Congenital adrenal hyperplasia (CAH) consists of a group of disorders of adrenal steroidogenesis. Each disorder results from an inherited deficiency of one of the several enzymes necessary for normal steroid synthesis. The different enzyme deficiencies produce characteristic patterns of hormonal abnormalities; the clinical symptoms of the different forms of CAH depend on the particular hormones that are deficient or that are produced in excess. The earliest documented description of CAH was by DeCrecchio in 1865 (DeCrecchio 1865). This Neapolitan anatomist described a cadaver having a penis with first degree hypospadias but no externally palpable gonads. Dis- section revealed a vagina, uterus, fallopian tubes, ovaries, and markedly enlarged adrenals. It is interesting that the subject suffered a confusion of sex assignment, being declared a female at birth and a male 4 years later. He conducted himself as a male sexually and socially. Since the original descrip- tion of this case, investigators have unravelled the pathophysiology of the inborn errors of steroidogenesis. 1 Steroidogenesis and Enzymatic Conversions of Adrenal Steroid Hormones A. Steroidogenesis The adrenal synthesizes three main classes of hormones: mineralocorticoids (17-deoxy pathway), glucocorticoids (17-hydroxy pathway), and sex steroids.

The European School of Oncology came into existence to respond to a need for informa tion, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidisciplinary approach which is difficult for the Univer sities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been 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 future developments in specific fields of oncology.

In the past 10 years hirsutism has been the object of a considerable number of fundamental studies. It provides endocrinologists with an experimental model for the investigation of androgen secretion, metabolism and mechanism of action. Plasma androgen assay, free testosterone measurement, hepatic and extrahepatic androgen metabolic clearance and androgen metabolism in the skin are the different steps which were studied by many groups and represent valuable parameters of the mechanisms of hirsutism. Determination of the origin of androgen oversecretion has become easier by technical progress in differential effiuent venous catheterism, which makes it possible to compare androgens in adrenal or ovarian effiuent veins to their peripheral levels, and to determine the ovarian or adrenal source of the androgen oversecretion as well as the side responsible, essential in the case of tumors. The study of androgen metabolism and the discovery of androgen receptors in the skin confIrm the latter as an actual target cell for androgens. This target cell uses the circulating active androgen, i. e., testosterone and can also metabolize local inactive androgens into active ones. This is the case of androstenedione and dehy droepiandrosterone which are the two main androgens secreted in women, since women secrete very little testosterone. The capacity of the skin to transform inactive androgens into active ones varies from one individual to another. That would support the concept of variable skin receptivity from one woman to another and from one ethnic group to another."

The physiology and metabolism of thyroid hormones were areas of intense research investigation during the 1970s. Radioimmunoassays were applied to study the concentration of iodothyronines in biologic fluids. These techniques proved to be highly sensitive, specific, and reproducible as well as rapid. The availability of specific radioimmunoassays led to the detection of several iodothyronines in human biologic fluids, e. g., reverse triiodothyronine (rT 3), diiodothyronines, monoiodothyronines, and acetic acid derivatives of thyroxine (T 4) and T 3, which were previously either unknown or briefly considered but forgotten in the 1950s. This monograph is intended for readers who desire an overview of thyroid hormone physiology as it was understood in 1979. It should be especially useful to trainees in endocrinology and individuals interested in potential research projects. The main focus has been on the studies conducted between 1969 and 1978, alt lOugh other information has been reviewed to provide an overall working knowledge of the field. A list of over 500 references, although probably still incomplete, should lead a reader to at least a few important articles in each area relevant to thyroid hormone physiology.

As far as we are aware, this is the first attempt to cover the com parative physiology of the pancreatic islets in a monograph. The topics discussed would probably have sufficed to fill about half a dozen monographs, a matter that becomes obvious from a look at the Contents. Hence, we have tried to present the ma terial more in the form of a digest, to emphasize evolutionary perspectives, to point out critical issues, and to identify challenging topics for future research. This approach required an arbitrary reduction of the num ber of references, and we therefore join the chorus of recent authors who beg their colleagues for understanding if some of their publications do not appear in the bibliography. Keeping up with the current literature was like fighting one of those monsters that grow a couple of new heads for each one that is cut off. Nevertheless, we hope that we have covered most of the key publications up to the autumn of 1986. We gratefully acknowledge the advice of many colleagues, and in particular the invaluable criticisms of Robert L. Hazelwood and Erika Plisetskaya. Special thanks are due to the series editor, Donald S. Farner, for his patience and guidance, both of which were fresh proof of his legendary diplomatic skills. Finally, we wish to thank Dr. D. Czeschlik and his staff at the Springer Verlag for their patience and support. Philadelphia, PA AUGUST EpPLE Greenville, NC JACK E. BRINN September 1987 v Contents Chapter 1. Introduction .......................... ."

Designed for easy revision of the key points, key references, and key management stages, the two volumes in this set review the evidence for best practice, presenting the reader with the right information, in the right format, summarized in easy-to-use tables and algorithms. Each guideline is designed to "make it easy to do it right", with appropriate use of proven interventions. The quality of evidence available is graded so that a well-informed clinician can improve the health of mother and baby by providing quality care. *Offers an easy-to-assimilate guide to the key points in maternal-fetal and obstetric practice *Supplies an invaluable resource for those revising topics for professional or clinical requirements *Ensures providers of care can locate the best intervention quickly and confidently

The term polycystic ovary syndrome (peOS) is meant to describe a clinical endocrinopathy characterized by menstrual irregularity and evidence of hyperandrogenism. While recognized since the 1800s, a clinical composite was not constructed until 1935 when Stein and Leventhal reported their findings of seven women with infertility, menstrual dysfunction, hirsutism, and enlarged ovaries. Notably, the ovaries contained numerous multiple cysts and the ovarian capsule was thickened. At the time, this preciseness of definition was sufficient to entitle the entity Stein-Leventhal syndrome. Subsequently, over the intervening years as investigators attempted to un ravel the pathophysiology and genesis of this disorder and the number of reported studies increased, there ensued a gradual and distinct terminologic conversion to polycystic ovary syndrome, which, whether intentional or not, connoted a less well-defined condition. Perhaps this is appropriately so, given the seemingly broadening spectrum of clinical presentations and the continuing debate over what constitutes peos. The expansive new knowledge about peos was discussed to a significant degree at an international symposium organized by Serono Symposia USA and held in Boston in the late spring of 1995. Ovarian physiology, including the fate of the follicular unit, was a central focus with several presentations on the genesis, growth, and death of ovarian cellular components. A discus sion of the regulation of ovarian cell function was also highlighted and comprised a major portion of the program."

The various congresses on growth hormone (GH) which have been held in Milan since 1967, the Milan Congresses, have witnessed over 25 years the tremendous expansion of a research field that was based initially upon the scarce knowledge of the biological properties of a protein. GH, whose chemical structure had just been identified and a radioimmunoassay developed for its measurement in blood, became in the following years a major area of biological research. The boundaries have since become blurred, as the research area has extended to the physiology and pathology of growth, puberty and reproduction, and the control of metabolism during the whole lifespan. Since the last GH Congress held in 1987, GH studies using the molecular biological approach have resulted in the puri fication, cloning and expression of the human GH (hGH) recep tor and binding protein, in new and exciting information on the insulin-like growth factors (IGF) and their paracrine and autocrine roles, and in the awareness that a panoply of binding proteins are present in the extracellular fluids and can, possibly, modulate IGF-receptor interactions and, thus, IGF actions. Finally, the availability of large amounts of biosynthetic hGH, besides allow ing more extensive clinical use in states of GH deficiency and extrasomatotrophic pathologies, has permitted disclosure of im portant metabolic effects of hGH during adulthood and, perhaps, aging and in many protein catabolic states."

It is fourteen years since insulin was last reviewed in The Handbook of Ex perimental Pharmacology, in volume 32. The present endeavor is more modest in scope. Volume 32 appeared in two separate parts, each having its own subeditors, and together the two parts covered nearly all areas of insulin pharmacology. Such comprehensiveness seemed impractical in a new volume. The amount of in formation related to insulin that is now available simply would not fit in a reasonable amount of space. Furthermore, for better or worse, scientists have be come so specialized that a volume providing such broad coverage seemed likely in its totality to be of interest or value to very few individuals. We therefore decided to limit the present volume to the following areas: insulin chemistry and structure, insulin biosynthesis and secretion, insulin receptor, and insulin action at the cellular level. We felt these areas formed a coherent unit. We also felt, perhaps as much because of our own interests and perspectives as any objective reality, that these were the areas in which recent progress has been most dramatic, and yet, paradoxically and tantalizingly, these were the areas in which most has yet to be learned. Even with this limited scope, there are some major gaps in coverage. Regrettably, two important areas, the beta cell ATP-sensitive potassium channel and the glucose transporter, were among these. Nevertheless, the authors who con tributed have done an excellent job, and we would like to thank them for their diligence.

In vitro fertilization has resulted in an estimated 4000-5000 births in the world. The procedure has been accepted in Europe, America and Australia and several hundred IVF clinics are operating successfully. The newer procedures of GIFf, embryo freezing and donor oocyte IVF have become established and are dealt with in several chapters. GIFf has become the procedure of choice for patients with infertility of unknown origin. Oocyte freezing represents an important new technology which is being developed. The routine IVF procedure has improved slightly; variation in results can be reduced by quality control of laboratory and clinical techniques. Male factor infertility has been dealt with by IVF in mild and moderate cases, but newer techniques will be required to deal with severe problems in the male. Most countries have accepted that the straightforward IVF pro cedure is ethical. Limitations concerning the use of donor oocytes and embryo experimentation exist in some religions and countries; legal control of the new reproductive technologies ranges from the passage of statutes to no control at all. Many countries are still considering the need for legislative control. The text endeavours to indicate new areas of importance and to guide those organizing services as to how to introduce newer technolo gies.

It is well established that progesterone plays a role in the brain and hypophysis as a facilitator and inhibitor of sexual behavior and gonadotropin release in the female rat (Everett 1961; Caligaris et al. 1971; Brown-Grant and Naftolin 1972; Dorner 1972; Meyerson 1972; Barraclough 1973; Goldman and Zarrow 1973; Mann and Barraclough 1973; Freeman et al. 1976; Feder and Marrone 1977; Goodman 1978; Attardi 1981), guinea pig (Morin and Feder 1974), and primates (Odell and Swerdloff 1968; Spies and Niswender 1972; Yamaji et al. 1972; Karsch et al. 1973; Dierschke et al. 1973; Knobi11974; Clifton et al. 1975). In an attempt to learn whether a specific progesterone uptake mechanism exists in the brain and the hypophysis, the distribution and retention pattern of radioactivity after in vivo injection of labeled progesterone was studied. Early work of Kato (1963) did not show a selective uptake of radioactivity in the hypo- thalamus of immature and estrogen-primed immature rats after injection oflow- specific-activity [14C]progesterone, but some tendency of the reticular formation to take up radiation was observed. Laumas and Farooq (1966) reported that after intravenous administration of labeled progesterone to ovariectomized estrogen- treated rats, radioactivity in the brain and pituitary appeared to show a very slight, insignificant increase 1-2 min after injection, but the uptake pattern was not definite, as had been seen with estradiol. Seiki et al.

Calcium in Human Biology provides an authoritative review of current knowledge and points the way to further progress in the understanding of this essential nutrient. In addition to considering the established importance of an adequate dietary source of available calcium for the formation of sound bones and teeth, there is detailed discussion of the part calcium plays in a variety of aspects of human metabolism. The book is written primarily for those working in the nutritional sciences and related fields. It will also be of interest to clinicians, nutritionists, and to those interested more generally in the biological sciences, as well as to those in the important sectors of the food industry which utilise or produce dairy products and other foods significant to the supply of dietary calcium.

more intuitive study to greater empiricism. Frequently, chapters are di vided into discrete sections to discuss each rather distinct era of inquiry. This approach, when used, can provide a valuable historical overview of the early clinical formulations about each disease. Even though many of the earlier research philosophies and techniques may seem so simplistic as to mitigate against their inclusion, early research hypotheses were often generated from astute observation of clinical findings and relationships. In addition to shaping later empirical questions, a review of historical ante cedents provides a yardstick by which to measure the progress of more current studies, even though much is yet to be learned. As is true of any refinement of knowledge, the juxtaposition of the two approaches of study reveals that some of the early postulations about patient attributes and disease consequences have been confirmed, while other suppositions have been discarded. Although the generally subjective assessment methods used in the early studies may not have provided an optimal data base, it is interesting to note which clinical impressions were able to withstand greater empirical rigor and which were not. The book at its inception was intended to provide a succinct introduc tion to psychoneuroendocrinology research for practitioners and scientists who might be relatively unfamiliar with the area. However, it quickly became apparent that the sophistication of the information could not be readily reduced without vast oversimplification and loss of substance."

Thyroid carcinoma is an uncommon malignan ing the available non-human lines, as models cy. In the vast majority of patients, if treated for cell cycle studies and oncogene/anti appropriately, it is associated with a benign oncogene regulation, because they are unaware clinical course. Why then does it hold a con of the often fundamental dichotomy between tinuing fascination for so many physicians? thyroid malignancy and prognosis. Third, the The answer is probably directly dependent very nature of the benign clinical course has suggested to the major health research fund on the very benign nature of most thyroid ing agencies that thyroid cancer is not worthy maligllancies. While there are terrible excep of study in a time of scarce resources. tions, the follicular and papillary thyroid can Nothing could be further from the truth. cers behave in a way quite alien to "common" This gratifying clinical course is the very reason neoplasia, since they grow and metastasize why the study of human thyroid cancer has the slowly. We believe that if only we could under potential for contributing further to our fun stand such a transformed state, we would be able to learn a great deal about the normal and damental understanding of malignancy and, abnormal regulation of the cell cycle and im perhaps more importantly, the mechanisms by prove our understanding of cancer. which the human body can resist neoplastic However, recent advances in the biology of cells."

The ability to measure accurately the hormones regulating calcium homeosta sis is the fundamental first step toward understanding the roles these hormones play in health and disease. Techniques for such measurements have only been available for the past 10 years or so and remain in a state of rapid development. Sensitive parathyroid hormone (PTH) radioimmunoassays appeared in the early 1970s, and with them came a whole new appreciation for the prevalence and implications of hyperparathyroidism, primary or secondary, in the popu lation. The calcitonin (CT) radioimmunoassay came later and achieved rapid success in the. diagnosis of a previously poorly understood cancer, medullary carcinoma of the thyroid, frequently associated with the familial multiple endo crine neoplasia type 2 syndromes (a and b). As the sensitivity of the calcitonin radioimmunoassay has improved, our understanding of the role of calcitonin in normal physiological processes has increased. The knowledge that vitamin D must be metabolized to produce its biologic effects is only 15 years old. This has had profound implications in our understanding of a variety of metabolic bone, kidney, and gastrointestinal diseases. Assays to measure the major cir culating form of vitamin D, 25-hydroxyvitamin D, were described 10 years ago. Assays for the other metabolites, in particular, 1,25-dihydroxyvitamin D, were described even more recently. As of today, we know of many vitamin D metabolites and have developed the techniques to measure most of them; how ever, many questions remain concerning their physiological role."

As I read this unique volume on diabetes and pregnancy edited by Lois Jovanovic, I was struck by two themes that run throughout these collected chapters. First, this volume provides an excellent assessment of past problems, present management, and future challenges presented by dia betes in pregnancy. Orury's unique, longitudinal experience with diabetes iIi pregnancy provides the reader with an important overview, as does Coetzee's discussion of gestational diabetes. Current problems-deter mining the etiology and prevention of congenital malformations in infants of diabetic mothers (10M), assessment of antepartum fetal condition, management of pregnant patients with diabetic retinopathy, recognition of thyroid dysfunction in the pregnant diabetic woman, and understanding the multitude of metabolic sequelae observed in the 10M-are thoroughly reviewed. Finally, important considerations for future treatment and ther apy such as the adaptation of the fetal pancreas to the disordered intra uterine environment often seen in maternal diabetes, the use of fetal pan creatic tissue for transplantation, the application of exercise in the management of the pregnant woman with diabetes, and the long-term con sequences for the 10M provide an exciting glimpse into the future. The second important theme that emerges is the critical role the problem of diabetes in pregnancy has played in our understanding of maternal and fetal physiology. Clinical observations supported by basic research have emphasized the role of fetal fuels in teratogenesis.

Obesity is a serious medical problem that affects millions of people, especially in Western societies. Although long considered a complicating factor in a variety of diseases, there is now widespread agreement that obesity itself should be classified and treated as a disease and that it has important conse quences for personal health, quality of life and cost to society. Understanding obesity and the means of treating it have been hampered in the past. There have been misperceptions that obesity is a behavioral disorder and that its treatments provides only cosmetic benefits. Pharmacologic approaches to treatment have suffered from problems of limited efficacy, reduced activity upon chronic use, and serious side effects, including abuse liability, cardiac disease, hypertension, and respiratory complications. Finally, there has been a proliferation of consumer and natural products with unproven benefits. This book attempts to address both the problems associated with obesity and the approaches to treating it. In the first section devoted to pathology, Drs. DIGIROLAMO, HARP, and STEVENS elaborate in Chap. 1 on how obesity and its medical complications develop. As described by Dr. PI-SUNYER in Chap. 2, obesity is a disease seen most often in affluent Western societies and is associated with the aforemen tioned medical problems, as well as Type II diabetes mellitus and gallbladder disease. Drs. CHAGNON, PERUSSE, and BOUCHARD review the human genetics of obesity in Chap. 3, and Drs."

In the years since the initial discovery that blood from diabetic patients contains increased amounts of a posttranslationally gluco sylated form of hemoglobin (hemoglobin Ale)' an impressive number of studies have clarified and expanded the use of glycohemoglobin levels to assess disease status. Many other structural proteins have been shown to undergo similar changes, including proteins from tissues most commonly affected in diabetes (e.g., lens, aorta, peripheral nerve, basement membrane). Thus, the nonenzymatic glycosylation of hemoglobin emerges as an invaluable model for the pathogenesis of certain chronic diabetes complications. In addition to reviewing a wealth of investigative possibilities in the area of these chronic complications-including eye, kidney, nerve, and vascular disease-Dr. Cohen indicates how enhanced nonenzymatic glycosylation in uncontrolled diabetes underscores the pressing need for maintenance of long-term euglycemia. Dr. Cohen is an endocrinologist and diabetes specialist whose research activities have largely focused on the chemistry and metabo lism of the basement membrane in diabetes. This superb monograph on nonenzymatic glycosylation clearly shows the major trends of her past and present research and clinical activities. This book is beautifully written and a pleasure to read. It provides great insight into the mechanisms of the pathogenesis of the oom- vii viii Foreword cations of diabetes and should be of immense value not only to basic and clinical investigators, but also to internists, diabetologists, and endocrinologists in clinical practice."

It has been a challenge for us to edit this volume of Endocrinology and Metabo lism: Progress in Research and Clinical Practice. The topic of the pathogenesis of insulin-dependent, type I diabetes mellitus is particularly appropriate for this series, since advances in this area have been made, to a large extent, by applying state-of-the-art laboratory techniques to clinical samples. Over the last several years, a number of lines of evidence have been gathered, suggesting that classic type I diabetes mellitus results from the autoimmune des truction of pancreatic beta-cells in genetically susceptible individuals. This hypothesis is particularly appealing because it offers a rational approach to the prevention of diabetes by immunosuppression. We have tried to present a balanced, authoritative summary of the information currently available to support the autoimmune hypothesis for the pathogenesis of human type I diabetes, to place this information in historical perspective, to include relevant information from animal models of type I diabetes in which more invasive experimentation is ethical, and, finally, to update the reader on the current status of attempts to intervene in the progression of diabetes with immunosuppressive drugs. New York, New York Fredda Ginsberg-Fellner Robert C. McEvoy Contents Preface.. . . .. .. .. . . . . . . . . . . . . ... . . . . . . . . . . . .. . . . . . . .. . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Xl . . . . . . . . . . . . . 1. The Autoimmune Hypothesis of Insulin-Dependent Diabetes: 1965 to the Present . . . . . . . . . . . . ..................... . . . . . .

In the first section of this volume, we have attempted to bring together some of the papers that reflect exciting new areas of development in relation to neuroendocrine investigation. Very recently, specific nucleotide recognition sequences for thyroid hormones, steroid hormones and the fundamental intracellular regulator, cyclic AMP, have been determined. In this section, the preliminary characterization and investigation of the nuclear binding proteins that mediate the actions of cAMP are described. Not only does this represent an important advance in cell biology, but it may represent a further level of alteration in control in normal and disease states. Intercellular pituitary "cross talk" is well described in the in vitro setting. The active molecules are clearly It is now important able to exert significant actions at the subnanomolar level. to design experiments in order to define the precise physiological relevance of these novel and potentially important observations. Paracrine and autocrine cellular interactions are of established importance in growth control in a variety of body tissues. But it is only very recently that the investigation of normal and abnormal anterior pituitary growth has reached the forefront of neuroendocrine research. This is perhaps surprising, beause the inhibitory effects of doapmine agonism on lactotroph growth and differentiation have been appreciated for some time. The anterior pituitary gland produces numerous growth factors that exert a variety of functional effects on pituitary hormone synthesis and release.

In the middle of the 17th century, the great French philosopher Rene Descartes wrote (L'Homme, J. Le Gras, Paris, 1669) that a suitable stimulation of the brain results in two types of "movements": exterior movements, designed to seek desirable ends and to avoid undesirable or harmful ones and interior movements or "passions" which through the release of "animal spirits" regulate the heart, the liver, and other organs. When it appears appropriate to meet a threat with force, the passion of rage causes the release of strong spirits, whereas when avoidance appears to be the better choice, the passion of fear causes the brain to release weak spirits. We do not know what influence, if any, Descartes had on the thinking of Walter B. Cannon (Bodily Changes in Pain, Hunger, Fear and Rage, Appleton and Co. , New York, 1920), of Hans Selye (The Story of the Adaptation Syndrome, Acta, Inc. , Montreal, 1952), ofG. W. Harris or of R. Guillemin (Hypothalamic-Hypophysial Interrelationships. A Sym posium. c. c. Thomas, Springfield, 1956), but it is interesting to reflect upon the durable value of great ideas which constantly resurface even if modified by other ideas and by new techniques, as if propelled by a preordained intellectual imperative.

Conceptual advances in the biological sciences are marked by the applica tion of new techniques and experimental strategies. Nowhere has this ge neric principle been more apparent than in the study of testicular cells, as judged by the evolution of themes presented at the Testis Workshop over the past 23 years. Like its predecessors, the 1995 Testis Workshop was structured to offer fresh insights and approaches for understanding the mechanisms of spermatogenesis and steroidogenesis. The chapters pre sented in this book emphasize three aspects of testicular cell function: first, the molecular analysis of the cell cycle; second, examination of the cell cycle, including the function and identification of specific macromolecules that direct the proliferation and differentiation of germ cells; and third, the development of Leydig cells and the role of specific macromolecules in the formation of testicular steroids. Each chapter is based on a lecture presented at the XIIIth Testis Work shop held on March 30 to April 1, 1995, at the Radisson Plaza Hotel in Raleigh, North Carolina. The selection of topics reflects the recommenda tions of the workshop'S organizing committee. Sincere thanks are due to the speakers who agreed to lecture and prepare chapters."

In the past, determination of bone maturity relied on visual evaluation of skeletal development in the hand and wrist, most commonly using the Greulich and Pyle atlas. The Gilsanz and Ratib digital atlas takes advantage of digital imaging and provides a more effective and objective approach to assessment of skeletal maturity. The atlas integrates the key morphological features of ossification in the bones of the hand and wrist and provides idealized, sex- and age-specific images of skeletal development New to this revised second edition is a description and user manual for Bone Age for iPad(r), iPhone(r) and iPod touch(r), which can be purchased and used separately from this book. The App can be easily employed to calculate the deviation of the patient's age from the normal range and to predict a possible growth delay. This easy-to-use atlas and the related App will be invaluable for radiologists, endocrinologists, and pediatricians and also relevant to forensic physicians.

The importance of osteoporosis in the United Kingdom as a cause of death and disability is now well recognised. There are in excess of 200,000 osteoporotic-related fractures in the UK per annum asso ciated with an estimated cost of GBP942,000,000. Following hip fracture it is known that about 50% of patients are unable to live indepen dently and about 20% of such patients die within the first 6 months. These figures, compelling as they are, reflect poorly on current medical practices which manifestly have failed to identify patients with low bone density at risk of fracture. The hope is that the techni cal advances which have enabled bone mineral density, and other allied indices, to be measured with high precision and accuracy offers the chance of identifying patients at risk of fracture and guiding the clinician to make treatment decisions which may reduce the patients' risk of fracture. In the UK, services for identifying patients at risk of fracture are still in their infancy and are not uniformly available throughout the country. This situation is, however, likely to improve particularly fol lowing the publication of the Royal College of Physicians report "Osteoporosis -clinical guidelines for prevention and treatment" and the recognition in "Our Healthier Nation" that osteoporosis pre vention should be included as a target to achieve a reduction of 20% in accidents by 2010.

Nineteen cutting-edge review articles by leading authorities provide a comprehensive overview of the normal function of the pituitary and of the diagnosis and treatment of pituitary disorders. Topics range from normal hypothalamic-pituitary interactions and the processes that disrupt them to new advances in pituitary imaging and appropriate surgical intervention in various pituitary disorders. Among the diseases discussed are congenital hypopituitarism, deficiency states, strategies for evaluating patients with hyperprolactinemia, Cushing's syndrome, acromegaly, and glycoprotein pituitary tumors.