Older persons often express disease differently than do younger adults; as a consequence, clinicians treating elderly patients need to be aware that both symptoms and laboratory tests require special consideration. This is so both to properly interpret clinical manifestations and to decide on an appropriate therapeutic approach. Disregarding these differences may lead to significant medical errors with dire consequences.
Many of the physiological age-related changes in metabolism and body composition resemble those typically seen with a variety of pathological disturbances in hormone balance. For example, there are decreases in lean body and muscle mass and in bone density, increases in percent body fat and insulin resistance, and reductions in resting metabolic rate, energy levels, and libido. These same phenomena are observed in young adults with deficiencies of growth hormone (GH), sex steroid hormones, and thyroid hormone, as well as with cortisol excess. To complicate matters further, such changes may also occur in the setting of a variety of chronic diseases and malnutrition. Furthermore, aging is associated with an increased incidence and prevalence of a host of illnesses, including endocrine disorders such as autoimmune hypo- and hyperthyroidism, among others.
Conceptually, it is well understood that endocrine disorders fall into the category of pathophysiology, so that any signs or symptoms of glandular dysfunction are generally explainable by pathophysiological analysis.
That is, as we age, physiological changes occur that can alter the pathophysiology and therefore the clinical picture. The main aim of this monograph is to explain the characteristic pathological expressions of hormonal alterations with advancing age. We hope that the reader will better understand and appreciate those changes.
The chapters of this book have been divided according to specific endocrine systems and will provide the reader, in an orderly fashion, with the most up-to-date published information regarding what is known about how functions of various endocrine systems are altered during the aging process. It is also the intention of the authors to provide perspective as to how such endocrine and metabolic changes may both be caused by, and contribute to, the pathophysiology of aging.
The first chapter briefly explore the biological basis of human aging, noting that it is a process primarily based on wear and tear that is modified by compensatory regulatory responses. This is where we differentiate ourselves from inert matter, which ages by wearing, without regulatory compensation or repair. As an example, if muscle tissue were to age just by cell attrition, individual prostration would be very premature. This is because without deposition of collagen as a repairing and stabilizing element, and repair of myofibers bymobilization of satellite cells, the gradual disappearance of myocyte tissue would soon lead to disorganization of muscle components, with loss of movement, so that functional collapse would occur as an early phenomenon. Therefore, the repair and stabilization of structures by collagen deposits and mobilization of stem cells correspond to one regulatory and compensatory mechanism of aging.
Another example of age-related regulation is the rise of LDL-cholesterol, demand for which increases with age, likely because cell membranes are subjected to the deleterious effects of free radicals that require cholesterol for stabilization. However, hypercholesterolemia may be atherogenic, as evidenced by inherited forms in the young. Hence, regulation itself may become pathogenic if it exceeds certain boundaries. In this example, it is the physician’s task to evaluate the data on natural history of a phenomenon with an analysis contrasting benefits for normal aging regulation with potential for damage (e.g., of hypercholesterolemia) as a risk factor.
Thus, dyslipidemia represents an example of the difficulty in distinguishing normal from pathological, in the metabolic-endocrine clinical presentation of an elderly patient. Other examples include type 2 diabetes and osteoporosis, which increase with age, and therefore, with the aging process.
Endocrine activity moves to the beat of aging. We only need mention the frequent finding that in men, testosterone production gradually declines with advancing age. Serum testosterone levels in the 5th decade may be reduced by 50% from those exhibited in young adults, often reaching remarkably low levels in the elderly. This phenomenon poses substantial difficulty in differentiating hypogonadism in the older male from aging per se. Here again, the endocrinological challenge is to distinguish physiology from pathology.
Endocrine diseases can interfere with the aging process either by accentuating wear and tear, by decreasing regulatory mechanisms, or both. For example, the typical restless hyperactivity of hyperthyroidism may manifest as exhaustion and inactivity in older patients (apathetic hyperthyroidism), leading to a clinical presentation similar to thyrotoxic myopathy. However, certain organs age almost exclusively by wear and tear.
Osteoarthritis is a disorder wherein continued operation and overload of the joints are the main determinants of pathology. Hormonal influences are also involved in the process, either protecting joints against degeneration or worsening its evolution. Androgens, on the one hand, and estrogens and thyroid hormones, on the other, can influence the progression of such events. Osteoporosis is also a comparable state. Therefore, we must carefully consider the association of endocrine diseases with osteoarthritic disorders, especially when hormone replacement therapy is needed.
Other relevant issues are discussed in this book, including whether elderly men and women with age-related reductions in sex hormones might or might not benefit from gender-appropriate hormone therapy, whether there is a “somatopause” and if human GH treatment is harmful or beneficial in older patients with low levels of GH secretion, and the problems of subclinical hyper- and hypothyroidism in elderly patients as manifest by slightly low or high TSH levels. We believe that the authors provide the relevant data, pro and con, vis-à-vis these important issues in a rational and balanced fashion. However, the sagacious clinician will understand that, while such decisions should be data driven, they can only be made one patient at a time and in accord with best practices and good clinical judgment.
Finally, we could not neglect discussions of benign prostatic hypertrophy and prostate cancer in this work. Although those are not endocrine disorders, both show a clear endocrine interaction in the context of their close relationship with aging.
In summary, this book presents endocrine physiology and pathophysiology in relation to the aging process, paying special attention to manifestations of advanced age. We trust that the reader will appreciate differences between the approaches of traditional clinical endocrinology and those that take into account the changes of aging. The latter features must be increasingly considered as the patient transitions from young adult to elderly. We will have achieved the goal to which we are committed if, henceforth, the reader considers age as an essential factor in her/his diagnostic and endocrine management of older patients.
The selected format of this book is composed of chapters with comprehensive text as well as visual content that have been developed as diagrams and graphic images. The book is aimed to become a friendly and quick reference guide, suitable for the practicing clinicians treating elderly patients with endocrine diseases and also for medical educators and trainees. We hope that you find it informative and useful.
Washington/Guadalajara and Madrid (Spain)/Phoenix (USA). July 2020.
Marc R. Blackman
S. Mitchell Harman
Dr. Emiliano Corpas wishes to thank his wife Trinidad and his daughter Sandra for their love, unwavering support, and endless patience. He also states his appreciation to all staff members of the Endocrinology Division of the Phoenix Veterans Administration Medical Center for their professional collaboration, and expresses warm gratitude to Drs. Ricardo Correa, Carolina Chen, and Karyne Vinales, and Darren Kristofic and Stephanie Kristofic RN, for their hospitality and friendship. The participation, support, and input of so many colleagues and persons involved in this book, especially from Elsevier, are very much appreciated. He would like to acknowledge as well the brilliant contributions and advice of his long-term friends, colleagues, and authors, Drs. Marc R. Blackman, S. Mitchell Harman, Álvaro Larrad-Jiménez, Franco Sánchez-Franco, and Antonio Ruiz-Torres, and the paintings on the book covers created by his friend, Antonio Heras Villanueva.
Dr. Marc R. Blackman wishes to thank his wife, Linda, for her unstinting support and endless patience during the writing and editing process. He would also like to thank his long-term friends and colleagues, Dr. Emiliano Corpas, for his inspiring and tireless efforts in bringing this book from concept to reality; Dr. S. Mitchell (Mitch) Harman, for sharing his deep knowledge and wisdom; Drs. Ricardo Correa and Antonio Ruiz-Torres, for their writing and editorial expertise; all the many coauthors, for their expert and informative contributions. He would also like to thank the Elsevier staff for their exceptional professionalism and helpfulness; and all patients with age related endocrinological and metabolic disorders as well as the health providers who care for them, to whom this book is dedicated.
Dr. Ricardo Correa first wants to thank God for giving him the strength to participate in this amazing piece of art and medicine. Thanks to his wife Carolina and children (Matthew and Elizabeth) for their support, cheering, and for the time that he was not able to spend with them. Thanks to his mentor, Dr. Harman, for believing in him, and to Dr. Corpas for trusting him with this big project and for becoming a friend and family member. Special thanks to Stephanie Kristofic, RN, and Dr. Karyne Vinales for always being willing to help, and to all the endocrine fellows (Ghada, Kelvin, Matthew, Mike, and Sonie) for serving as the inspiration for this book. Teaching the next generation of endocrinologists and focusing on endocrinology in the elderly give us the strength to continue.
Dr. S. Mitchell Harman would like to acknowledge the unswerving support of his wife Carol who “kept the home fires burning” during the writing and editing of his chapters as well as the insightful collaboration of his long-term personal and professional friend and coauthor, Dr. Marc R. Blackman; the shared clinical and linguistic insights of the energetic and enthusiastic Dr. Ricardo Correa; and most of all the vision and inspiration of his dear colleague, Professor Emiliano Corpas, without whose lifetime dedication to the expansion of knowledge in endocrinology this wonderful opus would never have seen the light of day.
Dr. Antonio Ruiz-Torres would mainly like to thank scientists Walter Beier (Leipzig), Gerhard Hofecker (Vienna), and the late Bernhard Strehler (United States), whose basic investigation contributed to a better understanding of the relationships between clinical manifestations and the aging process, also in endocrinology. Dr. Ruiz-Torres’ contribution to this book is based on the results and theories of those basic researchers. He also expresses his thanks to the associate editors, especially to editor Dr. Emiliano Corpas for his idealistic engagement, dedication, and hard work to make this book.