- Pre-order Price Guarantee! Order now and if the Amazon.com price decreases between your order time and the end of the day of the release date, you'll receive the lowest price. Here's how (restrictions apply)
The first three chapters are keys to this philosophy. They deal with the processes underlying adrenal organogenesis and steroidogenesis. Ramayya's presentation of the interaction of steroidogenic factor 1, DAX-1, and the estrogen receptor in adrenal steroidogenesis is a model of clarity. In the history of several adrenal disorders, there are a number of intriguing twists and turns. This is nicely portrayed in the puzzle of congenital lipoid adrenal hyperplasia. Almost 50 years after Andrea Prader first described the condition, we now have a solution. For many years, the disorder was thought to reside in the cholesterol side-chain cleavage enzymes. However, detailed analysis of these early stages in adrenal and gonadal steroidogenesis led to the discovery of the steroidogenic acute regulatory protein. This observation, coupled with knowledge of the role of the peripheral benzodiazepine receptor in cholesterol incorporation, has transformed our view of adrenal and gonadal steroidogenesis. And what of the problem of the side-chain cleavage enzyme? Originally, it was thought to be incompatible with life, because progesterone would not be formed in the placenta and pregnancy would not continue to term. This view is now challenged, because a heterozygous mutation of the gene encoding the enzyme has been described in a Japanese family. Thus, in the space of 50 years and since the introduction by Lawson Wilkins of hydrocortisone for the treatment of congenital adrenal hyperplasia, an example of human disease for each step in steroidogenesis now exists.
In the second part of the book, there is a wealth of carefully thought-out approaches to clinical problems. The result, in many of the chapters, is a personal approach that avoids the anecdotal and is based on sound evidence and tested experience. This is particularly useful in discussions of rare conditions, such as micronodular adrenal disease. The clinical content is well illustrated with clinical-management pathways, which greatly enhance the text. At first it may seem perverse to allocate the same number of pages to the commonest form of congenital adrenal hyperplasia (21-hydroxylase deficiency) as to rare forms (such as 11-hydroxylase deficiency or even adrenal hypoplasia congenita). But given that these are unusual conditions that present management issues, the editors are right to highlight them, since they rarely get good coverage in standard textbooks. The editors have gone one step further in promoting evidence-based practice by soliciting chapters from research groups with large numbers of patients. This is well represented by the studies on Cushing's disease and the treatment of adrenal carcinoma and pheochromocytoma. Does this approach justify limiting the treatment of rare conditions to a few centers that do it well? I think it does, and the message to health care insurers and physicians is clear. Concentrated expertise creates adequate data sets, which inform diagnostic strategies and treatment options. Yes, managing an occasional case of Cushing's disease might be exciting for a doctor, but is it really in the patient's best interests?
Perhaps one of the most interesting issues arising from this collection is where adrenal disorders fit within the hierarchy of human disease. At first glance and on reading the chapter titles, it might seem that they are conditions so uncommon as to represent the tip of human pathology. A prevalence of 1 in 15,000 for congenital adrenal hyperplasia and a much lower prevalence for Cushing's disease scarcely suggest that we are dealing with major disease entities and seem to confirm the prejudice that endocrinology is a Cinderella specialty.
Look closer, however, and similarities between abnormalities of cortisol secretion and metabolism and disorders such as syndrome X begin to emerge. Observations of the association between environmental stress and adrenal function raise issues to a global level. The World Health Organization estimates that by 2020, cardiovascular disease will be, by far, the leading cause of death in all countries except those in sub-Saharan Africa. Could the differences between ethnic groups in mortality and morbidity from cardiovascular disease have their basis in altered adrenal function? Do the recent epidemiologic maps of heart disease in the United States (from the Centers for Disease Control and Prevention) track with poverty or stressful environments, and is adrenal dysfunction the linking mechanism? Early evidence of this relation appears in several of the chapters. These concepts -- whether they relate to a stressful environment or programming of the hypothalamic-pituitary-adrenal axis -- deserve consideration, development, and careful testing with use of animal and human paradigms.
Peter Hindmarsh, M.D.
Copyright © 2001 Massachusetts Medical Society. All rights reserved. The New England Journal of Medicine is a registered trademark of the MMS.
--This text refers to the Hardcover edition.