Acromegaly: Causes, Symptoms, Diagnosis, Treatment

The pituitary gland is considered the master gland of the endocrine system. The anterior pituitary gland secretes growth hormone (GH), prolactin, and 4 tropic hormones---adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone...

The pituitary gland is considered the master gland of the endocrine system. The anterior pituitary gland secretes growth hormone (GH), prolactin, and 4 tropic hormones---adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). These hormones affect growth, sexual maturation, reproduction, metabolism, stress response, and fluid balance. As a result, pituitary gland disorders manifest in a variety of ways. FIG. 54.1  Progressive development of facial changes from acromegaly. Courtesy Linda Haas, Seattle, WA. Pituitary gland tumors account for 5% to 20% of primary intracranial tumors.1 The most common, a pituitary adenoma, is a slow-growing, benign tumor. It often occurs in adults between 40 and 60 years of age. Hypersecretory pituitary adenomas secrete an excess of a specific hormone causing manifestations related to the action of that hormone. The most common are prolactinomas and GH- and ACTH-secreting adenomas.1 Acromegaly Acromegaly is a rare condition characterized by an overproduction of GH. Around 3 cases per 1 million people in the United States are diagnosed annually.2 It affects both genders equally. The mean age at the time of diagnosis is 40 to 45 years old. Etiology and Pathophysiology Acromegaly most often occurs because of a benign GH-secreting pituitary adenoma. The excess GH results in an overgrowth of soft tissues and bones in the hands, feet, and face. Because the problem develops after epiphyseal closure, the bones of the arms and legs do not grow longer. Clinical Manifestations The changes resulting from excess GH in adults can occur slowly, over many years. They may go unnoticed by the person, family, and friends. Thickening and enlargement of the bony and soft tissues on the face, feet, and head occur (Fig. 54.1). Patients may have proximal muscle weakness and joint pain that can range from mild to crippling. Carpal tunnel syndrome and peripheral neuropathy may be present. Tongue enlargement causes dental and speech problems. The voice deepens because of hypertrophy of the vocal cords. Sleep apnea may occur because of upper airway narrowing and obstruction from increased amounts of pharyngeal soft tissues. The skin becomes thick, leathery, and oily with acne outbreaks. Vision changes may occur from pressure on the optic nerve from a pituitary adenoma. Headaches are common. Since GH antagonizes the action of insulin, glucose intolerance and manifestations of diabetes may occur, including increased thirst and polyuria (increased urination). The life expectancy of those with acromegaly is reduced by 5 to 10 years. They are prone to cardiovascular disease (CVD), diabetes, and colorectal cancer.3 Even if patients are cured or the disease is well controlled, manifestations such as joint pain and deformities often remain. Diagnostic Studies In addition to the history and physical assessment, a diagnosis requires evaluating plasma insulin-like growth factor-1 (IGF-1) levels and GH response to an oral glucose tolerance test (OGTT). IGF-1 mediates the peripheral actions of GH. As GH levels rise, so do IGF-1 levels. Since GH is released in a pulsatile fashion, we need several samples to obtain an accurate assessment. Serum IGF-1 levels are more constant, giving a reliable diagnostic measure of acromegaly. During an OGTT, GH concentration normally falls because glucose inhibits GH secretion. In acromegaly, GH levels do not fall and in some cases GH levels rise. MRI or high-resolution CT scan with contrast can detect pituitary adenomas. A complete eye examination, including visual fields, is done because a tumor may cause pressure on the optic chiasm or optic nerves. Interprofessional and Nursing Care The patient's prognosis depends on the age at onset, age when treatment started, and tumor size. The overall goal is to return the patient's GH levels to normal. Treatment consists of surgery, radiation therapy, drug therapy, or a combination of these. Treatment can stop bone growth and reverse tissue hypertrophy. However, sleep apnea, diabetes, and cardiac problems may persist. Surgery (hypophysectomy) is the treatment of choice. It offers the best chance for a cure and optimal symptom management, especially for smaller pituitary tumors.4 Surgery results in an immediate reduction in GH levels. IGF-1 levels fall within a few weeks. Patients with larger tumors or those with GH levels greater than 45 ng/mL may need adjuvant radiation or drug therapy. Surgery and radiation therapy for pituitary tumors are discussed later in this chapter. Drug therapy is an option for patients whose surgery did not result in a cure and/or in combination with radiation therapy. The main drug used is octreotide (Sandostatin), a somatostatin analog. It reduces GH levels to normal in many patients. Octreotide is given by subcutaneous injection 3 times a week. Long-acting somatostatin analogs, octreotide (Sandostatin LAR), pasireotide (Signifor), and lanreotide SR (Somatuline Depot), are available as IM injections given every 4 weeks. GH levels are measured every 2 weeks to guide drug dosing and then every 6 months until the desired response is achieved. Dopamine agonists (e.g., bromocriptine, cabergoline) may be given alone or with somatostatin analogs if surgery does not result in a complete remission. These drugs reduce GH secretion from the tumor. GH antagonists (e.g., pegvisomant \[Somavert\]) reduce the effect of GH in the body by blocking liver production of IGF-1. Most patients taking this drug achieve normal IGF-1 levels with symptom improvement.3 Serial photographs showing improvement in appearance may be helpful to the patient's recovery. Psychosocial effects of acromegaly include body image problems, sexual problems, and depression. Fatigue and sleep problems may persist after surgery. Patients will need strategies for dealing with these symptoms. Referral to a support group may be helpful. Excesses of Other Tropic Hormones Excess prolactin or tropic hormone (e.g., ACTH, TSH) secretion by the anterior pituitary gland will cause other endocrine glands to overproduce certain hormones. An excess of these hormones (discussed later in the chapter) can cause significant problems in metabolism and general health. A prolactin-secreting adenoma is known as a prolactinoma. They account for about 40% of pituitary tumors.5 Women with prolactinomas may have galactorrhea, anovulation, infertility, infrequent or absent menses, decreased libido, and hirsutism. In men, impotence, decreased sperm density, and libido may result. Compression of the optic chiasm can cause vision changes and signs of increased intracranial pressure, including headache, nausea, and vomiting. Because prolactinomas do not typically grow, drug therapy is usually the first-line treatment. The dopamine agonists cabergoline and bromocriptine are given to block prolactin release. Surgery may be an option, depending on the extent and size of the tumor. Radiation therapy can reduce the risk for tumor recurrence for patients with large tumors. Pituitary Gland Hypofunction Hypopituitarism is a rare disorder that involves a decrease in 1 or more of the pituitary hormones. A deficiency of only 1 pituitary hormone is called selective hypopituitarism. Total failure of the pituitary gland results in deficiency of all pituitary hormones---a condition called panhypopituitarism. The most common hormone deficiencies from hypopituitarism involve GH and gonadotropins (e.g., LH, FSH). Etiology and Pathophysiology The usual cause of pituitary hypofunction is a pituitary tumor. Autoimmune disorders, infections, pituitary infarction (Sheehan syndrome), or destruction of the pituitary gland (from trauma, radiation, surgery) can also cause hypopituitarism. The incidence varies among populations, with a higher mortality in women. Anterior pituitary hormone deficiencies can lead to end-organ failure. TSH and ACTH deficiencies are life threatening. ACTH deficiency can lead to acute adrenal insufficiency and hypovolemic shock from sodium and water depletion. Clinical Manifestations and Diagnostic Studies The manifestations vary with the type and degree of dysfunction. Early manifestations of a space-occupying lesion include headaches, vision changes (decreased visual acuity, decreased peripheral vision), loss of smell, nausea and vomiting, and seizures. Manifestations associated with hyposecretion of the target glands vary widely (Table 54.1). TABLE 54.1 Manifestations of Hypopituitarism Hormone Deficiency Manifestations Adrenocorticotropic hormone (ACTH) Involves cortisol deficiency: weakness, fatigue, headache, dry and pale skin, ↓axillary and pubic hair, ↓ resistance to infection, fasting hypoglycemia Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Women: Menstrual irregularities, loss of libido, changes in secondary sex characteristics (e.g., ↓ breast size) Men: Testicular atrophy, ↓ spermatogenesis, loss of libido, impotence, ↓ facial hair and muscle mass Growth hormone (GH) Subtle, nonspecific findings: truncal obesity, osteoporosis, ↓ muscle mass and strength, weakness, fatigue, depression, or flat affect Thyroid-stimulating hormone (TSH) Mild form of primary hypothyroidism: fatigue, cold intolerance, constipation, lethargy, weight gain In addition to a history and physical assessment, diagnostic studies such as MRI and CT can identify a pituitary tumor. Laboratory tests generally involve the direct measurement of pituitary hormones (e.g., TSH) or an indirect determination of the target organ hormones (e.g., triiodothyronine \[T3\], thyroxine \[T4\]). See Chapter 52 for more information about diagnostic studies. Interprofessional and Nursing Care The treatment for hypopituitarism often consists of surgery or radiation therapy followed by lifelong hormone therapy. Surgery and radiation therapy for pituitary tumors are discussed in the next section. Appropriate hormone therapy is used (e.g., corticosteroids, thyroid hormone). Hormone therapies for thyroid hormone and corticosteroids are discussed later in this chapter. Somatropin (Genotropin, Humatrope, Omnitrope) is recombinant human GH. It is used for long-term hormone therapy in adults with GH deficiency. These patients respond well to GH replacement. They have increased energy, increased lean body mass, a feeling of well-being, and improved body image. Side effects include fluid retention with swelling in the feet and hands, muscle and joint pain, and headache. GH is given daily as a subcutaneous injection, preferably in the evening. The dosing is variable and adjusted based on symptoms, IGF-1 levels, and side effects. Although gonadal deficiency is not life threatening, hormone therapy will improve sexual function and general well-being. It is contraindicated in those with certain medical conditions, such as phlebitis, pulmonary embolism, breast cancer, and prostate cancer. Estrogen and progesterone replacement therapy may be given to hypogonadal women to treat hot flashes, vaginal dryness, and decreased libido (see Chapter 58). Testosterone is used to treat men with gonadotropin deficiency. The benefits of testosterone therapy include a return of male secondary sex characteristics, improved libido, and increased muscle mass, bone mass, and bone density. Hormone therapy for men is discussed in Chapter 59. FIG. 54.2  Surgery on the pituitary gland is most often done by a transsphenoidal approach. An incision is made in the inner aspect of the upper lip and gingiva. The sella turcica is entered through the floor of the nose and sphenoid sinuses. An illustration shows the surgery procedure on the pituitary gland with the trans-sphenoidal approach. The bulb-like structure shows the pituitary gland in the brain. The small rectangle-shaped bone diagonal to the pituitary gland shows the sella turcica. The small oval-shaped cavity inferior to the gland shows the sphenoid sinus. The tube is inserted into the esophagus through the mouth. The small tube is inserted into the nose with a bent dissection scissor. The tip of the scissor reaches the sinus region. Pituitary Surgery A hypophysectomy is the surgical removal of the pituitary gland. It is the treatment of choice for tumors in the pituitary area, especially smaller pituitary adenomas. Most surgeries are done by an endoscopic transsphenoidal approach (Fig. 54.2). When the entire pituitary gland is removed, there is permanent loss of all pituitary hormones. The patient will need lifelong replacement therapy of thyroid hormone, sex hormones, and glucocorticoids.6 Radiation therapy can reduce the size of a tumor before surgery. It is also used when surgery does not produce a cure or when patients are not candidates for surgery. The full effects may take months to years. Radiation therapy may lead to hypopituitarism, which then requires lifelong hormone replacement therapy. Stereotactic radiosurgery (Gamma Knife surgery, proton beam, linear accelerator) is an option for small, surgically inaccessible pituitary tumors or in place of conventional radiation. Nursing Management: Pituitary Surgery After surgery, assess the patient for the presence of a hematoma compressing the optic nerve or optic chiasma. Monitor peripheral vision, visual acuity, extraocular movements, and pupillary response. Report changes at once. Prompt intervention may prevent vision changes from becoming permanent (Table 54.2). Cerebrospinal fluid (CSF) leaks and nosebleeds are other common complications after surgery. The HCP may place a petroleum jelly--coated ribbon of gauze or a balloon-tipped catheter (like an indwelling urinary catheter) in the sphenoid sinus. It is usually removed after 24 hours. It can be left in for 2 to 3 days if there is concern for bleeding or CSF leak. The patient must not blow the nose for at least 48 hours after surgery. They need to avoid vigorous coughing, sneezing, and straining at stool. Monitor the "moustache" dressing regularly for any drainage. Check any clear drainage with a urine dipstick for glucose and protein. If present, notify the HCP of a possible CSF leak. A sample can be sent to the laboratory. A glucose level greater than 30 mg/dL (1.67 mmol/L) indicates CSF leakage from an open connection with the brain. If this happens, the patient is at increased risk for meningitis. TABLE 54.2  NURSING MANAGEMENT Care of the Patient After Pituitary Surgery   Monitor vital signs. Assess peripheral pulses and watch for orthostatic hypotension. Monitor neurologic and cognitive status (e.g., level of consciousness, orientation, speech) hourly for the first 24 h and then every 4 h. Assess extremity strength and reflexes. Monitor field of vision, visual acuity, extraocular movements, and pupillary response. Notify HCP of any changes. Assess dressing for type and amount of drainage. Notify HCP for excessive bleeding or CSF drainage. Maintain strict intake and output and monitor fluid balance. Assess for DI or SIADH. Keep head of bed elevated at least 30 degrees. Encourage deep-breathing exercises and incentive spirometer use. Monitor for pain and give analgesic medications as prescribed. Encourage high-fiber diet to decrease risk for constipation. Perform oral care every 4 hr. Teach the patient to: Avoid vigorous coughing, sneezing, and blowing the nose Avoid bending over at the waist or straining at stool (Valsalva maneuver) due to risk for increased intracranial pressure Avoid use of toothbrushes until incision heals Follow replacement hormone therapy plan A persistent and severe generalized or supraorbital headache may indicate CSF leakage into the sinuses. A CSF leak usually resolves within 72 hours when treated with head elevation and bed rest. If the leak persists, daily spinal taps can reduce pressure to below-normal levels. Keep the head of the bed elevated at a 30-degree angle. This avoids pressure on the sella turcica and decreases headaches. Monitor pupillary response, speech patterns, and extremity strength to detect neurologic complications. Gentle mouth care every 4 hours keeps the surgical site clean and free of debris. Have the patient avoid brushing their teeth for at least 10 days to protect the suture line. Fluid and electrolyte problems can occur if diabetes insipidus (DI) develops.7 Transient DI may occur because of the loss of antidiuretic hormone (ADH), which is stored in the posterior lobe of the pituitary gland, or cerebral edema from manipulation of the pituitary during surgery. DI may be permanent after surgery. To assess for DI, monitor urine output and measure specific gravity. Report a urine output of more than 200 mL/hr for more than 3 consecutive hours or a specific gravity level of less than 1.005. Patients with DI will have a high serum sodium and extreme thirst. We treat DI by giving desmopressin acetate (DDAVP). Fluid replacement may be needed to avoid hypovolemia from high urine output. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) can occur after any intracranial surgery. SIADH typically occurs later than DI, usually around the 4th postoperative day. It may occur due to manipulation of the pituitary and other structures causing release of ADH. The fluid retention caused by circulating ADH leads to dilutional hyponatremia. Sodium levels of less than 125 mEq/L will present as headache, vomiting, and decreased level of consciousness. DI and SIADH are discussed in the next section. FIG. 54.3  Pathophysiology of SIADH. Modified from Urden LD, Stacy KM, Lough ME: Critical care nursing: diagnosis and management, ed 6, St Louis, 2010, Mosby. A schematic flow diagram of the pathophysiology of the syndrome of inappropriate antidiuretic hormone. The increased antidiuretic hormone leads to increased water reabsorption in renal tubules, increased intravascular fluid volume, dilutional hyponatremia, and decreased serum osmolality. The patient needs lifelong ADH, cortisol, and thyroid hormone replacement after a hypophysectomy. Surgery may result in permanent loss or deficiencies in FSH and LH. This can lead to decreased fertility. Assist the patient in working through the grieving process associated with these losses. Posterior Pituitary Gland Problems The hormones secreted by the posterior pituitary are ADH and oxytocin. ADH, also called arginine vasopressin (AVP) or vasopressin, has a key role in regulating water balance and serum osmolarity (see Chapter 52). The main problems result from either overproduction or underproduction of ADH. Syndrome of inappropriate Antidiuretic Hormone Etiology and Pathophysiology Syndrome of inappropriate antidiuretic hormone (SIADH) results from an overproduction of ADH or the release of ADH despite normal or low plasma osmolarity (Fig. 54.3). ADH increases the permeability of the renal distal tubule and collecting duct, which leads to the reabsorption of water into the circulation. Extracellular fluid volume expands, plasma osmolality declines, glomerular filtration rate increases, and sodium levels decline (dilutional hyponatremia). Thus features of SIADH are fluid retention, serum hypoosmolality, dilutional hyponatremia, hypochloremia, and concentrated urine in the presence of normal or increased intravascular volume. SIADH occurs more often in older adults. The most common cause is cancer, especially small cell lung cancer (Table 54.3). SIADH tends to be self-limiting when caused by head trauma or drugs. It can be chronic when caused by tumors or metabolic diseases.   TABLE 54.3 Causes of SIADH Cancer Colorectal cancer Lymphoid cancers (Hodgkin lymphoma, non-Hodgkin lymphoma, lymphocytic leukemia) Pancreatic cancer Prostate cancer Small cell lung cancer Thymus cancer CNS Disorders Brain tumors Cerebral atrophy Guillain-Barré syndrome Head injury (skull fracture, subdural hematoma, subarachnoid hemorrhage) Infection (encephalitis, meningitis) Stroke Systemic lupus erythematosus Drug Therapy Carbamazepine (Tegretol) Chemotherapy agents (vincristine, vinblastine, cyclophosphamide) General anesthesia agents Opioids Oxytocin Thiazide diuretics Selective serotonin reuptake inhibitor (SSRI) antidepressants Tricyclic antidepressants Miscellaneous Conditions Adrenal insufficiency COPD HIV Hypothyroidism Lung infection (pneumonia, tuberculosis, lung abscess) Positive pressure mechanical ventilation Clinical Manifestations and Diagnostic Studies The patient with SIADH has low urine output and increased body weight. At first, the patient has thirst, dyspnea on exertion, and fatigue. Mild hyponatremia causes muscle cramping, irritability, and headache. As the serum sodium level falls (usually below 120 mEq/L \[120 mmol/L\]), manifestations become more severe and include vomiting, abdominal cramps, and muscle twitching. As plasma osmolality and serum sodium levels continue to decline, cerebral edema may occur, leading to lethargy, confusion, seizures, and coma. The diagnosis is made by simultaneous measurements of urine and serum osmolality. Dilutional hyponatremia is indicated by a serum sodium less than 135 mEq/L, serum osmolality less than 280 mOsm/kg (280 mmol/kg), and urine specific gravity greater than 1.030. A serum osmolality much lower than the urine osmolality shows the body is inappropriately excreting concentrated urine in the presence of dilute serum. Interprofessional and Nursing Care When assessing patients at risk and those who have confirmed SIADH, be alert for low urine output with a high specific gravity, a sudden weight gain without edema, or a decreased serum sodium level. Monitor intake and output, vital signs, and heart and lung sounds. Obtain daily weights. Observe for signs of hyponatremia, including seizures, headache, vomiting, and decreased neurologic function. Treatment is directed at the underlying cause.8 Medications that stimulate ADH release should be avoided or discontinued (Table 54.3). If symptoms are mild and serum sodium is greater than 125 mEq/L (125 mmol/L), the only treatment may be a fluid restriction of 800 to 1000 mL/day. This restriction should result in weight loss and a gradual rise in serum sodium concentration and osmolality. An improvement in symptoms should accompany normalization of serum sodium and osmolality. Provide the patient with frequent oral care and distractions to decrease discomfort related to thirst from the fluid restriction. A loop diuretic, such as furosemide (Lasix), may be used to promote diuresis. Since loop diuretics cause sodium loss, the serum sodium must be at least 125 mEq/L (125 mmol/L). Because furosemide increases potassium, calcium, and magnesium loss, the patient may need supplements. Demeclocycline also may be given. It blocks the effect of ADH on the renal tubules, resulting in more dilute urine. Initiate seizure and fall precautions if the patient has an altered sensorium or is having seizures. Keep the head of the bed flat or elevated no more than 10 degrees. This promotes venous return to the heart and increases left atrial filling pressure, thus reducing ADH release. Frequent turning, positioning, and range-of-motion exercises are important to maintain skin integrity and joint mobility. In cases of severe hyponatremia (less than 120 mEq/L), especially in the presence of neurologic manifestations, such as seizures, small amounts of IV hypertonic saline solution (3% sodium chloride) may be given. We must correct hyponatremia slowly. The level should not increase by more than 8 to 12 mEq/L in the first 24 hours. Quickly increasing levels can cause osmotic demyelination syndrome with permanent damage to nerve cells in the brain. A fluid restriction of 500 mL/day may be needed for those with severe hyponatremia. Vasopressor receptor antagonists block the activity of ADH. They are used to treat euvolemic hyponatremia in hospitalized patients. Two drugs are approved for use in the United States: conivaptan (Vaprisol) and tolvaptan (Samsca). Conivaptan is given IV; tolvaptan is given orally. Neither should be given to patients with liver disease because they worsen liver function. Help the patient with chronic SIADH to self-manage their treatment. In chronic SIADH, a fluid restriction of 800 to 1000 mL/day is recommended. Ice chips or sugarless chewing gum help decrease thirst. Teach them to supplement the diet with sodium and potassium, especially if taking loop diuretics. Have the patient obtain a daily weight to monitor changes in fluid balance. Teach the patient the symptoms of fluid and electrolyte imbalances, especially those involving sodium and potassium (see Chapter 17). Diabetes Insipidus Etiology and Pathophysiology Diabetes insipidus (DI) is caused by deficient production or secretion of ADH or a decreased renal response to ADH.9 The decrease in ADH results in fluid and electrolyte imbalances caused by increased urine output and increased plasma osmolality (Fig. 54.4). Depending on the cause, DI may be transient or a chronic, lifelong condition. There are several types of DI (Table 54.4). Central DI is the most common form. FIG. 54.4  Pathophysiology of diabetes insipidus. A schematic flow diagram of the pathophysiology of the diabetes insipidus. The decreased antidiuretic hormone leads to decreased water reabsorption in renal tubules, decreased intravascular fluid volume, increased serum osmolality, and excessive urine output. TABLE 54.4 Types of Diabetes Insipidus Type Cause Central (neurogenic) DI Interference with ADH synthesis, transport, or release Examples: Brain tumor, head injury, brain surgery, CNS infections Nephrogenic DI Inadequate renal response to ADH despite presence of adequate ADH Examples: Drug therapy (especially lithium), renal damage, hereditary renal disease Primary DI Excess water intake Examples: Structural lesion in thirst center, psychologic disorder Clinical Manifestations Key features of DI are polydipsia and polyuria. The patient excretes large quantities of urine (2 to 20 L/day) with a very low specific gravity (less than 1.005) and urine osmolality of less than 100 mOsm/kg (100 mmol/kg). Serum osmolality is increased (usually greater than 295 mOsm/kg \[295 mmol/kg\]) because of hypernatremia (serum sodium greater than 145 mg/dL) from pure water loss in the kidneys. Most patients compensate for fluid loss by drinking large amounts of water so that serum osmolality stays normal or is somewhat increased. The patient may be tired from nocturia and have generalized weakness. Uncorrected hypernatremia can cause brain shrinkage and intracranial bleeding. The onset of central DI is usually acute and accompanied by excess fluid loss. After intracranial surgery, central DI has a triphasic pattern: (1) an acute phase with an abrupt onset of polyuria, (2) an interphase in which urine volume normalizes, and (3) a third phase in which central DI may become permanent. The third phase occurs 10 to 14 days after surgery. Central DI from head trauma is often self-limiting. It improves with treatment of the underlying problem. Although the manifestations of nephrogenic DI are like those of central DI, the onset and amount of fluid loss are less dramatic. Severe dehydration can result if oral intake cannot keep up with urinary losses. The patient will have hypotension, tachycardia, and hypovolemic shock. Increasing serum osmolality and hypernatremia can cause central nervous system (CNS) manifestations, ranging from irritability and mental dullness to coma. Diagnostic Studies Patients with DI excrete dilute urine at a rate greater than 200 mL/h with a specific gravity of less than 1.005. We diagnose central DI with a water deprivation test. Before the test, we measure body weight, and urine osmolality, volume, and specific gravity. The patient is deprived of water for 8 to 12 hours and then given DDAVP subcutaneously or nasally. Patients with central DI have a dramatic increase in urine osmolality (from 100 to 600 mOsm/kg) and a significant decrease in urine volume. The patient with nephrogenic DI will not be able to increase urine osmolality to greater than 300 mOsm/kg. Another test to distinguish central DI from nephrogenic DI is to measure the ADH level after giving an analog of ADH (e.g., desmopressin). If the cause is central DI, the kidneys will respond to the hormone by concentrating urine. If the kidneys do not respond in this way, the cause is nephrogenic. Interprofessional and Nursing Care Management of DI includes early detection, maintaining adequate hydration, and patient teaching for self-management. A clinical goal is maintaining fluid and electrolyte balance. For central DI, fluid and hormone therapy are the cornerstone of treatment. We replace fluids orally or IV, depending on the patient's condition and ability to drink copious amounts. In acute DI, IV hypotonic saline or dextrose 5% in water (D5W) is given and titrated to replace urine output. If IV glucose solutions are used, monitor serum glucose levels. Hyperglycemia and glycosuria can lead to osmotic diuresis, which increases the fluid volume deficit. Monitor BP, heart rate, urine output, level of consciousness, and specific gravity. They may be done hourly in the acutely ill patient. Assess for signs of acute dehydration. Maintain an accurate record of intake and output and daily weights to determine fluid volume status. Adjustments in fluid replacement should be made accordingly. DDAVP, an analog of ADH, is the hormone replacement of choice for central DI. Another ADH replacement drug is aqueous vasopressin. DDAVP can be given orally, IV, subcutaneously, or as a nasal spray. Assess the response to DDAVP by monitoring pulse, BP, level of consciousness, intake and output, and specific gravity. Medications such as carbamazepine (Tegretol) can help decrease thirst associated with central DI. Because the kidney is unable to respond to ADH in nephrogenic DI, hormone therapy has little effect. Instead, the treatment includes a low-sodium diet and thiazide diuretics (e.g., chlorothiazide), which may reduce flow to the ADH-sensitive distal nephrons. Limiting sodium intake to no more than 3 g/day often helps decrease urine output. If a low-sodium diet and thiazide drugs are not effective, indomethacin may be prescribed. It is a nonsteroidal antiinflammatory drug (NSAID) that helps increase renal responsiveness to ADH. FIG. 54.5  Continuum of thyroid dysfunction. A schematic of the continuum of thyroid dysfunction. The thyrotoxicosis and hyperthyroidism show hyperthyroid dysfunction. The hypothyroidism and myxedema coma shows hypothyroid dysfunction. Between the hyper and hypo, it shows euthyroid.   TABLE 54.5 Goitrogens Thyroid Inhibitors Iodine in large doses Methimazole (Tapazole) Propylthiouracil (PTU) Other Drugs Amiodarone Lithium p-Aminosalicylic acid Salicylates Sulfonamides Select Foods Broccoli Brussels sprouts Cabbage Cauliflower Kale Mustard Peanuts Strawberries Turnips Thyroid Gland Problems Thyroid gland problems are among the most common endocrine disorders. The thyroid hormones T4 and T3 regulate energy metabolism and growth and development. Thyroid gland problems include goiter, benign and malignant nodules, inflammatory conditions leading to hyperthyroidism, and hypothyroidism (Fig. 54.5). Goiter A goiter is an enlarged thyroid gland. The person may have an overactive thyroid (hyperthyroidism) or an underactive thyroid (hypothyroidism). The most common cause of goiter worldwide is a lack of diet iodine. In the United States, where most people use iodized salt, goiter is more often due to the overproduction or underproduction of thyroid hormones or to nodules that develop in the thyroid gland. Goitrogens (foods or drugs that contain thyroid-inhibiting substances) can cause a goiter (Table 54.5). A nontoxic goiter is a diffuse enlargement of the thyroid gland that does not result from cancer or inflammation. The thyroid hormone levels are normal. Nodular goiters are thyroid hormone--secreting nodules. They function independently of TSH stimulation. There may be multiple nodules (multinodular goiter) or a single nodule (solitary autonomous nodule). The nodules are usually benign follicular adenomas. If these nodules cause hyperthyroidism, they are called toxic nodular goiters.10 This type of goiter is often found in patients with Graves disease (Fig. 54.6). Toxic nodular goiters occur equally in men and women. Although they can appear at any age, they most often occur in people over 40 years of age. FIG. 54.6  Goiter. From Iyomasa RM, Tagliarini JV, Rodrigues SA, et al.: Laryngeal and vocal alterations after thyroidectomy, Braz J Otorhinolaryngol 85:3, 2019. We measure TSH and T4 levels to determine whether a goiter is associated with normal thyroid function, hyperthyroidism, or hypothyroidism. Thyroid antibodies (e.g., thyroid peroxidase \[TPO\] antibody) show the presence of thyroiditis (inflammation of the thyroid). Treatment with thyroid hormone may prevent further thyroid enlargement. Surgery can remove large goiters. Goiter as a manifestation of thyroid disorders is discussed in the next sections. Thyroiditis Thyroiditis, an inflammation of the thyroid gland, encompasses several clinical disorders. It is a frequent cause of goiter. We think that subacute granulomatous thyroiditis is caused by a viral infection. Acute thyroiditis is due to bacterial or fungal infection. Subacute and acute forms of thyroiditis have an abrupt onset. The patient reports pain in the thyroid area or radiating to the throat, ears, or jaw. Systemic manifestations include fever, chills, sweats, and fatigue. Hashimoto thyroiditis (chronic autoimmune thyroiditis) is caused by the destruction of thyroid tissue by antibodies.11 It is the most common cause of hypothyroid goiters in the United States. Risk factors include female gender, a family history, older age, and White ethnicity. The goiter, which is the hallmark of Hashimoto thyroiditis, may develop gradually or rapidly. If it enlarges rapidly, it may compress structures in the neck (e.g., trachea, laryngeal nerves), changing the voice and affecting breathing. As antibodies destroy thyroid tissue, there may be a transient phase of hyperthyroidism due to leaking thyroid hormone from the damaged tissues. Silent, painless thyroiditis, which may be early Hashimoto thyroiditis, can occur in postpartum women. This condition is usually seen in the first 6 months after delivery. It may be due to an autoimmune reaction to fetal cells in the mother's thyroid gland. At first, T4 and T3 levels increase in subacute, acute, and silent thyroiditis. They decrease with time. Suppressed radioactive iodine uptake (RAIU) occurs in subacute and silent thyroiditis. In Hashimoto thyroiditis, T4 and T3 levels are usually low and the TSH level is high. Antithyroid antibodies are present in Hashimoto thyroiditis. Recovery from acute or subacute thyroiditis may be complete in weeks or months without any treatment. If the cause is bacterial, treatment may include antibiotics or surgical drainage. In the subacute and acute forms, NSAIDs (e.g., aspirin, naproxen) can relieve symptoms. With more severe pain, corticosteroids (e.g., prednisone up to 40 mg/day) can relieve discomfort. Propranolol (Inderal) or atenolol (Tenormin) may relieve cardiovascular symptoms related to a hyperthyroid state. The patient who is hypothyroid needs thyroid hormone therapy. Nursing care includes patient teaching about the disease process and treatment. Teach the patient not to stop medications abruptly. Tell the patient to remain under close health care supervision so that progress can be monitored. Teach the patient to report to the HCP any change in symptoms, such as trouble breathing or swallowing, swelling to face and extremities, or rapid weight gain or loss. Those receiving thyroid hormone need to know the expected side effects and ways to manage them. The patient with Hashimoto thyroiditis is at risk for other autoimmune diseases, such as Addison disease, pernicious anemia, or Graves disease. Teach the patient the signs and symptoms of these disorders, especially Addison disease. Hyperthyroidism Hyperthyroidism is hyperactivity of the thyroid gland with sustained increase in synthesis and release of thyroid hormones.12 It occurs in women more than men, with the highest frequency in persons 20 to 40 years old (Box 54.1). The most common form is Graves disease. Other causes include toxic nodular goiter, thyroiditis, excess iodine intake, pituitary tumors, and thyroid cancer. Since hyperthyroidism may be caused by iodinated contrast media used in CT scans and other radiologic studies, monitor those who are at risk closely after iodinated contrast media exposure. Thyrotoxicosis refers to the physiologic effects or clinical syndrome of hypermetabolism resulting from excess circulating levels of T4, T3, or both. Hyperthyroidism and thyrotoxicosis usually occur together. Subclinical hyperthyroidism occurs when the patient has a serum TSH level below 0.4 mU/L but normal T4 and T3 levels. Overt hyperthyroidism is defined by low or undetectable TSH and increased T4 and T3 levels. The patient may or may not have symptoms of hyperthyroidism. Etiology and Pathophysiology Graves disease is an autoimmune disease characterized by thyroid enlargement and excess thyroid hormone secretion. It accounts for 75% of the cases of hyperthyroidism. We do not know the exact cause. Risk factors, such as a lack of iodine, smoking, infection, and stress, may interact with genetic factors to cause Graves disease. Box 54.1 BIOLOGIC SEX CONSIDERATIONS Endocrine Problems Men Ectopic ACTH production is more common. Women Thyroid disorders are more common. Graves disease affects 5 times more women. Thyroid nodules and thyroid cancer affect up to 4 times as many women. Hyperparathyroidism affects twice as many women. Cushing disease and primary hyperaldosteronism are more common. In Graves disease, the patient develops antibodies to TSH receptors. These antibodies attach to the receptors and stimulate the thyroid gland to release T3, T4, or both. Excess thyroid hormones lead to the manifestations of thyrotoxicosis. Remissions and exacerbations occur, with or without treatment. It may progress to destruction of the thyroid tissue, causing hypothyroidism. Graves disease is associated with the presence of other autoimmune disorders, including rheumatoid arthritis, pernicious anemia, systemic lupus erythematosus, Addison disease, celiac disease, and vitiligo. Clinical Manifestations The manifestations are related to the effect of excess circulating thyroid hormones. They directly increase metabolism and tissue sensitivity to sympathetic nervous system stimulation. Palpation of the thyroid gland may reveal a goiter. When the thyroid gland is excessively large, you may be able to see a goiter (Fig. 54.6). Auscultating the thyroid gland may reveal bruits from the increased blood supply. Another common finding is ophthalmopathy, a term used to describe abnormal eye appearance or function. A classic finding in Graves disease is exophthalmos, a protrusion of the eyeballs from the orbits (see Fig. 22.9). Exophthalmos results from increased fat deposits and fluid (edema) in the orbital tissues and ocular muscles. The increased pressure forces the eyeballs outward. The upper lids are usually retracted and elevated, with the sclera visible above the iris. When the eyelids do not close completely, the exposed corneal surfaces become dry and irritated. Corneal ulcers and loss of vision can occur. Changes in the ocular muscles result in muscle weakness, causing diplopia. Other manifestations are outlined in Table 54.6. Abnormal laboratory findings are shown in Table 54.7. A patient in the early stages of hyperthyroidism may only have weight loss and increased nervousness. Acropachy (clubbing of the digits) may occur with advanced disease (Fig. 54.7). Manifestations (e.g., palpitations, tremors, weight loss) in older adults do not differ significantly from those of younger adults (Table 54.8). In older patients who are confused and agitated, we may suspect dementia and delay the diagnosis. Complications Acute thyrotoxicosis (thyrotoxic crisis or thyroid storm) is an acute, severe, rare condition that occurs when excess amounts of thyroid hormones are released into the circulation. Although considered a life-threatening emergency, death is rare when treatment is started early. We think that it results from stressors (e.g., infection, trauma, surgery) in a patient with preexisting hyperthyroidism. Patients having a thyroidectomy are at risk because manipulation of the hyperactive thyroid gland results in the increased release of hormones. In acute thyrotoxicosis, all the symptoms of hyperthyroidism are prominent and severe. Manifestations include severe tachycardia, heart failure, shock, hyperthermia (up to 106°F \[41.1°C\]), agitation, delirium, seizures, abdominal pain, vomiting, diarrhea, and coma. Diagnostic Studies The primary laboratory findings used to confirm the diagnosis of hyperthyroidism are low or undetectable TSH levels (\