Reviews & Analysis

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dopamine agonists can stabilize disease and recent evidence suggests that in many cases therapy can be subsequently withdrawn without relapse.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.

Excess free fatty acids, an imbalance of adipocytokines and mitochondrial dysfunction all contribute to abnormalities in hepatocellular lipid content in diabetes and can lead to steatosis and insulin resistance. Thus liver fat is a novel target for therapies such as fat-reduced diets and thiazolidendiones.

New insulin-producing β cells are produced throughout adult life and could potentially be exploited in regenerative therapies for diabetes. Although pancreatic progenitor cell differentiation has been proposed to drivede novoβ-cell generation, this Viewpoint argues that new β cells arise from the proliferation of pre-existing β cells.

Although pancreatic islet transplantation can restore normal β-cell function to patients with diabetes, success is limited by tissue availability. An alternative strategy is to stimulate development of the patients' own β cells; however, the postnatal origin of new β cells remains controversial. This Viewpoint proposes that progenitor cells could exist in the pancreatic ducts.

Genetic disorders of ACTH action lead to rare syndromes of glucocorticoid deficiency. Many common disorders are accompanied by disturbance of the pituitary-adrenal axis, which may contribute to their morbidity. This Review describes the evidence that in some circumstances—septic shock and depressive illness—disturbed ACTH responsiveness may contribute to the disease.

Biosynthetic human growth hormone (GH) is now used to treat GH deficiency and promote growth in conditions such as Turner syndrome, intrauterine growth restriction, chronic renal failure and idiopathic short stature. The net effect in these conditions is less than in GH deficiency. Vigilance for long-term complications of GH use is essential.

This article describes the different conditions that embrace the diagnosis of diabetic neuropathies—the Cinderella complication of diabetes. Distinction between the proximal and distal large and small fiber, focal mononeuritides and entrapments is essential since each has a unique presentation and requires specific therapeutic intervention for a successful outcome.

Molecular analysis has transformed our current understanding of the etiology of papillary thyroid carcinoma (PTC). Activating mutations of components of the mitogen-activated protein kinase signal transduction pathway, including the serine/threonine kinase B-RAF, are frequently detected. The prognostic significance of theseBRAFmutations and the therapeutic implications for managing PTC are discussed.