Review Articles in 2013

Genetic factors influence obesity risk with numerous variants and genes associated with differences in BMI and obesity. Here, Julia El-Sayed Moustafa and Philippe Froguel outline current knowledge in the field of obesity genetics and discuss how this information might translate into personalized patient care.

Determining the genetic contribution to autoimmune thyroid disease has helped unravel how immune disruption leads to disease onset. Breakthroughs in genome-wide association studies have facilitated screening of a greater proportion of the genome. This Review will focus on the new susceptibility loci identified by genome-wide association studies and what insights these loci provide into disease pathogenesis.

In this Review, the authors discuss the auditory system as an example of how T₃ is involved in the development of the sensory systems. Sensory defects in human genetic disorders featuring impaired T₃signalling are also outlined.

The success of bariatric surgery, together with emerging data from preclinical studies, illustrates the rationale and feasibility of using two or more agonists for the treatment of obesity and type 2 diabetes mellitus (T2DM). This Review summarizes advances in the science of co-agonist therapy and mechanisms of action for combinations of endocrine hormones that enhance weight loss whilst preserving glucoregulatory efficacy in experimental models of obesity and T2DM.

Early diagnosis and treatment of overt thyroid dysfunction are crucial in the elderly given the marked effects of abnormal circulating thyroid hormone concentrations on a number of organ systems. However, diagnosis and treatment of this disorder in the elderly are complicated by the nonspecific clinical presentation and the physiological changes inherent to ageing. This Review describes the current evidence on the prevalence, diagnosis, management and long-term consequences of thyroid dysfunction in the elderly.

Multiple subtle changes in hypothalamic–pituitary function occur with ageing. This Review discusses the mechanisms mediating these changes in pituitary function during ageing and the implications for patient care. The article also considers how factors such as illnesses and medication use that accompany ageing co-determine and obscure the effects of ageing on pituitary function.

The ageing brain retains the capacity for regeneration. This Review highlights the potential of the neurosteroid allopregnanolone as a regenerative therapeutic to promote self-renewal and repair in the brains of ageing individuals and those with Alzheimer disease. Windows of therapeutic opportunity for regeneration, and critical systems-biology factors that will determine the efficacy of regeneration are considered.

A progressive decline in cellular function and organismal fitness and an increase in age-related diseases are associated with ageing; many theories have attempted to explain this phenomenon. This Review outlines the current knowledge of the effects of oxidative stress on endocrine organs and tissues and suggests that inflammation is the link between oxidative stress and ageing.

Postmenopausal hormone therapy (PMHT) is used for the relief of menopausal symptoms; however, the doses used have varied greatly over time. This Review provides an overview of the risks and benefits of PMHT. The authors also suggest how to optimize therapy in different clinical situations.

Conventional clinical risk factors are currently used to assess fracture risk, but genome-wide association studies conducted in the past decade have identified genetic variants associated with fracture risk. This Review discusses the potential of integrating genetic profiling into existing risk assessment models for the individualization of fracture risk prediction.

In this Review, Gherardo Mazziotti and Andrea Giustina discuss the latest advances in our understanding of how glucocorticoids affect the secretion of growth hormone. The implications for diagnosis and treatment of growth hormone deficiency in patients with a lack or excess of glucocorticoids will also be outlined.

Understanding the role of vitamin D in health and disease is an important issue in the nutritional management of children. This Review focuses on the effects of vitamin D on key disease states in children, including acute and chronic illnesses, a topic that has received minimal coverage in current guidelines.

Age-related bone loss can eventually result in osteoporosis. In this Review, Pierre Marie describes an emerging therapy that involves targeting certain integrin transmembrane proteins to promote the differentiation of mesenchymal stromal cells into osteoblasts, thereby counteracting bone loss.

In this Review the authors describe the hepatokines—proteins secreted from the liver that directly regulate metabolic processes. They discuss the role of hepatokines in the pathogenesis of type 2 diabetes mellitus and cardiovascular disease. Possible ways in which research in this area could be used to improve screening or in drug development are also touched upon.

In this Review, the authors discuss the genetics of height, including examples of rare sequence variants that can result in large effects on height and common variants with small effects on height. The key challenges in discovering further genes associated with height and the transition from gene discovery to mechanistic insights are also outlined.

In this Review, the authors examine how the development of diabetes mellitus has come full circle from initiation to complications and suggest that the development of diabetes mellitus and the progression to chronic complications both require the same mechanistic triggers.

Immune therapy for type 1 diabetes mellitus can be approached at three different stages: primary prevention, secondary prevention and intervention. This Review discusses the different types of immune therapies being attempted at these three different stages and the findings of completed and ongoing trials of these therapies.