Reviews & Analysis

Not only the levels, but also the function and components of HDL-cholesterol appear to play a role in atherosclerosis. Levels of anti-oxidants and pro-oxidants can vary in HDL-cholesterol, as can its effects on LDL-induced inflammation. This Review describes recent progress that might lead to new therapeutic approaches.

Thyroid hormone transport across the plasma membrane is essential for hormone functions. As detailed here, novel mutations in monocarboxylate transporter 8 reveal important roles in thyroid hormone access to the brain and might explain the pathogenesis of Allan–Herndon–Dudley syndrome, which is now known to feature thyroid hormone resistance.

In many countries, the clinical profile of primary hyperparathyroidism has changed to one with few of the disease's “classical” features. Although the reason for this change is unknown, various organs remain targets of the hyperparathyroid process. NIH treatment guidelines were recently updated, as the need for surgery in all patients remains controversial.

There is no agreed definition for cachexia, and this hampers research and treatment. This Viewpoint emphasizes the importance of definitive cut-off limits for weight loss over time, and the need for straightforward diagnostic criteria. The authors suggest cut-off values for cardiac cachexia but acknowledge that the values might differ in other conditions.

According to the National Cholesterol Education Program, an optional LDL goal of less than 1.81 mmol/l might now be considered for patients at the highest risk of coronary heart disease. This Viewpoint discusses whether these LDL target levels are safe and describes which agents might help achieve this goal.

Many chronic diseases produce a condition called cachexia, which involves anorexia, decreased lean body mass and increased energy expenditure, worsening the prognosis for the underlying disease. This article describes a promising new approach to treating cachexia, targeting a key appetite-regulating center in the hypothalamus called the melanocortin system.

The level of insulin-like growth factor 1 (IGF-I) is influenced by many factors but, as detailed here, IGF-I measurements are useful to screen for growth hormone deficiencies in children and young adults. IGF-I levels are an excellent diagnostic test for acromegaly but are also useful to assess disease severity and the response to treatment.

This Review examines the biochemistry that underlies the behaviors of obesity, in particular the relationship between hyperinsulinemia and leptin resistance. Hyperinsulinemia promotes the behaviors of increased calorie intake, decreased exercise and altered hedonic reward responses to food that are associated with the current obesity epidemic.

Cortistatin is a member of the somatostatin family of peptide hormones. Although cortistatin and somatostatin display many structural and functional similarities, there are also notable differences including tissue distribution and receptor selectivity. This Viewpoint describes how these differences might reflect novel actions of cortistatin in the brain and immune system.

Although LDL-cholesterol is commonly targeted in treatment regimens aiming to reduce coronary heart disease, the value of elevating HDL-cholesterol levels is still debated. The authors suggest that raising levels of HDL-cholesterol with drugs such the experimental agent torcetrapib might prove beneficial, particularly when used in combination with statins.

Partly because of increased use of sonography, thyroid nodules are now detected more frequently but are usually asymptomatic. Very few thyroid nodules are malignant, and so management is particularly important but remains controversial. This Review details the various options available, and assesses the indications for each one.

This Review describes the many clinical, endocrine and genetic abnormalities that cause growth hormone (GH) insensitivity disorders, listing all the known GH-receptor mutations and describing the current therapy with insulin-like growth factor 1 (IGF1) and a novel therapy using complexes of IGF1 and IGF-binding protein 3.

This Review summarizes the data showing that adipocytes express the specific receptors for nearly all known pituitary hormones and hypothalamic releasing factors. The existence of a hypothalamic–pituitary–adipose axis is therefore most likely. The name “adipotropins” is suggested to characterize pituitary hormones and hypothalamic releasing factors that act directly on adipocytes.

Prolactinomas are the most common hormone-secreting pituitary tumors. Treatment with dopamine agonists can stabilize disease and recent evidence suggests that in many cases therapy can be subsequently withdrawn without relapse. This Viewpoint discusses the safety and efficacy of dopamine agonist withdrawal and the optimal timing of this approach.

Niacin therapy has beneficial effects on lipid profiles and might afford some protection against coronary artery disease; however, prescription of niacin has been limited. In this Viewpoint, the author considers whether using niacin might pose a risk in patients presenting with insulin resistance or the metabolic syndrome in the absence of diabetes.

At the molecular level, puberty remains an enigmatic process. This article details the discovery of a novel pathway involving GPR54 and its ligand, kisspeptin-1, in control of the gonadotropin-releasing-hormone pulsatility that characterizes sexual maturation and the female estrus cycle. These findings have clear implications for treatment of reproductive disorders.

As detailed in this Review, leptin seems to act primarily in states of energy deficiency, and common forms of obesity are characterized by leptin resistance. Clinical trials have shown leptin to be effective in subjects with relative or complete leptin deficiency.