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Doris Gorka Bartuska, M.D., and Joan A. Lit, M.D.

The endocrine system acts as a control mechanism for the entire body. Complex and finely tuned, it coordinates the body's activities and its responses to changes in the environment, both internal and external. The endocrine system affects height, weight, metabolism, growth, sexual development, menstruation, hair and bone growth, fertility, pregnancy, and breast milk production, as well as some aspects of personality and behavior.

The endocrine system (Figure 30.1) consists of glands that work interdependently: the two adrenal glands, located on the top of each kidney; the pancreas, found in the abdominal cavity behind the stomach; the parathyroid and thyroid, located at the base of the neck; the pituitary, located at the base of the brain; and the ovaries and testes, the female and male sex glands (see Chapter 15).

The endocrine glands produce hormones, chemicals released into the bloodstream that regulate the activity of various organs, tissues, and body functions. (Other organs and systems, such as the kidneys and the gastrointestinal system, also produce hormones, which affect the body; see Chapters 32 and 33.) Each gland produces different hormones that are targeted to a particular area of the body. The endocrine glands work in tandem with the organ, efficiently controlling the ebb and flow of hormones so that the body's glandular activity remains constant, much the way that a thermostat turns off a heater when the temperature reaches the appropriate level. Occasionally, an endocrine gland may produce too much or too little of a hormone and upset the balance.

When the delicate hormonal balance that the endocrine system controls is maintained, your body efficiently performs many vital functions. Because the endocrine system is so complex and carefully calibrated, however, a variety of problems, both great and small, can result if it malfunctions. Women experience endocrine system abnormalities much more commonly than men, including thyroid diseases and osteoporosis, and must therefore be more alert to the prevention, early diagnosis, and appropriate treatment of this type of disorder.

Some endocrine disorders are related to diet, so the single most effective preventive measure a woman can take is to eat nutritious, healthy meals. Calcium intake is especially important, as a lack of sufficient dietary calcium -- the mineral that gives bones their strength and density -- and a low estrogen level are the most common causes of osteoporosis. Osteoporosis, the loss of bone density, is found in one in every four older women in the United States today. Sufficient calcium intake throughout your life is, therefore, essential.

Another diet-related endocrine disorder is goiter, or enlargement of the thyroid, which can result from lack of iodine in the diet. After the introduction of iodized table salt, however, goiter became uncommon in the United States.

Keeping your body at a healthy weight will greatly diminish your risk of developing type II diabetes mellitus, the most common endocrine disorder in the United States. Diabetes affects almost 10 million people, about half of them women, and type II diabetes accounts for more than 85 percent of all cases. Obesity is believed to increase the body's resistance to the action of insulin , the hormone that stimulates cells and tissues to use the energy produced by the food we eat. Maintaining a healthy weight is vital to preventing and controlling this condition.

Knowing your family medical history is also important. Among the familial endocrine disorders are diabetes and hypothyroidism. Some genetically linked disorders involve more than one gland. If one member of the family has hypothyroidism, for instance, then others may be at risk for other endocrine disorders (polyglandular autoimmune diseases). Although you cannot change your genes, recognizing that you are at risk, taking preventive measures, and seeking early diagnosis and treatment can greatly limit the effects of the condition.

If you are at risk for developing an endocrine disorder, or are currently suffering from one, you may be referred to an endocrinologist. An endocrinologist is a specialist in internal medicine, with additional training in endocrinology, diabetes, and metabolism.

Problems and Treatments In the following pages, we discuss the glands and hormones of the endocrine system, as well as the problems that result when these glands malfunction.

The Adrenal Glands

The two adrenal glands are each located on top of a kidney. About the size of the end section of your thumb, each gland consists of two basic parts. The central portion, or medulla, is made up of cells that secrete hormones called catecholamines , the most important of which is adrenaline, also called epinephrine. The outer layer, or cortex, surrounding the medulla is responsible for producing several groups of steroid hormones, including glucocorticoids , mineralocorticoids , and the sex steroids.

The cortex portion of the adrenal gland is controlled by a pituitary gland hormone called adrenocorticotropin or ACTH. ACTH stimulates the conversion of cholesterol to cortisol .

Congenital Adrenal Hyperplasia

This condition occurs when there is a blockage in the process that converts cholesterol to cortisol . The pituitary gland, sensing the low cortisol level caused by the blockage, then produces more of the hormone ACTH to stimulate the adrenal glands so they can produce a normal amount of cortisol. But the increased stimulation causes an excess of other hormones, including androstenedione, DHEA, and DHEA-S, which are androgen, or male, hormones.

Most forms of congenital hyperplasia are discovered in infancy or in childhood because of the symptoms that result from low cortisol levels or high androgen levels. If your blockage is only partial and the hormone levels are normal or only slightly elevated, you may not have problems in childhood.

Symptoms : Growth of hair in areas that are typically associated with males, including the upper lip, chin, breast bone, and below the navel. Acne is common. Irregular menstruation and infertility may occur.

Diagnosis : After a medical history and physical examination, diagnosis is made through blood studies, specifically tests of testosterone, androstenedione, LH and FSH, DHEA-S, and 17-hydroxyprogesterone levels. A cosyntropin stimulation test may confirm the diagnosis.

Treatment : Treatment depends on the severity of the hormonal disturbance as well as the symptoms. If your symptoms are not severe and infertility is not a problem, then no treatment may be necessary. If the symptoms are severe or if conceiving a child is an issue, treatment would include small oral doses of steroid hormones such as hydrocortisone, prednisone, or dexamethasone. By ingesting the hormones rather than stimulating the adrenal glands to produce cortisol, fewer androgens will accumulate and symptoms may improve. When congenital adrenal hyperplasia is diagnosed in infancy or childhood, lifelong treatment with supplements to replace missing hormones is necessary.

Addison's Disease

Also known as adrenocortical insufficiency, this condition occurs when the adrenal gland stops producing the steroid-based hormones, especially cortisol.

Adrenal insufficiency is often considered an autoimmune disease as it most commonly occurs as a result of the body reacting to the adrenal gland as foreign matter and producing antibodies to attack and destroy it. The adrenal gland can be attacked independently in this way or in association with other auto- immune disorders such as Graves' disease, and Hashimoto's thyroiditis , rheumatoid arthritis, and pernicious anemia, to name a few. The gland can also be destroyed by an infection, such as tuberculosis. The secretion of adrenal hormones could also be blocked if the gland is affected by pituitary injury, surgery, radiation treatment, or bleeding into the pituitary gland. In addition, symptoms of adrenal insufficiency can occur if a glucocorticoid steroid hormone medication, such as prednisone, is administered for a long period of time in high doses and is then stopped abruptly.

Symptoms : The physical examination may reveal low blood pressure, darkening of the skin, weakness and lethargy, and abdominal pains. The pain may be accompanied by nausea, indigestion, diarrhea, and vomiting. Laboratory evaluation may discover low sodium and high potassium levels in the blood.

Diagnosis : The symptoms of Addison's disease usually develop slowly over a period of months. Sometimes the disorder appears suddenly. For a diagnosis, your physician will conduct a series of tests, including a cosyntropin stimulation test. This test, which measures adrenal gland function, consists of two separate tests. The first measures hormone levels as they normally occur in the bloodstream; the second -- taken 30 to 60 minutes after an injection of an artificial adrenal gland stimulator called cosyntropin -- establishes whether the adrenal gland is functioning normally. Sometimes the test is not fully informative and a longer test, requiring a 48-hour continuous infusion of cosyntropin, is required. The longer test is also indicated if a pituitary disorder is suspected.

Treatment : If you suffer from an adrenal insufficiency, you will have to take an oral replacement of the deficient hormones, usually synthetic hormones such as hydrocortisone or prednisone. If your blood pressure or sodium levels drop, a second drug, fludrocortisone (Florinef), is necessary as well. These medications are vital to your continued health and well- being, and you will have to take them on a regular basis to avoid acute adrenal failure. Acute adrenal failure includes dehydration from severe diarrhea and vomiting, shock, and loss of consciousness.

Cushing's Syndrome

Cushing's syndrome, also known as adrenocortical excess, is the opposite of Addison's disease. This disorder results from excess cortisol or other glucocorticoid hormone levels in the body, which leads to breakdown of protein and the depositing of fat in the tissues. Elevation of other hormones, particularly androgens, may accompany the increase in the cortisol levels.

Adrenocortical excess has a number of different causes: The adrenal gland can produce too much cortisol because of an adrenal-stimulating tumor in the pituitary gland or the lung. The adrenal gland can develop benign tumors called adrenal adenomas, which can produce the cortisol. Adrenal carcinomas can also cause the syndrome. Finally, the extended use of medications that contain glucocorticoid hormones, including cortisone, prednisone, and dexamethasone -- commonly used in the treatment of asthma, rheumatoid arthritis, and systemic lupus erythematosus -- can also result in Cushing's syndrome.

Symptoms : The most common symptom is unexplained weight gain, especially in the abdomen, above the collar bone, or behind the neck. The face may appear rounded (Figure 30.2), and the complexion is typically ruddy. Increased facial hair may also develop. There may be wide, dark purple stripes (striae) on the abdomen, buttocks, or near the armpits. Because of the breakdown of muscle tissue, you may feel weakness, especially when getting out of a chair or climbing steps. Thinning of the skin may result in easy bruising and poor wound healing. Skin often darkens, menstrual periods may change, and the sexual drive may decrease.

Diagnosis : A medical history and a physical examination are often enough to raise the question of Cushing's syndrome. A thorough history will reveal whether medications might be the cause. Tests must be done to confirm elevated cortisol levels under normal conditions and after medical manipulation to suppress the production of this hormone. One test is the dexamethasone suppression test : A dose of dexamethasone is administered at 11:00 p.m. to try to turn off the adrenal gland's production of cortisol. Blood cortisol levels are measured at 8:00 a.m. A series of urine specimens is then collected over a 24-hour period. The first collection is considered the baseline and reflects the amount of cortisol eliminated in the urine over a one-day period (the more cortisol present in the blood, the more that will be present in the urine). The next step is to try to suppress the body's cortisol production with a small amount of another glucocorticoid hormone called dexamethasone, taken every six hours for two days. Urine is collected only on the second day. The dose of dexamethasone is increased and the process is repeated. Some doctors prefer to do the suppression testing by giving the medication and then measuring the levels of cortisol in the blood. The information gathered from the test helps the doctors decide among different causes of Cushing's syndrome. Once the characteristics of the cortisol level are established, then further radiologic studies, or a CAT scan or MRI, may be necessary to localize the problem.

Treatment : If the syndrome is due to a pituitary or adrenal tumor, then surgery is indicated. If it is the result of medication used in treatment of another illness, the dosage should be decreased to the lowest amount possible for adequate treatment of that illness.

Hirsutism

Hirsutism is the name given to male-patterned hair growth in a woman. The hair may grow on the face, chest, and abdomen. Hirsutism occurs when the fine hair follicles are stimulated by the male hormone testosterone to become coarse, or terminal, hairs. Hair on the chin, upper lip, chest, and abdomen contain hair follicles that are especially sensitive to the growth- promoting effect of testosterone.

Every woman has low levels of testosterone in her body. The testosterone comes from the ovaries and from precursor hormones that originate in the adrenal glands. Some women have hair follicles that are very sensitive even to normal female testosterone levels and develop some coarse hair as they age. In others, the problem stems from excess testosterone produced by the ovaries or adrenal glands, the result of polycystic ovarian syndrome or ovarian tumors (see Chapter 15).

Excess androgen hormones can also be produced by the adrenal glands, often from uncontrolled stimulation of the adrenal glands by a pituitary tumor. A blockage in the process through which cholesterol is converted to cortisol can lead to a build-up of androgens that the body can convert to testosterone. Adrenal gland tumors can also cause hirsutism.

Symptoms : Development of coarse hair on the upper lip, chin, breast bone, or abdomen. (Some women naturally have a layer of dark, fine hair over the upper lip. This visible hair may be cosmetically annoying, but it is not necessarily a symptom of hormonal abnormality. Hair around the areola [nipple area of the breast] is also normal.) Excess testosterone can also interfere with the body's normal hormonal functions, so menstrual irregularities, infertility, and acne can occur.

Diagnosis : The first step in diagnosing the underlying problem is a medical history and a complete physical examination. Blood tests will be done to measure the amounts of the adrenal hormones. If there is a high suspicion that the hair growth is the result of a blockage of the adrenal hormone production pathway, then a cosyntropin stimulation test is performed. If the work-up suggests there is an adrenal or ovarian tumor, then you may have to have an abdominal CAT scan to locate the tumor.

Treatment : Treatment depends on the cause of the hair growth. If the problem is a tumor of the adrenal gland or ovary, then surgery is the treatment of choice. If the hair growth is due to a block in the normal hormonal pathways of the adrenal gland, the treatment might include hormonal supplements such as hydrocortisone, prednisone, or dexamethasone. Ovarian causes can sometimes be treated with estrogen/progesterone medications such as the birth control pill (see Chapter 15).

Unfortunately, these treatments only address the source of the excess testosterone. If the hormonal problem is mild and uncomplicated by infertility, then medications that block testosterone's action on the hair follicle, such as Spironolactone, are helpful. Eliminating the source of the testosterone or blocking its effects will only prevent new follicle development, not cure the current problem. The hair follicles that have already been stimulated may require years to turn off. In that case, electrolysis, which destroys the follicle and prevents further growth, is recommended. Despite popular belief, shaving does not make hair grow thicker and darker; therefore, if hair growth is slow, this also can be a simple but effective method to get rid of excess hair.

Pheochromocytoma

Tumors that typically develop in the central portion (medulla) of the adrenal gland are called pheochromocytomas. Tumors of this type prooduce symptoms that are related to the secretion of the hormones adrenaline and norepinephrine. Usually solitary (although they can develop in both adrenal glands [multiple endocrine neoplasia]), these tumors are most often benign. Pheochromocytomas may develop in association with other endocrine tumors, and in neurofibromatosis. These tumors run in families and occur in individuals with hypertension.

Symptoms : Episodes of palpitations, fainting, and severe headaches are the classic symptoms associated with pheochromocytomas. Blood pressure that is erratically elevated and/or difficult to control may also indicate the presence of an adrenal tumor. Other symptoms include anxiety attacks, increased sweating, tremor, and weight loss.

Diagnosis : The first step in diagnosing a pheochromocytoma is a medical history and physical examination. The physical exam should include measurements of pulse and blood pressure both lying down and standing up. Diagnosis is made by documenting elevated adrenal medulla hormones (epinephrine, norepinephrine, and dopamine) or their breakdown products in a 24-hour urine collection. Sometimes more than one urine collection is required to identify the abnormality. If there is an increase in the level of hormones in the urine, the next test is an MRI of the abdomen to locate the tumor. Ninety percent of tumors are found in the adrenal gland; of that number, 10 percent will be present in both adrenal glands. Another 10 percent will be located elsewhere in the abdomen. If the MRI is unable to locate the tumor, then a body or MIBG scan (see Appendix), which uses a small amount of radioactive material, can be performed.

Treatment : Once identified, pheochromocytomas should be surgically removed. Prior to any operation, you will need to take medications that block the effects of a sudden release of the adrenaline that may occur under the stress of surgery.

The Pancreas

Located behind the stomach, the pancreas is a long, thin organ, approximately the length of the hand. Playing a key role in the digestive process, the pancreas produces enzymes essential to the digestion of food and also hormones that enable your body to metabolize the food you eat. These hormones regulate your body's use of glucose, a simple form of sugar that is an energy source for the daily activity of all your cells.

Three hormones are produced by the pancreas:

• Insulin is produced when the concentration of glucose in the body increases, such as after eating. Muscle and fat cells are stimulated by insulin to absorb the glucose they need as fuel for their activities. Surplus glucose is stored
  by the liver in the form of a starch called
  glycogen.
• Glucagon breaks down the stored glycogen and raises the concentration of sugar in the blood when needed by the body.
• Somatostatin is thought to be a factor in regulating the production and release of both insulin and glucagon. It also inhibits release of growth hormones.

Diabetes Mellitus

Diabetes occurs when the body cannot efficiently use food as energy because of a lack of the hormone insulin or as a result of a blockage in the function of insulin. (Contrary to what some people believe, diabetes is not caused by consuming too much sugar.) The most common endocrine disorder in the United States, diabetes occurs in about 3 percent of the population, or 10 million people. Diabetes mellitus is a serious disorder. In the United States, 5,000 patients with diabetes each year will develop blindness from the disease, 4,000 will develop severe kidney disease, and uncontrolled diabetes accounts for 80 percent of medically amputated legs and toes. In addition, people with diabetes are at risk for heart disease, heart attacks, nerve damage, infections, and strokes.

The symptoms of both types of diabetes are similar, because both result from the body's inability to metabolize carbohydrates.

There are two types of diabetes mellitus. About 10 or 15 percent of diabetics have type I diabetes. Usually occurring in childhood, type I diabetes results when the pancreas makes little or no insulin. Type II diabetes, also known as insulin-resistant diabetes, is far more common, accounting for 85 to 90 percent of all diabetes cases. Type II occurs when there is interference with the body's ability to use the insulin produced by the pancreas. Type II is seen in older people and is frequently associated with obesity.

Types of Diabetes

Type I diabetes occurs when the pancreas is unable to make insulin . About one in ten people with diabetes, or about 800,000 Americans, have type I diabetes. The exact cause of type I diabetes is not known, but it is considered to be an autoimmune disease in which antibodies destroy the cells in the pancreas that make insulin. It is more common in families with a history of type I diabetes. If the pancreas has been injured by a viral infection, type I diabetes may also result.

Treatment consists of daily insulin injections as well as the maintenance of a balanced diet and regular exercise regime. The number of daily insulin injections depends on the patient's weight, height, level of physical activity, and food intake. Most people with type I diabetes require two or more insulin shots a day. Insulin injections and meals should be taken at the same time. It is also important not to use other medicines that may increase blood sugar infections, and to avoid stress.

Type II diabetes results from insulin resistance, interference with the ability of insulin to lower blood sugar. The exact cause of type II diabetes is not known, but the condition is more likely to develop if you:

• are overweight
• have a family history of diabetes
• have high blood sugar levels when pregnant
• had a newborn baby weighing more than 9 pounds
• are over 40 years of age
• have high blood pressure
• are African-American, Hispanic, or Native American.

If you have type II diabetes or have a family history of the disease, the keystone of treatment includes eating nutritious, low-fat foods and maintaining a healthy weight.

If you cannot control the disease through diet and exercise alone, you will probably be required to take oral hypoglycemic agents, drugs that will lower your blood sugar. Not to be confused with insulin, oral hypoglycemic agents help the pancreas put out more insulin and aid the insulin in moving sugar from the bloodstream into the cells of the body. Take the oral hypoglycemic once or twice a day, about 30 minutes before a meal. The medication may need to be changed as you age or if you alter your eating habits.

Type I and type II diabetes have different symptoms, as well as some effects in common.

Diagnosis: When diagnosed by a blood test, diabetes is present if fasting blood sugar is above 140 mg/dl on two occasions (the normal level of blood sugar is about 115 mg/dl) or if fasting blood sugar is over 200 mg/dl two hours after a meal (normal is less than 140 mg/dl). If you have borderline readings, you will be encouraged to take a glucose tolerance test. In a glucose tolerance test, a large amount of sugar, usually in a sweet drink, is given by mouth. Your blood will be tested at periodic intervals over three hours to see if the blood glucose levels rise into the diabetic range.

Treatment : For both types of diabetes, the goal of treatment is to keep blood sugar normal or as near to normal as possible. Treatment also consists in preventing the condition from affecting the eyes, kidneys, heart, or nerves, and decreasing the incidence of infection. A combination of diet, exercise, and medication is usually prescribed.

A healthy diet for a person with diabetes is high in starches and fiber and low in sugar, fats, and salt.

Regular physical activity also helps to decrease blood sugar and is an important part of controlling diabetes. Exercise:

• uses up sugar in the body;
• burns off extra body fat;
• improves muscle strength and blood flow;
• improves physical appearance;
• improves energy and sense of well being.

Many type II diabetics who eat a healthy diet, maintain a healthy weight, and exercise can avoid the need for medication.

If you have diabetes, schedule regular appointments with your physician to check your blood sugar levels, as well as to diagnose and treat any complications. If you take insulin or oral hypoglycemic agents, notify your doctor if you contract a virus or another infection so that your medication can be adjusted. It is also recommended that anyone with diabetes have an annual eye examination, regular blood and urine tests to check kidney function, and a regular examination of the feet to check for sores that may indicate the development of circulatory problems.

Complications of Diabetes

Two immediate health problems may arise from poorly controlled diabetes: diabetic coma and h ypoglycemia (low blood sugar). Both conditions can cause a dia betic to become suddenly unconscious. If you are on medication for diabetes, always carry identification that includes your medical history so that the problem can be quickly recognized and treated.

Diabetic coma: Also known as ketoacidosis, this condition is a medical emergency requiring immediate attention. A relatively common complication of diabetes mellitus (usually type I), diabetic coma occurs when there is little or no insulin in the body, causing blood sugar levels to soar. Without insulin, the body cannot burn sugar and begins to burn fat, producing by- products called ketones. Ketones acidify the blood, causing widespread metabolic abnormalities that can result in coma and, eventually, death.

Most often, failure to receive scheduled insulin injections is the cause of ketoacidosis. An accidental injury resulting in unconsciousness, acute infection, or loss of fluids through vomiting or diarrhea may precipitate the coma. Symptoms of impending coma are increased urination and an unquenchable thirst developing over the course of several hours. Weakness and drowsiness follows, along with vomiting, diarrhea, and abdominal pain. The breath often begins to smell fruity, a symptom that may be mistaken for alcohol consumption. At a more advanced stage, breathing becomes deeper and more rapid. Unconsciousness soon ensues.

Treatment : This condition requires immediate administration of insulin and an intravenous infusion to replace lost body fluids. Blood glucose levels and fluid status must be closely monitored.

Hypoglycemia : This condition results when the concentration of glucose in the blood falls below normal, less than 60 mg/dl. When too little glucose circulates to the nervous system and other cells, they become starved for energy.

Hypoglycemia is a symptom, not a disease. Too often, people are erroneously diagnosed with hypoglycemia when the source of their problem lies elsewhere. Most cases of hypoglycemia occur in people who are taking insulin or oral hypoglycemic drugs. In rare cases, low blood sugar may result from liver or kidney disease, drug reactions, too much alcohol, or malnutrition. Hormonal imbalances, such as a lack of cortisol or overproduction of insulin due to a pancreatic tumor, may also cause hypoglycemia.

Symptoms: Common symptoms of hypoglycemia include sweating, nervousness, inability to concentrate, fast heartbeat, dizziness, blurred vision, weakness, fatigue, headache, irritability, hunger, abdominal pain, sudden drowsiness, confusion, and tingling or numbness of the mouth, hands, or body. When hypoglycemia is severe (when glucose levels fall below 20 -30 mg / dl), it can lead to convulsions and unconsciousness (coma).

Treatment : Immediately ingest a source of sugar, such as cup of orange juice, apple juice, or soda, three teaspoons of sugar, a cup of milk, several hard candies, or a tablespoon of honey. You can also take glucose tablets or gel, or glucagon (an injection to raise blood sugar).

If the symptoms persist after 15 -20 minutes, repeat the same dosage of sugar. If it will be more than an hour until regular meal time, eat a sandwich or some other snack to prevent a further decrease in blood sugar. If symptoms continue, go to the nearest emergency room, with an escort if possible. Later, discuss the hypoglycemic reaction with your physician. You may need to change your medication to prevent further episodes.

Diabetes in Pregnancy

The health of your baby depends on your having normal blood sugar levels before conception and during pregnancy. High blood sugar crosses the placenta, and your baby may run the risk of having birth defects. For that reason, an experienced health care team is required to care for pregnant diabetic women. The team includes an obstetrician, a diabetologist, a pediatrician, a diabetes educator, and a nutritionist. All pregnant women with diabetes must have their blood sugar checked frequently and receive counseling about nutrition, diet, and adjustment of insulin doses. Type II diabetics taking oral hypoglycemic agents should switch to insulin injections before conceiving.

Gestational Diabetes

This is a type of functional diabetes that appears during pregnancy and then vanishes immediately upon delivery. Unless your blood glucose is checked periodically, the diabetes may go unnoticed. The disease still poses a risk to the fetus, however, so every attempt should be made to regulate and maintain normal blood glucose. Women at risk for gestational diabetes are most commonly over 35, overweight, have had big babies, and have a family history of high blood sugar.

The Thyroid Gland

Located at the base of the neck, the thyroid gland helps set the rate at which your body functions. It produces thyroid hormone, which helps regulate important aspects of your body's metabolism and determines how fast you burn up calories.

Hyperthyroidism

Also known as an overactive thyroid, hyperthyroidism occurs when the thyroid gland produces excessive amounts of thyroid hormone, causing an increase in the body's normal expenditure of energy, or its basal metabolic rate. Two forms of hyperthyroidism are Graves' disease, which is most common in women, and Plummer's disease. In Graves' disease, the thyroid gland is stimulated excessively by an abnormal antibody instead of by the normal thyroid-stimulating hormone (TSH) from the pituitary gland. In older women, the disease can be caused by a thyroid nodule producing too much thyroid hormone.

Symptoms : Hyperthyroidism causes increased appetite, rapid heart rate, weight loss, tremor of the hands, sweaty palms, protruding eyes, difficulty in sleeping, and muscle weakness. The excessive stimulation of the thyroid also may lead to a goiter, an enlargement of the thyroid gland (Figure 30.2).

Treatment : The first line of treatment is antithyroid medication to suppress the excessive amounts of thyroid hormone. In many cases, this drug can completely relieve the symptoms. The signs of hyperthyroidism often return, however, when the drug is discontinued. If that happens, radioactive iodine is administered by mouth. The radioiodine is absorbed by the thyroid cells and the gland slows down its production of the hormone.

Hypothyroidism

The reverse of hyperthyroidism, this condition is the result of an underactive thyroid. The gland fails to produce enough hormone, causing the body's basal metabolic rate to slow down. Hypothyroidism can occur at any age, but it most commonly affects middle-aged women. The symptoms of hypothyroidism often go unrecognized in older people and can be mistaken for the normal signs of aging.

In some cases, hypothyroidism results from the failure of the pituitary gland to produce enough thyroid-stimulating hormone. The cause is commonly an autoimmune disorder known as Hashimoto's thyroiditis, in which antibodies attack and destroy the thyroid. Hypothyroidism may also stem from the medical treatment given to those suffering from hyperthyroidism, when the drugs work too well, causing the reverse symptoms.

Symptoms : The first signs of hypothyroidism are a constant fatigue, muscle aches, and weakness. More advanced symptoms are a slowed heart rate, weight gain, intolerance to cold, constipation, dry skin and hair, and heavy and prolonged menstrual periods.

Diagnosis : Hypothyroidism usually develops slowly over months and even years. The most effective way to diagnose the condition is through laboratory tests, particularly blood tests, to measure the amounts of hormone being produced in the thyroid, TSH, and thyroid antibodies.

Treatment : If you have a thyroid deficiency, your doctor will prescribe a thyroid replacement supplement. In most cases, the condition improves noticeably within a week or so after therapy is begun; all symptoms disappear in a few months. You will probably have to continue the treatment for the rest of your life.

The Parathyroid Gland

The parathyroid glands are found in the neck behind or near the thyroid gland. The four glands produce parathyroid hormone (PTH), which regulates the amount of calcium in the blood. When the calcium level goes down, more PTH is secreted; when the calcium level is elevated (hypercalcemia), the amount of PTH decreases. PTH causes calcium to be released from bone, increases calcium absorption in the intestines, and stimulates the kidney to make a very potent form of vitamin D, which enhances calcium absorption from the gastrointestinal tract.

Hypercalcemia, or mild elevations of calcium in the blood, may be caused by hyperparathyroidism, other endocrine disorders, drugs, cancer, and diseases such as tuberculosis, sarcoidosis, and AIDS.

Hyperparathyroidism

Hyperparathyroidism results when one or more of the parathyroid glands produce an excess of PTH, the hormone that increases the amount of calcium and decreases the amount of phosphorous in the bloodstream. Hyperparathyroidism is more common in women than in men, and most patients are over 50 when the disease is discovered. About 85 percent of hyperparathyroidism is caused by a benign parathyroid tumor. Other causes are enlargement of the parathyroid glands (hyperplasia) and, rarely, multiple endocrine neoplasia syndromes , called MEN I and MEN II.

Symptoms : Patients with mild elevations of calcium known as hypercalcemia may experience no symptoms at all or feel only mild fatigue. Lethargy, apathy, nausea, personality changes, muscle weakness, abdominal pain, increased urination, and constipation are other symptoms. Severe hypercalcemia is associated with nausea, vomiting, kidney stones, peptic ulcer, pancreatitis, stupor, and coma.

Diagnosis : If elevated calcium levels are found in routine blood tests, hyperparathyroidism may be suspected. To confirm the diagnosis, physicians will take blood tests to measure serum calcium, phosphorous, total proteins, 24-hour urine calcium, and parathyroid hormone. During the evaluation, other causes of hypercalcemia must also be considered.

Treatment : Parathyroid surgery, called parathy- roidectomy, is the treatment of choice to prevent the development of severe hypercalcemia, bone pain, severe osteoporosis, kidney disease, kidney stones, or peptic ulcers. More conservative treatment such as increased water intake, nonthiazide diuretics, estrogen, and increased physical activity may be helpful if the patient is older, is asymptomatic, or has other illnesses that make surgery inadvisable.

Hypoparathyroidism

When the parathyroid glands produce too little PTH, preventing the body from making proper use of calcium, hypoparathyroidism results. This is a rare condition, however, and is far less common than hyperparathyroidism.

The most common cause of hypoparathyroidism is damage to the parathyroids during surgery to treat hyperthyroidism, neck cancer, and, less commonly, hyperparathyroidism. Because most people with hyperthyroidism are now treated with drugs or radioactive iodine rather than surgery, consequent postsurgical hypoparathyroidism is now also rare.

Symptoms : Numbness and tingling of the hands, feet, and mouth, muscle cramps, and spasms are common. Cataracts may also develop.

Treatment : Calcium and vitamin D supplements can help alleviate the symptoms. Calcium carbonate is particularly recommended as it has a high calcium content (40 percent). Usually 1 to 2 grams are taken in divided doses (one chewable tablet three or four times a day). Calcium levels are retested after four to six weeks and medications are readjusted accordingly. After appropriate doses are established, calcium blood levels should be checked about four times each year.

Osteoporosis

A disease that causes the bones to become more porous and the skeleton to weaken, osteoporosis is most common in postmenopausal women. One out of every four women over 45 and nine out of ten women over 75 have some degree of osteoporosis. This common type of osteoporosis is called primary osteoporosis. Excessive loss of bone after menopause occurs when certain hormones essential for bone formation and maintenance decrease substantially. Secondary osteoporosis is much more rare and usually accompanies other endocrine disorders such as acromegaly and Cushing's syndrome and can result from excessive use of corticosteroid drugs.

The endocrine system keeps the correct level of calcium circulating in the bloodstream; if your body does not receive enough dietary calcium to meet its needs, it takes calcium from the bones to make up the difference. The sex hormone estrogen protects bones from being robbed of calcium by other demands of the body and helps produce and maintain collagen, an important component of bone. Another hormone, calcitonin, may help facilitate the uptake of calcium from the blood into the bone and, at the same time, inhibit the loss of calcium from the bone.

Risk factors for osteoporosis include a family history of the disease, early menopause, a lack of physical activity, cigarette smoking, alcoholism, and some medications. A high dosage of thyroid medication, for example, can lead to bone weakness in the hips and wrists. Caucasians are most at risk, as are thin, small- boned women.

Preventing osteoporosis and limiting bone loss after menopause are vital. Once bone mass is lost, it is difficult or impossible to replace. Preventive measures include maintaining adequate levels of calcium and vitamin D and exercising regularly. High intake of calcium after menopause will also help reduce age-related bone loss. Estrogen replacement therapy helps prevent bone thinning.

Estrogen replacement therapy ( ERT ) : ERT relieves most menopausal symptoms (hot flashes, sweating, vaginal dryness) as well as other side effects of estrogen loss, including coronary artery disease and osteoporosis. ERT is usually advised for women who experience early menopause (before age 40) or who have had their ovaries removed. In addition, women who have had a spine fracture due to low bone mass or have low bone mass as measured by a bone density test should also consider taking ERT. Women who have other risk factors for osteoporosis may want to consider taking ERT as well. (For further information on osteoporosis, see Chapter 11.)

The Pituitary Gland

Although small in size, the pituitary gland is the most important of all the endocrine glands, because it acts as a control center for the body's long-term growth, daily functioning, and reproductive capabilities. Located at the base of the brain behind the nasal passages, the pituitary is stimulated by hormones from the part of the brain called the hypothalamus. The pituitary secretes hormones necessary for growth, reproduction, and sexual development, as well as for thyroid and adrenal function. The hormones are luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin , growth hormone (GH), adrenocorticotropin (ACTH), and thyroid-stimulating hormone (TSH).

Pituitary disorders in adult women are caused by one of two types of tumors: a craniopharyngioma , which exerts pressure on the pituitary as it grows and results in decreased hormone production; or an adenoma , a benign pituitary tumor that can result in increased hormone production.

Symptoms : A pituitary disorder can cause severe headaches, changes in vision, too rapid or too slow growth and/or sexual development, changes in menstruation, fatigue, weight gain or loss, dizziness, increase or decrease of body hair, and sometimes the production of breast milk not related to a pregnancy (galactorrhea).

Diagnosis : The examining physician will take a thorough history. Special blood and urine tests can determine the amounts of hormones circulating in the bloodstream and being excreted. If abnormal amounts are found, a CAT or MRI scan may be done to determine if a pituitary tumor is present.

Acromegaly

The overproduction of growth hormone by the pituitary can affect the limbs and internal organs. The cause is usually a tumor on the pituitary. In children, this condition is known as gigantism and leads to abnormal skeleton growth. In adults, the overproduction of growth hormone after normal growth has been completed results in the gradual overgrowth of certain bones in the body and a thickening of the skeleton. This condition is called acromegaly.

Symptoms : When acromegaly occurs after puberty, the bones of the hands, feet, and head enlarge. Increased shoe, glove, ring, and hat sizes are common. The chin may get larger and spaces between the lower front teeth may appear. The skin becomes coarse and thick, and sweating increases.

Diagnosis : Blood tests can determine whether growth hormone and somatomedin C levels are elevated. An MRI will reveal an enlarged pituitary.

Treatment : Surgery and/or X-ray treatment is usually recommended. Post-treatment blood tests can confirm the removal of the tumor. New drugs, specifically bromocriptine and octreotide, are being developed for patients who continue to have elevated growth hormone after surgery.

Cushing's Syndrome

This syndrome results from a tumor of the pituitary which causes overproduction of ACTH and stimu- lates the adrenal glands to make increased amounts of cortisol.

Diabetes Insipidus

Diabetes insipidus is a disease that develops when too little antidiuretic hormone (ADH), which controls the balance of water in the body, is produced by the posterior pituitary gland. This condition should not be confused with diabetes mellitus, which is the result of an insulin deficiency.

A pituitary tumor is the most common identified cause of this condition. Other causes include damage to the pituitary from a head injury or from surgery for pituitary tumors. In more than half of the cases, the cause is unknown.

Symptoms : Excessive urination and severe thirst are the main signs of this disease.

Diagnosis : If diabetes insipidus is suspected, your physician will probably conduct a water deprivation test as well as blood tests to determine salt and water balance.

Treatment : Increased fluid intake and the administration of an antidiuretic hormone, available as an injection or a nasal spray, is usually the treatment of choice. You may have to adopt a salt-restricted diet. If a tumor is present, surgery should be performed to remove it.

Hypopituitarism

A disorder in which the pituitary gland produces insufficient quantities of one or more of the pituitary hormones, hypopituitarism is usually the result of a tumor on the pituitary gland. It also can develop after a serious head injury. Some women experience hypopituitarism after childbirth (Sheehan's syndrome, see below).

Symptoms : Depending on which hormones are deficient, symptoms may include cessation of menses, infertility, the inability to lactate after childbirth, fatigue, depression, loss of pubic hair, and decreased appetite. Because the pituitary gland also produces hormones that activate other glands, conditions such as hypothyroidism and adrenal insufficiency can result.

Diagnosis : Blood tests are performed to measure levels of TSH, ACTH, GH, thyroid, cortisone, and estrogen.

Treatment : The deficient hormone can be replaced by a synthetic version.

Prolactinoma

The overproduction of the hormone prolactin, which stimulates milk production after childbirth, is most commonly caused by an adenoma, a benign tumor. Other causes of elevated prolactin include the use of certain oral contraceptives, tranquilizers, and hypothyroidism.

Symptoms : Irregular or lack of menstrual periods, infertility, and the appearance of breast milk not related to pregnancy (galactorrhea) are common signs of this condition. Visual disturbances, indicating the presence of a large tumor compressing the optic nerve, may also occur.

Diagnosis : Blood tests can establish prolactin and thyroid hormone levels. If prolactin levels are high, thyroid function is normal, and you are not taking any of the drugs listed above, then a picture of your pituitary will be made with an MRI . In addition, a complete eye examination will be made for acuity and fields of vision.

Treatment : Tumors can be treated with drugs, surgery, or both. Certain drugs can decrease prolactin levels and lead to normal menstrual periods. If a large tumor is causing visual problems, neurosurgical removal is recommended. Very small tumors (microadenomas) can be monitored with careful follow-up, repeated blood tests measuring prolactin levels, and an MRI, unless the patient wants to become pregnant. If conception is desired, it is necessary to decrease prolactin levels so that ovulation and regular menstrual cycles can be established.

Sheehan's Syndrome

This is a type of hypopituitarism that occurs after childbirth. The pituitary gland, which normally increases in size during pregnancy, grows so large that the body is unable to provide it with oxygen and the other nutrients it needs, causing some or all of the gland to die. It can also occur if heavy bleeding and a sharp drop in blood pressure cause the pituitary to lose its blood supply, causing a decrease in pituitary hormones. Symptoms of Sheehan's syndrome include the failure to have breast milk, no menstrual periods, loss of body hair in the axilla and pubic regions, and depression.

Causes Of Addison's Disease

Autoimmunity
Tuberculosis
Fungal disorders (histoplasmosis)
Drugs (ketoconazole, rifampin, anticoagulants)
Congenital defects (inability to produce cortisol)
Surgery (bilateral adrenalectomy)
Acquired Immuno-Deficiency Syndrome (AIDS)

Causes Of Cushing's Syndrome

Pituitary tumor
Hypothalamus (over-production of ACTH-releasing
hormone)
Adrenal adenoma or carcinoma
Too much glucocorticoid medication
Other cancer (not adrenal or pituitary) that produces
ACTH

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