Medical discipline dealing with regulation of body functions by hormones and other biochemicals and treatment of endocrine system imbalances. In 1841 Friedrich Gustav Henle first recognized “ductless glands,” which secrete products directly into the bloodstream. The field was essentially established in the early 20th century, when Ernest H. Starling, who introduced the term hormone, proposed that chemical and nervous regulation of physiological processes were linked. Endocrine therapy is based on replacing deficient hormones with purified extracts. Nuclear technology has led to new treatments; use of radioactive iodine for hyperthyroidism greatly reduced the need for thyroid gland surgery. The detection of minute amounts of hormone with radioimmunoassays (see radiology) permits early diagnosis and treatment of endocrine disorders.
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All multicellular organisms need coordinating systems to regulate and integrate the function of cells. Two mechanisms perform this function in higher animals: the nervous system and the endocrine system. The endocrine system acts through the release (generally into the blood) of chemical agents and is vital to the proper development and function of organisms. As Hadley notes, the integration of developmental events such as proliferation, growth, and differentiation (including histogenesis and organogenesis) and the coordination of metabolism, respiration, excretion, movement, reproduction, and sensory perception depend on chemical cues, substances synthesised and secreted by specialised cells.
Endocrinology is concerned with the study of the biosynthesis, storage, chemistry, and physiological function of hormones and with the cells of the endocrine glands and tissues that secrete them.
The endocrine system consists of several glands, in different parts of the body, that secrete hormones directly into the blood rather ok than into a duct system. Hormones have many different functions and modes of action; one hormone may have several effects on different target organs, and, conversely, one target organ may be affected by more than one hormone.
In the original 1902 definition by Bayliss and Starling (see below), they specified that, to be classified as a hormone, a chemical must be produced by an organ, be released (in small amounts) into the blood, and be transported by the blood to a distant organ to exert its specific function. This definition holds for most "classical" hormones, but there are also paracrine mechanisms (chemical communication between cells within a tissue or organ), autocrine signals (a chemical that acts on the same cell), and intracrine signals (a chemical that acts within the same cell). A neuroendocrine signal is a "classical" hormone that is released into the blood by a neurosecretory neuron (see article on Neuroendocrinology).
Hormones act by binding to specific receptors in the target organ. As Baulieu notes, a receptor has at least two basic constituents:
Between these is a "transduction mechanism" in which hormone binding induces allosteric modification that, in turn, produces the appropriate response.
Griffin and Ojeda identify three different classes of hormone based on their chemical composition:
Although most of the relevant tissues and endocrine glands had been identified by early anatomists, a more humoral approach to understanding biological function and disease was favoured by classical thinkers such as Aristotle, Hippocrates, Lucretius, Celsus, and Galen, according to Freeman et al, and these theories held sway until the advent of germ theory, physiology, and organ basis of pathology in the 19th century.
In medieval Persia, Avicenna (980-1037) provided a detailed account on diabetes mellitus in The Canon of Medicine (c. 1025), "describing the abnormal appetite and the collapse of sexual functions and he documented the sweet taste of diabetic urine." Like Aretaeus of Cappadocia before him, Avicenna recognized a primary and secondary diabetes. He also described diabetic gangrene, and treated diabetes using a mixture of lupine, trigonella (fenugreek), and zedoary seed, which produces a considerable reduction in the excretion of sugar, a treatment which is still prescribed in modern times. Avicenna also "described diabetes insipidus very precisely for the first time", though it was later Johann Peter Frank (1745-1821) who first differentiated between diabetes mellitus and diabetes insipidus.
In the 12th century, al-Jurjani, another Persian physician, provided the first description of Graves' disease after noting the association of goitre and exophthalmos in his Thesaurus of the Shah of Khwarazm, the major medical dictionary of its time. Al-Jurjani also established an association between goitre and palpitation. The disease was later named after Irish doctor Robert James Graves, who described a case of goiter with exophthalmos in 1835. The German Karl Adolph von Basedow also independently reported the same constellation of symptoms in 1840, while earlier reports of the disease were also published by the Italians Giuseppe Flajani and Antonio Giuseppe Testa, in 1802 and 1810 respectively, and by the English physician Caleb Hillier Parry (a friend of Edward Jenner) in the late 18th century.
In 1902 Bayliss and Starling performed an experiment in which they observed that acid instilled into the duodenum caused the pancreas to begin secretion, even after they had removed all nervous connections between the two. The same response could be produced by injecting extract of jejunum mucosa into jugular vein, showing that some factor in the mucosa was responsible. They named this substance "secretin" and coined the term hormone for chemicals that act in this way.
Von Mering and Minkowski made the observation in 1889 that removing the pancreas surgically led to an increase in blood sugar, followed by a coma and eventual death—symptoms of diabetes mellitus. In 1922, Banting and Best realized that homogenizing the pancreas and injecting the derived extract reversed this condition. The hormone responsible, insulin, was not discovered until Frederick Sanger sequenced it in 1953.
Neurohormones were first identified by Otto Loewi in 1921. He incubated a frog's heart (innervated with its vagus nerve attached) in a saline bath, and left in the solution for some time. The solution was then used to bathe a non-innervated second heart. If the vagus nerve on the first heart was stimulated, negative inotropic (beat amplitude) and chronotropic (beat rate) activity were seen in both hearts. This did not occur in either heart if the vagus nerve was stimulated. The vagus nerve was adding something to the saline solution. The effect could be blocked using atropine, a known inhibitor to heart vagal nerve stimulation. Clearly, something was being secreted by the vagus nerve and affecting the heart. The "vagusstuff" (as Loewi called it) causing the myotropic effects was later identified to be acetylcholine and norepinephrine. Loewi won the Nobel Prize for his discovery.
Recent work in endocrinology focuses on the molecular mechanisms responsible for triggering the effects of hormones. The first example of such work being done was in 1962 by Earl Sutherland. Sutherland investigated whether hormones enter cells to evoke action, or stayed outside of cells. He studied norepinephrine, which acts on the liver to convert glycogen into glucose via the activation of the phosphorylase enzyme. He homogenized the liver into a membrane fraction and soluble fraction (phosphorylase is soluble), added norepinephrine to the membrane fraction, extracted its soluble products, and added them to the first soluble fraction. Phosphorylase activated, indicating that norepinephrine's target receptor was on the cell membrane, not located intracellularly. He later identified the compound as cyclic AMP (cAMP) and with his discovery created the concept of second-messenger-mediated pathways. He, like Loewi, won the Nobel Prize for his groundbreaking work in endocrinology.
The diagnosis and treatment of endocrine diseases are guided by laboratory tests to a greater extent than for most specialties. Many diseases are investigated through excitation/stimulation or inhibition/suppression testing. This might involve injection with a stimulating agent to test the function of an endocrine organ. Blood is then sampled to assess the changes of the relevant hormones or metabolites. An endocrinologist needs extensive knowledge of clinical chemistry and biochemistry to understand the uses and limitations of the investigations.
A second important aspect of the practice of endocrinology is distinguishing human variation from disease. Atypical patterns of physical development and abnormal test results must be assessed as indicative of disease or not. Diagnostic imaging of endocrine organs may reveal incidental findings called incidentalomas, which may or may not represent disease.
Endocrinology involves caring for the person as well as the disease. Most endocrine disorders are chronic diseases that need life-long care. Some of the most common endocrine diseases include diabetes mellitus, hypothyroidism and the metabolic syndrome. Care of diabetes, obesity and other chronic diseases necessitates understanding the patient at the personal and social level as well as the molecular, and the physician–patient relationship can be an important therapeutic process.
In the United Kingdom, the Society for Endocrinology and the British Society for Paediatric Endocrinology and Diabetes are the main professional organisations. The European Society for Paediatric Endocrinology is the largest international professional association dedicated solely to paediatric endocrinology. There are numerous similar associations around the world.
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