Reviews & Analysis

In 2016, four studies were published that provided crucial new information on the endocrine actions of the hormone fibroblast growth factor 21 (FGF21). These studies provide a framework for the nutritional stimuli that regulate FGF21 expression and demonstrate a major role for FGF21 in primates and humans in regulating food intake, macronutrient preference and central reward pathways.

The hypothalamus and pituitary gland can undergo many functional adaptations to control hormonal output. In this Review, the authors describe our current understanding of the neuroendocrine changes in these structures that maximize reproductive success, and highlight how new imaging techniques have transformed our interpretation of these processes.

Endocrine-disrupting chemicals (EDCs) can contribute to the development of certain disorders and are known to have a high health-care burden in some countries. A new analysis has revealed the substantial impact of EDCs on health and associated costs in the USA.

The link between mood disorders and hormonal fluctuations has long been known, but the direction of this correlation has been questioned. New research suggests that initiation of hormonal contraception leads to increased risk of first-time diagnosis of or treatment for depression over a short time frame, particularly for adolescents.

As a large number of genes have been implicated in the development of hereditary phaeochromocytomas and paragangliomas (PPGLs), next-generation sequencing (NGS) technology is ideally suited for carrying out genetic screening. This Consensus Statement proposes specific recommendations for the use of diagnostic NGS in hereditary PPGLs.

Endocrine-disrupting chemicals (EDCs) can increase the risk of childhood diseases by disrupting hormone-mediated processes critical for growth and development. Here, Joseph Braun discusses epidemiological evidence of associations between early-life exposure to EDCs and childhood neurodevelopmental disorders and obesity.

Early attempts at the reinduction of ¹³¹I uptake by redifferentiation of ¹³¹I-negative differentiated thyroid cancer (DTC) had limited success. Novel therapies targeting the pathways that restore expression of the sodium iodine symporter now offer new hope of success for redifferentiation therapy in DTCs with the BRAF^V600E mutation.

Islet transplantation has become a realistic treatment option for a subset of patients with type 1 diabetes mellitus. This Review outlines the techniques involved in the procedure, as well as the risks, long-term outcomes and advances in the care of patients after they have received an islet transplant.

Treatment of type 2 diabetes mellitus with GLP1 receptor agonists can result in long-term glycaemic control or can fail over time, in which case insulin can be used as an alternative or as an additive treatment. New research shows that the latter is more likely to achieve glycaemic targets than the former.

In a recent study by Cosman and colleagues, romosozumab — a humanized monoclonal antibody targeting sclerostin — is shown to reduce the risk of vertebral and clinical fractures at 12 months compared with placebo. However, the low fracture risk of study participants necessitates the completion of an on-going clinical trial before romosozumab can be fully adopted into clinical practice.

Patients with anorexia nervosa severely restrict their food consumption. In this Review, Schorr and Miller discuss the endocrine abnormalities that arise in these patients as a result of their reduced calorie intake and potential therapies that can help restore endocrine function.

Dyslipidaemia is a major contributor to the onset of metabolic disease. Here, Meikle and Summers discuss lipidomic research into relationships between diet, lipid metabolism and metabolic disease. The Review also highlights promising potential therapeutics that target lipid metabolism to counteract obesity, insulin resistance and type 2 diabetes mellitus.

In this Review, Sylow and colleagues discuss the molecular mechanisms and signalling pathways that regulate glucose uptake from the blood into the muscle during exercise, and the roles of both known and candidate molecules in the process.

In the Steno-2 trial, 160 individuals with type 2 diabetes mellitus, mostly in their 50s, were randomly assigned to multifactorial interventions or conventional care. Whereas microvascular and macrovascular complications were reduced during the 7.8 years of the trial period with intensive therapy, the observational follow-up data at 13.3 years and, now, 21 years demonstrate a benefit on mortality.

Clinical practice regarding the use of hormone-replacement therapy (HRT) has undergone many changes since its introduction in the 1940s. Here, Roger Lobo frames the current thinking on the use of HRT in postmenopausal women, beginning with a historical perspective and then discussing how the interpretation of HRT data has changed over time.

Here, Chow and colleagues discuss the endocrine manifestations of mitochondrial diseases, a group of multisystem disorders characterized by great clinical, biochemical and genetic heterogeneity. The authors describe the clinical features, genetic causes and pathological mechanisms underlying these diseases, the understanding of which will be key to developing innovative therapies for these patients.

A new population-based cohort study in patients with type 2 diabetes mellitus has found that systolic blood pressure below the level currently recommended by hypertension guidelines is associated with a lower risk of cardiovascular events than the present threshold. However, whether blood pressure goals should be lowered remains contentious.

In 1998, two children with congenital adrenal insufficiency and early-onset morbid obesity were found to have causative null mutations in POMC. In a new study, therapy with the melanocortin-4 receptor agonist setmelanotide has for the first time brought hope of a normal life to patients with POMC-deficiency.

Diabetes mellitus is associated with an increased risk of fragility fractures. Here, Napoli and colleagues discuss the complex interactions between glucose homeostasis and bone fragility, the epidemiology of fractures in patients with diabetes mellitus and the effects of antidiabetic drugs on bone health.

Polycystic ovary syndrome (PCOS) is associated with adverse metabolic and reproductive outcomes and guidelines recommend early diagnosis, screening and management. However, new stricter definitions of the diagnostic features of polycystic ovaries on ultrasonography might in fact exclude some women from a diagnosis of PCOS who could benefit from preventive management.