable glucocorticoids.

Obesity is a key feature of the metabolic syndrome and increased adiposity has been associated with inflammation in the visceral compartment. In this Review, the authors describe inflammatory processes that occur in adipose tissue, focussing on how adaptive immune system cells promote inflammation.

Gestational diabetes mellitus is one of the most common medical complications of pregnancy. The disease has important health implications for mother and child. This Review discusses current evidence for the importance of gestational diabetes mellitus, opportunities to reduce risk to mother and child and recommendations for clinical care.

Parathyroid cancer is a rare cause of primary hyperparathyroidism, but a missed diagnosis is often fatal. This Review highlights genetic, imaging and laboratory findings that can generate a preoperative diagnosis (or strong suspicion) of parathyroid cancer. The authors describe the management of these patients, which should include oncological resection and histological disease staging to predict prognosis and the need for adjuvant treatment.

Functional neuroimaging techniques have been used to gain insights into the brain's role in energy balance. This Review discusses the aetiology of hypoglycaemia unawareness, which can be a complication of therapy for type 1 diabetes mellitus, and examines the dysregulation of appetite control and energy balance associated with insulin resistance and type 2 diabetes mellitus.

Considerable advances in the understanding of acromegaly have been made in the past two decades, and improvements in diagnosis of this condition probably underlie the increased prevalence. This Review explores how our knowledge of acromegaly has changed and discusses the novel treatments being developed as part of the evolving approach to acromegaly therapy.

To date, more than 350 nuclear receptor coregulators have been reported in the literature and a larger number of coregulator-interacting proteins have also been identified. Coregulators have been implicated in diverse pathological states, genetic syndromes and cancer. This Review focuses on their broad physiological and pathological functions and their promise as new drug targets for diseases such as hormone-dependent cancers.

Excess or insufficient adipose tissue accumulation can lead to metabolic complications such as insulin resistance, type 2 diabetes mellitus, dyslipidaemia and hepatic steatosis. Klotho increases adipocyte differentiation and could affect glucose metabolism. This Review describes the role of Klotho in energy metabolism and examines its effects on adipogenesis and obesity.