Reviews & Analysis

Health-care professionals must be educated about the existence of obese individuals who are metabolically healthy and normal-weight individuals who are metabolically unhealthy. A better understanding of obesity subgroups could provide new insights into the development of cardiovascular diseases and type 2 diabetes mellitus and help chose adequate treatments.

The contribution of antipsychotic medications to an increased risk of type 2 diabetes mellitus and cardiovascular disease is controversial. Despite existing guidelines and recommendations, many antipsychotic-drug-treated patients are not routinely assessed for metabolic and cardiac risk factors. This Review outlines the metabolic and cardiovascular risks of various antipsychotic medications in adults and children, defines the disparities in health care and makes recommendations for screening and monitoring of patients taking these agents.

Neonate screening for congenital hypothyroidism is the most successful population-based screening test in pediatrics. The purpose of this Review is to summarize the current knowledge on the etiology underlying thyroid dysgenesis and dyshormogenesis and to provide an update on the evidence concerning the diagnosis and treatment of patients with congenital hypothyroidism.

The aim of this Review is to examine the possible additional benefits of neonatal gonadotropin therapy in male patients with congenital hypogonadotropic hypogonadism. Encouraging results of neonatal therapy, together with a few reports of prepubertal treatment, support the use of this novel therapeutic strategy aimed at improving sexual and reproductive functions in adulthood.

The trace element selenium is increasingly recognized for its importance in health and disease. Supplementing selenium may improve the severity of autoimmune thyroid diseases. Positive supplementation effects have been reported for both Graves disease and Hashimoto thyroiditis. This Review discusses potential mechanisms of action, prospects, and risks associated with selenium supplementation, and highlights current research needs.

Glycemic control for many patients with type 2 diabetes mellitus (T2DM) is elusive, and the adverse effects of treatment, including hypoglycemia and weight gain, are partially culpable. Until recently, glycosuria has been regarded only as a consequence of T2DM, but dapagliflozin employs glycosuria as a mechanism of treatment. Will this paradigm shift gain acceptance?

Chronic fatigue syndrome (CFS) is a disabling and medically unexplained condition with no readily demonstrable organic or psychiatric explanation. The bulk of evidence supports the presence of several factors related to hypothalamic–pituitary–adrenal axis dysfunction in patients with CFS. Here, the authors review the literature on CFS since 2003, put the new findings into context and evaluate progress against previously made recommendations.

A novel study by Del Mastro and colleagues suggests that the occurrence of early menopause as a consequence of chemotherapy can be reduced by triptorelin-induced temporary ovarian suppression during chemotherapy in premenopausal patients with early-stage breast cancer. But does this treatment preserve fertility, and will the benefits of continued menstrual function outweigh the risks?

Animal studies have identified endocrine disrupting chemicals as potential, albeit unproven, contributors to human disorders, especially to those with fetal origins. These disorders can be detected early if pediatricians are vigilant. Recent evidence for population-level changes in young men and girls, which involve developmental endocrine alterations, underscores the urgency for action.

Selective estrogen receptor modulators (SERMs) hold the promise of an ideal estrogenic compound. Moderate efficacy for the prevention of osteoporotic vertebral fractures has now been found after 5 years of treatment with the SERM bazedoxifene; however, expectations for one SERM to provide multiple benefits for postmenopausal women might be a pipe dream.

Body adipose tissue changes and metabolic abnormalities are common among HIV-infected patients receiving highly active antiretroviral therapy and contribute to the risk of cardiovascular disease. This Review highlights the pathogenesis and clinical management of these disorders, focusing on the efficacy of treatment strategies, newly available medications, and potential interactions between HIV medications and medications used to treat metabolic disorders.

This Review highlights the milestones in the field of kisspeptin research, in particular developments in the putative interplay of kisspeptins and their cotransmitters, such as neurokinin B, in the central control of GnRH neurons; and the possible role of Kiss1 neurons as conduits for the metabolic regulation of puberty and fertility, with emphasis on intermediate regulatory signals and mechanisms involved.

This Review discusses the association between mitochondrial function and insulin sensitivity in various tissues, such as skeletal muscle, liver and heart, with a main focus on studies in humans, and addresses the effects of therapeutic strategies that affect mitochondrial function and insulin sensitivity.

Diabetes mellitus has been linked to brain abnormalities and cognitive decline. A report from the Framingham Offspring Study now demonstrates that, in middle-aged and older adults, the core metabolic indicators of diabetes mellitus correlate with continuously distributed properties of brain and cognition, within a clinically normal range.

This Case Study illustrates some of the potential pitfalls of diagnosis and demonstrates a combination of problems of follow-up biochemical screening in a patient operated for a large pheochromocytoma at increased risk of malignant disease. The difficulty in assessing the presence of disease after initial surgical resection and reaching a diagnosis of malignancy are highlighted.

Antiresorptive therapies, such as bisphosphonates, estrogens, selective estrogen receptor modulators, calcitonin and denosumab, are used to increase bone strength in individuals with osteoporosis. However, no single antiresorptive therapy is appropriate for all patients or clearly superior to other therapies. This Review describes the advances in our understanding of antiresorptive therapies and summarizes the benefits and risks associated with various drugs with an antiresorptive effect.

30 years have passed since the first trials of immunotherapy aimed to halt the progression of autoimmune type 1 diabetes mellitus. Today, these efforts are beginning to pay off by generating real hope. Results from recent extensive phase II and III trials lay the foundation for the design of future studies.

Thyroid nodules are frequent clinical findings, but only a small proportion is malignant. Differential diagnosis and risk stratification for thyroid malignancy is, therefore, required to avoid unnecessary surgery. Could immunostaining of two protein markers ramp up a clinician's ability to distinguish lesions that require surgical intervention from those that do not?

Knowledge of genetic alterations occurring in thyroid cancer has rapidly expanded in the past decade. This Review discusses genetic alterations in follicular cell-derived thyroid cancers and outlines new insights into thyroid cancer etiology; in addition, the article describes how mutational markers can be used to improve cancer diagnosis and prognostication.

Medullary thyroid carcinoma is a rare endocrine malignancy that, when diagnosed during childhood, is almost always associated with multiple endocrine neoplasia type 2 and a germline mutation in theRETproto-oncogene. This Review discusses a contemporary approach to the diagnosis and treatment of medullary thyroid carcinoma and multiple endocrine neoplasia type 2 syndromes in the pediatric population.