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.

Table 1 (Continuation) Reference Subject J. DAVIS, 1957, 1960b, 1961b, 1962b, 1963a; Regulation of secretion FARRELL, 1958; BARTTER et aI. , 1959; DENTON et aI. , 1959, 1960; COGHLAN et aI. , 1960; FOURMAN, 1962; MULRow and GANONG, 1962, 1964; WRIGHT, 1962; BLAIR-WEST et al. , 1963b; HOUDAS and FAVAREL- GARRIGUES, 1963 Relation of secretion to changes BARTTER, 1958 in intravascular volume Angiotensin (see Renin-angiotensin system) Blood volume and tonicity Regulation BLACK, 1954; E. BROWN et aI. , 1957; WELT, 1957; BARTTER, 1963; GAUER and HENRY, 1963 Receptors regulating SMITH, 1957 Oerebral cortex and cardiovascular function HOFF et aI. , 1963 Drugs affecting endocrine function GAUNT et al. , 1961 Erythropoietin JACOBSON, 1963; JACOBSON and DOYLE, 1963 Growth hormone (including action on adrenal cortex) FrnKEL, 1962 Hypertension Clinical and physiological aspects PAGE, 1962 SKELTON, 1959 During adrenal regeneration Renal (see Renin-angiotensin system) Russian work on SIMONSON and BROZEK, 1959 Juxtaglomerular cells Anatomy and physiology TOBIAN, 1960a, b, 1962, 1964; HATT et aI. , 1962; P. HARTROFT, 1963 Pineal and related organs KELLY, 1962 Comparative anatomy Renin-angiotensin system Chemistry, physiology, and structure- BRAUN-MENENDEZ et aI. , 1946; activity relationships BRAUN-MENENDEZ, 1956; BUMl'uS et aI. , 1961; SKEGGS, 1960; SKEGGS et aI. , 1957, 1964; PEART, 1959; GROSS and TURRIAN, 1960; PAGE and BUMl'us, 1961, 1962 Relation to hypertension in man WAKERLIN, 1955; GROSS, 1958, 1960, 1964; and animals Proceedings, Conference on Hypertension, 1958; KORNEL, 1959; TAQUINI and TAQUINI, 1961; GROSS et aI.

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."

Leading workers in the field of human reproduction provide both basic knowledge and useful practical information in this book about the most critical phase in the development of a new human being: the first twelve weeks of life. The period from fertilization and implantation to the end of the first trimester is still insufficiently understood and marks a new frontier. The knowledge necessary for applying our present diagnostic capabilities and for venturing into the problematic areas of fertilization technology and embryonic treatment is made easily available in this comprehensive textbook. The book is divided into two parts. The first presents basic information about physiology, anatomy, in vivo investigations, biochemistry and legal aspects. The second part focuses on pregnancy development, monitoring and the clinical diagnosis and management of disorders in the early stages of life. A full section is devoted to assisted conception and the newest possibilities in fertilizationtechnologies, whereby the ethical aspects are also discussed.

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.

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.

The cytochemical bioassay system was described in a short abstract in 1971, and more fully, in the cytochemical bioassay of corticotrophin, in 1972. Since then, cytochemical bioassays have been described for several polypeptide hormones, and these assays are already widely used. It is expedient that the subject should be reviewed, as it is in this monograph, by one writer who has had the good fortune to have taken part in the growth of cytochemistry from its early origins to its present position as the basis of possibly the most sensitive bioassay system currently available. However, it should be noted that major contributions have been made by many, both to the development of the subject and to the establishment of the bioassays. The object of this preface is to try to give some perspective to the growth of this subject and to record that the cytochemical bioassay system has been fostered by many outstanding scientists in an atmosphere of remarkable goodwill. To begin with, there could have been no cytochemical bioassays until cytochem istry had been converted from its rather unsure origins into a precise and quantitative form of cellular biochemistry. This was done with skill and enthusiastic dedication by my colleagues, Dr. Lucille Bitensky, Dr. F. P. Altman, Dr. R. G. L. W. Poulter and Mr. A. A. Silcox, first at the Royal College of Butcher, Dr."

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.

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

Traditions are dangerous; doubly so in science. Traditions are unchanging; science is about change. This was the 4th International Colloquium on Carbohydrate Metabolism in Pregnancy and the Newborn to be held in Aberdeen, and by now the form is set. How much its content has changed is a matter of nice judgement and not under the control of the organizers. It is not within their power to bring news of revolution, if there has been no revolution. Certainly many of the speakers had kent faces from previous Aberdeen meetings, but so they would be at any meeting on diabetes anywhere in the world. The written proceedings of scientific conferences have purposes other than to record changes: sometimes they need to state a consensus. The 3rd Colloquium came to an agreement about the importance of prepregnancy recognition and control of abnormalities of carbohydrate metabolism. The 4th set out to examine what results it had achieved. Much of this book is taken up with follow-up studies of the applications of similar regimes in different parts of the world. Since the first Aberdeen meeting in 1973, progress in the manage ment of diabetic pregnancy has been slow and steady, but the change in the city and the society where the meetings took place has been fast.

Endocrine Neoplasia is a comprehensive, updated, and clearly-written text covering the diseases for which endocrine surgical expertise is often needed. We look towards advances in the science and the art of endocrine surgery to continuously improve outcomes for our patients. The goal of this text was to provide a detailed description of both the underlying science of disease as well as the art of clinical management.

The book is divided into five sections addressing neoplasms of the thyroid, parathyroid, adrenal gland, neuroendocrine pancreas, and multiple endocrine neoplasia. Experts from the United States, Canada, and Australia have contributed chapters addressing both the biology of endocrine tumors and the clinical management of disease. Recent discoveries regarding the genetic underpinnings of disease are highlighted. Updated consensus guidelines were used for clinical recommendations. The management of complex and often confusing clinical problems is discussed in detail.

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.

The unraveling of our knowledge of the functions of the adrenal gland constitutes one exciting development of modern medicine and biochemistry. We owe these advances to the felicitous cooperative efforts of the clinical investigator and the biochemist. Three centuries elapsed between the first recorded anatomical descrip tion of the adrenals and the demonstration by Dr. Addison in the mid-nineteenth century of the fatal results of the destruction of these glands by disease. It became evident from this observation that the adrenals secreted a "factor" or "factors" essential to life. It took approximately 90 years to isolate this elusive vital factor - cortisone - from beef adrenal cortices, independently by both Reichstein and his co-workers in Basle and Kendall and his group in the United States and another 10-15 years before it became more generally available for experimental and clinical use. It is perhaps difficult to believe that as recently as 35-40 years ago, before cortisone and cortisol were clinically available, the surgical removal of a benign adrenal cortical tumor in patients with Cushing's syndrome was associated with a prohibitive postoperative mortality rate. Within 12-36 h after operation, most of such patients developed an intractable state of shock, which was not manifested by significant electrolyte abnormalities or hypoglycemia and was unresponsive to the usual treatment for shock plus the generous use of salt-retaining hormone.

Endocrine glands may be involved in patients with thalassemia major. In the last 20 years, new therapies have significantly improved life expectancy, while several endocrine abnormalities have been described in children, adolescents, and young adults suffering from thalassemia major.
The practical objective of this book is to establish guidelines for the management of endocrine disorders underlying the various phases of thalassemic life. Internationally acknowledged experts give a state-of-the-art account of physiopathological and therapeutical approaches to endocrine disorders in thalassemia and focus on such topics as growth hormones, thyroid diseases, puberty, hypogonadism, diabetes, and bone metabolism.

The breadth of research efforts represented by the many excellent papers in these proceedings is an eloquent testimonial to the idea of one man Dr. Josiah Brown-to whose memory this volume is dedicated. His tragic and unexpected loss in a swimming accident in August 1985 brought to an abrupt close a long and distinguished career as a physician and scientist. The possibility of using fetal pancreas tissue for transplantation into insulin-deficient diabetic recipients had intrigued Dr. Brown for several years prior to 1972, when he began in earnest to assemble a research team to explore this idea in detail. He felt that improvements in the formulation and administration of insulin (even the later recombinant human insulin) had taken us about as far as we could go in treating diabetes, and that methods for achieving complete cures must be explored. Numerous advantages of the fetal pancreas quickly became apparent, and were explored scientifically by Dr. Brown and his group. Transplanted pancreas tissue from a fetal donor of the appropriate developmental stage engrafts quickly, and can reverse diabetes very efficiently (1-3). By shunting the venous'drainage of the graft into the hepatic portal vein, a single pancreatic rudiment can, in time, provide enough insulin to restore normoglycemia and urine volume in a diabetic adult recipient (4). As with fetal pancreas rudiments in culture, transplanted fetal pancreas tissue loses its exocrine character, while continuing to develop and maintain endocrine function.

The past 15 years have witnessed a marked increase in attempts to identify safe and effective treatment alternatives to prostatectomy. This book is a review of the current therapeutic efforts in the management of patients with benign prostatic hyperplasia. It is presented by a group of highly regarded basic and clinical scientists with a major interest in prostatic diseases.
The information provided in this book is aimed at a wide audience including private practice and academic urologists, research fellows and doctors in postgraduate training, and basic scientists interested in prostatic pathology.

The regulation of the organism has traditionally been ascribed to two distinct systems-the nervous and the endocrine. Though coordination between the two systems has been acknowledged, researchers and authors have tended to deal with them as comprising separate categories of cells involved in different activities. With this approach, a given regulatory mechanism would be evaluated as to whether it should be accounted for by nervous or endocrine functions. The past 15 years, however, have witnessed numerous important discoveries and conceptual developments concerning the morphological, physiological, and bio chemical relations between the nervous and endocrine systems. Advances in im munocytochemical studies have revealed that there are a wide variety of messenger substances that function in both regulatory systems. As a result, researchers have been stimulated to investigate neuronlike properties of endocrine cells and, con versely, endocrine or secretory features of neurons. It has thus become obvious that the rigidities in the classic criteria of neurotransmitters and hormones may rather impede further advances in these research fields. The activities of neurons are no longer evaluated simply in terms of EPSP, IPSP, and the release of classic trans mitters such as acetylcholine, noradrenaline, and GABA. Hormonal actions are no longer analyzed solely with regard to concentrations of classic aminic and peptidic hormones in the systemic blood circulation. The concept of the paraneuron, which we proposed in 1975, has become one of the theoretical bases for the development of this trend of study.

How to treat advanced prostatic cancer remains controversial, despite intense basic and clinical research investigating the pathogenesis and natural history of this unique cancer highly prevalent in elderly males. Nine experts were asked to meet and discuss the facts. This resulting monograph gives an overview of the available knowledge on all aspects of the subject. The objective evaluation and consensus opinion of the authors presented here set this book apart from other publications with conflicting viewpoints. For readers eager to obtain a comprehensive and balanced view of the thousands of clinical contributions and clear advice on the choices, this book is a must.

This book was written at the invitation of Dr. H. GOTZE of Springer-Verlag for the series "Monographs in Endocrinology." It is not a comprehensive account of the prostaglandins but has been writ ten with a deliberate emphasis upon those aspects of the field in which I am particularly interested and to which, in some cases, I have made a contribution. I am grateful to Miss E. PFISTERER and her colleagues of Springer Verlag for their excellent work. I should also like to thank my wife without whose patience, encouragement and help this book would never have been completed. Finally this is an appropriate time to express my sincere gratitude to those scientists who over the years have given me samples of prostaglandins-namely Professors S.BERGSTROM and B.SAMUELSSON of the Karolinska Institute, Stockholm, Professor D. A. VAN DORP of the Unilever Research Laboratories, Vlaardingen and Dr. J. E. PIlm of the Upjohn Company, Kalamazoo. Without their help work in this field would have been extremely difficult."

This study assembles current and new information on the mechanisms involved in intracellular calcium regulation and their actual or potential relationship to cellular calcium transport. Topics discussed in detail are calcium channels, cellular calcium extrusion, sodium/calcium exchange, calcium-binding proteins with special reference to the vitamin D-induced calbindin, calcium transport and disorders thereof. Each topic is introduced with an overview followed by research papers dealing with relevant topics in each category. New information deals with calcium channels which are not voltage-sensitive, the structure and function of the plasma membrane Ca ATPase, the role of the Na/Ca exchanger in intracellular Na and proton regulation, a comprehensive overview of calcium transport with quantitative analysis of the role of the intestinal and renal calcium-binding proteins, description of the structure and function of the calbindin genes, and identification of calcium transport defects in diabetes and hypertension. Readers will be brought up-to-date on current knowledge and concepts in this rapidly expanding field and be directed to the relevant primary and secondary literature.

Following 50 years of glucocorticoid use in a clinical setting, an international body of expert scientists and physicians presents the most expansive survey of glucocorticoid pharmacology to date. This work traces the history of glucocorticoid biology from the seminal description of glucocorticoid insufficiency by Thomas Addison in the mid-19th century, up to current advances in elucidating the molecular basis of glucocorticoid action. Important discoveries are presented, as well as milestones in drug development, a survey of current clinical practice, and prospects for novel glucocorticoid-based therapeutics. Scientists and clinicians will appreciate the scope of this work, which is of special interest to workers in the fields of endocrinology, inflammation and autoimmune disease.

Reproduction is the origination of new organisms from pre-existing ones. Among more than 35 separated forms of reproduction including several types of gamogony, parthenogenesis, agamogenesis, fission and division, and plas motomy, the bisexual mode of reproduction via fertilization provides genetic variability that allows species to adapt quickly to competitive and constantly changing environments. Several excellent reviews and books have been written in the past to analyse the mechanisms of fertilization in different eukaryotic species. During the last few years, however, renewed attention has been paid to examining the process of oocyte fertilization at the cellular/molecular level not only within a single species/group but also through different phylogenetic lineages. As a result of this effort, knowledge of the molecular pathways used by oocytes and spermatozoa at fertilization has increased, but still many ques tions remain to be answered. Being aware of the necessity of providing an inte grated view of the process of fertilization, this book has been entirely devoted to reviewing the process of oocyte fertilization at the cellular/molecular level in two different and separated groups of eukaryotic organisms: protozoa and metazoan animals. The book is organized into six sections dealing with oocyte fertilization in protozoa, invertebrates, teleost fishes, amphibians, birds and mammals. These sections are followed by a summary/concluding chapter that provides a com parative overview of the process of fertilization in these groups of eukaryotes."