Reviews & Analysis

The past decade has seen exciting progress in the field of thyroid disease, especially in the evaluation of thyroid nodules, the genomic characterization of carcinomas and the treatment of carcinomas after surgery. An improved understanding of hyperthyroidism during pregnancy, as well as the causes of 'low T₃ syndrome' and consumptive hypothyroidism have also been achieved.

The mechanistic link between the FTO locus and risk of obesity has remained elusive. However, a new study presents compelling evidence suggesting that the browning of white adipocytes into beige adipocytes (together with regulation of thermogenesis), might be an important and potentially modifiable pathway for development of obesity therapeutics.

In this Review, Jeffrey Baron and colleagues explore the latest discoveries in the molecular and cell biology of childhood growth and in the clinical genetics of childhood growth disorders. These findings challenge the established theory that childhood growth is primarily controlled by growth hormone and insulin-like growth factor 1, leading the authors to suggest a broader framework for understanding linear growth disorders.

T cells are generated in the thymus and exported to peripheral lymphoid organs, a process that is under hormonal control. In this article, the authors discuss the mechanisms of thymus-specific T-cell development and how hormone therapy can counteract the effects of ageing and disease on thymus function.

In an analysis of data from NHANES spanning from 1999 to 2010, Tuot et al. address two linked questions. Which patients with diabetes mellitus and renal insufficiency are reasonable candidates for metformin therapy and how does this treatment depend on the approach used to measure renal function?

This Review outlines the physiologic role of the iodothyronine deiodinases, as well as the changes that occur in hypothyroidism, with a particular focus on their role in preserving thyroid hormone levels in the brain. Novel findings that underscore the clinical importance of iodothyronine deiodinases in hypothyroidism are also discussed.

A subclass of endocrine-disrupting chemicals, so-called 'obesogens', have been proposed to predispose certain individuals to weight gain, despite their efforts to limit caloric intake and increase levels of physical activity. In this Review, Jerrold Heindel and colleagues discuss the experimental and epidemiological findings on obesogens, their modes of action, and their role in the obesity epidemic.

The past 10 years have seen substantial advances in many areas of paediatric endocrinology. Major progress has been made in our understanding of the aetiology of many disorders with the advent of next-generation sequencing. Furthermore, the introduction of novel therapies has revolutionized clinical management.

In this Viewpoint, six members of our Advisory Board comment on advances in the past 10 years that have revealed new hormones, new functions for known hormones and endocrine organs and new endocrine roles for well-known organs. The authors discuss how bone was recognized as an endocrine organ, the emerging understanding of the importance of gut hormones, targeting ectopic adipose tissue and the pathogenesis and treatment of type 2 diabetes mellitus.

Antisense oligonucleotides have proven effective at preventing protein synthesis as a result of their on-target specificity. Recent data from several clinical trials including a phase I trial targeting Lp(a), published in The Lancet, highlight the therapeutic potential of antisense oligonucleotides in regulating plasma lipid levels.

Our understanding of bone biology and the subsequent development of therapies to treat bone diseases have both expanded greatly in the past 30 years. This article reviews some of the key advances made in these fields during the past decade.

Over the past decade, the growing epidemic of type 2 diabetes mellitus (T2DM) and its associated complications has presented both challenges and opportunities. Progress has been made in incretin-based therapies, bariatric surgeries and inhibiting renal glucose reabsorption; however, long-term safety and efficacy studies are required. Advances in the prevention of macrovascular complications of T2DM from ongoing clinical trials are expected soon.

Long-chain acylcarnitines (LCACs) are widely used as diagnostic markers in several metabolic disorders; however, research into the potential effects of excessive accumulation of LCACs or the roles of acylcarnitines as physiological modulators of cell metabolism is lacking. This Review, therefore, aims to provide a theoretical framework for the potential consequences of tissue build-up of LCACs among individuals with metabolic disorders.

Parathyroid hormone/parathyroid hormone-related peptide receptor (PTHR1) is a family B G-protein-coupled receptor and is involved in the regulation of skeletal development, bone turnover and mineral ion homeostasis. This Review discusses fundamental aspects of ligand-binding and signalling mechanisms at PTHR1, highlighting the relationship between ligand structural modification and variation in PTHR1 signalling responses. The action of these signalling mechanisms in disease states in which PTHR1 function has an important role are also discussed.

In a new study published in The Lancet Diabetes & Endocrinology, metformin use is associated with significantly increased all-cause mortality in patients with type 2 diabetes mellitus and stage 5 chronic kidney disease (CKD). The findings support current recommendations that metformin should not be used in patients with stage 5 CKD.

In a new trial, provision of antenatal dietary and lifestyle advice to pregnant women who are obese is associated with modest improvements in maternal diet. This intervention is, however, inadequate to affect pregnancy and birth outcomes, and challenges the notion that limiting gestational weight gain can improve pregnancy outcomes.

For individuals with diabetes mellitus, the lifetime risk of developing a foot ulcer can be as high as 25%, but these complications are preventable. Here, Bowling and colleagues discuss the mechanisms that lead to foot ulcers in patients with diabetes mellitus. The authors emphasise the need for a multidisciplinary management strategy to prevent and treat diabetic foot complications.

Paget's disease is a disorder of bone that manifests in one or several bones and is initiated by osteoclast-induced osteolytic lesions. In addition to a genetic cause, environmental factors, including measles virus, have been proposed to have a role in the pathogenesis of Paget's disease. Here, Frederick R. Singer discusses the present knowledge and controversies surrounding the aetiology of Paget's disease.

A recent study shows that preceding teriparatide treatment with 2 years of denosumab treatment leads to lower BMD after 4 years than either administering these interventions in the opposite order or combining them initially. However, BMD measurements could be biased in favour of using teriparatide first, owing to the time required for completion of secondary mineralization.

Liraglutide is an agonist of glucagon-like receptor-1, which is a component of an important biological system that inhibits food intake and enhances insulin secretion from the pancreas in the presence of glucose. This drug can therefore facilitate weight loss and glucose control at the same time.