This book provides a concise summary across all aspects of endocrine surgery, covering the major endocrine organs and discussing aspects of surgical care. It comprises five sections covering the major endocrine organs/systems, each with a specialist section editor. Within each section there are a number of brief (2-3 page) chapters, written in a combination of prose and bullet points, a format that is conducive to both detailed reading and quicker, "dipping in", review. Each chapter contains a "Pearls and Pitfalls" summary box. The text takes into account the latest evidence and current expert opinion from an internationally renowned list of authors.

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.

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.

"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.

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.

This volume of Molecular Biology of Hematopoiesis is dedicated to many inter national scientists and clinicians for their contribution to the field of Hematology/ Oncology presented at the 11th International Symposium on Molecular Biology of Hematopoiesis, which was held in Bormio, Italy, June 25-29, 1998. The continuous support of the Presidents of the meeting, Professor F. Takaku, President of Jichi University, and E. D. Thomas, Nobel Laureate, was greatly acknowledged, especially Professor Takaku, for his vision and support for development of gene therapy in Japan. New information on BMT for autoimmune disease and organ transplantation was presented at the symposium and is published in this volume. Several new findings on gene therapy/transfer into HSC were presented by E. F. Vanin and A. Nienhuis, K. Humphries, 1. A. Nolta, H. E. Heslop, and M. K. Brenner. Professors S. Asano and K. Tani presented new studies on gene transfer into primates. Among the highlights were the new papers on gene transfer presented by G. Wage maker, N. G. Abraham, and M. Onoderea from R. M. BJaese's group. The use of BMT for organ transplant and autoim mune disease was updated and a representative paper is presented in this volume."

Sex matters! Are there differences between the sexes when it comes to brain function and the behaviours that result? This volume attempts to answer this fundamental question. If the answer is 'yes' then this should impact upon our approach to treating mental illness in humans, and to modelling it in animals, as we look for aetiological and pharmacological solutions.

This fifth edition of Autonomic Failure covers the many recent advances made in our understanding of the autonomic nervous system. There are numerous new chapters and extensive revisions of all other contributions. This book makes diagnosis increasingly precise by fully evaluating the underlying anatomical and functional deficits, thereby allowing more effective treatment. This new edition continues to provide a rational guide to aid in the recognition and management of autonomic disorders for practitioners from a variety of fields, including neurology, cardiology, geriatric medicine, diabetology and internal medicine.

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 or pituitary 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 of thyroid 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 and triiodothyronine 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 logical approach 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.

A panel of outstanding investigators surveys and explains the major cutting-edge methods used in thryroid receptor (TR) research and explains their practical experimental details. Described in step-by-step detail to ensure robust experimental results, the techniques presented cover a wide variety of key areas, including TR in development and knockout (mouse and Xenopus), transcriptional regulation by TRs in both cell-free systems and in living cells, and TR mutant analysis of patients. Additional methods provide powerful tools for the isolation of TR-regulated protein complexes, for studying the oncogene v-Erba in blood cell differentiation, and for target gene analysis in the brain. Microarray chip methods are also presented for analyzing the organs of transgenic mice to identify target genes in the liver.

The subject of this book is neuroendocrinology, that branch of biological science devoted to the interactions between the two major integrative organ systems of animals-the endocrine and nervous systems. Although this science today reflects a fusion of endocrinology and neurobiology, this synthetic ap proach is relatively recent. At the beginning of the 20th century, when the British physiologists, Bayliss and Starling, first proposed endocrinology to be an independent field of inquiry, they went to great lengths to establish the autonomy of chemical secretions in general and their independence from nervous control in particular (Bayliss, W. M. , and Starling, E. H. , 1902, The mechanism of pancreatic secretion,]. Physiol. 28:325). They argued with Pav lov, who said that there was a strong influence of the nervous system on the gastrointestinal phenomena the endocrinologists were studying. For several decades, the English physiologists prevailed, at least in the West; and Pavlov's critique was not taken to heart by the practitioners of the newly emerging discipline of endocrinology. Through the work of Harris, the Scharrers, Sawyer, Everett, and others, there has been something of a scientific detente in the latter half of this century; the hybrid field of neuroendocrinology is now regarded as one of the corner stones of modern neural science and is of fundamental importance in basic and clinical endocrinology.

This volume provides a brief resume of the history of testosterone research, from the early pioneers through to the most recent advances in the field. We discover how steroid hormones were first identified and how testosterone was shown to be essential for male development. Moving forward we explore how and where testosterone is produced, and how the body controls testosterone production. We then investigate the impact testosterone has on different body systems both during their development and function, and how perturbation of testosterone action is associated with disease. We complete our story with an exploration of the emerging roles of testosterone in clinical therapy, and the future potential for manipulation of the testosterone signaling system for human health benefit.

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.

Endocrine conditions requiring surgical intervention in the pediatric age group are uncommon. When diagnosed, they are the source of great in terest and, often, considerable debate. This is understandable, since few centers and even fewer individual surgeons can draw on vast experience of this subject. The great divergence of opinion regarding management is also understandable in that pediatric endocrine lesions often differ considerably from their adult counterparts in histology, natural history and response to treatment. Pediatric endocrine lesions are also, as a rule, less frequently malignant. In addition to the great strides made in surgical and anesthetic technique and operative monitoring, progress in four areas has substantially advanced the management of endocrine dis orders in the pediatric age group in the last decade: imaging, pathology, pharmacology and genetics. The new imaging tools, ultrasonography, computed tomography and magnetic resonance imaging, have added great diagnostic possibilities. More recent developments, such as radio nuclide imaging for the adrenal gland and the possibility of using tagged antibodies, promise to expand our imaging horizons even further. In the field of pathology, the develop ment of immunocytochemical markers (e. g. , monoclonal antibodies), the refinement in special stains and the continuous perfection of fine needle aspiration biopsies offer great new diagnostic as well as research capabil ities. Newer pharmacological agents, such as the alpha and beta blockers, the calcium channel blockers and thyroxine analogs, add a whole new level of safety to the management of the potentially lethal pheochromocytoma.

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.

The Third Advanced Seminar in Neurosurgical Research was held in the Palazzo Pisani Moretta, Venice, Italy from 30th April to 1st May, 1987 and was devoted to "Neuroendocrinological Aspects of Neurosurgery." The general aim of these advanced seminars is to bring together European Neurosurgeons interested or involved in research work, either clinically, experimentally or both, in a given field in order to achieve in-depth informal discussions not possible in the more conventional large congress. In particular, these advanced seminars seek to provide high level teaching by experienced basic scientists, to provide "state of the art" assessment of the subject and to highlight areas of controversy that may be suitable for future research. A special effort is made to identify younger neurosurgeons through the auspices of the European Directory of Neurosurgical Research, who have a particular interest in the subject under discussion, not all of whom will have immediate access to the most advanced, modern technology. The topic of Neuroendocrinology was chosen because clinically it is an area of controversy that should be amenable to application of new techniques, including molecular biology. There is a tendency on the part of Endocrinologists not to appreciate always that disturbances seen by Neurosurgeons may be different and need special attention. Inevitably there has been a little delay in publication of the manuscripts but these have been updated appropriately.

Starting in 1986, the European School of Oncology has expanded its activities in postgraduate teaching, which consisted mainly of traditional disease-orientated courses, by promoting new educational initiatives. One of these is the cloister seminars, short meetings intended for highly qualified oncologists and dealing with specific, controversial aspects of clinical practice and research. Another is the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on developments and treatment in specific fields of oncology. This series of ESO Monographs was designed with the specific purpose of disseminating the results of the most interesting of the seminars and study groups, and providing concise and updated reviews of the subjects discussed. It wa& decided to keep the layout very simple in order to keep costs to a minimum and make the monographs available in the shortest possible time, thus overcoming a common problem in medical literature: that of the material being outdated even before publication.

This volume emphasizes the comparative approach to under standing vertebrate renal function. I am convinced that this approach is of particular value in understanding both the details of renal function at the cellular and subcellular levels and the renal role in regulating fluid volumes and solute concentrations. My exposure to this approach first occurred during a student research experience in the laboratory of Wilbur H. Sawyer, who also provided an introduction to the works of Homer W. Smith and August Krogh. The importance of this approach was reinforced by doctoral and postdoctoral research in the laboratory of Bodil Schmidt-Nielsen. It has been confirmed through years of personal experience since then. My research and my understanding of renal function have been aided through the years by collaboration and discussion with numerous students and associates. Of particular impor tance in developing my views on comparative renal function, and especially on the relationship of structure to function, has been my long association with my colleague and friend, Eldon J. Braun. Donald S. Farner, who suggested the writing of this volume, provided valuable editorial assistance. Much of my personal research in this area has been supported over the years by grants from the United States National Science Foundation and National Institutes of Health. The writing of this volume was completed while I was in Wiirzburg, Federal Republic of Germany, supported by a Senior U.S. Scientist Award from the Alexander von Humboldt Foundation."

A panel of expert clinical and basic investigators summarize the state-of-the-art in the use of transgenic technology in a broad range of endocrinological applications. Up-to-date and comprehensive, Transgenics in Endocrinology reviews the most recent developments in the analysis of endocrine physiology and its pathologies through mouse models, and provides a host of creative approaches to understand better the complex processes that are characteristic of hormonal systems.

Experimental and clinical researchers from a wide range of disciplines present a wealth of fresh scientific information on the biochemistry, molecular biology, pharmacology, and clinical activity of SERMs. The basic science chapters of the book focus-with an eye to the development of the ideal SERM-on the complex mechanisms of estrogen action, including ligand-dependent conformational changes in alpha and beta, and the recruitment of co-activators and co-repressors which modulate the estrogen receptor transcriptional activity and contribute to its crosstalk with growth factor signaling. The clinical presentation reviews the data accumulated on currently available SERMs, primarily tamoxifen and raloxifene, in cancer treatment and prevention, as well as their effects on the reproductive, vascular, skeletal, and central nervous systems. A tentative approach to menopause-related health issues is also provided for women with and without a previous diagnosis of localized breast cancer.

From our current knowledge, it is obvious that estrogen action in volves more than reproduction and fertility. Rather, estrogens affect and influence a number of other organ systems such as the immune, cardiovascular and central nervous system as well as the gastrointes tinal tract, urinary tract and skeleton. The importance of estrogens and estrogen receptor activity is appreciated from the spectrum of significant physiological dysfunctions that occur when there is a loss The participants of the workshop VI Preface of the hormone or the receptor activity. Loss of estrogen, however (for instance during menopause), occurs with time and results in a variety of clinical conditions. We know that the developmental loss of estrogen, as seen in clinical cases of aromatase gene mutations and experimental models, has dramatic effects in both men and women alike. The evidence that these effects are mediated through the estrogen receptor(s) is based on similar but not always identical phenotypes as observed in experimental animal models of estrogen receptor mutations as well as the single clinical case of an estrogen receptor alpha mutant patient. Developing an understanding of the spectrum of estrogen in a variety of tissues related to the condition of estrogen loss is a major and highly active clinical as well as basic scientific research area. Following the discovery of a second estrogen receptor and possible receptor ligand-independent activity as well as the genomic and non genomic actions of estrogen, it is clear that the mechanisms of the effects of estrogen are multifaceted.

Diagnostic Methods in Clinical Thyroidology provides a forum for discussion of controversial issues in three major categories: diagnosis of thyroid function, non-invasive evaluation of structural abnormalities, and needle biopsy diagnosis of thyroid nodules. For each category, a free interchange of ideas based on extensive clinical experience is followed by a summary that strives to resolve these controversial issues within a framework of sound clinical practice. The volume will this serve as a ready reference for the many physicians who evaluate thyroid patients.

Acromegaly is a relatively rare chronic disease. Nevertheless, it is life-threatening in its sequelae, for example, hypertension and cardiovascular disease. Since it also has disfiguring properties - especially of the head and face - acromegaly has serious psychological consequences which are reinforced by the awareness of factors such as excessive sweating. It is precisely on these signs and symptoms that Sandostatin R has a rapid effect, thus improving the patient's quality of life as well as counteracting the underlying processes. SandostatinE

All the important pharmacological interactions affecting thyroid function are described in this book. The first section is devoted to the physiology and biochemistry of thyroid disease, putting the pharmacological interactions into perspective. The second section reviews all the important pharmacological effects on thyroid function and also deals with the impact of other environmental agents. The chapters are written by internationally recognised experts and extensively referenced to provide an up-to-date review of the pharmacological interactions important to the thyroid and its diseases.