The Endocrine System


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The Endocrine System

  1. 1. The Endocrine System 87 The Endocrine System 1. Many endocrine disorders are the result of problems within the endocrine gland itself. The endocrine system provides long-term regula- Causes of hyposecretion include the following: tion and adjustment of homeostatic mechanisms and a variety of body functions. For example, the • Metabolic factors: Hyposecretion may result endocrine system is responsible for the regulation from a deficiency in some key substrate of fluid and electrolyte balance, cell and tissue needed to synthesize that hormone. For metabolism, growth and development, and repro- example, hypothyroidism can be caused by ductive functions. The endocrine system also inadequate dietary iodine levels or exposure assists the nervous system in responding to stress- to drugs that inhibit iodine transport or ful stimuli. utilization at the thyroid gland. The endocrine system is composed of nine major endocrine glands and several other organs, • Physical damage: Any condition that inter- such as the heart and kidneys, that have other rupts the normal circulatory supply or important functions. The hormones secreted by that physically damages the endocrine these endocrine organs are distributed by the circu- cells in some other way will suppress hor- latory system to target tissues throughout the body. mone production temporarily. If the dam- Each hormone affects a specific set of target tissues age is severe, the condition may be that may differ from that of other hormones. The permanent. Examples of problems that selectivity is based on the presence or absence of may cause temporary or permanent hormone-specific receptors in the cell membrane, hypothyroidism include infection or cytoplasm, or nucleus of the target cells. inflammation of the gland (thyroiditis), Homeostatic regulation of circulating hormone interruption of normal circulation, and levels primarily involves negative feedback control exposure to radiation as part of treatment mechanisms. The feedback loop involves an inter- for cancer of the thyroid or adjacent tis- play between the endocrine organ and its target tis- sues. The thyroid may also be damaged in 1 sues. Release of a particular hormone by an an autoimmune disorder that results in the 0 endocrine gland may occur in response to one of production of antibodies that attack and three different types of stimuli: destroy normal follicle cells. 1. Some hormones are released in response to • Congenital disorders: The individual may be variations in the concentrations of specific sub- unable to produce normal amounts of a stances in the body fluids. Parathyroid hor- particular hormone because (a) the gland mone, for example, is released when calcium itself is too small, (b) the required enzymes levels decline. are abnormal in some way, or (c) the gland 2. Some hormones are released only when the cells lack the receptors normally involved in gland cells receive hormonal instructions from stimulating secretory activity. other endocrine organs. For example, the rate of production and release of T3 and T4 by the 2. Endocrine disorders can also result from prob- thyroid gland is controlled by thyroid stimulat- lems with other endocrine organs involved in ing hormone (TSH) from the anterior pituitary the negative feedback control mechanism. For gland. The secretion of TSH is in turn regulated example: by the release of thyrotropic releasing hormone (TRH) from the hypothalamus. • Secondary hypothyroidism can be caused by inadequate TSH production at the pitu- 3. Some hormones are released in response to itary gland or by inadequate TRH secretion neural stimulation. The release of epinephrine at the hypothalamus. and norepinephrine from the adrenal medulla during sympathetic activation is an example. • Secondary hyperthyroidism can be caused by excessive TRH or TSH production; sec- Endocrine disorders can therefore develop due to ondary hyperthyroidism may develop in abnormalities in (a) the endocrine gland, (b) the individuals with tumors of the pituitary endocrine or neural regulatory mechanisms, or (c) the gland. target tissues. Figure A-33 provides an overview of the major classes of endocrine disorders. In the dis- 3. Endocrine abnormalities can also be caused by cussion that follows, we will use the thyroid gland the presence of abnormal hormonal receptors in as an example because the text introduces major target tissues. In this case the gland and the types of thyroid gland disorders. These primary dis- regulatory mechanisms may be normal, but the orders may result in overproduction (hypersecre- peripheral cells are unable to respond to the cir- tion) or underproduction (hyposecretion of culating hormone. The best example of this type hormones. For example, clinicians may categorize a of abnormality is type 2 diabetes (maturity- thyroid disorder as primary hyperthyroidism or pri- onset, NIDDM), where peripheral cells do not mary hypothyroidism if the problem originates with- respond normally to insulin. (Maturity-onset in the thyroid gland. diabetes is discussed further on p. 92.)
  2. 2. 88 The Body Systems: Clinical and Applied Topics Effects on cardiovascular function Addison’s disease (produces hypotension) Hyperthyroidism (increases heart rate; arrhythmias) Pheochromocytoma (produces hypertension) Primary effects on growth Diabetes mellitus Gigantism Primary effects on Acromegaly fluid and electrolyte balance Pituitary growth failure Addison’s disease ENDOCRINE Hypoaldosteronism Diabetes insipidus DISORDERS Syndrome of inappropriate Primary effects on reproductive function ADH secretion (SIADH) Hyperparathyroidism Hypoparathyroidism Precocious puberty Adrenogenital syndrome Gynecomastia Primary effects on metabolism Glucose metabolism: Addison’s disease Cushing’s disease 1 Diabetes mellitus 0 Metabolic rate abnormalities: Hyperthyroidism Hypothyroidism Cretinism Figure A-33 Disorders of the Endocrine System THE SYMPTOMS OF • Cushing’s disease results from an oversecre- tion of glucocorticoids by the adrenal cortex. As ENDOCRINE DISORDERS the condition progresses there is a shift away Knowledge of the individual endocrine organs and from the normal pattern of fat distribution in their functions makes predictions possible about the body. Adipose tissue accumulates in the the symptoms of specific endocrine disorders. For abdominal area, the lower cervical area (caus- example, thyroid hormones increase basal meta- ing a “humpback”), and in the face, but the bolic rate, body heat production, perspiration, rest- extremities become relatively thin. lessness, and heart rate. An elevated metabolic • Acromegaly results from oversecretion of rate, increased body temperature, weight loss, ner- growth hormone in the adult. In this condition vousness, excessive perspiration, and an increased the facial features become distorted due to or irregular heartbeat are common symptoms of excessive cartilage growth, and the lower jaw hyperthyroidism. On the other hand, a low meta- protrudes, a sign known as prognathism. The bolic rate, decreased body temperature, weight hands and feet also become enlarged. gain, lethargy, dry skin, and a reduced heart rate often accompany hypothyroidism. The symptoms • Adrenogenital syndrome results from the over- associated with over- and under-production of secretion of androgens by the adrenal glands of major hormones are summarized in Table A-19. a female. Hair growth patterns change, and the condition of hirsutism (p. 45) develops. The Diagnosis of Endocrine Disorders • Hypothyroidism due to iodine deficiency pro- The first step in the diagnosis of an endocrine dis- duces a distinctively enlarged thyroid gland, or order is the physical examination. Several disor- goiter. ders produce characteristic physical signs that reflect abnormal hormone activities. Several exam- • Hyperthyroidism can produce protrusion of the ples were introduced in the text: eyes, or exophthalmos.
  3. 3. The Endocrine System 89 Table A-19 Clinical Implications of Endocrine Malfunctions Under- Over- production Principal production Principal Hormone Syndrome Signs & Symptoms Syndrome Signs & Symptoms Growth hormone Pituitary Retarded growth, Gigantism, Excessive growth (GH) growth abnormal fat acromegaly failure distribution, low (pituitary blood glucose dwarfism) hours after a meal Antidiuretic Diabetes Polyuria, dehydration, SIADH (syndrome Increased body hormone (ADH) insipidus thirst of inappropriate weight and ADH secretion) water content Thyroxine (T4), Myxedema, Low metabolic rate and Hyperthyroidism, High metabolic triiodothyronine cretinism body temperature; Graves’ disease rate and body (T3) impaired physical temperature and mental development Parathyroid Hypopara- Muscular weakness, Hyperparathyroidism Neurological, mental, hormone (PTH) thyroidism neurological muscular problems problems, formation due to high blood of dense bones, calcium concen- tetany due to low trations; weak and blood calcium brittle bones concentrations Insulin Diabetes High blood glucose, Excess insulin Low blood glucose mellitus impaired glucose production levels, possibly 1 (type 1) utilization, dependence or administration causing coma and death on lipids for energy; 0 glycosuria, possibly causing coma and death Mineralocorticoids Hypoaldo- Polyuria, low blood Aldosteronism Increased body (MC) steronism volume, high blood weight due to sodium potassium and low and water retention; sodium concentrations low blood potassium concentration Glucocorticoids Addison’s Inability to tolerate Cushing’s disease Excessive breakdown (GC) disease stress, mobilize energy of tissue proteins reserves, or maintain and lipid reserves; normal blood glucose impaired glucose concentrations metabolism Epinephrine (E), None identified Pheochromocytoma High metabolic rate, norepinephrine body temperature, (NE) blood pressure and heart rate Estrogens Hypogonadism Sterility, lack of Adrenogenital Overproduction of (females) secondary sexual syndrome androgens by characteristics innermost adrenal cortex leads to masculinization Menopause Cessation of Precocious Premature sexual ovulation puberty maturation and related behavioral changes Androgens Hypogonadism Sterility, lack of Adrenogenital Abnormal production (males) (male) secondary sexual syndrome of estrogen, some- characteristics (gynecomastia) times due to adrenal or interstitial cell tumors; leads to breast enlargement Precocious Premature sexual puberty maturation and related behavioral changes
  4. 4. 90 The Body Systems: Clinical and Applied Topics These signs are very useful, but many other the individual’s metabolic processes accelerate out signs and symptoms related to endocrine disorders of control. During a thyrotoxic crisis, or “thyroid are less definitive. For example, the condition of storm,” the subject experiences an extremely high polyuria, or increased urine production, may be the fever, rapid heart rate, and the dangerous malfunc- result of hyposecretion of ADH (diabetes insipidus) or tioning of a variety of physiological systems. a form of diabetes mellitus, and a symptom such as hypertension (high blood pressure) can be caused by a variety of cardiovascular or endocrine problems. In Disorders of Parathyroid Function these instances diagnostic decisions are often based EAP p. 325 on blood tests, which can confirm the presence of an When the parathyroid gland secretes inadequate or endocrine disorder by detecting abnormal levels of excessive amounts of parathyroid hormone, calci- circulating hormones, followed by procedures that um concentrations move outside of normal homeo- determine whether the primary cause of the problem static limits. Hypoparathyroidism may develop lies within the endocrine gland, the regulatory mech- after neck surgery, especially a thyroidectomy, if anism(s), or the target tissues. the blood supply to the parathyroid glands is restricted. In other cases the primary cause of the Thyroid Gland Disorders EAP p. 323 condition is uncertain. PTH is extremely costly, and because supplies are very limited, PTH administra- Hypothyroidism typically results from some prob- tion is not used to treat this condition, despite its lem involving the thyroid gland rather than with probable effectiveness. As an alternative, a dietary pituitary production of TSH. In primary hypothy- combination of vitamin D 3 and calcium can be roidism TSH levels are elevated because the pitu- used to elevate body fluid calcium concentrations. itary gland attempts to stimulate thyroid activity, (As noted in Chapter 6 of the text, vitamin D3 stim- but levels of T3 (triiodothyronine) and T4 (tetra- ulates the absorption of calcium ions across the iodothyronine or thyroxine) are depressed. One form 1 of hypothyroidism results from a mutation that lining of the digestive tract.) In hyperparathyroidism, calcium concentra- 0 affects the structure of the G-proteins at TSH recep- tions become abnormally high. Calcium salts in the tors. The structural change reduces the receptors’ skeleton are mobilized, and bones are weakened. sensitivity to TSH and depresses thyroid activity. On X-rays the bones have a light, airy appearance Treatment of chronic hypothyroidism, such as the because the dense calcium salts no longer domi- hypothyroidism that follows radiation exposure, nate the tissue. CNS function is depressed, think- usually involves the administration of synthetic thy- ing slows, memory is impaired, and the individual roid hormones (thyroxine) to maintain normal blood often experiences emotional swings and depres- concentrations. sion. Nausea and vomiting occur, and in severe A goiter is an enlargement of the thyroid cases the patient may become comatose. Muscle gland. The enlargement usually indicates increased function deteriorates, and skeletal muscles become follicular size, despite a decrease in the rate of thy- weak. Other tissues are often affected as calcium roid hormone production. A goiter usually develops salts crystallize in joints, tendons, and the dermis, when the thyroid gland is unable to synthesize and and calcium deposits may produce masses, called release adequate amounts of thyroid hormones. kidney stones, that block filtration and conduction Under continuing TSH stimulation, thyroglobulin passages in the kidney. production accelerates and the thyroid follicles Hyperparathyroidism most commonly results enlarge. One type of goiter occurs if the thyroid from a tumor of the parathyroid gland. Treatment fails to obtain enough iodine to meet its synthetic involves the surgical removal of the overactive tis- requirements. (This condition is now rare in the sue. Fortunately there are four parathyroids, and U.S. due to the use of iodized table salt.) With the secretion of even a portion of one gland can treatment, over time the resting thyroid may return maintain normal calcium concentrations. to its normal size. Hyperthyroidism, also known as thyrotoxico- sis, occurs when thyroid hormones are produced in Disorders of the Adrenal Cortex excessive quantities. In Graves’ disease excessive thyroid activity leads to goiter and the symptoms of EAP p. 326 hyperthyroidism. Protrusion of the eyes, or exoph- Clinical problems related to the adrenal gland vary thalmos (eks-ahf-THAL-m|s), may also appear, for depending on which groups of adrenal cells become unknown reasons. Graves’ disease has a genetic involved. The conditions may result from changes autoimmune basis and affects many more women in the functional capabilities of the adrenal cells than men. Treatment may involve the use of (primary conditions) or disorders affecting the reg- antithyroid drugs, the surgical removal of portions ulatory mechanisms (secondary conditions). In of the glandular mass, or destruction of part of the hypoaldosteronism, adrenal cells fail to produce gland by exposure to radioactive iodine. enough aldosterone, usually either as an early sign Hyperthyroidism may also result from inflam- of adrenal insufficiency or because the kidneys are mation or, rarely, thyroid tumors. In extreme cases not releasing adequate amounts of renin. Low
  5. 5. The Endocrine System 91 aldosterone levels lead to excessive losses of water origin). Microsurgery can be performed through the and sodium ions at the kidneys, and the water loss sphenoid bone to remove the adenomatous tissue. in turn leads to low blood volume and a fall in Some oncology centers use pituitary radiation rather blood pressure. The resulting changes in electrolyte than surgery. Several drug therapies act at the hypo- concentrations, including hyperkalemia (high thalamus, rather than the pituitary gland, to prevent extracellular K + levels) affect transmembrane the release of corticotropin-releasing hormone (CRH). potentials, eventually causing dysfunctions in Alternatively, the adrenal glands can be surgically neural and muscular tissues. removed (a bilateral adrenalectomy), but further Hypersecretion of aldosterone results in the complications can arise as the adenoma enlarges. condition of aldosteronism, or hyperaldosteronism. The chronic administration of large doses of Under continued aldosterone stimulation, the kid- steroids is required in some cases to treat severe neys retain sodium ions in exchange for potassium asthma and some cancers and to prevent organ ions that are lost in the urine. Hypertension and transplant rejection. Prolonged use of such large hypokalemia occur as extracellular potassium lev- doses can produce symptoms similar to those of els decline. Aldosteronism increases the concentra- Cushing’s disease, but such treatment is usually tion gradient for potassium ions across cell avoided. membranes. This leads to an acceleration in the rate of potassium diffusion out of the cells and into the interstitial fluids. The reduction in intracellular Disorders of the Adrenal Medullae and extracellular potassium levels eventually inter- EAP p. 328 feres with the function of excitable membranes, The overproduction of epinephrine by the adrenal especially cardiac muscle cells and neurons, and medullae may reflect chronic sympathetic activation. kidney cells. A pheochromocytoma (fƒ-|-kr|-m|-sª-T«-muh) is a Addison’s disease may result from inadequate tumor that produces epinephrine and norepineph- stimulation of the adrenal cells by ACTH or from their inability to synthesize the necessary hor- rine in massive quantities. The tumor usually devel- 1 ops within the adrenal medullae, but it may also mones usually due to autoimmune problems or involve other sympathetic ganglia. The most danger- 0 infection. Affected individuals become weak and ous symptoms are rapid and irregular heartbeat and lose weight, due to a combination of appetite loss, high blood pressure; other symptoms include uneasi- hypotension, and hypovolemia. They cannot ade- ness, sweating, blurred vision, and headaches. This quately mobilize energy reserves, and their blood condition is rare, and surgical removal of the tumor glucose concentrations fall sharply within hours is the most effective treatment. after a meal. Stresses cannot be tolerated, and a minor infection or injury may lead to a sharp and fatal decline in blood pressure. A particularly inter- Light and Behavior EAP p. 328 esting symptom is the increased melanin pigmen- tation in the skin. The ACTH molecule and the Exposure to sunlight can do more than stimulate a MSH molecule are similar in structure, and at high tan or promote the formation of vitamin D3. There concentrations ACTH stimulates the MSH recep- is evidence that daily light-dark cycles have wide- tors on melanocytes. President John F. Kennedy spread effects on the central nervous system, with suffered from this disorder. melatonin playing a key role. Several studies have Cushing’s disease results from overproduction indicated that residents of temperate and higher of glucocorticoids. The symptoms resemble those of latitudes in the Northern Hemisphere undergo sea- a protracted and exaggerated response to stress. sonal changes in mood and activity patterns. These (The stress response is discussed in the text on p. people feel most energetic from June through 334.) Glucose metabolism is suppressed, lipid September, whereas the period of December reserves are mobilized, and peripheral proteins are through March finds them with relatively low spir- broken down. Lipids and amino acids are mobilized its. (The situation in the Southern Hemisphere, in excess of the existing demand. The energy where the winter and summer seasons are reserves are shuffled around, and the distribution reversed, is just the opposite.) The degree of sea- of body fat changes. Adipose tissues in the cheeks sonal variation differs from individual to individual; and around the base of the neck become enlarged some people are affected so severely that they seek at the expense of other areas, producing a “moon- medical attention. The observed symptoms have faced” appearance. The demand for amino acids recently been termed seasonal affective disorder, falls most heavily on the skeletal muscles, which or SAD. Individuals with SAD experience depres- respond by breaking down their contractile pro- sion and lethargy and find it difficult to concen- teins. This response reduces muscular power and trate. Often they sleep for long periods, perhaps 10 endurance. The skin becomes thin and may devel- hours or more per day. They may also go on eating op stria, or stretch marks. binges and have a craving for carbohydrates. If the primary cause is ACTH oversecretion at the Melatonin secretion appears to be regulated by anterior pituitary gland, the most common source is sunlight exposure, not simply by light exposure. a pituitary adenoma (a benign tumor of glandular Normal interior lights are apparently not strong
  6. 6. 92 The Body Systems: Clinical and Applied Topics enough or do not release the right mixture of light state, stress, and other factors that are hard to wavelengths to depress melatonin production. assess or predict. It is therefore difficult to main- Because many people spend very little time out- tain stable and normal blood glucose levels over doors in the winter, melatonin production increases long periods of time. during that season, and the depression, lethargy, Type 1 diabetes most often appears in individu- and concentration problems appear to be linked to als under 40 years of age. Because it frequently elevated melatonin levels in the blood. Comparable appears in childhood, it has been called juvenile- symptoms can be produced in a normal experimen- onset diabetes. Most people with this type of dia- tal subject by an injection of melatonin. betes (roughly 80 percent) have circulating Many SAD patients may be successfully treated antibodies that target the surfaces of beta cells. by exposure to sun lamps that produce full-spectrum The disease may therefore be an example of an light. Experiments are under way to define exactly autoimmune disorder, a condition that results when how intense the light must be and determine the the immune system attacks normal body cells. minimal effective time of exposure. (Autoimmune disorders are discussed in the text, p. 446.) Consequently, attempts have been made to prevent the appearance of type 1 diabetes with aza- Diabetes Mellitus EAP p. 330 thioprine (Imuran®), a drug that suppresses the immune system. This procedure is somewhat dan- There are two major types of diabetes mellitus: gerous, however, because compromising immune insulin-dependent (type 1) diabetes and non- function increases the risk of acquiring serious insulin-dependent (type 2) diabetes. infections or developing cancer. The primary cause of insulin-dependent dia- Non-insulin-dependent diabetes mellitus betes mellitus (IDDM), or type 1 diabetes, is (NIDDM), or type 2 diabetes, typically affects obese inadequate insulin production by the beta cells of individuals over 40 years of age. Because of the age the pancreatic islets. In this condition insulin pro- factor, this condition was called maturity-onset 1 duction declines due to a drop in the number of diabetes. Unfortunately, with increased childhood beta cells. Glucose transport in most cells cannot 0 occur in the absence of insulin. When insulin con- obesity more teenagers are developing Type 2 dia- betes mellitus. Insulin levels are normal or elevat- centrations decline, cells can no longer absorb glu- ed, but peripheral tissues no longer respond cose from their surroundings. Under these normally, often due to a reduction in the number of conditions peripheral tissues remain glucose- insulin receptors. Treatment consists of weight loss starved despite the presence of adequate or even and dietary restrictions that may elevate insulin excessive amounts of glucose in the circulation. production and tissue response. The drug met- After a meal rich in glucose, blood concentra- formin (Glucophage®) lowers blood glucose concen- tions may become so elevated that the kidney cells trations, primarily by reducing glucose synthesis cannot reclaim all of the glucose molecules enter- and release at the liver. The use of metformin in ing the urine. The high urinary concentration of combination with other drugs that affect glucose glucose limits the ability of the kidney to conserve metabolism promises to improve the quality of life water, so the individual urinates frequently and for many type 2 diabetes patients. may become dehydrated. The chronic dehydration Up to 6 percent of the U.S. population has dia- leads to disturbances of neural function (blurred betes mellitus, over 90% with the type 2 form. vision, tingling sensations, disorientation, fatigue) Diagnosis is based on high fasting blood glucose, and muscle weakness. symptoms of diabetes plus a high random blood Despite the high blood concentrations, glucose glucose, and an inability to reduce elevated blood cannot enter endocrine tissues, and the endocrine glucose levels 2 hours after drinking a fixed system responds as if glucose were in short supply. amount of glucose. These criteria have largely Alpha cells release glucagon, and glucocorticoid replaced the 6 hour glucose tolerance test that production accelerates. Peripheral tissues then involved drinking glucose and testing the blood breakdown lipids and proteins to obtain energy. glucose level multiple times over 4 to 6 hours. The breakdown of large numbers of fatty acids gen- Probably because glucose levels cannot be stabi- erates molecules called ketone bodies. The accu- lized adequately, even with treatment, patients mulation of large numbers of these acids can cause with long-term diabetes mellitus often develop a dangerous reduction in blood pH. This condition, chronic medical problems. In general, these prob- called ketoacidosis, commonly triggers vomiting. In lems are related to cardiovascular abnormalities. severe cases, it can precede a fatal coma. The most common examples include the following: Long-term treatment involves a combination of dietary control, monitoring blood glucose levels up 1. Vascular changes at the retina, including pro- to several times a day, and administration of liferation of capillaries and hemorrhaging, often insulin, either by periodic injection or through cause disturbances of vision. This condition is more continual subcutaneous delivery with an called diabetic retinopathy. insulin pump. The treatment is complicated by the fact that tissue glucose demands cycle up and 2. Changes occur in the clarity of the lens, pro- down, depending on physical activity, emotional ducing cataracts.
  7. 7. The Endocrine System 93 3. Small hemorrhages and inflammation at the bodybuilders, the proportion using steroids in this kidneys cause degenerative changes that can country may be as high as 80 percent. lead to kidney failure. This condition is called Black market sales of anabolic steroids proba- diabetic nephropathy. bly exceed $100 million annually. The compounds 4. A variety of neural problems appear, including are administered orally or by injection, typically in nerve palsies, paresthesias and pain, and auto- doses 10–1000 times higher than those normally nomic dysfunction. These disorders, collectively prescribed in medical treatment. (Legitimate rea- termed diabetic neuropathy, are probably sons for androgen use include the generalized related to disturbances in the blood supply to wasting and debilitation of cancer or AIDS and neural tissues, since neurons do not require treatment of hypogonadism.) insulin to absorb and utilize glucose. One supposed justification for this practice has been the unfounded opinion that compounds 5. Degenerative changes in cardiac circulation manufactured in the body are not only safe but can lead to early heart attacks. For a given age “good for you.” In reality the administration of nat- group, heart attacks are 3–5 times more likely ural or synthetic androgens in abnormal amounts in diabetic individuals. carries unacceptable health risks. Androgens 6. Other peripheral changes in the vascular sys- affect many tissues in a variety of ways. Known tem can disrupt normal circulation to the complications include (1) premature epiphyseal extremities. For example, a reduction in blood closure; (2) various liver problems (including jaun- flow to the feet can lead to tissue death, ulcera- dice and hepatic tumors); (3) prostate enlargement tion, infection, and loss of toes or a major por- and urinary tract obstruction; (4) testicular atro- tion of one or both feet. phy and infertility; and, (5) severe acne. A link to heart attacks, impaired cardiac function, and strokes has also been suggested. Moreover, the Endocrinology and Athletic normal regulation of androgen production involves a feedback mechanism comparable to that 1 Performance EAP p. 332 described for adrenal steroids earlier in this chap- 0 One of the first endocrinological “mass experi- ter. A releasing hormone stimulates the produc- ments” on humans occurred early in World War II, tion of LH, and LH in turn stimulates the secretion when the German government administered testos- of testosterone and other androgens by the inter- terone to Nazi SS officers in an attempt to make stitial cells of the testes. The circulating androgens them more aggressive. (There is no evidence that then inhibit the production of both the releasing the experiment succeeded.) Nowadays, such prac- hormone and LH, as indicated in Figure 10-7a, p. tices are universally deplored in all civilized soci- 320. Thus when synthetic androgens are adminis- eties, and medical research involving humans is tered in high doses, they can (1) suppress the nor- generally subject to tight ethical constraints and mal production of testosterone, and (2) depress the meticulous scientific scrutiny. Yet a clandestine, manufacture of the associated releasing hormone unscientific, and potentially quite dangerous pro- by the hypothalamus. This suppression may be gram of “experimentation” with hormones is today permanent. being pursued by athletes in many countries. The use of androgenic “bulking agents” by Despite being banned by the International Olympic female bodybuilders may not only add muscle Committee, the United States Olympic Committee, mass but alter muscular proportions and sec- the NCAA, and the NFL, and condemned by the ondary sexual characteristics. For example, American Medical Association and the American women taking steroids can develop irregular men- College of Sports Medicine, a significant number of strual periods and changes in body-hair distribu- amateur and professional athletes continue to use tion (including baldness). Finally, androgen abuse hormones to improve their performance at the risk may cause a generalized depression of the immune of damaging their health. Although synthetic forms system. of testosterone are used most often, young athletes may use any combination of testosterone, growth EPO Abuse hormone, and a variety of synthetic hormones. Because it is now being synthesized using recombi- nant DNA techniques, erythropoietin, or EPO, is Androgen Abuse readily available. Athletes engaged in endurance The use of androgens, or “anabolic steroids,” has sports, such as cycling or marathon running, may become common with many athletes, both amateur use it to boost the number of oxygen-carrying red and professional. The goal of steroid use is to blood cells in circulation. Although this improves increase muscle mass, endurance, and “competi- the oxygen content of the blood, it also makes the tive spirit.” It has been suggested that as many as blood more dense, and the heart must work harder 30 percent of college and professional athletes and to push it around the circulatory system. Between 10–20 percent of male high school athletes may be 1991 and 1994, the deaths of 18 young, otherwise using anabolic steroids (with or without growth healthy European cyclists were attributed to heart hormone) to improve their performance. Among failure related to EPO abuse.
  8. 8. 94 The Body Systems: Clinical and Applied Topics GHB and Clenbuterol Francisco alone. Symptoms experienced included confusion, hallucination, seizures, and coma at Androgens and EPO are known hormones with rea- doses from 0.25 teaspoons to 4 tablespoons. sonably well understood effects. Because drug test- Clenbuterol abuse is reportedly widespread, ing is now widespread in amateur and professional although exact numbers are difficult to obtain. sports, people interested in “getting an edge” are Clenbuterol, sometimes used to treat asthma, experimenting with other drugs whose long-term mimics epinephrine by increasing the diameter of and short-term effects are difficult to predict. Two the respiratory passageways and accelerating blood examples are the recent use of GHB and clen- flow through active skeletal muscles. Although it is buterol by amateur athletes. also rumored to have anabolic properties, there is Gamma-hydroxybutyrate, or GHB, was tested no evidence to support this. Heavy usage can for use as an anaesthetic 30 years ago and rejected cause severe headaches, tremors, insomnia, and in part because it was linked to epileptic seizures. potentially dangerous abnormal heartbeats. During In 1990 this drug appeared in health-food stores, the 1992 Olympics in Barcelona, Spain, two where it was sold as an anabolic agent and diet American athletes were disqualified because they aid. During a 5-month period in 1990, 16 cases of tested positive for this drug. severe reaction to GHB were treated in San CRITICAL-THINKING QUESTIONS 5-3. Bill develops a benign tumor of the parathyroid glands that causes the level of 5-1. Pheochromocytomas are tumors of the parathyroid hormone in his blood to be higher than adrenal medullae that cause hypersecretion of the normal. Which of the following would you expect to hormones produced by this region of the adrenal occur as a result of this condition? gland. What symptoms would you associate with a person who suffers from this condition? a. decreases in the blood levels of calcium a. hypertension b. convulsions b. sweating c. decreased muscle strength c. nervousness d. increased bone density d. elevated metabolic rate e. all of the above e. all of the above 5-4. Sixteen-year-old John is a promising ath- lete who is below the average height for his age. He 5-2. Fifty-year-old Barbara B. reports to the wants to play football in college but is convinced emergency room with heart palpitations (rapid, that he needs to be taller and stronger in order to irregular heart beat). EKG recording shows atrial accomplish his dream. He persuades his parents to fibrillation. Barbara’s medical history includes visit a doctor and inquire about GH treatments. If recent weight loss of 10 pounds and complaints of you were his physician, what would you tell him increased irritability and nervousness within the about the potential risks and benefits of such last month. Some of Barbara’s abnormal diagnostic treatments? and lab test results are as follows: 5-5. Angie is diagnosed with abnormal periph- Radioactive iodine uptake test (RAIU) at eral vision. After performing several tests, her 2 hours: 20% absorption (normal: 1-13%) physician decides to remove a tumor of her pitu- Serum thyroxine (T4) test: 13 ng/dl itary gland. Shortly after the surgery, her eyesight Serum triiodothyronine (T3) test: 210 ng/dl returns to normal. What was the apparent cause of Angie’s problem? Serum TSH: <0.1 5-6. A patient is suffering from secondary What is the probable diagnosis? hypothyroidism. Assuming you had available all a. hypothyroidism the modern testing materials, how could you deter- mine if the problem was due to hypothalamic or b. hyperthyroidism pituitary dysfunction? c. myxedema d. goiter
  9. 9. The Endocrine System 95 NOTES