Review Articles in 2007

This Review details the epidemiological, mechanistic, clinical, biological and pathological features of nonalcoholic fatty liver disease—the liver manifestation of the metabolic syndrome that can progress to end-stage liver disease, and the commonest liver disease in Western countries. The article also describes the treatment options, which include dietary modification and exercise.

This Review describes effects of maternal factors such as diet and glucocorticoid levels on disease development later in the child's life. In particular, the barrier function of placental 11β-hydroxysteroid dehydrogenase type 2 in controlling fetal glucocorticoid exposure, and mechanisms that affect glucocorticoid receptor promoter usage and gene methylation are discussed.

This Review describes in detail the assessment and management of Graves' ophthalmopathy, a common manifestation of Graves' disease. It describes the role of smoking cessation,¹³¹I therapy, immunosuppression and rehabilitative surgery. After severity and activity are assessed, optimal management is multidisciplinary and should be tailored to the individual patient.

Oncogenic mutations associated with childhood thyroid cancers are predominantly gene rearrangements; point mutations are exceedingly rare. As discussed in this article, although no 'signature' pattern of gene mutations has emerged from studies of radiation-induced thyroid cancers, the distribution of certain gene abnormalities displays important correlations with particular clinicopathological features of disease.

This article reviews the known cases of aromatase deficiency, which causes virilization of affected female fetuses and their mothers. In girls the deficiency causes pseudohermaphroditism at birth, and a lack of transition through puberty. Males are generally diagnosed later in life. This condition shows important roles for estrogen in metabolism of many systems other than reproduction.

Disorders of cortisol biosynthesis can lead to congenital adrenal hyperplasia, the most common form of which is 21-hydroxylase deficiency (21-OHD). This Review details the clinical features and prenatal diagnosis of 21-OHD, and describes how prenatal dexamethasone treatment can prevent genital ambiguity in affected females.

In boys, delayed puberty can result from transient or permanent (primary or secondary) hypogonadism. As detailed in this Review, patients benefit from short-term or long-term testosterone therapy, enabling them to reach adult body composition. Testosterone can be given intramuscularly or—more recently—in the form of cutaneous gels or patches.

As well as their huge impact on biological research, molecular techniques are increasingly being applied in a variety of clinical situations. This Review describes several technical aspects and the applicability of such methods for endocrinologists and covers aspects such as genomics and proteomics, detection methods, and experimental genetic manipulation.

This Review discusses the ways in which obesity in general and adipose tissue in particular might contribute to breast cancer. It details how the balance of adipokines such as leptin and adiponectin might affect tumorigenesis, and the contribution of peritumoral adipose tissue to a cancer-promoting microenvironment.

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.

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.