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 pancreatic islets of Langerhans have been intensively investigated for many years, largely because of their central role in the pathogenesis of type 1 and type 2 diabetes mellitus. Notable advances in 2015 related to glucose-stimulated insulin secretion in β cells, β-cell death and the role of epigenetics in β-cell heterogeneity.

Successful management of obesity requires integration of pharmaceutical agents and bariatric surgeries with traditional lifestyle modifications. Notable developments for managing obesity in 2015 included the demonstration of weight-beneficial outcomes for liraglutide and empagliflozin, and the first 5-year follow-up of patients with type 2 diabetes mellitus and obesity randomly assigned to receive bariatric surgery or conventional medical therapy.

In 2015, large-scale genetic and functional studies brought us closer to understanding the underlying aetiology of polycystic ovary syndrome (PCOS), implicating genes involved in modulation of gonadotropin and neuroendocrine action, ovarian androgen biosynthesis and possibly insulin action, providing clues to the evolutionary path and potential evolutionary advantages of PCOS.

Studies published in 2015 have continued to unravel the genomic landscape of thyroid cancer, particularly of its less common forms (such as medullary and anaplastic carcinomas) and of familial forms of thyroid cancer. As a result, new diagnostic and therapeutic markers have been identified and validated for clinical use.

In 2015, four studies demonstrated that hepatic glucose metabolism is altered by targeting the farnesoid X-activated receptor in the gut, the insulin receptor in extrahepatic tissues such as the brain and an S-nitrosylation–endoplasmic reticulum-stress-dependent pathway in the liver. Targeting nutrient-dependent and hormone-dependent signalling pathways in these organs could help regulate hepatic glucose production in patients with diabetes mellitus and obesity.

Endocrine disruptors are critical environmental exposures that influence health and can promote epigenetic transgenerational inheritance of disease and abnormal physiology. Advances in 2015 included analyses of the effects of endocrine disruptors on human disease, further examples of endocrine disruptors promoting transgenerational behavioural effects, insights into effects of endocrine disruptors on epigenetic programming of primordial germ cells and the finding that endocrine disruptors can transgenerationally promote genetic mutations.

2014 was a good year for developments in automated insulin delivery systems for patients with diabetes mellitus. Clinical trials shifted from research units to the outpatient setting, included both adult and adolescent individuals and were conducted over periods from overnight to 24 h, with improvements seen in time spent in the target glycaemic range and reduced risk of hypoglycaemia.

In 2014, many articles focusing on pituitary tumours were published, including studies on genetics, surgery, radiotherapy and medical treatment. This commentary highlights advances in the management of patients with acromegaly, Cushing disease and TSH-secreting tumours. Together, these advances will benefit the care and management of patients with pituitary tumours.

2014 has seen advances in our understanding of benign and malignant tumours of the adrenal cortex, particularly in Cushing syndrome. Modern genetics has generated a flurry of data. The challenge is to give sense to them; however, the difficulties of collecting the clinical data must not be underestimated.

In 2014, numerous noteworthy papers focusing on adipose tissue physiology were published. Many of these articles showed the promise of adipose-tissue-targeted approaches for therapeutic intervention in obesity and type 2 diabetes mellitus. Here, we highlight advances in the development and maintenance of brown and/or beige adipocytes and the metabolic implications of inflammation in adipose tissues.

In 2014, two phase II clinical studies reported rapid, impressive increases in BMD in women with low bone mass who were treated with sclerostin inhibitors for 1 year. The antifracture efficacy and tolerability of these new, bone-building therapies are currently being investigated in phase III clinical trials.

Studies published in 2014 have helped in our understanding of the epigenetic mechanisms by which suboptimal nutritional exposures during in utero development are transmitted to subsequent generations through the maternal and the paternal germlines. Advances include identification of common genetic loci that are vulnerable to the effects of in utero undernutrition and overnutrition, as well as those that are epigenetically modified tissue-wide.

2013 was a good year for adrenocortical cancer, as the new knowledge gained holds great promise for patients. Advances were made in genetics, epigenetics, the advent of related technological and bioinformatic tools, and the feasibility of massive screening of people and samples.

2013 has revealed interesting mechanisms that explain how glucocorticoid signalling responses can be influenced by childhood trauma, activity of other signalling molecules, glucocorticoid circadian rhythms and the sequence of DNA regulatory regions. In particular, studies this year highlight how different signalling environments can determine the molecular and physiological responses of glucocorticoids themselves, and how glucocorticoids can affect other signalling systems.

In 2013, studies in rodents and humans have reaffirmed the essential role of the gut microbiota in host metabolism. More importantly, several converging results have increased our knowledge regarding the taxa and functions of the gut microbiota that contribute to the management of energy homeostasis, glucose metabolism and metabolic inflammation.

Metabolic surgery has been proven to be effective in inducing remission of type 2 diabetes mellitus prior to any significant weight reduction. Studies in 2013 have investigated the mechanisms of action of these procedures and have highlighted a central role of the small intestine in the effects on glucose homeostasis.

Studies published in 2013 have addressed the question of whether the rising incidence of differentiated thyroid cancer is actually the result of overdiagnosis. Advances have also been made in the treatment of differentiated thyroid cancer, including improvements in radioiodine therapy.

In 2013, considerable progress was made towards deciphering the molecular foundations of puberty. Loss of transcriptional repression was identified as a core mechanism underlying the onset of puberty, and this loss was found to be precipitated by epigenetic cues. It was also discovered that nutritional deprivation delays puberty by repressing reproductive neuroendocrine function.

In 2012, we learned that functional thyroid tissue can be generated in vitro, and that thyroid hormones stimulate autophagy. Patients with defects in TRα have been identified, and di-iodothyropropionic acid has been shown to ameliorate MCT8 deficiency. Finally, we found that gene expression profiling can identify benign thyroid nodules.