Reviews & Analysis

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.

Endometriosis is a chronic inflammatory disease affecting around 5% of reproductive age women, often causing pelvic pain and infertility. This Review addresses current knowledge on the pathogenesis of the condition, medical, surgical and potential new treatments, the role of assisted reproduction, prevention of recurrences, and the association with ovarian cancer.

With improvements in the care of patients with congenital adrenal hyperplasia (CAH), more adults are now living with the condition. However, no consensus exists for managing adult patients with CAH, who generally have a poor health status. In this Review, investigators from the congenital adrenal hyperplasia in adults executive study discuss the treatment and health outcomes of adults with CAH.

The recommended daily iodine intake is 150 µg in adults who are not pregnant or lactating. Most people can tolerate levels above this threshold, but excess iodine exposure or ingestion can result in thyroid dysfunction in certain susceptible individuals. This article discusses the consequences of excess iodine.

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.

An Endocrine Society-appointed task force has developed an evidence-based clinical practice guideline for the diagnosis and treatment of polycystic ovary syndrome. The guidelines provide suggestions for the management of patients with polycystic ovary syndrome and highlight many areas of uncertainty requiring further scientific efforts.

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.

The authors review the roles of T₃ in skeletal muscle development, homeostasis and pathology, with a focus on the emerging local deiodinase-mediated control of T₃signalling. Moreover, this Review addresses how manipulation of deiodinase activity in skeletal muscle might be therapeutically harnessed to improve satellite-cell-mediated muscle repair in patients with skeletal muscle disorders, muscle atrophy or injury.

This Review provides an overview of the diagnostic applications of various imaging modalities for intestinal and pancreatic neuroendocrine tumours. The role of imaging in therapy response evaluation and controversies in neuroendocrine tumour imaging are also discussed.

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.

This Review focuses on the roles of the natriuretic peptides and the sympathetic nervous system in regulating adipocyte metabolism. The potential for manipulating the natriuretic peptide pathway to increase energy expenditure in patients with obesity and to manage the complications of cardiometabolic disease is also discussed.

Polycystic ovary syndrome (PCOS) is frequently associated with metabolic dysfunction. A new study suggests that in women with PCOS the severity of menstrual dysfunction serves as a predictor of the presence, and possibly the degree, of insulin resistance. This finding might serve to refine the indications for metabolic screening in PCOS.

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.

Optogenetic activation of a distinct, inhibitory pathway that connects the bed nucleus of the stria terminalis with the lateral hypothalamus leads to voracious eating in mice. This study adds yet another piece to the brain-feeding-circuit puzzle and makes use of a functional circuit-mapping technique that enables interrogation of neuronal connectivity in an unprecedented way.

Many important associations have been found between the newly discovered myokine irisin and measures of metabolic disease. However, not much is known regarding the role of irisin in human disease. Two recent reports now identify novel metabolic associations for this molecule in humans.

Enormous differences exist between human studies, which show a strong association of low vitamin D status with obesity, and mouse data, where low vitamin D signalling causes resistance to obesity. Understanding these discrepancies may provide better insight into the spectrum of activities of vitamin D and should be of interest considering the world epidemic of obesity and the metabolic syndrome.

MicroRNAs (miRNAs) have emerged as a class of powerful gene expression regulators with a fundamental role in the onset and progression of human cancers. This Review summarizes the emerging knowledge on miRNA deregulation in thyroid neoplasias, the mechanisms through which miRNA deregulation might promote thyroid cell transformation, and how this knowledge could be harnessed for the diagnosis and treatment of thyroid neoplasias.

Emerging data onFTO, the first obesity gene to be identified by genome-wide association studies, suggest a role for the encoded demethylase in nutrient sensing, regulation of mRNA translation and general growth. This Review discusses the genetic epidemiology of FTO and how its complex biology might link to the regulation of body weight.

Alefacept, a fusion protein approved for psoriasis, has been trialled in patients with new-onset type 1 diabetes mellitus. However, the withdrawal of the drug from the US market and the unmet primary end point do not raise hope for this drug, even though some secondary end points were met and the study highlighted interesting immunological efficacy.

Mounting evidence suggests that immune-mediated processes and autoimmunity affect female reproductive success. This Review summarizes the effect of individual autoimmune endocrine diseases on female fertility, and points towards selected developments expected in the near future.