Reviews & Analysis

The findings from the DCCT–EDIC and UKPDS epidemiological studies suggest that early exposure to hyperglycemia predisposes individuals to the development of diabetic complications, a phenomenon referred to as metabolic memory or the legacy effect. Transient exposure to hyperglycemia results in long-lasting epigenetic modifications that lead to changes in chromatin structure and gene expression, resulting in vascular dysfunction.

Glycogen storage disease type I (GSD-I) consists of a group of autosomal recessive disorders that cause metabolic abnormalities and/or myeloid dysfunction. This Review addresses the etiology of GSD-Ia and GSD-Ib and of glucose-6-phosphatase-β deficiency and highlights advances in diagnosis and treatment, including transplantation and gene therapy.

Two recent reports suggest that differences in levels of thyroid-related hormones within the euthyroid reference range can affect BMD and the risk of fracture. The mechanism by which differences in the concentration of these hormones affect bone is probably complex, and the implications for patients with bone disease remain uncertain.

Accurate testing of the integrity of the hypothalamic–pituitary–adrenal axis in children at risk of central adrenal insufficiency is difficult and a subject of debate. Findings of a new study by Di Iorgi et al. reveal the usefulness of a potential alternative to the insulin tolerance test—the glucagon stimulation test.

Various symptoms are typical of severe testosterone deficiency in young men; in aging men, however, these symptoms are nonspecific and overlap with symptoms of other prevalent disorders. A new study offers evidence-based criteria for the identification of late-onset hypogonadism in the general population on the basis of an association between symptoms and a low testosterone level.

Evidence about the relative risks and benefits of thiazolidinediones, such as rosiglitazone and pioglitazone, for the treatment of type 2 diabetes mellitus has been inconsistent. Meta-analyses and epidemiologic reviews suggest that rosiglitazone may increase cardiovascular risk, but two randomized trials do not. A novel epidemiologic analysis has been a focal point of recent FDA deliberations on this issue.

A novel report in the Journal of Bone and Mineral Research describes the aggressiveness of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 (MEN1) syndrome on kidney and bone complications. Will these findings influence the future management of parathyroid disease in patients with MEN1 syndrome?

Surgical resection of pituitary tumors is the treatment of choice for patients with hormone-secreting tumors or those that impair vision and other neurological functions. A recent study by Grossman et al., however, found transsphenoidal surgery to be associated with increased mortality and morbidities in elderly patients, which suggests the need for careful individualized decision-making in this vulnerable population.

This Case Study describes an 18-year-old Somali man who initially presented to medical care with behavioral problems and was later diagnosed as having Klinefelter syndrome. Presented from the perspective of the primary care provider, this case illustrates the challenges in the clinical diagnosis and issues associated with long-term management of this relatively under-recognized condition.

Growth hormone, insulin-like growth factor I and insulin have potent growth-promoting and anabolic actions. Their potential involvement in tumor promotion and progression has been of concern for several decades. In this Review Peter Clayton and colleagues examine the complex evidence regarding growth hormone, the insulin-like growth factor axis, insulin and cancer risk.

The diabetogenic effect of glucagon has long overshadowed the potential of this pancreatic hormone as an endogenous satiety and anti-obesity factor. This Review discusses the role of glucagon as a beneficial endocrine factor in lipid and energy metabolism and its potential as a therapeutic agent on the basis of studies that combine the agonism of glucagon receptor and glucagon-like peptide 1 receptor.

The prognosis of patients with childhood craniopharyngioma is impaired owing to the vicinity of the tumor to the optic tract and to pituitary and hypothalamic areas. Long-term sequelae after treatment—notably severe hypothalamic obesity—negatively effect patients' quality of life. This Review discusses risk-adapted treatment strategies that aim to improve prognosis and prevent sequelae.

This Review addresses the pharmacology and physiology of aspirin use and how it may differ in patients with diabetes mellitus. The clinical trial evidence for the primary prevention of cardiovascular disease with aspirin therapy in patients with diabetes mellitus will then be examined in light of these potential mechanisms. Finally, suggestions for clinical practice are provided, and the limitations in current evidence as well as the upcoming trials that may help resolve these important clinical issues are highlighted.

The THERAPY trial investigators conclude that, when pregnancy is confirmed in adequately treated women with hypothyroidism, doubling the dose of prepregnancy levothyroxine on 2 days each week safely prevents maternal hypothyroidism in the first trimester of pregnancy in most cases. Is this really the best strategy to adopt?

Controversy surrounds the importance and potential benefits (or lack thereof) of identifying and treating women whose pregnancies are complicated by gestational diabetes mellitus. A meta-analysis of five randomized, controlled trials has now demonstrated that adverse outcomes are reduced by specific treatment for gestational diabetes mellitus when compared with routine obstetrical management.

Most breast-fed and many formula-fed infants in the USA have an inadequate daily intake of vitamin D—below the amounts recommended by the American Academy of Pediatrics (AAP)—according to the results of a study by Perrine et al. The majority of infants might, therefore, need daily vitamin supplementation to meet the 2008 AAP recommendation.

Isolated growth hormone deficiency is the most common pituitary hormone deficiency and can originate from congenital or acquired causes, although the majority of cases are idiopathic. This Review summarizes currently available evidence on the genetic factors involved in isolated growth hormone deficiency, and highlights diagnostic challenges and novel advances in treatment.

Clinical manifestations of hypovitaminosis D, a highly prevalent disorder worldwide, include musculoskeletal disorders as well as nonclassical manifestations, such as increased risk of respiratory infections, diabetes mellitus and possibly cardiovascular diseases. This Review discusses the prevalence of hypovitaminosis D across the lifecycle, and risk factors and health outcomes associated with it in developing countries.

This Case Study describes an infant diagnosed as having focal congenital hyperinsulinism associated with septo-optic dysplasia, highlighting the importance of maintaining a high degree of suspicion in all infants who are investigated for chronic hypoglycemia. The authors report an as yet unidentified genetic etiology that may account for both focal congenital hyperinsulinism and septo-optic dysplasia.

With the growing epidemic of obesity, the number of bariatric surgeries in adolescent patients has continuously increased over the past years. This Review addresses the indications for and against bariatric surgery in adolescents, as well as currently available evidence on clinical outcomes, and summarizes measures to provide adequate postoperative care in this patient population.