Reviews & Analysis

Functional hypothalamic amenorrhea is associated with low levels of leptin, consistent with a state of energy deprivation. The author of this Viewpoint discusses whether administration of recombinant human leptin could replace the nutrition and behavioral interventions that are currently the treatment of choice for this disorder.

Transsphenoidal surgery is the first-line treatment for non-functioning pituitary adenomas (NFPA); however, optimal management of residual tumor after surgery remains actively debated. Although dopamine agonists do not promote appreciable tumor shrinkage in NFPA, the author of this Viewpoint suggests that these agents could be used to prevent tumor re-enlargement.

Anovulatory infertility is a major problem associated with polycystic ovary syndrome; however, several treatment options are now available to induce ovulation in affected individuals. The pros and cons of these medications, which include clomifene citrate, follicle-stimulating hormone, insulin-sensitizing agents, and aromatase inhibitors, are discussed in this Viewpoint.

The insulin-sensitizing agent metformin has been heralded as a novel therapy for women with polycystic ovary syndrome-associated anovulatory infertility. The author of this Viewpoint reviews the evidence from clinical trials and asks whether metformin will become the first-line therapy for ovulation induction in polycystic ovary syndrome.

Postoperative diabetes insipidus usually occurs transiently, owing to temporary compromise of arginine vasopressin secretion. Sometimes, however, a triphasic pattern occurs: initial diabetes insipidus is followed by a period of inappropriate antidiuresis that finally culminates in chronic diabetes insipidus. The authors discuss the pathophysiology of this process and the importance of adjusting treatment according to the pattern of the disease.

This Review details the complex problems that Graves′ disease can cause for both mother and fetus. The authors describe physiological aspects of maternal thyroid function and the effects on fetal thyroid development. They then discuss the diagnostic testing and therapy of Graves′ disease, and review the ramifications of treatment for the fetus.

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.

Simultaneous kidney–pancreas transplantation (SKPT) is the preferred treatment for patients with diabetes and end-stage diabetic nephropathy. Both immunologic and non-immunologic factors can affect patient outcome after SKPT. In this Viewpoint, the role of the metabolic syndrome as a risk factor for chronic renal transplant dysfunction is discussed.

Data from clinical trials have suggested that short-term treatment with estrogen (<10 years) results in a reduced incidence of breast cancer, whereas long-term treatment (>20 years) is associated with an increased risk of breast cancer. The authors of this Viewpoint describe possible mechanisms to account for these seemingly paradoxical effects.

Enrollment of children in clinical trials raises many ethical and regulatory issues, particularly when there is no prospect of direct benefit to the participant. The author of this Viewpoint discusses the US federal regulatory guidelines and asks whether they offer appropriate access and protection for all participants in pediatric diabetes research.

Graves' orbitopathy is an inflammatory syndrome that affects orbital tissues in about half of patients with Graves' disease. Therapy should be planned on the basis of disease severity and activity. This case illustrates the therapeutic approach to a patient with severe, active Graves' orbitopathy complicated by optic neuropathy, and discusses treatment alternatives.

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.

Traumatic brain injury (TBI) can result in hypopituitarism, which in turn affects survival and reduces quality of life. Although this problem is recognized, TBI-related pituitary dysfunction remains underdiagnosed. There is currently no consensus about which patients should be screened; however, the authors of this Viewpoint suggest that case-finding might be the most effective approach.

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.