Review Articles in 2014

Approximately one-third of follicular thyroid carcinomas containPAX8–PPARG gene fusions, which result in the production of an oncogenic Pax 8–PPAR-γ fusion protein (PPFP). Here, Raman and Koenig describe the structure and function of PAX8 and PPARGand their protein products. They discuss possible mechanisms underlying the oncogenic action of PPFP and highlight the potential of PPFP as a diagnostic marker in thyroid nodule evaluation and as a therapeutic target.

Antiangiogenic therapies that target VEGF signalling are often used in combination with chemotherapeutic agents to treat a variety of cancers. In this Review, the author discusses the paradox of the beneficial and detrimental consequences of systemic administration of anti-VEGF drugs on endocrine organs in preclinical models and in clinical trials.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. This article provides an overview of the pathophysiology, aetiology, diagnosis, and management of the most common presenting features of PCOS, including hyperandrogenism, menstrual irregularity and infertility. Management of cardiometabolic risk, an important concern in these patients, is also discussed.

The diagnosis of disorders of sex development (DSDs) in individuals and the subsequent management of patients and their families requires a multidisciplinary approach. In this Review, Olaf Hiort and colleagues discuss the latest developments in diagnostic procedures for identifying DSDs and strategies for managing patients, including the creation of centres of expertise.

The management of differentiated thyroid cancer (DTC) is undergoing a paradigm shift, with the recognition that personalized therapies might lead to improved outcomes with reduced severity and frequency of complications. In this Review, Markus Luster and colleagues discuss aspects of DTC management that are suitable for individualization, including the extent of surgery, the dosage of¹³¹I and the use of levothyroxine. Advances in imaging techniques and the potential benefit of multitargeted kinase inhibitors are also discussed in the context of DTC management.

In this Review, the authors explore the endocrine and neural basis of reward mechanisms triggered in response to food, and how they are influenced by obesity and overeating. They also discuss the relationship between excessive food intake and addiction-like eating behaviours.

Obesity is associated with an increased risk of certain cancers, such as breast and colon cancers and hepatocellular carcinoma. In this Review, the authors discuss the mechanisms that underlie the interplay between tumour cells and adipocyte-rich stromal tissues that drives the creation and maintenance of a unique microenvironment that favours tumour growth and metastasis.

Accumulating evidence suggests that common reproductive problems, such as male infertility and testicular cancer, originate during fetal development. In this Review, Anders Juul and colleagues discuss the current knowledge of a variety of male reproductive issues, focusing on the developmental origins of testicular pathologies in the context of male infertility.

Disruption of the precise timing of gonadal differentiation and the exposure to adequate levels of specific hormones during critical periods that is required for normal genital development leads to disorders of sex development. This Review summarises the malformation syndromes associated with disorders of sex development and discusses the recent research into their aetiology.

Fetal exposure to increased levels of glucocorticoids can lead to long-term 'programming' of hypothalamic–pituitary–adrenal function and behaviours. This Review discusses the mechanisms underlying fetal glucocorticoid programming, including epigenetic modifications, as well as the mechanisms of transgenerational programming.

Adequate circadian oscillation of endocrine factors is essential in the maintenance of metabolic homeostasis. The authors of this Review explain the influence of extrinsic and intrinsic factors on endocrine circadian rhythms and how dysregulation of these rhythms can lead to disease in animals and humans. They also discuss therapeutic strategies to restore circadian rhythmicity and improve metabolism.

The fetal hypothalamic–pituitary–adrenal (HPA) axis is particularly susceptible to long-term programming by glucocorticoids, which can have long-term effects. Here, the evidence regarding fetal programming of the HPA axis and behaviour in humans and animals after prenatal glucocorticoid exposure (either endogenous or synthetic) are discussed.

In this article, Kuipers and colleagues review how bile acids modulate glucose and lipid metabolism. The authors discuss the mechanisms by which bile acids, agonists of bile acid signalling pathways and bile acid sequestrants influence glucose levels in animal models and patients with insulin resistance and type 2 diabetes mellitus and how altered bile acid metabolism might contribute to the beneficial effects of bariatric surgery.

The WHO classification of pituitary tumours (typical adenomas, atypical adenomas and pituitary carcinomas) does not distinguish between aggressive and nonaggressive tumours. This Review highlights the need to recognize aggressive pituitary adenomas as a distinct clinical entity, taking into account not only clinical behaviour, but also histopathological, molecular and radiological features. It also discusses promising biomarkers that might facilitate the early detection of clinically aggressive pituitary tumours and subsequent management of selected patients.

The three most prevalent types of osteoporotic fractures occur in the hip, vertebrae and distal forearm. With ageing populations, such fractures contribute to an increasing economic burden on healthcare systems. In this Review, Cauley and colleagues discuss the variation in osteoporotic fracture rates throughout the world, with a specific emphasis on the geographical and ethnic differences both within and between countries.

GLOW is a large-scale international study of osteoporosis in women. Here, Nelson Watts discusses the findings of the first 3 years of the GLOW study, including data on prevalence and incidence of fractures in different geographical regions, the predictive values of different sites of fracture and various comorbidities, and implications for appropriate therapy of individuals at risk.

Obesity and hypertension are associated with high morbidity and mortality. In this Review, DeMarco and colleagues describe the pathophysiological mechanisms that can lead to obesity-related hypertension and discuss potential therapies that might be used to treat the condition.

The utility of gonadotropin-releasing hormone agonists (GnRHa) treatment in girls with early puberty are much debated, as are its limitations. Here, the authors outline the different types of early puberty, the short-term and long-term effects of GnRHa treatment, life-course consequences of early pubertal development and areas in need of additional research.

This Review outlines the cell and tissue-specific mechanisms that lead to cardiovascular events in patients with type 1 and type 2 diabetes mellitus. The authors discuss how these complications relate to classic cardiovascular risk factors and highlight a common mechanism that might link coronary artery disease to both forms of diabetes mellitus.

Emerging evidence implicates autophagy in the maintenance of energy homeostasis, both at the cellular level and within the organism as a whole. The authors of this Review discuss the control of cellular autophagy by nutrients, the regulation of energy metabolism by autophagy and the consequences of autophagy dysfunction and modulation in metabolic disease.