Over recent years, impressive advances in genetic/epigenetic technology have greatly improved the understanding of the pathogenesis of pediatric endocrine diseases due to hormone resistance and hypersensitivity.This book presents reviews of thyroid hormone and thyroid hormone receptor resistance, and genetics and epigenetics of parathyroid hormone resistance. Abnormalities of the pituitary-gonadal axis affecting puberty as well as androgen receptor are covered. Novel insights into the diseases affecting ACTH, glucocorticoid and aldosterone receptors are discussed. Further chapters address new aspects of the physiology of the GH and IGF-1 axis as well as the diseases related to GH-IGF-1 receptor and post-receptor signaling defects. A key chapter on metabolic insights into insulin resistance is also included. Covering clinical and genetic aspects of hormone resistance and hypersensitivity, this book will be a useful tool in the hands of scientists, physicians and other healthcare professionals who wish to be up to date with novel research findings in this area.

"Meeting on hormone resistance and hypersensitivity - from genetics to clinical management held in Genoa, Italy, on May 13-15, 2012"--Pref.

This volume represents the first attempt to present in one place the clinical syndromes and the pathophysiologic basis for the "resistance states" to each of the classes of steroid hormones. Glucocorticoids, mineralocorticoids, androgens, estrogens, progesterone and vitamin D have widely diverse roles ranging from the control of homeostasis to reproduction and bone formation. They are similar in that they share a chemical structure and that their action is in the cell nucleus where they induce transcription of specific genes leading to synthesis of function-specific proteins. Clinical syndromes of steroid hormone resistance to androgens (complete and partial testicular feminization), aldosterone (pseudo hypoaldosteronism) and vitamin D (vitamin D-dependent rickets type II) have been known for many years. Progesterone and glucocorticoid resistance syndromes have been described only recently. Resistance to estrogens has not been reported in man or in animals. It is hoped that a detailed reexamination of what is known about each of these conditions at the clinical and molecular levels will enhance our understanding of the function of these hormones and their mechanisms of action. New insight and research initiatives should result. G.P. Chrousos D.L. Loriaus M.B. Lipsett vii ACKNOWLEDGMENTS The contents of this volume are based in part on the proceedings of an International Conference held in Bethesda in the summer of 1984. This conference was sponsored by the National Institute of Child Health and Human Development, Bethesda, Maryland.

This book provides a comprehensive overview of the genetic basis underlying endocrine diseases. It covers both the molecular and clinical consequences of these genetic defects, as well as the relevance for clinical care, highlighting issues of genetic counseling. Several endocrine diseases have a genetic background, and contemporary research in the field plays a crucial role in the clinical care of endocrine diseases. In recent years, there have been major developments in our understanding of the genetic basis of endocrine diseases. Several novel genes and mutations predisposing individuals to monogenic endocrine diseases have been discovered, and with the advent of next generation sequencing, a huge amount of new data has become available. Further, novel molecular mechanisms, such as genomic imprinting, have been implicated in the pathogenesis of endocrine diseases. A better understanding of the genetic background of these diseases is relevant not only from the research perspective, but also in terms of clinical care. As such, this book is an essential read for both researchers and clinicians working in the field.

This timely volume provides a comprehensive overview of glucocorticoids and their role in regulating many aspects of physiology and their use in the treatment of disease. The book is broken into four sections that begin by giving a general introduction to glucocorticoids and a brief history of the field. The second section will discuss the effects of glucocorticoids on metabolism, while the third section will cover the effects of glucocorticoids on key tissues. The final section will discuss general topics, such as animal models in glucocorticoid research and clinical implications of glucocorticoid research. Featuring chapters from leaders in the field, this volume will be of interest to both researchers and clinicians.

This volume includes the latest diagnostic criteria for PCOS and comprises the most up-to-date information about the genetic features and pathogenesis of PCOS. It critically reviews the methodological approaches and the evidence for various PCOS susceptibility genes. The book also discusses additional familial phenotypes of PCOS and their potential genetic basis. All four editors of this title are extremely prominent in the field of PCOS.

Severe asthma is a form of asthma that responds poorly to currently available medication, and its patients represent those with greatest unmet needs. In the last 10 years, substantial progress has been made in terms of understanding some of the mechanisms that drive severe asthma; there have also been concomitant advances in the recognition of specific molecular phenotypes. This ERS Monograph covers all aspects of severe asthma – epidemiology, diagnosis, mechanisms, treatment and management – but has a particular focus on recent understanding of mechanistic heterogeneity based on an analytic approach using various ‘omics platforms applied to clinically well-defined asthma cohorts. How these advances have led to improved management targets is also emphasised. This book brings together the clinical and scientific expertise of those from around the world who are collaborating to solve the problem of severe asthma.

Outlines a three-step program designed to correct hormonal imbalances for potential health benefits, explaining how to identify problem areas in order to address such challenges as weight gain, insomnia, and mood disorders.

Glucocorticoids regulate multiple metabolic and developmental processes and play a vital role in the maintenance of basal and stress-related homeostasis. For the last 50 years, pharmacologic doses of glucocorticoids have been used in the treatment of inflammatory, autoimmune, and lymphoproliferative diseases and in the prevention of allograft rejection, while substitution doses have been employed in the management of adrenocortical insufficiency. aspects of glucocorticoid action, in particular, (i) the impact of maternal and early life stress on stress-related gene regulation in the offspring; (ii) the importance of glucocorticoids and their receptors; (iii) further understanding of the mechanisms of GR action, including its effect on chromatin modulation, its interaction with coactivators and corepressors, and the genetic dissection of GR function in mice; (iv) The interaction of hGR with other transcription factors, such as NF-kappa-B, p53, transforming growth factor beta (TGF-beta) and the chicken ovalbumin upstream promoter transcription factor II (COUP-TFII); recycling, ubiquitination and degradation of the receptor, actions of the GR-beta isoform, a novel synthetic nonsteroidal target gene-specific agonist, the importance of target tissue activity of 11-beta-hydroxysteroid dehydrogenase type 1 in glucocorticoid action in health and disease, the interaction of the receptor with the nutrient carnitine, the anthrax products protective antigen (PA) and lethal factor (LF), and the human immunodeficiency virus type-1 (HIV-1)-encoded molecules Vpr and Tat; (vi) an update on the effects of glucocorticoids on the immune system; and (vii) the clinical implications of glucocorticoid action, including glucocorticoid resistance/hypersensitivity, familial and sporadic glucocorticoid resistance, and the effects of stress and depression.