Reviews & Analysis

This Review covers clinical characterization of endoderm-derived endocrine tumors, apart from small-cell carcinoma. Classification is complex but crucial because it impacts diagnosis, imaging, prognosis and therapy; nevertheless, the tumors can be managed as a single clinical entity. Diagnosis of poorly differentiated endocrine tumors in particular has an important impact on therapy.

Insulin-like growth factor 1 is a major effector of growth hormone. IGF1 binds the IGF1 receptor with high affinity and the insulin receptor with lower affinity. IGF1 has actions distinct from growth hormone in carbohydrate, lipid and protein metabolism; it can lower blood glucose levels and might prove efficacious for diabetes.

The measurement of prolactin levels is commonly requested for patients with reproductive disorders. This Review describes the causes of hyperprolactinemia and the steps to take once it is suspected. In particular, the various pitfalls that can cause falsely low or high prolactin levels in immunoassays are detailed.

As discussed in this Review, thyroid cancer tissue alters the metabolism of iodide by affecting gene expression and post-transcriptional processes and can thereby decrease delivery of radioiodide during screening and therapy. This Review details these processes and discusses the clinical implications for different patient groups.

Novel strategies are needed to treat metastatic medullary thyroid cancers (MTC), and gene therapy offers several potential avenues for this and many other types of tumors. This Review outlines the many MTC-specific strategies currently under investigation experimentally and describes several that are now being assessed in clinical trials in a range of other tumor types.

Gene control mediated by nuclear thyroid hormone receptors is important for normal brain maturation. As discussed in this Review, the lack of thyroid hormone ligand, experimental deletion of a receptor, or expression of dominant negative mutant receptors can have different effects on gene transcription and therefore on brain development and function.

Hyperglycemia often occurs in patients who are acutely ill. This Review details the findings of several recent studies showing that using insulin to maintain normoglycemia for a few days significantly improved survival and morbidity in patients in medical or surgical intensive care units.

Primary aldosteronism in its normokalemic form accounts for about 10% of cases of hypertension. This Review details the etiology, and the clinical and biochemical features of the subtypes of primary aldosteronism. It also describes the advantages of the various screening and confirmatory strategies and the available treatment options.

The recent increase in detection of thyroid papillary microcarcinoma by imaging studies, including ultrasonography, has led to a new problem: how should we handle these minute lesions? They can show multifocality and lymph-node metastasis, but are usually slow growing. This Review suggests that observation without surgery is an attractive alternative to surgery, at least in low-risk patients.

Although niacin reduces cardiovascular events in patients with type 2 diabetes mellitus or the metabolic syndrome, it is considered a reserve therapeutic agent because of adverse effects on glycemic control. The author of this Viewpoint argues, however, that the lipoprotein-altering effects of niacin might outweigh the potential hazards of niacin-mediated hyperglycemia.

Peroxisome proliferator-activated receptors (PPARs) are important regulators of energy homeostasis and inflammation. They modulate cardiovascular disease, type 2 diabetes and the metabolic syndrome. This Review describes these mechanisms, and the drugs that modulate PPARs and are in current clinical use, as well as potential new drug-development strategies targeting PPARs.

Polycystic ovary syndrome (PCOS) is a common endocrine disease with a strong genetic component. Genetic dissection of PCOS is being intensively investigated and over 70 genes have been evaluated for their role in its etiology. This Review details results obtained from analyzing four of the best-characterized candidate genes and gene regions.

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.