Endocrine Updates – serie

The discovery of leptin by Friedman and his colleagues in 1994 was a seminal discovery in the study of metabolism, providing a new tool to study energy expenditure and appetite regulation. Early studies actively investigated many aspects of metabolism, obesity, and diabetes but it was soon evident that leptin was much more than a metabolic hormone. Today leptin, with almost 11,000 reports in the world's literature, is recognized to be important in many areas of physiology with strong suggestions for involvement in clinical conditions as well. Leptin, of course, remains of great interest in obesity and diabetes but other, previously unimagined, areas are now in the realm of leptin physiology. Perhaps leptin and its involvement in many areas of reproductive physiology may be of greatest interest outside of obesity, but other physiological arenas are becoming increasingly involved in the broader understanding of leptin and its pleiotropic functions. These areas include cardiovascular disease, bone physiology, immune regulation, and even cancer and genetics. Clinical trials have suggested other areas of leptin pharmaceutical potential beyond the original promise of obesity management. These topics and others, for the first time, have been collected in one volume as the first comprehensive review of leptin and its many actions. This area will continue to increase and is now compounded by new endocrine factors that have been elucidated in the wake of leptin's explosion onto the physiological scene.

Overweight and the Metabolic Syndrome will provide an overview of topics related to obesity, including associated health risks, childhood obesity, genetics, evaluation, treatment, behavioral strategies, and successes and failures in preventing obesity. The body composition that underlies obesity and the metabolic syndrome is key to understanding the problem. The mechanisms by which energy balance is maintained is key to how the problem goes wrong. The metabolic syndrome is in part a consequence of central fat storage, but includes more issues such as insulin resistance, low levels of inflammation, and endothelial dysfunction. This volume will cover evaluation guidelines, different approaches to treatment, including diet, exercise, behavior, drugs, and surgery to deal with the current world-wide obesity epidemic.

Polycystic ovary syndrome (PCOS) is a classic female infertility problem affecting an estimated 6-10% of all women and many of whom are unaware of the problem. PCOS is the single most common endrocrinologic abnormality that affects women. It is a disease that affects women from adolescence to menopause. Patients with PCOS are seen by a variety of specialists, including: reproductive, medical and pediatric endocrinologists; general internists, and dermatologists.This book is an edited collection from diagnosis and epidemiology of PCOS to clinical evaluation. There are additional factors that complicate this disease, such as insulin levels and obesity. Women with PCOS are known to be at a high risk for type 2 diabetes.

This text endeavors to bring together knowledge that has been accumulated in the area of GH and the heart, from basic to clinical studies, by research groups working on this topic throughout the world. Lessons from different experimental models and from several human diseases (acromegaly, adult GH deficiency, heart failure) suggest to endocrinologists and cardiologists that GH may not only have a role in the physiology and pathophysiology of heart function, but that GH itself may have a place in the treatment of primary heart diseases (such as dilated cardiomyopathy) or of cardiac complications of hypopituitarism. The book should be a useful update of the research produced in the field of cardiovascular endocrinology. The editors also hope that this book will serve as the primary step in the recognition of the wide physiological and clinical significance of GH and heart interactions.

This work is intended to be a resource for both researchers in the field as well as endocrinologists, diabetologists, and geneticists who seek to learn more about this rapidly changing and important field. The text contains chapters from experts in the area who review aspects of the genetics of both type 1 and 2 diabetes mellitus as well as various syndromic forms of diabetes. The chapters are approachable for those who are not experts in the field of genetics but also comprehensive, so as to serve as an important resource for researchers interested in the genetics of diabetes mellitus. A description of basic concepts of the genetics of complex diseases like type 1 and type 2 diabetes is provided as background. Type 1 diabetes is addressed in chapters exploring genetic determinants that affect the autoimmune process characterisic of type 1 diabetes, the role of the insulin gene in the pathogenesis of type 1 diabetes and additional genes that may impact upon the risk of type 1 diabetes. The impact of genetic determinants on the pathophysiology of type 2 diabetes is covered, as are chapters that address specific genes that are important for the development of type 2 diabetes.Finally, syndromic forms of diabetes, including maturity onset diabetes of the young and mitochondrial diabetes, and the insight that these disorders provide into more common forms of diabetes are reviewed. Thus, this comprehensive text should serve as an important resource for those actively engaged in research in this area or clinicians treating these patients and for those needing an up-to-date entree to become more knowledgeable in the area.

The purpose of this book is to bring together the many different aspects of and recent discoveries in the understanding of pancreatic endocrine development and its close links to endocrine cell physiology and dysfunction in diabetes. The intention is to combine the knowledge from clinical observations in certain diabetic syndromes with the rapidly growing insights derived from basic molecular biological investigation. At the end of the book, future impacts of these studies are outlined in which the knowledge that is gained from basic studies will be translated into new forms of treatment for diabetes. It is hoped that this book will serve established investigators, newcomers to the diabetes research community, and clinicians interested in the molecular basis of the syndromes that they encounter.

This volume is devoted to all the aspects of prolactin. Medical management of prolactinomas can be based on our understanding of the physiology of hypothalamic control of the lactotroph. Armed with this knowledge, therapies for prolactinomas are highly successful and well tolerated. Because of the historical and practical importance of knowledge regarding the hypothalamus-lactotroph axis, the first chapters of this volume are dedicated to reviewing the physiology, development, and cell biology of lactotroph regulation. Chapters focusing on prolactinomas and related clinical issues follow these. Our understanding of the roles of PRL in the integration of maternal physiology is still very incomplete. The merger of genetics, developmental biology, and physiology has offered new avenues to study these essential functions. Several chapters in the text review our understandings of behavioural, reproductive, metabolic and developmental functions of PRL that relate to maternal care. The fundamental PRL signaling pathways, including relevant kinases, transcription factors, and comodulatory protein findings are reviewed from the receptor level to the nucleus.This volume gives a complete review on prolactin.

The dramatic expansion in genomic information has motivated the development of new approaches to characterize gene expression and function. A critical issue for both basic and clinical endocrinologists is the physiological role of genes involved in regulating endocrine functions. Transgenic technologies allow the translation of genotypic information into specific phenotypes by using gene overexpression or loss of specific gene functions. This book has been designed to reflect a multidisciplinary approach to transgenics in endocrinology, encompassing contributions from internationally recognized experts in many aspects of endocrine physiology. These range from the basic technologies underpinning the generation of transgenic rats and mice, to knock-out mice and also transgenics using viral vectors for gene delivery. The authors have aimed to exemplify the use of transgenic technologies and models for the study of a wide range of endocrine topics, including, reproductive functions, the stress axis, control of lactation, water and electrolyte balance, appetite control and pituitary tumour therapy.

This title is an addition to the Endocrine Updates series. The aim of these publications is to provide the clinician with cutting edge, yet succint, access to the latest advances in endocrinology. Dr. Bahn and her colleagues present exciting developments. These investigators are increasing the quality of life for thyroid eye disease patients. "Thyroid Eye Disease" continues the standard of excellence as the 14th volume in this series of topical updates. Full patients afflicted with thyroid eye disease or Graves' ophthamopathy (GO) may experience not only pain and visual loss, but also disfigurement. Understanding of pathogenesis has been elusive, and treatment modalities are imperfect. As with other conditions, more effective intervention will follow only after a better understanding of pathogenesis is reached. The goal of this volume is to give an overview by leaders in the field of the present state of the art both in pathogenesis and clinical aspects of GO.

Pituitary adenomas account for 10-15 per cent of all intracranial tumours and they frequently impair fertility. The development of medical and surgical therapy for such tumours has turned pregnancy into a reality for women harbouring pituitary adenomas. However, gestation risks for both mother and foetus are still of concern for endocrinologists, gynecologists and paediatricians. This book intends to update knowledge on this topic, mainly regarding fertility restoration as well as gestational and post gestational management of patients with pituitary tumours. It is a fitting addition to the Endocrine Updates series, the aim of which is to provide the clinician with cutting edge, yet succinct, access to advances in endocrinology.

RNA binding proteins are an exciting area of research in gene regulation. A multitude of RNA-protein interactions are used to regulate gene expression including pre-mRNA splicing, polyadenylation, editing, transport, cytoplasmic targeting, translation and mRNA turnover. In addition to these post-transcriptional processes, RNA-protein interactions play a key role in transcription as illustrated by the life cycle of retroviruses. Unlike DNA, the structure of RNA is highly variable and conformationally flexible, thus creating a number of unique binding sites and the potential for complex regulation by RNA binding proteins. Although there is a wide range of topics included in this volume, general themes have been repeated, highlighting the overall integrative nature of RNA binding proteins. The chapters have been separated into three different sections: translational control; mRNA metabolism; and hormonal and homeostatic regulation. The chapters of this volume were written with the seasoned investigator and student in mind. Summaries of key concepts are reviewed within each chapter as well as guiding questions that can be used to stimulate class discussions.

Multicellular organisms require a means of intracellular communication to organize and develop the complex body plan that occurs during embryogenesis and then for cell and organ systems to access and respond to an ever changing environmental milieu. Mediators of this constant exchange of information are growth factors, neurotransmmitters, peptide and protein hormones which bind to cell surface receptors and transduce their signals from the extracellular space to the intracellular compartment. Via multiple signaling pathways, receptors of this general class affect growth, development and differentiation. Smaller hydrophobic signaling molecules, such as steroids and non-steroid hormones, vitamins and metabolic mediators interact with a large family of nuclear receptors. These receptors function as transcription factors affecting gene expression, to regulate the multiple aspects of animal and human physiology, including development, reproduction and homeostasis.The aim of this book is to cover various aspects of intracellular signaling involving hormone receptors.

From the perspective of the investigator, Graves' disease is a fascinating disorder with unique features and opportunities for study. The discovery in 1956 that Graves' disease was caused by a humoral factor, later shown to be an antibody to the TSH receptor, was a triumph for modern investigative medicine. Rapid progress is now being made in (i) understanding the molecular interaction between autoantibodies and the TSH receptor, (ii) identifying the genes that contribute to the predisposition to disease, (iii) developing an animal model of Graves' disease, and (iv) identifying the long-sought orbital antigen in ophthalmopathy. From the clinical standpoint, although Graves' disease is eminently treatable, there is no definitive cure. None of the therapeutic options are ideal. It is hoped that rapid progress in understanding the pathogenesis of the disease will lead to the ultimate goal of some form of immunotherapy that will make antithyroid drugs, radioiodine and thyroidectomy obsolete. This text represents the viewpoints of many prominent clinicians and investigators working in the field.

Morphological imaging and functional imaging are nowadays mainstays for the diagnosis and successive treatment of patients with endocrine disorders. This text provides the reader with concise insights into the application of modern imaging techniques and imaging protocols for the diagnosis and treatment of a variety of endocrine disorders.

This volume addresses important issues in contemporary endocrinology. Its main emphasis is on the consequences of the menopause and on androgen deficiency in the absence of overt disease of the hypothalamus and/or pituitary in men. The use of hormone therapy for the primary prevention of cardiovascular disease in post-menopausal women has become an area of major debate, and the pros and cons are examined in detail. Secondary prevention also remains controversial and is addressed in this volume. An issue of particular concern is the treatment of oestrogen deficiency symptoms in women with the diagnosis of breast cancer. Whether older men with some androgen deficiency symptoms and equivocally low plasma testosterone concentrations should be treated with androgens is also a matter of great debate, as is the efficacy and safety of plant oestrogens in the treatment of menopause-related complaints.

This text is part of the Endocrine Update Series. The aim of these publications is to provide the clinician with access to advances in endocrinology. Historically, our understanding of hormonal disturbances was restricted to the classical secretory glands and their targets. However, as this volume indicates, endocrinology is no longer constrained by our early physiologic understanding of glandular disorder. Factors such as IGF-1 play important roles in cardiovascular cell hypertrophy and the response to acute vascular injury. From another perspective, traditional endocrine hormones, such as estrogen, have been found to participate in preventing the development of atherosclerosis in women, acting through novel mechanisms on target vascular cells. Other "endocrine" hormones, such as PTHRP and adrenomedullin, also modulate cardiovascular and renovascular dynamic states, suggesting new roles for these peptides as vasodilators. This multi-authored text is dedicated to highlighting information regarding the endocrinology of the cardiovascular system. Ellis R. Levin, M.D.

Because of its relative rarity and favorable outcome, it has not been feasible to assess medical interventions for thyroid cancer using randomized prospective trials. The approach to diagnosis and treatment relies to a great extent on information derived from retrospective studies. Overall prognosis and survival rates have been edging upward over the past two decades. This is attributed to a wider acceptance of total thyroidectomy as the primary surgical strategy. The appropriate indication of radioiodine therapy remains controversial, and physicians must be familiar with staging criteria to make educated decisions. We are now beginning to understand the genetic mechanisms of thyroid tumor initiation and progression. There are still major challenges ahead. Thyroid Cancer provides comprehensive updates on the epidemiology, pathogenesis, diagnosis and treatment of thyroid neoplasms. Although the material should be of particular interest to scholars in the field, the contributors have striven to make it of practical use to physicians who treat patients with thyroid disease.

Modern society is altering the lifestyle and longevity of its members much more quickly than evolutionary adaptation to these changes can take place. The problem of calcium deficiency in the population is compounded by the growing percentage of aged individuals with relatively fragile, less massive skeletons. Placing emphasis on the genetic predisposition, early recognition and prevention of osteoporosis, this book aims to expand the practitioner's view of this disease as one beginning at birth and one in which susceptibility is manifest at the conclusion of adolescence, not at menopause. The book concludes with an informed view of the future in terms of the recognition, prevention and management of osteoporosis.

In the 1980s, many endocrinologists were still sceptical that growth hormone (GH) played an active role in adult metabolism. This is, perhaps, surprising given that GH deficiency (GHD) in adulthood had been recognized as long ago as the 1960s. Studies have shown that GHD in adulthood is a far-reaching syndrome associated with abnormal body composition, reduced bone mineral density with an increased fracture rate, increased cardiovascular morbidity and impaired cardiac function, as well as reduced exercise performance and decreased psychological well-being. Importantly, it is also clear, from placebo-controlled trials, that GH replacement therapy can normalize body composition, increase bone mineral content and improve the cardiovascular risk factor profile. GH replacement therapy also improves cardiac performance and exercise capacity, increases muscle strength and improves well-being and quality of life.

This work gives an up-to-date review of the physiology and disease processes associated with the male reproductive system. The first few chapters describe the regulation of the functions of the testis and the integration of its components, germ cells, Sertoli cells and Leydig cells. This is followed by a description of puberty and ageing, and the disorders or dysfunction that may be associated with these physiological processes. Discussions on methods for the diagnosis and treatment of male hypogonadism, male infertility and male sexual dysfunction follow, with detailed descriptions of types of androgen replacement and the benefits and risks of such treatment. The book concludes with the development of male contraception and the possible influence of the environment on the male reproductive system. It represents an amalgamation of the efforts of experts in andrology from all over the world, both in basic cellular/molecular biology as well as in clinical science and practice. This book is suitable for endocrinologists, urologists, general internists, gynaecologists and other students in the field of male reproduction.

The population of the Indian subcontinent consists of a fine amalgamation of people from diverse tribal, cultural, religious and social backgrounds. Mortality and morbidity from a vast number of medical and surgical conditions is significant and well above compared to the developed countries. Although, a large component of the human health problem is related to infection, malnutrition and other preventable causes, a significant proportion is linked to hereditary factors reflecting in the form of chromosomal, single gene and complex medical diseases. Unusual and unique Mendelian disorders are not uncommon and a number of common medical conditions, such as ischemic heart disease and diabetes mellitus are relatively more prevalent among those living in the developing countries of the Indian subcontinent and as well as among the migrant population groups in the western world. However, true burden of the inherited disorders among the Asian Indians is not known, and probably underestimated.This text includes a detailed and concise account of the social and cultural diversity, medical demography, genetic epidemiology, consanguinity and common genetic disorders affecting people from the Indian subcontinent. In addition, specific issues of genetic services in various regions are addressed. This volume also provides a glossary for the benefit of non-genetic professionals, and is aimed at a wide audience including physicians, genetic professionals, public health consultants, medical demographers, medical/ social anthropologists and health administrators.

This text brings together an international panel of experts who summarize the most contemporary advances in the diagnosis and treatment of pituitary disease. Coverage includes pathogenesis and pathology of pituitary tumours; clinical scenarios underpinning each type of pituitary tumour, as well as their diagnosis and treatment. It should prove a useful resource for clinicians, students or researchers with an interest in the pituitary and its disorders.

Pituitary Adenylate Cyclase-Activating Polypeptide is the first volume to be written on the neuropeptide PACAP. It covers all domains of PACAP from molecular and cellular aspects to physiological activities and promises for new therapeutic strategies. Pituitary Adenylate Cyclase-Activating Polypeptide is the twentieth volume published in the Endocrine Updates book series under the Series Editorship of Shlomo Melmed, MD.

Calcium-Sensing Receptor provides an overview of various aspects of the calcium receptor's biochemistry, physiology and pathophysiology that is suitable both for those who have been working in the field of Ca2+0-sensing as well as those who are new to this discipline. Calcium-Sensing Receptor is the nineteenth volume published in the Endocrine Updates book series under the Series Editorship of Shlomo Melmed, MD.

In this volume, Dr. Gaillard has assembled a team of international experts who have written a comprehensive treatise on this topic. Ranging from fundamental molecular developmental mechanisms of the corticotroph cell, to the treatment of Cushing's Disease, these chapters provide a cutting edge overview of the pathogenesis, diagnosis and treatment of disordered hypothalamic-pituitary-adrenal function. Especially noteworthy are the inclusion of chapters on appetite control and neuro-immunomodulation, reflecting the recent exciting advances in these fields. The student of Cushing's Disease and the HPA axis will find elucidation of the latest basic scientific advances, coupled with patient friendly guidelines for clinical diagnosis and management of an extremely challenging neuroendocrine disorder. This volume should be useful for clinical and basic endocrinologists, neuroscientists, postdoctoral fellows and graduate students.

Thirty years have passed since somatostatin was discovered and its hormonal function defined [1,2]. The wide range of anatomical distribution and actions of somatostatin and its receptors stimulated intense scientific and clinical interest, and fostered extensive research into all aspects of its biology including regulation of its gene expression, processing of its precursor, biological and cellular actions relating to regulation cell secretion, motility and proliferation. The development of metabolically stable peptide analogs helped define its usefulness in the treatment of endocrine diseases and cancer. The heterogeneity of somatostatin receptors recognized in 1981 [3] was later shown to result from the existence and variable expression of five distinct subtypes that constitutes two distinct subfamilies with distinguishing pharmacological characteristics [4,5]. The molecular cloning of these receptor subtypes reignited the interest in this field leading to a major increase in our insight into the biology of somatostatin and its receptor subtypes, and has led to the design and development of subtype-selective peptide and non-peptide agonists and antagonists. Significant progress has been made in both basic and clinical research on somatostatin. Noteworthy developments include the role of somatostatin in neuronal patterning, delineation of subtype-selective cytostatic / cytotoxic antiproliferative actions, manipulation of cellular signaling by oligomeric association of somatostatin receptor subtypes amongst themselves or with other G protein-coupled receptors, application of radionuclide-tagged derivatives to localize somatostatin receptor positive tumors and their treatment through targeted delivery of radionuclide or chemotoxin tagged agonists through receptor-mediated endocytosis.

This volume covers the most recent scientific findings of the syndromes of hormone resistance in the HPT axis, i.e., thyroid hormone resistance and resistance to TSH action. Mechanisms of action of the various hormones, etiopathology of the syndromes, instruments for diagnosis, as well as the difficulties in managing these diseases are covered. In general, these disorders of HPT axis are uncommon and thus difficult to diagnose and treat. As a result, this book is a useful resource to clinicians and helps delineate the clinical flow-chart for both diagnosis and treatment.

Thyroid function tests are utilized by essentially all medical practitioners, across every clinical setting, in patients from newborns to the elderly. They are the most frequently measured endocrine tests. The sensitive thyrotropin (TSH) assay reflects thyroid hormone feedback to the pituitary, and is diagnostic of both thyroid h- mone excess as well as deficiency. The log–linear relationship between serum TSH and thyroxine concentrations means that small changes in serum thyroxine are amplified by changes in serum TSH. The availability of the sensitive TSH assay in essentially all clinical laboratories has improved and simplified the assessment of thyroid function for the diagnosis of thyroid disease and to monitor treatment. Serum free thyroxine and thyrotropin concentrations, as well as other thyroid tests, can be measured utilizing an automated immunoassay platform that provides rapid and accurate results. This simplified approach to thyroid assessment, often requ- ing only a serum TSH measurement, and rapid availability of the thyroid function tests results, has expanded the scope of thyroid testing and clinicians ordering and interpretingth yroid tests. There remain, however, many challenges in selecting the appropriate thyroid function test to order, the correct interpretation of results, and applying these results to the diagnosis and management of thyroid diseases. It is especially important to be aware of limitations of thyroid function tests, as well as special clinical c- cumstances that can influence thyroid function measurements. The serum TSH concentration, for example, may not accurately reflect thyroid status in many si- ations including after prolonged hyperthyroidism when serum TSH remains s- pressed for months, in the presence of hypothalamic orpituitary disease, or due to a number of interfering medications. The serum free thyroxine, measured by the analog method, is not accurate with high or low serum binding proteins and d- ing pregnancy. Hospitalized patients often have thyroid function test abnormalities that are transient and return to normal after recovery from the acute illness. Iodine excessand deficiency candramatically influence thyroid function tests. Significant insights have been gained into the regulation of thyroid hormone synthesis and especially the role of thyroid hormone metabolism in supplying t- sues locally with an adequate supply of thyroid hormone. In a number of instances, these factors influence the selection and interpretation of thyroid function tests. Polymorphisms, common sequence variations, in genes of components that regulate thyroid function and thyroid hormone action may also contribute to variability in thyroid function tests in a population. v vi Preface This volume draws on an outstanding international panel of experts in thyroid function tests and thyroid function assessment. They represent clinicians, clinical researchers, and basic science researchers, all with a focus on some aspect of the assessment of thyroid function. The chapters all provide a clinical perspective, but are informed by themost recent scientific advancements. The first section of the book (Chaps. 1–3) presents the most recent advances in thyroid physiology, a review of genetic influences on thyroid function tests, and a discussion on the influence of iodine on thyroid function. In Chap. 1, Drs. Huang and de Castro Neves describe thyroid hormone metabolism, emphasizing the key role of thyroid hormone activation and inactivation in thyroid hormone action. Dr. Visser is a world leader in studies ofthyroid metabolism and genetic influences on thyroid function. In Chap. 2, Dr. Visser and his colleagues, Drs. van der Deure, Medici, and Peeters, provide a clear view of this important and r- idly expanding field. The population variation in the TSH “set point” (relationship between serum TSH and thyroxine in an individual), for example, is thought to be genetically determined, and influences the evaluation of thyroid function and thyroid function targets for treatment of thyroid disease. Dr. Zimmerman, an int- nationally recognized expert in iodine, and his colleague, Dr. Andersson, provide in Chap. 3 an in-depth treatment of the most significant influence on thyroid function throughout the world—iodine intake. The influence of iodine deficiency and excess on individual thyroid function is discussed, as well as the population effects on t- roid diseases and especially fetal and neonatalde velopment. The basics of thyroid function measurements, approaches, limitations, and cl- ical applications are described for the major categories of thyroid function tests (Chaps. 4–7). The authors of these chapters are innovators in the field, strongly id- tified with the origination or significant refinement of the core tests utilized in t- roid assessment. In Chap. 4, Dr. Hershman describes the measurement of TSH, the clinical application and utilization. This remains the cornerstone of thyroid testing, but must be interpreted with an understanding of the dynamics of thyroid regulation. An active controversy in thyroid measurement involves the appropriate use of serum thyroxine measurements and especially the value of the analog free thyroxine me- urement, the most commonly used thyroxine assay. In Chap. 5, Dr. Stockigt p- vides a detailed assessment of thyroxine andtriiodothyronine measurements and a clear message for their use and limitations. The most common etiology of thyroid disease is autoimmune, and the appropriate use of thyroid autoantibody measu- ments remains confusing to many clinicians. In Chap. 6, Dr. Weetman and his c- league, Dr. Ajjan, clearly describe the range of thyroid autoantibody tests and how they should be utilized clinically. Thyroglobulin measurement is the key tumor marker to follow thyroid cancer patients and Dr. Spencer and her colleague, Ivana Petrovic, describe the essential features of this measurement in Chap. 7. It is ess- tial that clinicians using thyroglobulin measurements to monitor thyroid cancer are aware of the performance of the assay being used and the factors that can interfere with the measurement. Application of thyroid function testing to the key clinical settings is discussed by expert clinicians and clinical researchers in Chaps.8–13. The appropriate selec- Preface vii tion of thyroid function tests in the diagnosis and monitoring of thyroid disease in the ambulatory setting is discussed by Drs. Farwell and Leung in Chap. 8. This is the most common setting for thyroid function test measurement and a rational approach is described. Specific issues of thyroid function in infants and children are discussed in Chap. 9 by Drs. LaFranchi and Balogh. Screening for thyroid disease among newborns has been a highly effective approach to prevent mental retar- tion. The assessment of thyroid function in newborns, especially premature infants, is challenging as are the interpretation of thyroid function tests in infancy through childhood. Illness has a significant impact on thyroid function tests and assessment in this group is described by Drs. LoPresti and Patil in Chap. 10. A logicalapproach to these patients is provided as are ways to identify those patients with thyroid disease that need to be treated. Assessment of thyroid function in pregnancy is ch- lenging and is being increasing recognized as a crucial time to normalize maternal thyroid status. Adverse outcome for mother and her child can result from thyroid hormone deficiency or excess. In Chap.11, Drs. Lazarus, Soldin, and Evans ca- fully describe the use and limitations of thyroid tests in pregnancy and provide an approach to testing and monitoring thyroid function. The incidence of autoimmune thyroid disease increases significantly with age and in Chap. 12 Dr. Samuels p- vides a clear approach to the assessment of thyroid status in the elderly and interp- tation of thyroid studies. The influence of drugs on thyroid function testing remains a major clinical issue with recognition of an ever increasing list of medications that influence thyroid function and thyroid testing. In Chap. 13, Drs. Pearce and An- thakrishnan comprehensively describe these medications with a special emphasis on their mechanism of action and on iodine-containing medications. I am most grateful to my colleagues for their enthusiasm and willingness to p- vide such outstanding contributions to this book. The editorial team at Springer is excellent and has been highly supportive and effective. My special thanks to E- tor Laura Walsh, Associate Editor Dianne Wuori, Editorial Assistant Stacy Lazar, Senior Production Editor Jenny Wolkowicki and Crest Premedia Solutions for final production.

The discovery of leptin by Friedman and his colleagues in 1994 was a seminal discovery in the study of metabolism, providing a new tool to study energy expenditure and appetite regulation. Early studies actively investigated many aspects of metabolism, obesity, and diabetes but it was soon evident that leptin was much more than a metabolic hormone. Today leptin, with almost 11,000 reports in the world's literature, is recognized to be important in many areas of physiology with strong suggestions for involvement in clinical conditions as well. Leptin, of course, remains of great interest in obesity and diabetes but other, previously unimagined, areas are now in the realm of leptin physiology. Perhaps leptin and its involvement in many areas of reproductive physiology may be of greatest interest outside of obesity, but other physiological arenas are becoming increasingly involved in the broader understanding of leptin and its pleiotropic functions. These areas include cardiovascular disease, bone physiology, immune regulation, and even cancer and genetics. Clinical trials have suggested other areas of leptin pharmaceutical potential beyond the original promise of obesity management. These topics and others, for the first time, have been collected in one volume as the first comprehensive review of leptin and its many actions. This area will continue to increase and is now compounded by new endocrine factors that have been elucidated in the wake of leptin's explosion onto the physiological scene.