Reviews & Analysis

Prader–Willi syndrome (PWS) is associated with uncontrolled appetite and morbid obesity. Management of PWS is particularly challenging and requires the involvement of both the family and health-care providers, as well as the affected individual. In this Viewpoint the efficacy of the strategies currently used to control obesity in PWS is discussed.

Many of the genes involved in development of adrenocortical tumors have been identified, and their effects on well-known signaling pathways (for example those involving cyclic AMP or β-catenin and Wnt) have been investigated. These advances have important implications for understanding disease development, identifying molecular markers and designing new therapeutic strategies for adrenocortical tumors.

Most tissues express glucocorticoid receptors but tissue-specific modulation of this receptor affects homeostasis, immune responses and cell differentiation mediated by glucocorticoids. This Review describes the mechanisms involved—including nucleocytoplasmic shuttling, degradation and gene polymorphisms—and details the effects on the metabolic syndrome.

Oxyntomodulin and peptide tyrosine–tyrosine are gut hormones that act as satiety signals and decrease food intake; oxyntomodulin may also increase energy expenditure. Studies in humans show these effects in normal-weight and overweight volunteers; these peptides and their derivatives are, therefore, potential therapies for conditions such as obesity.

Experimental studies have implicated GH in the initiation and/or promotion of tumorigenesis, suggesting that patients treated with GH might be at increased risk of cancer. In this Viewpoint, the author reviews several cohort studies and finds that GH therapy could be associated with an elevated incidence of cancer, particularly of the colon.

Although there is some evidence that high levels of GH might cause cancer, patients with acromegaly do not have an increased cancer incidence. This Viewpoint argues, therefore, that GH replacement therapy is not associated with an increased risk of malignancy and that the benefits of treatment probably outweigh the perceived risks.

Excess local tissue production of prolactin may be associated with development and progression of breast and prostate cancers. Pure prolactin-receptor antagonists, such as described here, block prolactin signaling, and may provide a novel therapeutic approach to these cancers, as well as a means of treating drug-resistant forms of hyperprolactinemia.

This Review details treatment of prolactinomas that do not respond to dopamine agonists. Cabergoline is the most effective agonist and options include maximizing the dose and changing agonists. Trans-sphenoidal surgery is an option if medical therapy is ineffective. Radiation therapy is reserved for invasive tumors that do not respond to medical or surgical therapy.

Multiple endocrine neoplasia type 1 can be caused by mutations in the gene encoding menin. By interacting with both transcription factors and histone-protein modifying factors, menin can activate or repress gene expression, and—as detailed here—specific pathways affected by menin have been identified. This offers hope for new screening and therapeutic strategies.

Gene expression profiling techniques have revolutionized molecular biology, allowing researchers to analyze the expression of thousands of genes in a single assay. This Viewpoint asks whether microarray technology can also be applied to clinical practice, and focuses on the diagnosis, prognosis and risk stratification of thyroid carcinoma.

FDA regulation of levothyroxine formulations aims to ensure consistent drug content and bioavailability of brand name and generic products. This Viewpoint suggests that the pharmacokinetic measure of therapeutic equivalence in current use—measurement of total T₄levels in the blood—might not be sufficiently reliable to achieve these goals.

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.

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.

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.