P Art 1 Foundations of Endocrinology

COPYRIGHTED MATERIAL Part 1 Foundations of Endocrinology 3 CHAPTER 1 Overview of e ndocrinology Key t opics ■ A brief history of endocrinology and diabetes 4 ■ The role of hormones 5 ■ Classification of hormones 8 ■ Organization and control of endocrine organs 9 ■ Endocrine disorders 13 ■ Key points 13 Learning o bjectives ■ To be able to define endocrinology ■ To understand what endocrinology is as a basic science and a clinical specialty ■ To appreciate the history of endocrinology ■ To understand the classification of hormones into peptides, steroids and amino acid derivatives ■ To understand the principle of feedback mechanisms that regulate hormone production This chapter details some of the history to endocrinology andd diabetes, and introduces basic principles that underpin the subsequent chapters Essential Endocrinology and Diabetes, Sixth Edition. Richard IG Holt, Neil A Hanley. © 2012 Richard IG Holt and Neil A Hanley. Publlished 2012 by Blackwell Publishing Ltd. 4 / Chapter 1: Overview of endocrinology An organism comprised of a single or a few cells A b rief h istory of e ndocrinology analyzes and responds to its external environment and d iabetes with relative ease. No cell is more than a short diffusion distance from the outside world or its neigh- The term ‘ hormone ’ , derived from the Greek word bours, allowing a constancy of internal environment ‘ hormaein ’ meaning ‘ to arouse ’ or ‘ to excite ’ , was ( ‘ homeostasis ’ ). This simplicity has been lost with first used in 1905 by Sir Ernest Starling in his the evolution of more complex, larger, multicellular Croonian Lecture to the Royal College of Physicians; organisms. Simple diffusion has become inadequate in larger animal species where functions localize to specific organs. In humans, there are ∼ 10 14 cells of (a) Endocrine (b) Autocrine (A) and 200 or more different types. With this compart- Paracrine (P) mentalized division of purpose comes the need for Target cell effective communication to disseminate informa- Hormone Target cell tion throughout the whole organism – only a few cells face the outside world, yet all respond to it. Two communication systems facilitate this: the A P endocrine and nervous systems (Box 1.1 ). Blood vessel Local hormone The specialized ductless glands and tissues of the endocrine system release chemical messengers – hormones – into the extracellular space, from where (c) Neuroendocrine (d) Neurotransmitter they enter the bloodstream. It is this blood - borne transit that defines endocrinology; however, the Nerve cell Neurone principles are similar for hormone action on a neighbouring cell ( ‘para crinology ’ ) or, indeed, itself ( ‘auto - or intra - crinology ’ ) (Figure 1.1 ). Axon The nervous and endocrine systems interact. Endocrine glands are under both nervous and hor- Axon Neurone monal control, while the central nervous system is terminal affected by multiple hormonal stimuli – features Neurotransmitter reflected by the composite science of neuroendo- crinology (Figure 1.1 ). Blood vessel Target cell Figure 1.1 Cells that secrete regulatory substances to communicate with their target cells and organs. (a) Endocrine. Cells secrete hormone into the blood vessel, where it is carried, potentially over large distances, to its target cell. (b) Autocrine (A): hormones Box 1.1 Functions of the such as insulin- like growth factors can act on the cell e ndocrine and n ervous s ystems, that produces them, representing autocrine control. the t wo m ain c ommunication Paracrine (P): cells secrete hormone that acts on nearby cells (e.g. glucagon and somatostatin act on s ystems adjacent β - cells within the pancreatic islet to influence • To monitor internal and insulin secretion). (c) Stimulated neuroendocrine cells external environments secrete hormone (e.g. the hypothalamic hormones that maintain • To allow appropriate regulate the anterior pituitary) from axonic terminals homeostasis adaptive changes into the bloodstream. (d) Neurotransmitter cells secrete • To communicate via substances from axonic terminals to activate adjacent chemical messengers } neurones. Chapter 1: Overview of endocrinology / 5 however, the specialty is built on foundations that crine syndromes. Since then, our understanding has are far older. Aristotle described the pituitary, while advanced through: the associated condition, gigantism, due to excess growth hormone (GH), was referred to in the Old • Successful quantification of circulating Testament, two millennia or so before the 19th hormones century recognition of the gland ’ s anterior and pos- • Pathophysiological identification of endocrine terior components by Rathke, and Pierre Marie ’ s dysfunction connection of GH - secreting pituitary tumours to • Molecular genetic diagnoses acromegaly. • Molecular unravelling of complex hormone Diabetes was recognized by the ancient action. Egyptians. Areteus later described the disorder in the second century ad as ‘ a melting down of flesh Some of the landmarks from the last 100 years and limbs into urine ’ – diabetes comes from the are shown in Box 1.2 , and those researchers who Greek word meaning siphon. The pancreas was only have been awarded the Nobel Prize for Medicine, implicated relatively recently when Minkowski real- Physiology or Chemistry for discoveries that have ized in 1889 that the organ ’ s removal in dogs mim- advanced endocrinology and diabetes are listed in icked diabetes in humans. Table 1.1 . The roots of reproductive endocrinology are Traditionally, endocrinology has centred on spe- equally long. The Bible refers to eunuchs and cialized hormone - secreting organs (Figure 1.2 ), Hippocrates recognized that mumps could result in largely built on the ‘ endocrine postulates ’ of Edward sterility. Oophorectomy in sows and camels was Doisy (Box 1.3 ). While the focus of this textbook used to increase strength and growth in ancient remains with these organs, many tissues display Egypt. The association with technology is also long - appreciable degrees of hormone biosynthesis, and, standing. For instance, it took the microscope in the equally relevant, modulate hormone action. All 17th century for Leeuwenhoek to visualize sperma- aspects are important for a complete appreciation tozoa and later, in the 19th century, for the mam- of endocrinology and its significance. malian ovum to be discovered in the Graafian follicle. The r ole of h ormones During the last 500 years, other endocrine organs and axes have been identified and character- Hormones are synthesized by specialized cells ized. In 1564, Bartolommeo Eustacio noted the (Table 1.2 ), which may exist as distinct endocrine presence of the adrenal glands. Almost 300 years glands or be located as single cells within other later (1855), Thomas Addison, one of the forefa- organs, such as the gastrointestinal tract. The chap- thers of clinical endocrinology, described the con- ters in Part 2 are largely organized on this anatomi- sequences of their inadequacy. Catecholamines were cal basis. identified at the turn of the 19th century, in parallel Endocrinology is defined by the secretion of with Oliver and Schaffer ’ s discovery that these hormones into the bloodstream; however, autocrine adrenomedullary substances raise blood pressure. or paracrine actions are also important, often mod- This followed shortly after the clinical features of ulating the hormone - secreting cell type. Hormones myxoedema were linked to the thyroid gland, when, act by binding to specific receptors, either on the in 1891, physicians in Newcastle treated hypothy- surface of or inside the target cell, to initiate a roidism with sheep thyroid extract. This was an cascade of intracellular reactions, which frequently important landmark, but long after the ancient amplifies the original stimulus and generates a final Chinese recognized that seaweed, as a source of response. These responses are altered in hormone iodine, held valuable properties in treating ‘ goitre ’ , deficiency and excess: for instance, GH deficiency swelling of the thyroid gland. leads to short stature in children, while excess Early clinical endocrinology and diabetes tended causes over - growth (either gigantism or acromegaly; to recognize and describe the features of the endo- Chapter 5 ). 6 / Chapter 1: Overview of endocrinology Box 1.2 Some l andmarks in e ndocrinology over the l ast 100 y ears or so 1905 First use of the term ‘ hormone ’ by Starling in the Croonian Lecture at the Royal College of Physicians 1909 Cushing removed part of the pituitary and saw improvement in acromegaly 1914 Kendall isolated an iodine - containing substance from the thyroid 1921 Banting and Best extracted insulin from islet cells of dog pancreas and used it to lower blood sugar Early 1930s Pitt - Rivers and Harrington determined the structure of the thyroid hormone, thyroxine 1935 – 40 Crystallization of testosterone 1935 – 40 Identification of oestrogen and progesterone 1940s Harris recognized the relationship between the hypothalamus and anterior pituitary in the ‘ portal - vessel chemotransmitter hypothesis ’ 1952 Gross and Pitt - Rivers identified tri - iodothyronine in human serum 1955 The Schally and Guillemin laboratories showed that extracts of hypothalamus stimulated adrenocorticotrophic hormone (ACTH) release 1956 Doniach, Roitt and Campbell associated antithyroid antibodies with some forms of hypothyroidism – the first description of an autoimmune phenomenon 1950s Adams and Purves identified thyroid stimulatory auto- antibodies Gonadectomy and

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