In a state-of-the-art synthesis of basic science and clinical practice, Roy Smith and a distinguished panel of researchers and clinicians review GH regulation and its action at the molecular level, and describe the basis for GH deficiency and the use of GH as therapy in a variety of clinical situations. The clinical presentation moves beyond the treatment of GH-deficient children to include the genetics of GH-deficiency, GH-deficiency in adults, osteoporosis, Syndrome X, sleep quality, GH in AIDS patients, GHRH in clinical studies. Timely and innovative, Human Growth Hormone: Research and Clinical Practice will benefit both basic and clinical researchers, as well as those clinical endocrinologists who want to use growth hormone not only in treating children, but also in treating adult disorders, including those associated with metabolic disease.

It has been ten years since the National Hormone and Pituitary Program (then called the National Pituitary Agency) sponsored a symposium on human growth hormone (hGH). Numerous advances have occurred during this period. This book does not attempt to summarize past achievements. Rather, it deals with the contemporary issues in hGH research. A discussion of the present state of the art, of necessity, includes a review of the past. Some of the topics herein discussed include the following: 1. Growth hormone releasing factor (GRF). In 1973, the growth hormone inhibitory factor (somatostatin) had recently been discovered. The search for a releasing factor in humans led to its discovery not in the pituitary but in a pancreatic tumor that secreted growth hormone. The advances are discussed in this book. The current hope is that GRF will eventually become an effective therapeutic agent for idiopathic hypopituitarism in childhood and adolescence. 2. Biosynthesis of hGR by recombinant DNA technology. Current advances are discussed. Although hGH is not yet an approved drug, it will eventually become one. This will broaden our horizons in terms of hGH effectiveness in disorders other than hypopituitary dwarfism. The current experience with this type of hGH in both the Vnited States and Europe is reviewed by several authors.

Human Growth Hormone is a compendium of papers that discusses all aspects of human growth hormone (HGH) relevant in the treatment of dwarfs who are HGH deficient. This book discusses the approach of growth hormone treatment including the preparation of the hormone, its effect and interactions with other hormones, the methods used to detect growth hormone in human plasma, as well as its clinical applications. One author discusses the preparation of human growth hormone, its storage, method of bioassay, and procedures for ampouling HGH for clinical use. A couple of authors review the metabolic actions of HGH, namely, on the anabolic and skeletal systems, on carbohydrate and fat metabolism, and miscellaneous effects (renotropic, aldosterone, haematopoietic). One paper evaluates the treatment of dwarfism with HGH, and reports that in cases of HGH deficiency, the use of such treatment can be effective as long as the growth potential of the patient remains, and antibodies do not interfere with the treatment. The compendium can prove helpful for endocrinologists, genetic scientists, cellular microbiologists, and scientists involved in pharmacology and developmental anatomy.

Growth hormone (GH) has been used therapeutically for over 50 years. Since the development of a nearly unlimited supply of recombinant human GH in the mid-1980s, children with less severe GH deficiency can also profit from GH replacement therapy. Careful and accurate diagnosis and specific dosing, both essential to ensure normal height development, require the clinician to understand the finer points of clinical trials, to acquire quality evidence and assess the benefits of therapeutic intervention. Furthermore, genetic and environmental factors influencing GH sensitivity and responsiveness need to be taken into account. In this second edition all these aspects are covered in depth. Clinical examination, detailed auxological measurements, bone age assessment, molecular analysis and neuro-radiological evaluation as well as an adaptive strategy of dosing focusing on a patient's individual responsiveness are discussed in detail. This volume of Endocrine Development is essential reading for pediatric endocrinologists, pediatricians and clinical nurse specialists involved in GH therapy.

The traditional concept of a neuroendocrine mechanism for regulation of growth hormone (GH) secretion is based in large part on the work of Roger Guillemin. The work of Dr. Guillemin, who was awarded the 1977 Nobel Prize in Physiology and Medicine, supported the view that quantita tive change in GH secretion was the net result of pituitary stimulation and inhibition by the hypothalamic neurohormones, GH releasing hormone (GHRH), and somatostatin (somatotropin release inhibiting factor; SRIF), respectively. During the 1970s, another endocrine research pioneer, Dr. Cyril Bowers, discovered that structural modification of enkephalin re sulted in a family of peptides with GH releasing properties. These com pounds, simply called GH releasing peptide (GHRP), were originally thought to mimic GHRH. However, upon subsequent investigation they were found to supplement the activity of the natural hormone through a different mechanism. Nearly two decades after their discovery, the differ ences between GHRP and GHRH have been described by many different laboratories throughout the world. The complementary GH secretagogues have different binding sites, second messengers, and effects on gene expres sion. Based on these differences, it has been suggested that expansion of the original two hormone mechanisms for GH regulation to include a third molecule may be appropriate, even though the naturally occurring ana logue of GHRP has not yet been identified. Despite our lack of knowledge concerning the natural product mimicked by GHRP, clinical development of the new family of GH secretagogues for diagnostic and therapeutic purposes has begun in earnest.

For 20 years, KIGS (Pfizer International Growth Database) has provided an outstanding tool for monitoring the use, efficacy and safety of growth hormone (GH) treatment in children with short stature of varying origin. This volume offers a comprehensive update of the continuing experiences in KIGS and is based on data from more than 50 countries and more than 60,000 patients. International experts analyse in detail the basic auxological characteristics of patients and their response to GH treatment for a broad spectrum of growth disorders. These include idiopathic GH deficiency, organic GH deficiency due to a variety of causes such as congenital malformations and syndromes, genetic disorders or treatment for leukaemia or central nervous system tumours and short stature in children born small for gestational age, specific syndromes and systemic disorders. Each growth disorder is also covered by a review of relevant published data by international experts. KIGS has also established itself as a primary source of information about adverse events during long-term GH treatment in children. The recent analysis of KIGS data has revealed no new adverse drug reactions since the 10-year follow-up. Therefore, treatment with GH seems a low-risk intervention in children and adolescents with various growth disorders. The process of developing disease-specific growth response prediction models has been ongoing in KIGS for many years. The available models are accurate, precise and have a relatively high degree of predictive power, although further predictors of the growth response remain to be identified. The KIGS prediction models can be applied prospectively to new patients, enabling their GH therapy to be better tailored and monitored to achieve optimal growth, safety and cost outcomes. The future of KIGS within the era of evidence-based medicine will continue to depend upon the quality of the data reported. Therefore, the commitment of participating physicians will continue to be a decisive element. The ongoing recognition of the importance of valid safety and efficacy information in the practice of paediatric endocrinology is exemplified by this valuable international collaboration of clinicians and the pharmaceutical community.

This book addresses a wide range of basic and clinical issues in the physiology and pharmacology of growth hormone. The volume is organized like a textbook. It begins with factors contributing to GH gene expression, the functional relationships of the GH receptor, molecular biological analysis of the GH-GH receptor complex and proceeds to describe the insulin-like growth factor axis. Transgenic models are discussed for analysis of discrete effects. These discussions provide a bridge to clinically oriented discussions of growth abnormalities in GH deficient children, GH insensitivity due to deficiency of the GH receptor, and the concept of aging as a GH/IGF-I deficiency state. Discussions also include the immune system as a source and a responder to GH, GHRH, IGF-I and the effects of GH excess.

Recognizing the urgent need for an up-to-date review of new and innovative research on growth hormone (GH) secretagogues, this exclusive work furnishes the state of the art on the mechanisms of action, design, synthesis, evaluation, and clinical applications of GH secretagogues, including orally active and xenobiotic GH-releasing compounds. Beg

The molecular era ushered in the cloning of the growth hormone (GH) gene and the production of unlimited amounts of GH through recombinant technology. The continuing momentum of research from basic science to clinical evaluation has brought unprecedented advances to the understanding of GH biology for the clinical endocrinologist. Growth Hormone Related Diseases and Therapy: A Molecular and Physiological Perspective for the Clinician distills all the new information of relevance to the endocrinologist over the last 20 years by offering five sections: physiology, molecular genetics, GH deficiency, acromegaly and pharmacotherapy. The first section on physiology focuses on GH action. A review on the structure and function of the GH receptor is followed by a perspective on the regulatory role of ghrelin on GH secretion. The second section on genetics covers pituitary function and adenomas, including new and fascinating information on familial pituitary adenomas, their genotype and phenotype. The adult GH deficiency section spans the epidemiology and diagnosis of GH deficiency with a strong reminder for the clinician that the transition period represents a critical time of somatic maturation, which continues for years after cessation of liner growth. The section on acromegaly focuses on management, giving practical guides to the value of GH and IGF-1 measurements, the place of somatostatin analogues and of radiotherapy while reminding the reader as to why evaluating quality of life is an important part of management. Finally, the section on GH pharmacology takes the reader through innovative developments of long-acting GH formulations with some products on the threshold of clinical use. This section provides a balanced evidence based review of the effects of GH supplementation in aging and in sports where recent data indicates an enhancing effect on a selective aspect of performance. Growth Hormone Related Diseases and Therapy: A Molecular and Physiological Perspective for the Clinician integrates a wealth of information and will prove an invaluable reference for pediatric endocrinologists, adult endocrinologists, endocrine scientists and internists interested in the human biology of GH.

Growth Hormone and the Heart endeavors to bring together knowledge that has been accumulated in the area of GH and the heart, from basic to clinical studies, by research groups working on this topic throughout the world. Lessons from different experimental models and from several human diseases (acromegaly, adult GH deficiency, heart failure) suggest to endocrinologists and cardiologists that GH may not only have a role in the physiology and pathophysiology of heart function, but that GH itself may have a place in the treatment of primary heart diseases (such as dilated cardiomyopathy) or of cardiac complications of hypopituitarism. Growth Hormone and the Heart will be a useful update of the research produced in the field of cardiovascular endocrinology. The Editors also hope that this book will serve as the primary step in the recognition of the wide physiological and clinical significance of GH and heart interactions.