Reviews & Analysis

Both agonists and antagonists of luteinizing-hormone-releasing hormone (LHRH) are in clinical use for a wide range of cancers, benign prostatic hypertrophy, fibroids and reproductive disorders. This article describes the existing applications, those under investigation, and potential applications for this type of drug to target diseases such as Alzheimer's.

This review describes the use of 2-[¹⁸F]-fluoro-2-deoxyglucose (FDG)-PET to localize recurrence of differentiated thyroid carcinoma. It focuses on patients with persistent disease and normal results from conventional imaging, on changes in therapeutic management because of FDG-PET results and on the role of TSH stimulated FDG-PET scanning, Finally, it focuses on the prognostic significance of FDG uptake in patients with differentiated thyroid carcinoma.

In the parathyroid gland, in thyroid C-cells and in many other tissues, the calcium-sensing receptor (CaR) plays a crucial role in calcium homeostasis. The molecular basis of several diseases resulting from abnormalities in the CaR has been characterized; this has provided the framework for the development of pharmacologic CaR activators for clinical use.

Chronic kidney disease can lead to secondary hyperparathyroidism, affecting vitamin D metabolism, the calcium and phosphate balance, and causing coronary artery disease. Vitamin D analogs are used to treat secondary hyperparathyroidism in these patients; early treatment can prevent or slow the progression of secondary hyperparathyroidism and increase patient survival.

Pheochromocytomas are rare, often hereditary, catecholamine producing tumors that can be difficult to diagnose and manage. This Review summarizes the recommendations for biochemical and genetic testing, localization and treatment, and is based on discussions at the First International Symposium on Pheochromocytoma, held in October 2005.

G-protein-coupled receptors play a crucial role in the signaling of many hormones, and the techniques of fluorescence or bioluminescence resonance energy transfer (FRET or BRET) have given insights into the role of multimer formation in receptor function. This Review outlines the principles behind these techniques and potential biological consequences.

The actions of cortisol in the brain are mediated by mineralocorticoid and glucocorticoid receptors, which operate in a complementary way in reacting to and recovering from stress. Certain genetic backgrounds and early-life events might, however, cause inappropriate cortisol responses and/or imbalances between the receptors, predisposing to depression later in life.

Hypoglycemia-associated autonomic failure (HAAF) describes the syndromes of defective glucose regulation and hypoglycemia unawareness. Originally characterized in type 1 diabetes, the author of this Viewpoint suggests that HAAF is also a component of iatrogenic hypoglycemia in patients with type 2 diabetes, and represents a barrier to glycemic control.

Although the success rate of islet transplantation for patients with type 1 diabetes has improved, many issues still need to be resolved. In this Viewpoint, the authors highlight areas of concern, including the inefficiency of current isolation protocols and the occurrence of adverse events, and ask how the efficacy of this procedure can be enhanced.

This Review examines the pros and cons of screening for coronary heart disease in asymptomatic subjects with diabetes. At present, there is insufficient evidence of clinical benefit to justify such a practice; therefore, carefully conducted clinical trials are urgently required to resolve the question.

Endothelial dysfunction occurs commonly in diabetes and insulin resistance. This Review describes mechanisms that promote development of atherosclerosis in these conditions through changes in endothelial cell signaling and function. Such mechanisms might be drug targets, and endothelium-dependent vasodilation and other tests could be used to monitor the efficacy of interventions.

Hyperinsulinism is the single commonest cause of hypoglycemia in infants. This Review describes the five known mutations that cause congenital hyperinsulinism, and the other forms of hyperinsulinism. It also details the diagnostic approach and treatment options, emphasizing the need for a multidisciplinary approach.

Foot problems are a very common complication of type 1 and type 2 diabetes. Most are neuropathic in origin and should be preventable. This Review details preventative strategies, and the many monitoring and treatment options currently available, for a condition that has major consequences for patients and health-care providers.

Fulminant type 1 diabetes appears to a disease subtype that features a characteristic range of clinical symptoms, with extremely rapid onset, and thus must be treated very quickly. It is currently prevalent in Japan, and might be associated with particular genotypes and possibly with viral infection.

Elevated levels of growth hormone (GH) and insulin-like growth factor 1 (IGF1) in conditions such as acromegaly have been implicated in increased cardiovascular risk. The authors of this Viewpoint argue, however, that hormone deficiency might pose a greater risk than hormone excess, and ask the question—what levels of GH and IGF1 can be considered 'safe'?

Osteoporosis is an increasingly prevalent condition that, currently, is underdiagnosed and thus undertreated, so that improved screening and preventative dietary and lifestyle changes are needed. For more-severe cases, there are also several drug classes available or in development that work in different ways; these are detailed in this Review.

Many hormones use G-protein-coupled receptors and G proteins in the target cell to transduce their signals. A range of disease-causing mutations have been characterized that mimic states of hormone deficiency or excess. This Review describes these mutations, and their resultant clinical and biochemical features.

Ectonucleotide pyrophosphatase phosphodiesterase 1 (E-NPP1) inhibits the insulin receptor. E-NPP1 mutations are associated with type 2 diabetes, and E-NPP1 expression is increased in nonobese, nondiabetic insulin-resistant subjects; E-NPP1 might therefore act as a marker for at-risk individuals and reveal new targets for prevention and treatment of diabetes and cardiovascular disease.

Ovarian hyperstimulation syndrome (OHSS) is a complication of pregnancy caused by an excessive response to follicle-stimulating hormone (FSH). OHSS can arise spontaneously or after exogenous FSH administration duringin vitrofertilization procedures. Novel genetic predictors of OHSS, including mutations and polymorphisms of the FSH receptor, are described in this Viewpoint.