Autoimmune Endocrinopathies

Dr. Robert Volpé and his distinguished contributors comprehensively review the latest thinking about the theoretical, experimental, and clinical aspects of autoimmune endocrine disorders. These world-renowned experts examine the pathogenesis and immunogenetics of these diseases, discuss the role of sex hormones in autoimmunity, and elucidate the nature of autoantigens. They also provide clinical detail on a wide variety of autoimmune endocrinopathies, including autoimmune thyroid disease, Graves' ophthalmopathy and dermopathy, human insulin-dependent diabetes mellitus, and autoimmune adrenocortical failure. Postpartum autoimmune endocrine syndromes, autoimmune hypophysitis, and the polyglandular autoimmune syndromes are also discussed in detail. Comprehensive and authoritative, Autoimmune Endocrinopathies provides today's most up-to-date understanding of the etiology and pathogenesis of autoimmune endocrine diseases.

This is a comprehensive and novel text that examines key features that predispose individuals to autoimmune diseases. The first section details the basic mechanism of autoimmunity and examines immunogenetic and environmental factors in autoimmunity. The next section examines autoimmune thyroid disease. The third section takes a look at Type 1 diabetes mellitus. In the final section, authors explain other autoimmune endocrinopathies.

Autoimmunity is the most common cause of endocrine disorders. This volume provides an up-to-date summary of recent advances in this important field. In addition, it describes developments in our understanding of conditions such as vitiligo and pernicious anaemia which are frequently associated with autoimmune endocrinopathies. There is a detailed review of animal models of endocrine disease which have contributed greatly to current knowledge. Furthermore, the aetiology, pathogenesis and treatment of the clinical disorders are discussed in depth. The book will be of interest to anyone working in the areas of endocrinology and immunology.

This book is a comprehensive, easy-to-read discussion of the organ-specific autoimmune endocrine diseases emphasizing new contributions and trends for research and management. It begins with a brief chapter introducing the general principles of immunology, followed by discussions covering topics such as immunogenetics and animal models and how they can be applied toward interpreting human autoimmune endocrine diseases, autoimmune thyroid diseases, insulin-dependent diabetes mellitus hypophysitis, and Addison's disease. The book also discusses future trends toward gaining an understanding of these disorders and possible therapeutic principles. It is well-illustrated and will prove to be a useful reference source for internists, endocrinologists, and postgraduate students interested in human autoimmune endocrine diseases.

The present monograph will concern itself with those disorders of the endocrine system, either associated with destruction, interference with function or hyper function, which are considered to be due to auto-immune processes. Endocrinopathies Non-endocrine auto-immune disorders associated with the endocrinopathies Graves' (Basedow's, Parry's) disease Pernicious anaemia Hashimoto's thyroiditis Vitiligo Idiopathic Addison's disease Myaesthenia gravis Insulinopenic diabetes mellitus Sjogren's syndrome Auto-immune oophoritis and orchitis Rheumatoid arthritis Auto-immune hypoparathyroidism Idiopathic thrombocytopenic purpura Auto-immune hypophysitis Chronic active hepatitis Possibly some cases of infertility Primary biliary cirrhosis due to anti-sperm antibodies Reproduced with permission from Volpe (1977) The above table indicates those organ-specific endocrinopathies considered to be due to auto-immune factors, as well as those non-endocrine, organ-specific auto-immune disorders which may be associated with them (Volpe 1977). It is evident that such disorders, occurring without any obvious external cause, raise the very elementary question of how immune processes directed against self constituents could be initiated. Generally, of course, the immune system acts as a regulatory and defence mechanism, and disorders of auto-immunity represent breakdowns in this regulatory system. The following chapters will be concerned with the individual components ofthe endocrine system so affected by auto-immune processes; it will first be necessary to provide an initial chapter for the purpose of summarizing some general principles of immunology, in order to place the immune disorders of the endocrine system in context.

Nineteen eighty-six is a most appropriate year in which to be writing about developments in the organ-specific, autoimmune endocrine diseases. It celebrates the publication 30 years ago in 1956 of the classic papers of Roitt and Doniach and their co-workers I , and of Rose and Witebsky2 and Adams 3 and Purves . These three sets of fundamental observations provided the initial building blocks upon which much of what has been established in the field in the last 30 years was built. No publication of this nature on endocrine autoimmune disease can cover every aspect of the subject. I have chosen to highlight the organs (thyroid and pancreeas) which have attracted the most attention, and the areas of work within these fields within which most research effort is currently focused. There are still some gaps; the insulin and TSH receptors are not considered, nor in any detail are the role of cytotoxic mechanisms in mediating gland destruction. Molecular biology will undoubtedly in the next few years clarify once and for all the controversy that surrounds the structure of the TSH receptor and T cell cloning, the role of cell-mediated cytotoxicity. The pathogenetic mechanisms underlying autoimmunity are increasingly well understood and the search for the aetiology has begun.

This book is one of the first to evaluate the role of Steroids in autoimmune rheumatic diseases from the basic mechanisms to the clinical involvements and focuses on the importance of steroidal hormones in the pathogenesis and therapeutic management of the autoimmune rheumatic diseases. In particular, the chapters analyze the mechanisms of action and the involvement of adrenal steroids (glucocorticoids) in the neuroendocrine immune system, including effects on the elderly. The perturbations of the HPA axis as a source of altered steroidal synthesis will be discussed and related to some interesting pathological conditions that commonly complicate the autoimmune rheumatic diseases such as psychosis or fibromyalgia. Concerning the role of gonadal steroids (sex hormones), several chapters will discuss clinical and epidemiological evidences of their role, as well as their effects as risk factors in autoimmune rheumatic diseases, including a section on pediatrics. The premier issue evaluating the role of steroids in autoimmune rheumatic diseases from the basic mechanisms to the clinical involvements Documents the latest research and indicate recent and coming new therapeutic-biological approaches to the therapy The book will present therapeutic perspectives concerning the new glucocorticoids, and the effects of biological drugs on their synthesis

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 . . . . . . . . . . . . ..................... . . . . . .