Reviews & Analysis

Different genes are potentially activated in lean and adipose tissue in response to recombinant human growth hormone (GH) or its mediator, insulin-like growth factor 1. Decker and colleagues now present evidence that levels of circulating protein markers give clues about the biological efficacy of GH therapy in various body tissue compartments.

Vitamin D is the nutrient du jour, yet scant evidence exists for various health claims related to vitamin D. This Perspectives article aims to dispel misconceptions about vitamin D, including discussion of osteoporosis, chronic disease risk, requirements in pregnancy and lactation, and vitamin D deficiency and supplementation.

Idiopathic short stature (ISS) is a term used for children with short stature that does not have a specific cause. This Review outlines the diagnostic evaluation and possible psychological consequences of ISS. Various strategies to treat children with ISS are discussed, together with an evaluation of the efficacy and safety of these approaches.

Combination of the gene-expression classifier (GEC), with its high negative predictive value, and the BRAF mutation test, with its high specificity, might have a synergistic effect in the diagnosis of thyroid nodules with indeterminate cytology. However, Kloos et al. demonstrate that the BRAF test is of no additional benefit in nodules categorized as 'benign' by GEC.

This Review summarizes data on mouse strains with mutations that affect growth hormone (GH) and insulin-like growth factor 1 (IGF-1) action and their effects on lifespan. The outcome of corresponding or similar mutations in humans is described, as well as the potential mechanisms underlying increased longevity and the therapeutic benefits versus risks of medical disruption of the GH/IGF-1 axis in humans.

In men with classic hypogonadism, testosterone therapy induces a number of beneficial effects. However, in older men with age-related decline in testosterone levels, the clinical benefits and long-term risks of testosterone therapy have not been adequately assessed in large, randomized clinical trials. This Review discusses potential benefits and risks of testosterone therapy in these individuals in the context of incomplete evidence on safety and efficacy.

A recent publication in the Journal of Clinical Endocrinology and Metabolism provides new data about the role of growth hormone (GH) in bone in Prader–Willi syndrome. The lack of positive effects of long-term GH therapy on BMD in young adults with Prader–Willi syndrome highlights the need to improve the transition from adolescent to adult health care.

Administration of recombinant human growth hormone (GH) or activation of endogenous GH production exhibits great potential to influence the onset and metabolic consequences of obesity; however, the clinical use of GH is not without controversy. This Review provides an introduction to the role of GH in obesity and summarizes clinical and preclinical data that describe how GH can influence the obese state.

Concerns about the use of calcium supplementation in the elderly and its effects on cardiovascular events are growing. A novel study published in JAMA Internal Medicine further highlights the dangers of calcium supplementation, raising the question whether the detrimental effects of these supplements are worth their supposed benefits on bone.

Makani and colleagues report that dual blockade of the renin–angiotensin–aldosterone system is associated with harm despite previous studies showing that this approach decreases blood pressure and albuminuria. Do these results imply that we should abandon surrogate markers? Or should we become more creative in using them?

HIV infection and antiretroviral therapy have long been associated with an increased risk of osteopenia and osteoporosis. This predisposition has now been shown to result in a significantly increased risk of osteoporotic fractures in the HIV-infected population even after controlling for known risk factors.

If a child has diabetic keotacidosis and the type of diabetes mellitus is unclear, immediately start them on insulin. This recommendation is one of a number from a recent guideline on paediatric type 2 diabetes mellitus. However, differences in the management of type 2 diabetes mellitus between the USA and Europe remain.

A major limitation in determining the effects of growth hormone (GH) therapy on overall health has been the duration of studies, which have previously ranged from 1 year to 5 years. Elbornsson et al. now report the outcome of 15 years of GH treatment on body composition and lipid profile in patients with GH deficiency, but some questions remain unanswered.

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.

Three major studies have made a brave attempt to quantify mortality and disability worldwide from 289 diseases and their sequelae. Striking data are presented that confirm the rising tide of noncommunicable diseases, particularly diabetes mellitus. The predictions for diabetes mellitus are, however, probably underestimated owing to underdiagnosis and under-reporting.

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.

Biochemical screening of neonates for congenital hypothyroidism permits early initiation of levothyroxine treatment and thus prevents the development of intellectual disability. Two novel studies now address whether brand-name and generic levothyroxine are interchangeable in this context.

Established prognostic scoring systems for thyroid cancer include factors such as age, tumour size and extent, and whether distant metastases are present. A novel nomogram has now been developed that could be used to predict the risk of all-cause mortality in patients with thyroid cancer.