Reviews & Analysis

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'?

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.

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.

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.

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.

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.

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.

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.

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.

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.

Strategies for assessing and modulating LDL-cholesterol levels are central to preventing coronary artery disease; however, there is currently a great deal of interest in the diagnostic measurement of lipoprotein subclasses, including apolipoprotein B100-containing particles. This Viewpoint examines LDL subclass analysis and asks whether this technique has any clinical relevance.

Hereditary disease should be suspected in pheochromocytoma, even when the etiology is apparently sporadic. Mutations have been described inRET, VHL and NF1, as well as in the succinate dehydrogenase genes. The authors discuss the need for genetic screening in possible cases of familial pheochromocytoma and recommend which patients to screen and when.

Although medication for Graves' hyperthyroidism can be withdrawn without adverse effects for the patient, the data regarding the optimal duration of therapy are still unsatisfactory. This Viewpoint discusses how long treatment for Graves' disease should be continued and how withdrawal of antithyroid drugs might affect remission and relapse.