The management of endocrine disorders requires a broad understanding of intermediary metabolism, reproductive physiology, bone metabolism, and growth. Accordingly, the practice of endocrinology is intimately linked to a conceptual framework for understanding hormone secretion, hormone action, and principles of feedback control. The endocrine system is evaluated primarily by measuring hormone concentrations, arming the clinician with valuable diagnostic information. Most disorders of the endocrine system are amenable to effective treatment once the correct diagnosis is determined. Endocrine deficiency disorders are treated with physiologic hormone replacement; hormone excess conditions, which usually are due to benign glandular adenomas, are managed by removing tumors surgically or reducing hormone levels medically.
The specialty of endocrinology encompasses the study of glands and the hormones they produce. The term endocrine was coined by Starling to contrast the actions of hormones secreted internally (endocrine) with those secreted externally (exocrine) or into a lumen, such as the gastrointestinal tract. The term hormone, derived from a Greek phrase meaning "to set in motion," aptly describes the dynamic actions of hormones as they elicit cellular responses and regulate physiologic processes through feedback mechanisms.
Unlike many other specialties in medicine, it is not possible to define endocrinology strictly along anatomic lines. The classic endocrine glands—pituitary, thyroid, parathyroid, pancreatic islets, adrenals, and gonads—communicate broadly with other organs through the nervous system, hormones, cytokines, and growth factors. In addition to its traditional synaptic functions, the brain produces a vast array of peptide hormones, and this has led to the discipline of neuroendocrinology. Through the production of hypothalamic releasing factors, the central nervous system (CNS) exerts a major regulatory influence over pituitary hormone secretion (Chap. 339). The peripheral nervous system stimulates the adrenal medulla. The immune and endocrine systems are also intimately intertwined. The adrenal hormone cortisol is a powerful immunosuppressant. Cytokines and interleukins (ILs) have profound effects on the functions of the pituitary, adrenal, thyroid, and gonads. Common endocrine diseases such as autoimmune thyroid disease and Type 1 diabetes mellitus are caused by dysregulation of immune surveillance and tolerance. Less common diseases such as polyglandular failure, Addison's disease, and lymphocytic hypophysitis also have an immunologic basis.
The interdigitation of endocrinology with physiologic processes in other specialties sometimes blurs the role of hormones. For example, hormones play an important role in maintenance of blood pressure, intravascular volume, and peripheral resistance in the cardiovascular system. Vasoactive substances such as catecholamines, angiotensin II, endothelin, and nitric oxide are involved in dynamic changes of vascular tone in addition to their multiple roles in other tissues. The heart is the principal source of atrial natriuretic peptide, which acts in classic endocrine fashion to induce natriuresis at a distant target organ (the kidney). Erythropoietin, a traditional circulating hormone, is made in the kidney and stimulates erythropoiesis in bone marrow (Chap. 57). The kidney is also integrally involved in the renin-angiotensin axis (Chap. 342) and is a primary target of several hormones, including parathyroid hormone (PTH), mineralocorticoids, and vasopressin. The gastrointestinal tract produces a surprising number of peptide hormones, such as cholecystokinin, ghrelin, gastrin, secretin, and vasoactive intestinal peptide, among many others. Adipose tissue produces leptin, which acts centrally to control appetite. Carcinoid and islet tumors can secrete excessive amounts of these hormones, leading to specific clinical syndromes (Chap. 350). Many of these gastrointestinal hormones are also produced in the CNS, where their functions are poorly understood. As hormones such as inhibin, ghrelin, and leptin are discovered, they become integrated into the science and practice of medicine on the basis of their functional roles rather than their tissues of origin.
Characterization of hormone receptors frequently reveals unexpected relationships to factors in nonendocrine disciplines. The growth hormone (GH) and leptin receptors, for example, are members of the cytokine receptor family. The G protein–coupled receptors (GPCRs), which mediate the actions of many peptide hormones, are used in numerous physiologic processes, including vision, smell, and neurotransmission.
Hormones can be divided into five major classes: (1) amino acid derivatives such as dopamine, catecholamine, and thyroid hormone; (2) small neuropeptides such as gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), somatostatin, and vasopressin; (3) large proteins such as insulin, luteinizing hormone (LH), and PTH produced by classic endocrine glands; (4) steroid hormones such as cortisol and estrogen that are synthesized from cholesterol-based precursors; and (5) vitamin derivatives such as retinoids (vitamin A) and vitamin D. A variety of peptide growth factors, most of which act locally, share actions with hormones. As a rule, amino acid derivatives and peptide hormones interact with cell-surface membrane receptors. Steroids, thyroid hormones, vitamin D, and retinoids are lipid-soluble and interact with intracellular nuclear receptors.
Hormone and Receptor Families
Many hormones and receptors can be grouped into families, reflecting their structural similarities (Table 338-1). The evolution of these families generates diverse but highly selective pathways of hormone action. Recognition of these relationships allows extrapolation of information gleaned from one hormone or receptor to other family members.
Table 338-1 Membrane Receptor Families and Signaling Pathways
| Save Table
Table 338-1 Membrane Receptor Families and Signaling Pathways
|G Protein–Coupled Seven-Transmembrane (GPCR)|
|β-Adrenergic LH, FSH, TSH||Gsα, adenylate cyclase||Stimulation of cyclic AMP production, protein kinase A|
|Glucagon PTH, PTHrP ACTH, MSH GHRH, CRH||Ca2+ channels||Calmodulin, Ca2+-dependent kinases|
Inhibition of cyclic AMP production
Activation of K+, Ca2+ channels
|TRH, GnRH||Gq, G11||Phospholipase C, diacylglycerol, IP3, protein kinase C, voltage-dependent Ca2+ channels|
|Receptor Tyrosine Kinase|
|Insulin, IGF-I||Tyrosine kinases, IRS||MAP kinases, PI 3-kinase; AKT, also known as protein kinase B, PKB|
|EGF, NGF||Tyrosine kinases, ras...|
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