Evidence accumulated over the past decade show that gonadal steroid hormones participate in an important way in the physiological and pa thophysiological regulation of the cardiovascular system. The hor monal profile appears to put males at a disadvantage biologically in terms of cardiovascular diseases. The incidence of hypertension is higher in men than in pre-monopausal women indicating an influence of gender on the hypertensive disease process. Males and females have equivalent cholesterol levels until puberty but males suffer an ex ponential increase in heart disease in their forties, while the female rise does not start until a decade later, after menopause. Animal and human studies provided ample evidence, that estrogens lower the levels of low density lipoproteins and keep high density lipoproteins elevated. These changes may be advantageous in the prevention of heart diesease. Co ronary artery atherosclerosis has been shown to be more pronounced in ovarectomized female monkeys as in intact females. Androgen, con versely, lowers the high density lipoproteins and elevates low density lipoproteins. Regarding blood pressure, it is well established that hypertension is more severe or develops more rapidly in male than fe male rats in several genetic forms of hypertension, and that gonadal steroid hormones are probably playing an important role in explaining this observation. Risk factors of human hypertension and coronary heart dies ease include menopause and ovarectomy."

Amenorrhea: A Case-Based Clinical Guide is a comprehensive review of the current knowledge regarding normal female reproductive physiology. Replete with interesting case vignettes and providing diagnostic algorithms and therapeutic strategies for amenorrhea, Amenorrhea: A Case-Based Clinical Guide is divided into three sections. The first section is composed of two chapters that provide a thorough review of basic science and clinical knowledge about the organ systems responsible for normal physiology of the menstrual cycle. The second section includes discussion about menstrual cycle disruption as it relates to hypothalamic-pituitary dysfunction, surgical and natural menopause, genetic defects, premature ovarian failure/insufficiency and the effects of caloric excess and restriction. The third section offers an update on the physiological effects of prolonged amenorrhea induced surgically or by hypothalamic dysfunction and also includes an original chapter that focuses solely on the impact of race and ethnicity on the prevalence and diagnosis of amenorrhea. Amenorrhea: A Case-Based Clinical Guide brings together chapters from renowned experts who offer state-of-the-art, clinically useful information in a case-based, reader-friendly fashion. This title will be a welcome addition to the bookshelves of all clinicians who practice in women's health settings.

Leading researchers comprehensively translate all the latest scientific information regarding endocrine physiology and development into an understanding of the clinical pathogenesis, diagnosis, and treatment of endocrine disease. Organized by endocrine system, each section of the book concisely describes the chronological development of the human organism, from the fetal/prenatal period through childhood, adolescence, and in some cases, into adulthood. The prenatal sections review recent discoveries concerning transcription factors, homeobox genes, and human molecular mutations-the basic processes governing prenatal development of the individual endocrine organs-and detail the pathophysiology, clinical characteristics, and treatment of pediatric endocrine disorders.

This volume will explore the epidemiology and the basic mechanisms of each of these prenatal phenomena, in an attempt to explain the role of the prenatal environment in promoting postnatal weight gain. This information will contribute to resolving the nature-nurture controversy. This information provides guidance to clinical practitioners involved in both prenatal and postnatal care. This volume further stimulates research into underlying mechanisms and prevention and treatment of this phenomenon.

The volume Appetite Control provides a comprehensive description of the mechanisms controlling food intake, and thereby energy balance, in the mammalian organism. During the last decade, research in this area has produced a remarkable wealth of information and has characterized the function of numerous peptides, transmitters, and receptors in appetite control. Dysfunction of these circuits leads to obesity, a growing health concern. However, the plethora of mechanistic information is in marked contrasts to an almost complete lack of anti-obesity drugs that meet the safety standards required for the chronic therapy of morbid obesity. Consequently, ongoing research aims to identify additional targets and agents for a pharmacological intervention. Thus, the mechanisms of appetite control as well as all agents interfering with its control are of considerable practical interest.

The authors of the volume are distinguished scientists who are leading experts in the field, and who have contributed important, original data to our understanding of the mechanisms of appetite control. They have quite different scientific backgrounds and, together, they represent all relevant disciplines. Thereby, the topics are presented from different points of view, not exclusively from that of pharmacology and neuroendocrinology. Thus, the volume addresses all scientists who are interested in the field of obesity research and the pathophysiology of appetite control."

The discovery of mammalian nitric oxide (NO-) synthesis from I-ar- ginine has led to profound increases in our understanding of basic physiological and pathophysiological processes. This understanding has been achieved by major advances in several areas. Three major ni- tric oxide synthase (NOS) isoforms have been identified at the protein and gene level and their specific tissue localization has been linked to processes subject to regulation by NO-. The molecular basis for the di- verse effects of NO- on cell function has been shown to derive from its chemical reactivity with oxygen-containing species and both heme and non-heme iron-dependent enzymes. The potential regulation of heme- dependent enzymes such as cytochromes P450, guanylate cyclase, cy- clooxygenase, and mitochondrial cytochrome oxidase continues to emerge as a key area in NO- research. In addition, it has become clear that the expression of NOS isoforms and NO- release from cells is subject to regulation by sexual steroids and that, in tum, NO- has the potential to regulate steroid biosynthesis via inhibition of cytochromes P450 involved in steroidogenesis. These recent observations on interactions between the NO-/NOS and cytochrome P450/sexual steroid pathways have important implica- tions for understanding fundamental mechanisms involved in endocri- nological processes. They are also likely to lead to novel insights and novel therapeutic approaches for the management of pathophysiologi- cal conditions associated with alterations in sexual steroid hormones.

Sex-Steroid Interactions with Growth Hormone presents the proceedings of an international symposium held from October 22-25 in Naples, Florida. The proceedings provide new insights and concepts gained by molecular, cellular and neuroendocrine research into mechanistic interactions of the reproductive and somatotrophic axes. Chapters include discussions of the impact of sex steroids on growth hormone secretion in both children and adults; sex steroids, growth hormone releasing factor, and somatostatin; how sex steroids modulate growth hormone action on target issues; and differential effects of growth hormone secretagogues in men and women. This volume is designed for physicians, scientists and other health professionals interested or trained in clinical and basic endocrinology, growth or reproduction.

The purpose of these volumes is to provide a reference work for the methods of purifying many of the receptors we know about. This becomes increasingly important as full-length recep- tors are overexpressed in bacteria or in insect cell systems. A major problem for abundantly expressed proteins will be their purification. In addition to purification protocols, many other de- tails can be found concerning an individual receptor that may not be available in standard texts or monographs. No book of this type is available as a compendium of purification procedures. Receptor Purification provides protocols for the purification of a wide variety of receptors. These include receptors that bind: neurotransmitters, polypeptide hormones, steroid hormones, and ligands for related members of the steroid supergene family and others including receptors involved in bacterial motion. The text of this information is substantial so as to require its publica- tion in two volumes. Consequently, a division was made by grouping receptors depending upon the nature of their ligands. Thus, in volume 1 there are contributions on serotonin receptors, adrenergic receptors, the purification of GTP-binding proteins, opioid receptors, neurotensin receptor, luteinizing hormone re- ceptor, human chorionic gonadotropin receptor, follicle stimulat- ing hormone receptor, thyrotropin receptor, prolactin receptor, epidermal growth factor receptor, platelet derived growth factor receptor, colony stimulating factor receptor, insulinlike growth factor receptors, insulin receptor, fibronectin receptor, interferon receptor, and the cholecystokinin receptor.

"Fertility Preservation in Males: Emerging Technologies and Clinical Applications" contains a selection of the valuable chapters and protocols of Seli and Agarwal s previously published hardcover text "Fertility Preservation: Emerging Technologies and Clinical Applications." Newly available in this convenient and affordable softcover format, this practical reference guide provides an update on options for fertility preservation in men, while also discussing important related epidemiologic, ethical, medico-legal, psychological, and social aspects. Using a format that combines concise scientific background with practical methodological information and easy-to-grasp algorithms, the chapters all conform to a uniform structure, including step by step protocol of laboratory procedures, key issues in commentary and a list of references. The result is a unique resource for reproductive endocrinologists, urologists, embryologists, reproductive scientists, and oncologists."

The purpose of these volumes is to provide a reference work for the methods of purifying many of the receptors we know about. This be comes increasingly important as full-length receptors are overexpressed in bacteria or in insect cell systems. A major problem for abundantly expressed proteins will be their purification. In addition to purification protocols, many other details can be found concerning an individual receptor that may not be available in standard texts or monographs. No book of this type is available as a compendium of purification procedures. Receptor Purification provides protocols for the purification of a wide variety of receptors. These include receptors that bind: neurotransmit ters, polypeptide hormones, steroid hormones, and ligands for related members of the steroid supergene family and others, including receptors involved in bacterial motion. The text of this information is substantial, so as to require its publication in two volumes. Consequently, a division was made by grouping receptors by the nature of their ligands. Thus, in Volume One there are contributions on serotonin receptors, adrenergic receptors, the purification of GTP-binding proteins, opioid receptors, neurotensin receptor, luteinizing hormone receptor, human chorionic gonadotropin receptor, follicle stimulating hormone receptor, thyro tropin receptor, prolactin receptor, epidermal growth factor receptor, platelet derived growth factor receptor, colony stimulating factor recep tor, insulin-like growth factor receptors, insulin receptor, fibronectin receptor, interferon receptor, and the cholecystokinin receptor.

The aim of this symposium was to provide basic and clinical investigators with the latest information on the biology of wound healing and tissue repair. Written and edited by eminent experts in the field, the papers cover the general concepts of wound healing; the role of nutrients; endogenous growth factors; clinical applications of growth hormone and IGF-1 therapy; and clinical applications of peptide growth factors.

Inhibin, activin, and follistatin were originally discovered as hormonal fac- tors a decade ago. Subsequent studies revealed that they are widely distrib- uted anatomically and have multiple biological functions in a wide range of cells and tissues. Since the last Symposium three years ago, there has been remarkable progress toward defining activin's roles in controlling hormone secretion, cell differentiation and proliferation, mesoderm induction in em- bryos, nerve cell survival, and promotion of bone growth. Furthermore, the characterization of activin receptors as serine and threonine kinases and the identification of intracellular mediators such as the Smads have provided key elements for the eventual understanding of signaling mechanisms for activin and the other members of the TGF-beta superfamily. The unknown in this integrative field, however, remains far greater than the known. For ex- ample, we are just beginning to exploit the recently improved activin, inhibin, and follistatin two-site assays for the evaluation of the physiological and pathophysiological functions of these proteins. Also, we have only a rudi- mentary understanding of the mechanisms by which inhibin blocks activin, and many steps in the pathways linking the formation of ligand-receptor(s) complexes to transcriptional regulation are unclear. The aim of the Third Symposium was to bring together scientists from diverse fields to share technical and conceptual developments. The program was framed with the intention to include a wide range of timely research topics.

Introduction Anthony J. Edis, Richard H. Egdahl, Tracy K. Mcintosh, Contents Lester F. Williams xi 1 Surgery of the Parathyroids General Introduction 1 SURGICAL ANATOMY Primary Hyperparathyroidism 7 PATHOLOGY 7 DIAGNOSIS 11 PREOPERATIVE LOCALIZATION STUDIES 22 TREATMENT 27 Secondary Hyperparathyroidism 35 SIGNS, SYMPTOMS, COMPLICATIONS 35 CLINICAL MANAGEMENT 36 Tertiary Hyperparathyroidism 37 Operative Technique 38 CERVICAL EXPLORATION WITH REMOVAL OF A PARATHYROID ADENOMA 46 SUBTOTAL PARATHYROIDECTOMY FOR HYPERPLASIA 59 PARATHYROIDECTOMY FOR CARCINOMA 60 MEDIASTINAL EXPLORATION FOR PARATHYROID TUMOR 61 References 66 2 Surgery of the Thyroid 71 General Introduction 71 SURGICAL ANATOMY 72 Nodular Goiter and Thyroid Carcinoma 79 PATHOLOGY 79 DIAGNOSIS 82 TREATMENT OF THYROID NODULES 94 TREATMENT OF THYROID CANCER RELATED TO PATHOLOGIC TYPE 97 Hyperthyroidism 110 Graves' Disease 111 PATHOLOGY 111 DIAGNOSIS 112 TREATMENT 115 Plummer's Disease 120 PATHOLOGY 120 DIAGNOSIS 120 TREATMENT 122 Complications of Thyroid Surgery 123 PREVENTION AND MANAGEMENT 123 viii CONTENTS 127 Operative Techniques TOTAL THYROID LOBECTOMY 127 REMOVAL OF A SUBSTERNAL GOITER 134 SUBTOTAL THYROID LOBECTOMY 136 MODIFIED NECK DISSECTION FOR PAPILLARY THYROID CARCINOMA 141 References 144 3 Surgery of the Adrenals 151 151 General Introduction SURGICAL ANATOMY 152 Pheochromocytoma 155 PATHOLOGY 155 156 DIAGNOSIS PREOPERATIVE 162 TREATMENT 166 172 Primary Aldosteronism PATHOLOGY 172 DIAGNOSIS 174 178 PREOPERATIVE LOCALIZATION STUDIES TREATMENT 180 Cushing's Syndrome 181 CLASSIFICATION 182 DIAGNOSIS 187 PREOPERATIVE LOCALIZATION STUDIES 192 TREATMENT 194 Adrenal Gland and Metastatic Breast Carcinoma 198 Adrenocortical Carcinoma 200 DIAGNOSIS 201 PREOPERATIVE LOCALIZATION STUDIES AND STAGING 201 TREATMENT 202 PROGNOSIS 203 Nonfunctioning Adrenal Tumors 203

Physiological, pharmacological and molecular biological data generated over the past three decades have demonstrated the existence of two major families of extracellular receptors, the P1, a family of four G-protein coupled receptors and the P2, a family of at least 12 receptors responsive to purine (ATP, ADP) and pyrimidine (UTP) nucleotides through which adenosine and ATP can function as extracellular messengers. The present two-part volume represents an integrated compendium of invited chapters by leading researchers in the area focusing on advances in the understanding of purinergic and pyrimidinergic signaling systems, their role(s) in tissue function and pathophysiology and advances in developing potential new medications based on the modulation of P1 and P2 receptor signaling processes. The volumes will thus provide the reader with a topical, comprehensive and integrated overview of this important area.

Many advances have been made in the field of thermoregulation in the past few years. These include our understanding of Fever, which is now considered not simply a rise in deep body temperature foHowing infection, but just one aspect, though perhaps the most easily measured, of the Acute Phase of the Immune Response. Classification and identification of the Cytokines and the availability of recombinant material has greatly aided this research. Similarly, our understanding of the Hypothalamo-Pituitary Adrenal Axis has altered our way of thinking about temperature regulation. Of importance are the problems associated with adverse climatic conditions and survival, and the problems encountered by the neonate and the hibernator. At the biochemical level, our knowledge of the control of heat production and the role of brown adipose tissue is rapidly advancing. All these issues and many others were discussed at a Symposium 'Thermal Physiology 1993' held in Aberdeen, Scotland in August 1993 under the auspices of the Thermal Physiology Commission of the International Union of Physiological Sciences. Six main aspects of the subject of temperature regulation are included in this book, namely, Fever (including the Acute Phase of the Immune Response and Thermoregulatory Peptides), Neurophysiology of Thermoregulation, Neonatal Thermoregulation, Mechanisms of Heat Production, Ecological and Behavioural Thermoregulation, and Emerging Themes in Thermoregulation.

"Theoretically, one should obtain essentially the same clinical picture from failure of an end-organ to respond to a hormone as from a decreased production or absence of said hormone. " With these words, Fuller Albright began his now classic paper describing a novel disease, pseudo hypoparathyroidism (PHP), and a novel concept, hormone resis- tance as a cause of disease. Soon, other hormone resistance disorders such as nephrogenic diabetes insipidus (NDI) were recognized, and the concept was extended to resistance to other substances such as calcium ions in familial hypocalciuric hypercalcemia (FHH). Later, diseases characterized by excess rather than deficient hormone action such as McCune-Albright syndrome (MAS) and familial male precocious puberty (FMPP) were recognized to be caused by autonomous endocrine hyperfunction. Although many i!!vestigators provided careful and detailed descriptions of the clinical features of these and other related endocrine disorders, an understanding of pathogenesis proved elusive for many years. In just the past few years, we have gone from clinical description to a molecular understanding of these interesting disorders. This remarkable progress reflects a synthe- sis of three distinct, but now overlapping, areas of biomedical research: the aforemen- tioned recognition and careful clinical description of specific diseases, the elucidation of the basic mechanisms of signal transduction, and the application of the powerful tools of molecular biology and genetics. Fundamental studies on the mechanisms of hormone action by Rodbell and colleagues at NIH culminated in the discovery of a major signal transduction pathway involving heterotrimeric G proteins.

"When a thing ceases to be a subject of controversy, it ceases to be a subject of interest. " WILLIAM HAZLITT (1778-1830) This is the fourth volume in a series which we started in 1997. In 1976, Varco and Delaney edited a "surgical bestseller" entitled Controversy in Surgery. This was fol lowed by a second volume in 1985. The immense success of these books among both surgical trainees and experienced surgeons, and their wide international ap peal, supported the editors' notion that a view of controversy is integral to teach ing. However, despite major advances in surgical science and practice, no other similar publication has since been put together with the objective of addressing major controversies in surgery. The aim of this series is to address such deficiency by covering the most crucial current controversies in general, vascular and trauma surgery. Since almost everything is controversial in surgery, we will be able to tackle different issues almost each year. The editors have selected a nationally/internationally recognized authority for each topic. Most books available today are either "North American: ' "British-Com monwealth" or "British-European: ' contributing to the constant transatlantic rival ry. Our series specifically aims to bridge this "culture gap" and includes North American, British, European, and other authors while maintaining a cohesive structure. This will hopefully also broaden the appeal of such a book across both sides of the Atlantic and beyond."

Stephen P. Ethier and a panel of leading investigators comprehensively analyze the cellular, molecular, and endocrine factors in the development of cancers of the breast, prostate, endometrium, and ovary. Concentrating on defining the most important unresolved issues in the field, the authors review how steroid hormones function to regulate normal mammary gland homeostasis in humans, with particular emphasis on the roles of estrogen, progesterone, and growth factors. Comprehensive and up-to-date, Endocrine Oncology offers both basic and clinical researchers not only the latest molecular and cellular findings on endocrine cancers, but also a powerful critical analysis that will prove invaluable to all endocrinologists and oncologists working in the area today.

The rapid developments in molecular genetics have clarified many of the muta tions in monogenic thyroid diseases over the last two decades; now the target of molecular thyroid genetics has become the oligogenic thyroid diseases. These include the autoimmune thyroid diseases and familial thyroid cancers, both of which are much commoner than the monogenic diseases. However, the method ological approach to the genetics of these more complex diseases is still far from being well established. Although the discovery of susceptibility genes has been partially accomplished in complex diseases such as asthma, Crohn's dis ease, and types I and II diabetes mellitus, the elucidation of susceptibility genes in complex diseases remains a major challenge. This volume contains papers presented at the International Symposium on the Genetics of Complex Thyroid Diseases. This meeting was held in association with the International Thyroid Congress in Kyoto in October 2000 and sup ported in part by the Japan Intractable Diseases Research Foundation and Knoll Pharmaceuticals Inc. The symposium was the first international symposium con cerning the genetics of complex thyroid diseases and was restricted to the study of the autoimmune thyroid diseases and familial thyroid cancer. Twenty distin guished researchers from the United States, the United Kingdom, France, Ger many, Italy, and Japan were invited. Each presentation precipitated intense dis cussion and there was much consensus during the meeting. Nevertheless, this volume will leave the reader with a clear understanding of how little we still know.

"Neuropeptides and Stress" presents a comprehensive survey by leading pioneers in the field of the knowledge and concepts implicating neuropeptides in the regulations of responses to stress. Topics covered include: recent advances on the regulation and modulation of the behavioral, endocrine, autonomic, gastrointestinal, immune and analgesic responses to stress by neuropeptides. Neuroanatomical and biological data are considered. Special emphasis is given to corticotropin-releasing factor (CRF) and opioid peptides.

A growing majority of women in the western hemisphere have been delaying initiation of childbearing to later in life. Consequently, more than ever before, women in their late 30s to early 40s are attempting their first pregnancy. Since the incidence of most cancers increases with age, delayed childbearing results in more female cancer survivors interested in fertility preservation." Fertility Preservation in Females: Emerging Technologies and Clinical Applications" contains a selection of the valuable chapters and protocols of Seli and Agarwal s previously published hardcover text "Fertility Preservation: Emerging Technologies and Clinical Applications." Newly available in this convenient and affordable softcover format, this unique and practical reference guide for reproductive endocrinologists, gynecologists, embryologists, reproductive scientists, and oncologists provides strategies for fertility preservation in women, using a format that combines concise scientific background with practical methodological information and easy-to-grasp algorithms."

In a state-of-the-art synthesis of basic science and clinical practice, Roy Smith and a distinguished panel of researchers and clinicians review GH regulation and its action at the molecular level, and describe the basis for GH deficiency and the use of GH as therapy in a variety of clinical situations. The clinical presentation moves beyond the treatment of GH-deficient children to include the genetics of GH-deficiency, GH-deficiency in adults, osteoporosis, Syndrome X, sleep quality, GH in AIDS patients, GHRH in clinical studies. Timely and innovative, Human Growth Hormone: Research and Clinical Practice will benefit both basic and clinical researchers, as well as those clinical endocrinologists who want to use growth hormone not only in treating children, but also in treating adult disorders, including those associated with metabolic disease.

The present volume is the results of 6 years' work by our team, during which time 2300 CT scans of the pituitary region were carried out. This was made possible by the close collaboration between physicians and technicians in our neuroradiological department, as well as by numerous corresponding physi cians. We wish to express our gratitude for their confidence and our sincere thanks to our colleagues at Besan90n, Dijon, Grenoble, Lyon, Montpellier, and Strasbourg. Furthermore, we especially wish to thank the patients who willingly accepted the difficult requirements of these studies. We are grateful to the technicians at the Neuroradiology Department of the Centre Hospitalier et U niversitaire de Besan90n, who have perfected the methodology so as to meet the ever increasing imperatives for precise anatomical mapping of the pituitary gland and the surrounding region; without their efforts, this book would never have been possible. Finally, we wish to express our thanks to the medical photographer of our group, as well as the secretarial staff for their contribution to the successful production of this work. We thank Labora toires Guerbet and General Electric for their excellent assistance, and Springer Verlag for their care and competence in the production of this book. In writing Computed Tomography of the Pituitary Gland, we have sought to develop morphological study of the pituitary gland to a degree of reliability comparable to that of laboratory findings in endocrine disorders.

In Cushing's Disease, leading authorities in the field offer a thorough review of the pathogenesis, diagnostic algorithm and treatment options for this complex disease. Beginning with a fascinating history of Cushing's disease that outlines its historical significance to both endocrinology and neurosurgery, the book goes onto to cover the full range of important issues, including the molecular pathogenesis of Cushing's, anatomic pathology, the diagnosis of Cushing's syndrome, the differential of pseudo-Cushing's syndromes, hypercortisolemia, surgical removal of the corticotroph adenoma, post-operative management and assessment of remission, radiotherapeutic options, and the exciting developments in medical therapy. In addition, the book also addresses Cushing's disease in the pediatric population, given that its clinical manifestations and impact on growth can be severe; silent corticotroph adenomas as a distinct clinical entity; diagnosis and management of Cushing's disease during pregnancy, bilateral adrenalectomy, and, finally, the long-term psychological manifestations of hypercortisolemia. Comprehensive and an invaluable addition the literature, Cushing's Disease is an essential reference for enhancing diagnosis and treatment of this debilitating disorder.

A cutting-edge review of how derangements in the hormonal and growth factor mechanisms controlling normal mammary development lead to breast cancer. Drawing on the multidisciplinary expertise of leading authorities, the book highlights the roles of oncogenes and tumor suppressor genes, spelling out the importance of autocrine/paracrine loops (e.g., stromal epithelial interactions) in supporting breast cancer cell proliferation and the progression to hormone independence. The book's many prominent contributors also illuminate significant recent advances in the biochemistry and physiology of hormone receptors and review the state-of -the-art in the endocrine therapy of breast cancer. Endocrinology of Breast Cancer provides a unique integrated overview of the most significant basic and clinical developments concerning the hormonal aspects of breast cancer.