R. B. GREENBLATT The original oral contraceptives contained more oestrogen in the form of ethinyloestradiol or mestranol and progestagen in the form of norethynodrel or norethisterone than was necessary f(x conception control. There has been a trend over the years to reduce dosages of both components in order to minimize side- eHects while ensuring eflcctiveness. However, as dosages were lowered, there has been an increase in spotting and break- through bleeding during the first few months of their adminis- tration. The sequential pill appeared more physiological in that it followed more closely physiological principles, but the need to employ large doses ofEE or EE3ME to inhibit O\'ulation and the higher pregnancy rate made the sequential regimen less attrac- ti\'e or useful. A triphasic formulation has become available that takes advantage of the synergism between ethinyloestradiol and the potent levonorgestrel so that low doses of the oestrogen and very low doses of the progestagen could be employed with great effectiveness. Such a preparation is relatively free from side- effects, partly because the basic pharmacological tenet of the minimal dose for the desired result and the division of'the cycle into three parts using 30 ,lIg ofEE for the first 6 days, then:) days of 40 ,lIg, followed by 30 ,fIg for 10 da ys, for a total of21 days, thus more or less mimicking the physiological rise and fall of 125 THE DEVELOP:'IE:-;T OF ,\ :-;E\\' TRIPH. \SIC OR.

HOWARD C. TAYLOR, JR. Medicine, through its long history, has continually striven to enlarge its scope. Success in these endeavors has come in sudden bursts with long intervals of relative quiescence between. As a result of the spectacular discoveries in the basic sciences during the last decades, medicine is again in a period of revolutionary advance in many fields. One of these is the subject of this report, "The Intrauterine Patient." Until recently the fetus signalized his presence only by the mother's enlarging abdomen and by his own movements, perceived by the preg nant woman herself and evident to the examining midwife and physician. Later, the sounds of the fetal heart heard by auscultation and the varia tions in its rate became the single important means by which the welfare of the fetus might be roughly determined and threats to his survival per haps detected. Otherwise, the fetus remained isolated, his condition unknown and any therapy consequent on diagnosis, except for the induc tion or termination of labor, nonexistent."

The enormous expansion seen over the last decade in the mammo graphic detection of breast cancer lesions, especially the use of screen ing procedures for the early detection of clinically unsuspected tumors, has made it necessary to summarize the experience made by various centers in the world. The 2nd International Copenhagen Symposium on Detection of Breast Cancer afforded an opportunity of gathering scientists from all over the world to discuss the various problems of early breast cancer detection with special reference to screening procedures. This book forms a synthesis of the information presented by leading scientists from many of the world's mammo graphic centers, particularly those in Sweden and the USA. Hence, the reader will have the opportunity to study the outstanding work carried out by various institutes and centers of breast cancer screening. It is our sincere hope that a study of this volume will encourage other scientists to join in the work on screening procedures. S. Brunner B. Langfeldt P. E. Andersen Contents S. A. Feig: 1 Hypothetical Breast Cancer Risk from Mammography S. A. Feig: Benefits and Risks of Mammography 11 R. L. Egan and M. B. McSweeney: Multicentric Breast Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . 28 M. B. McSweeney and R. L. Egan: Breast Cancer in the Younger Patient: A Preliminary Report 36 M. B. McSweeney and R. L. Egan: Bilateral Breast Carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . ' 41 N. Bjurstam: The Radiographic Appearance of Normal and Metastatic Axillary Lymph Nodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 M. Moskowitz, S. A. Feig, C. Cole-Beuglet, S. H."

Since the pioneering work of Donald and his first Lancet paper in 1958, the use of ultrasound in obstetrics and gynaecology has evolved rap idly. The introduction of grey scale techniques enhanced our ability to identify different tissues on the basis of their texture. However, it was the introduction of the linear array real-time scanner in the mid seven ties that changed ultrasound from being an "eccentric art form" to a readily available and usable technique. This led to the first reports of the diagnosis of neural tube defects using ultrasound by Campbell, as well as the establishment of fetal biometry. In the midst of this activity the parallel development of the transvaginal probe by Kratochwill went almost unnoticed by most gynaecologists. Yet the application of this technique has since had a major impact on many areas of gyna ecological practice, and on infertility in particular. Since the demon stration of transvaginal follicle aspiration, the vaginal route has become standard for most invasive ultrasound guided gynaecological procedures. The relatively new technical advance of transvaginal colour Doppler may potentially have just as great an impact. The introduction and use of transvaginal colour flow imaging has facili tated the study of vascular changes within the pelvis.

The state of health care is reflected by perinatal and neonatal morbidity and mortality as well as by the frequencies of long-term neurologic and developmental disorders. Many factors, some without immediately rec ognizable significance to childbearing and many still unknown, undoubt edly contribute beneficially or adversely to the outcome of pregnancy. Knowledge concerning the impact of such factors on the fetus and sur viving infant is critical. Confounding analyses of pregnancy outcome, especially these past two or three decades, are the effects of newly un dertaken invasive or inactive therapeutic approaches coupled with the advent of high technology. Many innovations have been introduced with out serious efforts to evaluate their impact prospectively and objectively. The consequences of therapeutic misadventures characterized the past; it seems they have been replaced to a degree by some of the complications of applied technology. Examples abound: after overuse of oxygen was recognized to cause retrolental fibroplasia, its restriction led to an in crease in both neonatal death rates and neurologic damage in surviving infants. Administration of vitamin K to prevent neonatal hemorrhagic disease, particularly when given in what we now know as excessive dos age, occasionally resulted in kernicterus. Prophylactic sulfonamide use had a similar end result. More recent is the observation of bronchopul monary dysplasia as a complication of respirator therapy for hyaline membrane disease."

Der Umfang der Erkenntnisse uber das Mammakarzinom in Theorie, Klinik und Praxis ist in den vergangenen drei lahrzehnten so groB geworden, daB ein eigener Band zur Abhandlung dieses Themas erforderlich wurde. 1m Rahmen dieses Werkes ist es naheliegend, daB die radiologischen Disziplinen sowohl in der Diagnostik als auch in der Therapie besonders zu Wort kommen. Die Atiologie, die entsprechende Ethnologie, die Stochastik der Zellentartung, die Experimen- talmedizin, die Immunologie und die ausfUhrliche Chirurgie werden nicht abgehandelt, weil dadurch der Umfang des Buches wahrscheinlich mehr als verdoppelt werden wurde. Die Diagnose des Mammakarzinoms wurde zum einen durch die Mammographie und Thermographie erweitert und zum anderen durch die gezielte pditherapeutische Gewebsentnahme mit einer entscheidenden Histopathologie betrachtlich verbessert. Die fruhe Entdeckung eines Carcinoma in situ und die Differenzierung in ein lobulares, intraduktales oder infiltrierendes Karzinom bestimmen entscheidend das Schicksal der Frau. Die Frage nach der radikalen Mastektomie mit postoperativer Bestrahlung und der einfachen Mastektomie mit Bestrahlung konnen nur nach sorgfaltigen statistischen Unter- suchungen auf breiter Basis unter Berucksichtigung alterer und neuerer klinischer Erfah- rungen entschieden werden. Zur Vermeidung der oft sehr verstiimmelnden Operation sind die Kombinationsthera- pien, wie einfache Ablation des fortgeschrittenen Karzinoms oder Tumorektomie bei fruhen Karzinomen zusammen mit der Bestrahlung, in den Vordergrund getreten. Die Bedeutung der immer wieder diskutierten pdioperativen Bestrahlung und die Indikation dazu werden sorgfaltig besprochen. Eine ganz besondere Beachtung verdienen die jahrelangen sorgfaltigen Untersuchun- gen uber die alleinige Strahlentherapie mit Megavoltstrahlen, weil sie sowohl kosmetisch als auch statistisch ausgezeichnete Ergebnisse aufweisen konnen.

Extensive reviews have been published on the mor aspects, anatomy, ultrastructure, physiology, bio phology, anatomy, and physiology of the mam chemistry, endocrinology, pharmacology, and physiopathology of the mammalian ovary. The malian ovary. However, little attention has been given to the gaps between the physiological, endo contributors, who prepared their chapters metic ulously, are recognized experts in their respective crine and histochemical parameters of the ovary as disciplines and their writings reflect extensive per it relates to clinical aspects. There is a wealth of sonal experience and unpublished data of both publications concerning the biology of the ovary: basic and clinical sciences. Without the assistance of the purpose of this volume is to integrate this information with emphasis on modern concepts in good friends and permission to draw extensively microanatomy, physiology, methodology, clinical from investigations, this volume would not have complications, and therapeutic approaches. An been possible. attempt is made to place fundamental research in Thanks are due to G. F. Franchitto, F. Barberini, clear perspectives. P. Stoops. Lori Rust and J. Squiers for their editorial It is hoped that this volume will fulfil a long skills and for checking the references to the original standing need and serve as an important source for sources. Thanks are particularly due to 1. K. Smith investigators and clinicians concerned with the of Martinus Nijhoff Publishers BV for his excellent physiopathology of the ovaries for years to come. It cooperation during the production of the book."

Alfons Staudach has been a long-time member of the Anatomic Institute of Karl Franzens University in Graz, where he has devoted particular atten tion to the deeper understanding, appreciation and visualizion of gross ana tomic details. In this work the author has achieved correspondence between sonograms and anatomic sections with a consistency and persuasiveness unequaled in all the previous literature on diagnostic ultrasound. The various planes of section andtheir characteristic features, and indeed the entire format of the text, are designed to provide even the less experienced sonographer with a valuable basis for conducting his examinations. The more experienced reader will find essential information on topographic relations and organ development that is not available in any other work dealing with fetal ana to y. I am certain that my high estimation of this volume will prove justified, and that it will provice its readers with a useful and stimulating resource. Univ. -Prof. Dr. Walter Thiel (Chairman of the Anatomic Institute of the University of Graz) Foreword Anyone setting this book down after an initial perusal must wonder why such a reference was not available ten years ago. The meticulous and fas cinating juxtaposition of gross anatomic sections with sonograms, together with explanatory drawings and many practical guidelines, should enable even the novice accurately to identify details and interpret sonographic findings with precision."

Controlled and predictable interference with hormonal feed- back mechanisms has become a major direction of preclinical and clinical research. There is a steadily increasing number of hormonal pep tides detected and characterized that are re- sponsible for endo-, para-, and autocrine cellular actions. Naturally, these peptides have been studied with regard to their cell growth stimulatory action and, in parallel, the re- spective antagonists are being investigated in terms of their antiproliferative (antineoplastic) function. Among the numerous pep tides of interest in this respect, somatostatin (somatotropin release inhibitory factor) and bombesin antagonizing factors have been the topic of inten- sive research during recent years. No presentation of the role of pep tides in oncology would be complete without a compre- hensive treatise of their physiological, preclinical and clinical functions in the context of their antineoplastic mechanism of action. Somatostatin and its various short- and long-acting analogs have the unique feature of suppressing and inhibiting a wide range of cellular processes including cell proliferation. Recep- tors for these peptides, which belong in a wider sense to the family of neuropeptides or neurotransmitters, are widely dis- tributed, a feature which is not in keeping with the general view of a growth hormone regulatory system. Thus, these substances are found in the gut in a variety of endocrine and exocrine glands including breast, pancreas, and prostate, and in the nervous system.

The majority of scientists interested in fertilization and early developmental processes will undoubtably have encountered the works of Alberto Monroy at some time in their careers. Alberto's contribution to this field spans oogenesis to embryogenesis, where he used physiological, biochemical and morphological tools to answer a number of basic problems in cell biology. This multi-disciplinary approach, together with his remarkable intellectual flexibility and humour has had an enormous impact on this field and all those fortunate enough to have worked with him. The chapters in this book have been divided into four sections. The initial presentations revolve around late events of gameteogenesis, that lead to a physiologically mature gamete. Probably the most exciting area for research at the moment is the identification of the cytoplasmic mechanisms responsible for the meiotic arrest of oocytes and the factors responsible for initiating their maturation (Chapters 3 and 4). Less is known about the physiological changes in the male gamete in preparation for fertilization and this may be identified as a major area for future research. Although comparable data for the plant kingdom is presently restricted to studies on marine algae, new techniques for isolating angiosperm gametes (Chapters 1 and 17) promise rapid advances in this field. The second section looks at the events and molecules involved in gamete recognition, binding and fusion. One of the most controversial topics is when does sperm-egg fusion actually occur (Chapter 14).

Obstetricians and pediatricians in daily practice will find here the answersand explanations they need concerning the major problem of perinatal asphyxia. Leading experts in pediatrics, obstetrics and neurophysiology havecome together to produce a single sourcebook covering all aspects of thesubject. Biochemical mechanisms and clinical aspects of perinatal asphyxia, fetal and neonatal assessment, and perinatal management are thoroughly discussed. Neurodevelopmental outcome is another important issue addressed. In light of newer technologies, the prognosis of infants suffering from asphyxia is examined. Many figures and typicalcases are provided, making the book easy to use and providing quick access to solutions. The reader can easily identify a problem in the fetus and its subsequent development. With such knowledge, the improved managementof perinatal asphyxia is made possible.

Over the past ten years, carbon dioxide laser surgery has made impressive strides and is now applied to every field of surgery without exception. It is the intention of this book to record the work done in this field in the Department of Plastic and Maxillofacial Surgery of the Beilinson Medical Center and Tel Aviv University Medical School, Israel, as well as that performed in association with other depart ments. In this context, one feels that it is incumbent upon one to acknowledge the cooperation of the medical and paramedical staff of the Department of Plastic and Maxillofacial Surgery of the Beilinson Medical Center, as well as that of Prof. Yehuda Shindel and Dr. Daniel Katenelson of the Department of Ear, Nose and Throat, Dr. Y ona Tadir of the Department of Obstetrics and Gynecology and Dr. Itamar Kott of the Department of General Surgery. I should like to make special mention of Dr. Ralph Ger of New York, who worked with me on the original clinical trials, and the engineer Uzi Sharon, who developed the Sharplan Laser with me. The progress of Laser Surgery is well demonstrated by the participation in the four meetings of the International Society for Laser Surgery, the first of which was held in Tel Aviv in 1975 with an attendance of 65 and the last in Tokyo in 1981 with an attendance of 1200.

Despite a plethora of theories, premenstrual syndrome (PMS) has remained an enigma. There has persisted in the literature a constant conflict as to the existence of the syndrome, a question as to whether it is one syndrome or several, and a debate as to whether the origin is psychic, somatic, or both. Advances in endocrinology, specifically in radioligand assays, allowing for accurate hormone measurements, have precipitated a more scientific evaluation of PMS in recent years. Nonetheless, diffi culties have persisted in accumulating well-documented data because of the protean nature of the syndrome. Indeed, even at this time, the question of what requires measurement during the follicular phase of the cycle and the premenstrual phase remains unresolved, and is difficult to place in perspective. In view of the persisting conflict between the organic and the psychological schools of thought, we, the editors of this book, considered the Sixth International Congress of Psychosomatic Obstetrics and Gynecology to be an ideal venue for a workshop in which both parties could be encouraged to participate. Towards this end, the organizing committee of the Inter national Society of Psychosomatic Obstetrics and Gynecology (ISPOG) was approached, and their response was extremely encouraging. In this respect, we wish to record our thanks to the Scientific Committee oflSOPG for allowing this workshop to be organized under their auspices, but totally under our direction. We, in turn, stand responsible for the format and content of the workshop."

Most textbooks are cumbersome to carry, expensive to buy, difficult to read, and boring. They have no plot, no characterization, no suspense, no climax. What they have are facts. If Dragnet's Sgt. Friday were Scientist Friday, the script wouldn't be much different "just the facts, ma'am." Students can't escape textbooks. But like death and taxes, they are necessary evils. of old ideas makes room for new ones. Death makes room for new people and the death Taxes are the dues we pay to live in a country. Everybody gets stuck with paying some kind of dues and students are no exception. Students pay dues in the form of tuition to listen to professors lecture, and they also pay dues in what a former governor of California called' 'psychic bucks" -time, concentration, independent study, reading textbooks like this one-to come up with the correct answers to exam questions. Textbooks on economics will tell you about where our tuition bucks come from. This book is about where our psychic bucks come from and the forces that can bankrupt our psychic nest eggs."

These four volumes comprlslng "GnRH Analogues in Cancer and Human Reproduction" are a distillation of the presentations of the invited speakers at alandmark International Symposium bearing the same name, organized by one of us (B. L. ) and held in Geneva, Switzerland in February 1988. lhe Symposium was truly interdisciplinary spanning gonadal hormone dependent disease including various forms of cancer and ranging to control of fertility, both pro- and conception. The international flavor can be caught from the 480 participants and 259 contributors drawn from 14 countries. The Symposium, and therefore this book, would not have been possible without the backing of lhe International CommitLee for Research in Reproduction and the sponsorship of the International Society of Gynecologic Endocrinology, The Swiss Society of Fertility and Sterility, lhe University of Geneva School of Medicine, The Swiss Society of Endocrinology and The US ~oundation for Studies in Reproduction Inc. , and help from the World Health Organizatlon. B. H. Vickery B. Lunenfeld June 1989 x~i LIST OF CONTRIBUTORS TO THE SERIES A. Abbondante H. Bartermann First Institute of Obstetrics and Urologische Universitatsklinik Kiel Gynecology Arnold-Heller Strasse 7 University "La Sapienza" 0-2300 Kiel 1, FRG Rome,ltaly M. Bartholomew P. Abel Department of Medicine/Endoerinology Department of Urology MUton S. Hershey Medical Center Hammersmith Hospital Pennsylvania State University DuCaneRoad PO Box 850, Hershey, PA 17033, USA London W12 OHS, UK D. Beck Departments of Obstetrics and H.

Technical improvements over the past twenty years have made endos copy the procedure of choice for examination of the hollow organs of the genitourinary and gastrointestinal tracts. The development of electro surgical techniques, laser technology, injection therapy, and a wide variety of other modalities now allow the endoscopist to treat many problems that in the past required open surgery. The simultaneous development of transcutaneous abdominal sonography has had an equally dramatic impact on the practice of gastrointestinal and geni tourinary surgery. The marriage of these proven technologies, known as endoscopic sonography, provides an exciting new modality that promises to further revolutionize the diagnosis and management of many intraabdominal diseases. Endoscopic sonography opens new frontiers by overcoming the primary limitations of its parent technologies. Fiberoptic endoscopy is limited by the inability to see beyond the luminal surface, this is particularly important when considering neoplastic disease because depth of wall invasion is a key factor in determining treatment. The limiting factor in transcutaneous sonography is the distance between the transducer and the target organ. With endoscopic sonography, the transducer is placed in close proximity to the target organ. This allows the use of high frequency waves (greater than 5 MHz), which provide better tissue resolution and eliminates the image distortion caused by overlying structures.

Almost all known tumors and tumor-like conditions of the fe- male lower genital tract are classified in this complete mo- nograph on the subject. Clinical features, treatment and prognosis ar included, making this book a practical refe- rence for the busy clinician.

ABOUT THE SUBJECT MATTER Adolescence is a time of significant change. The adolescent era spans the interval between childhood and adulthood. It is a time of physical, social, and even emotional upheaval. During this relatively brief period of time not only does physical growth accelerate but, of more significance in the biology of any species, the individual attains reproductive maturity. Within this time frame, the human being acquires the capacity to procreate and perpetuate our species. From a reproductive standpoint, throughout adeolescence the individual is being prepared for perhaps what might be considered the most important function an organism has during his/her brief sojourn on earth, namely to endow successor(s) with a minute quan tity of DNA to enable continuation of its form of life. The interlude be tween childhood and adulthood is not always socially or emotionally sim ple. The anatomic and physiologic modifications that come to pass during adolescence are not necessarily paralleled by a capacity to assume the societal responsibilities associated with reproductive maturity. Although the physiologic changes normally proceed in a predetermined fashion, adaptation to a changing role is a far more trying process. Accustomed to living in a child's world, the subject of adolescent change requires considerable time and understanding to facilitate exis tence in the adult world. The early stages of sexual awareness, for ex ample, are generally extremely confusing and, as evidenced by the in ordinately high frequency of teenage pregnancy and sexually transmitted diseases, can be extraordinarily dangerous."

We often hear physicians, health care professionals, poli ticians, and patient advocates that "nothing has happened in the treatment of breast cancer," since patients with breast cancer, the most frequent neoplastic condition in women in industrialized countries, are continuing to suffer relapse and succumb to this dreadful disease This negativistic attitude does not seem to be justified, but, why is the transmission of clinical trial results into general practice, and with it progress, such a slow process? After many decades of frustrating stagnation of long-term survival expectations, in all stages of early, oper/lble breast cancer treated only by surgery and locoregional radio therapy, adjuvant systemic therapy (chemo- as well as endocrine treatments) clearly showed to significantly benefit in terms of disease-free and overall survival. This evolution has been extensively expounded on by the Worldwide Oxford Overview and the Expert Consensus Panel at the fourth International Conference 'on Adjuvant Therapy of Primary Breast Cancer in St. Gallen (Early Breast Cancer Trialists' Collaborative Group 1992; Glick et al. 1992). What has happened since then? During the past 3-5 years, several new concepts and treatment strategies have emerged and have been studied in various major breast cancer groups and treatment centers worldwide. Some of these can already be considered to assist in the primary treatment of operable breast cancer today, while others are . still undergoing clini, cal trials for better definition of their practical usefulness."

This book is based on the 20th Study Group of the Royal College of Obstetricians and Gynaecologists, which concerned the important topic of fetal growth. Basic scientific and both obstetric and paediatric aspects of the subject were addressed in contributions from many different disciplines. The deliberations covered the broad topics of normal fetal growth, fetal overgrowth and fetal undergrowth. Clinical implications of these entities, especially fetal undergrowth, played a large part in the proceedings as dictated by clinical concerns. Definitions, epidemiology, aetiology and screening were covered, as were technological developments, with special reference to blood flow and volume flow measurements, both fetal and placental. Other aspects of clinical fetal monitoring, including fetal activity measurements, and biophysical evaluation were rationalised and placed in context, and the important newly emerging areas of cordocentesis and therapy in IUGR addressed. Finally, neonatal management of the SGA baby, mortality and long-term morbidity were discussed.The formal papers presented by the members of the Study Group are given together with edited versions of the ensuing discussions and the Group's conclusions.

The International Life Sciences Institute (ILSI) was estab lished to stimulate and support scientific research and edu cational programs in nutrition, toxicology, and food safe ty; and to encourage cooperation in these programs among scientists from universities, industry, and government in order to facilitate the resolution of health and safety issues. The officers and trustees of ILSI believe that questions re garding health and safety are best resolved when govern ment and industry rely on scientific investigations, analy ses, and reviews by independent experts. This process is furthered by the examination and discussion of issues on an international basis. ILSI is pleased to sponsor this set of monographs on the pathology of laboratory animals. This project collectively brings together the most comprehensive information on non-neoplastic and neoplastic lesions that occur in com monly used laboratory animals. The international compo sition of the authors, editors, and editorial board who have contributed to these monographs strengthens our expecta tions that understanding and cooperation will be strength ened worldwide through this series."

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.

an adequate oxygen supply is vital for the undisturbed development of the fetus and its functions. This book gives a synopsis of the ruling influence that oxygen has in multiple regulation sytems in the mother and especially in the fetus. The authors consider oxygen as a manipulated variable or as a corrective element during normal pregnancy, during delivery and during acute and chronic oxygen deficiency. Furthermore, they deal with the consequences that oxygen deficiency has on the fetus.

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.