XII. E NDOCRINE AND M ETABOLIC D ISORDERS — A NSWERS 319 XII-62. The answer is E. (Chap. 333. Rits, Orth, N Engl J Med 341:1127 – 1133, 1999.) Patients with type 2 diabetes mellitus are at an increased risk for the development of renal failure. The risk of nephropathy is strongly determined by genetics, and familial clustering is typically seen in diabetic patients. Factors that increase the risk of progression to end- stage renal failure include hypertension, albuminuria, poor glycemic control, smoking, high dietary intake of protein, and hyperlipidemia. Once nephropathy is developed, patients can decrease the risk of progression by achieving better glycemic control and maintaining better control of their blood pressure. In addition, cessation of smoking as well as the restriction of dietary protein are also thought to be helpful. Patients with diabetes who have microalbuminuria have not yet begun to lose glomerular filtration, but are at a high risk for the development of renal complications. Microalbuminuria is defined as a urinary albumin excretion rate of 30 to 300 mg per 24 h on two of three measurements. The test results cannot be interpreted correctly in the presence of a urinary tract infection, fever, uncontrolled hyperglycemia, or hypertension or in the presence of congestive heart failure. Patients with diabetes who have microalbuminuria also have an extremely high risk for the development of cardiovascular complications. A 1995 consensus statement recom- mended antihypertensive treatment, preferably with ACE inhibitors, be started once mi- croalbuminuria has been documented. XII-63. The answer is E. (Chap. 328) Because the half-life of T is ϳ1 week, the total T will 44 still be normal the day after the pituitary ceases to function. T is derived primarily from 3 T , and so it will still also be normal. IGF-I is a useful test for detecting growth hormone 4 excess as occurs in acromegaly, but it is not a sensitive test of growth hormone deficiency. In addition, IGF-I would not fall rapidly to a new steady level. Likewise, an ACTH stim- ulation test would be normal even though the patient had adrenal insufficiency. The adrenal glands would not yet have atrophied and could still respond to exogenous ACTH. A test more likely to detect adrenal insufficiency in this case would be an insulin tolerance test, in which a small dose of regular insulin is administered in a monitored setting to induce hypoglycemia therapy stimulation and the release of counterregulatory hormones, includ- ing cortisol. Increased cortisol secretion in this case relies on the pituitary’s ability to release ACTH, not just on the adrenal’s ability to respond to ACTH. The insulin tolerance test should never be performed in elderly patients and patients with heart disease. XII-64. The answer is D. (Chap. 330) This patient has postpartum thyroiditis, which occurs in 5 to 9% of all postpartum women. Appropriate treatment is symptomatic because the hyperthyroidism is caused by the release of preformed thyroid hormone from a damaged thyroid gland. Therefore, therapies aimed at decreasing the formation of thyroid hormone, such as methimazole, or at inhibiting its release, such as SSKI, will be ineffective. Radio- active iodine also will be ineffective, since it will not be taken up by the damaged thyroid gland (reflected in the 1% 24-h iodine uptake). In addition, the hyperthyroidism will resolve spontaneously. Steroids are effective in subacute thyroiditis, which is characterized by a tender thyroid and often is preceded by a viral illness, but are not used in postpartum thyroiditis. Therapies, such as beta blockers, aimed at treating symptoms are the most effective treatment. Postpartum thyroiditis is a form of lymphocytic thyroiditis, a painless inflammation of the thyroid that is thought to be autoimmune in etiology. About one-third of patients enter a hypothyroid phase after experiencing hyperthyroidism. Eighty percent of these women recover normal thyroid function, but 20% remain hypothyroid and require indefinite re- placement therapy. Therefore, serial thyroid function testing is indicated. XII-65. The answer is B. (Chaps. 7, 330. Daniels, Endocrine Pract 1:287, 1995.) Radioactive iodine should never be given to a pregnant woman. In addition, both methimazole and beta blockers should be avoided in pregnant women. Methimazole may lead to an increased incidence of aplasia cutis, a fetal scalp defect. Beta blockers may lead to neonatal hypo- glycemia. Antithyroid drugs, including propylthiouracil, cross the placenta and affect fetal thyroid function. Studies have shown that when a treated pregnant woman’s thyroid func- XII. E NDOCRINE AND M ETABOLIC D ISORDERS — A NSWERS 320 tion is in the mid-normal range, the fetus is hypothyroid. When the mother’s thyroid tests are maintained in the high-normal or slightly hyperthyroid range, the fetus is likely to have normal thyroid function. Severe maternal hyperthyroidism is potentially dangerous for the fetus, but mild maternal hyperthyroidism poses a much smaller risk. XII-66. The answer is C. (Chap. 328) Although the most common pituitary tumor is a pro- lactinoma, this tumor is more likely a nonfunctioning pituitary adenoma. Though the pro- lactin level is elevated, one would expect it to be much higher with a prolactinoma this large. The mildly elevated prolactin most likely results from compression of the infundib- ular stalk. This tumor should be removed, as it is macroscopic and near the optic chiasm. Further growth could result in impairment of the patient’s vision. The surgery usually is performed using a transsphenoidal approach, a technique that avoids the morbidity of a craniotomy and carries minimal risk in the hands of an experienced surgeon. XII-67. The answer is A. (Chap. 334. DeFronzo, N Engl J Med 333:541, 1995. Groop, Diabetes Care 15:737, 1992.) Sulfonylureas have long half-lives. One such agent, chlorpropa- mide, has a half-life of 24 h. Though the patient’s glucose is normal after an intravenous dextrose infusion, he may become hypoglycemic again hours later. He therefore should be hospitalized with careful monitoring of glucose and mental status until the effects of the sulfonylurea have resolved. Though metformin does not cause prolonged hypoglyce- mia, it is contraindicated in patients with organ failure, as the combination may predispose to lactic acidosis. Sulfonylurea administration is by far the most likely cause of this man’s first episode of hypoglycemia, and a workup for insulinoma is unlikely to be revealing. XII-68. The answer is D. (Chap. 344) Cigarette smoking has been shown to be associated with low HDL but not with hypertriglyceridemia. Alcohol, diabetes mellitus, obesity, and preg- nancy are all causes of hypertriglyceridemia. In addition, many medications may cause hypertriglyceridemia, including estrogen, isotretinoin, beta blockers, glucocorticoids, and thiazides. XII-69. The answer is A. (Chap. 340. Liberman, N Engl J Med 333:1437, 1995; Mincey et al, Mayo Clin Proc 75:821 – 829; 2000.) Alendronate and raloxifene are currently approved in the United States for the prevention of osteoporosis. Alendronate, raloxifene, and cal- citonin are approved for treatment. While estrogen therapy is considered standard for the prevention and treatment of osteoporosis, use of estrogen in women with a history of breast cancer is usually contraindicated. Alendronate has been shown to increase bone density and decrease fracture rates. Alendronate is available as a once-a-week formulation, which allows for more convenient dosing and greater compliance. Its most common complication is esophagitis, and so it is recommended that it be taken with a full glass of water and that the patient remain upright for at least half an hour after taking the pill. Pamidronate, another bisphosphonate, can be given only intravenously and is not used for osteoporosis. Estrogen replacement therapy, weight-bearing exercise, and nasal calcitonin have all demonstrated efficacy in the treatment of osteoporosis. Nasal calcitonin may not be as effective as estrogen or alendronate and usually is not chosen as a first-line treatment. XII-70. The answer is C. (Chap. 341) Hypoparathyroidism would cause a high, not low, phos- phate. Transient hypoparathyroidism caused by atrophy of the remaining parathyroid glands may occur after parathyroid adenoma removal. However, this condition would be expected to resolve over 24 to 48 h. Magnesium deficiency may cause hypocalcemia, but this process is mediated through impairment of parathyroid hormone (PTH) secretion and end-organ resistance to PTH. Therefore, magnesium deficiency also would be expected to result in a high serum phosphate. Parathyroid cancer would be expected to cause hyper- calcemia if it was not completely removed at surgery. However, complete excision could result in hypoparathyroidism because of atrophy of the other parathyroid glands. Again, one would expect this to resolve rapidly. Hungry bone syndrome occurs when calcium- XII. E NDOCRINE AND M ETABOLIC D ISORDERS — A NSWERS 321 starved bones that have been under the influence of high PTH take up calcium avidly after the removal of a parathyroid adenoma. Aggressive calcium supplementation may be nec- essary for months after surgery. Risk factors for the development of this syndrome include a high preoperative alkaline phosphatase level and a large tumor. XII-71. The answer is A. (Chap. 328) This patient has postoperative diabetes insipidus, a common complication of surgery in the area of the hypothalamus. A water deprivation test is not necessary for the diagnosis because the patient already manifests the elements necessary to make the diagnosis: a serum sodium greater than normal, accompanied by inappropriately dilute urine. Fluid restriction could be dangerous in this patient, who could develop life-threatening hypernatremia. Instead, the patient should be encouraged to drink when thirsty and should be given one dose of desmopressin. If the patient’s thirst mech- anism is intact, he will be thirsty until his serum sodium level corrects. He should not be placed on a standing dose of desmopressin bid, as the effects of the first dose may not have resolved 12 h later. In addition, postoperative diabetes insipidus can be followed by SIADH, leading to iatrogenic hyponatremia caused by this regimen. Instead, the patient should be given one dose of desmopressin, be encouraged to drink when thirsty, and have his serum sodium monitored twice a day. The urine osmolality or specific gravity and urine output also should be monitored. A brain MRI is not necessary unless there is no other evidence of a central nervous system complication, since this is a common, expected, and usually transient complication of this type of neurosurgery. Classically, these patients experience a short period of diabetes insipidus, followed by an episode of SIADH, followed by diabetes insipidus. In practice, many patients do not experience all three stages. XII-72. The answer is C. (Chap. 328) This patient may have hypopituitarism, but it is unclear from his laboratory results. A random cortisol of 135 nmol/L (4.8 ␮ g/dL) in the middle of the stress of hypotension and an illness severe enough to warrant an intensive care unit are quite suggestive of adrenal insufficiency (though one cannot differentiate between primary and secondary causes with a cortisol alone). However, the patient’s cortisol level is not diagnostic, and dexamethasone should be given to this critically ill patient to provide him with adequate glucocorticoid coverage while a cosyntropin stimulation test is per- formed. Dexamethasone will not interfere with the performance of the cosyntropin stim- ulation test. This will ensure that an accurate diagnosis is made before the patient is committed to lifelong glucocorticoid therapy. Hydrocortisone, prednisone, and methyl- prednisolone all cross-react with the cortisol assays and produce falsely elevated values. The thyroid function tests could reflect secondary hypothyroidism, but it is more likely that they represent the sick euthyroid state, since the TSH is only mildly low and the total T is proportionally lower than the free T index. Thyroid hormone replacement in patients 34 with the sick euthyroid syndrome has not been shown to improve the outcome. The low testosterone, accompanied by the low LH and FSH, provides evidence of secondary hy- pogonadism. Of note, severe illness can produce temporary hypogonadism. In these cases, testosterone recovers when the patient recovers. This patient could have hypogonadism, but one must wait until he recovers from his illness to determine this definitively. Further, though testosterone is important for his long-term health, it will not contribute to recovery from his acute illness. XII-73. The answer is C. (Chap. 330. Laderson, Am J Med 77:261, 1984.) A TSH of 81 mU/L is evidence of primary hypothyroidism. Studies have shown that hypothyroidism does not significantly increase cardiac surgery mortality, and giving thyroid hormone be- fore surgery could exacerbate cardiac ischemia angina. Therefore, cardiac surgery should not be delayed while one waits for thyroid hormone levels to be restored. In patients with primary hypothyroidism and heart disease, thyroid hormone should be replaced gradually, starting with a low dose of 0.025 mg a day and increasing the dose slowly. Rapid replace- ment with the shorter-acting T (Cytomel) may exacerbate the patient’s angina, as might 3 the fluctuations in thyroid hormone levels. There is no evidence that this patient has hy- XII. E NDOCRINE AND M ETABOLIC D ISORDERS — A NSWERS 322 popituitarism, since the high TSH provides evidence of primary, not secondary, hypothy- roidism. Propylthiouracil is a medication that may be given to a person with hyperthy- roidism, not one with hypothyroidism. XII-74. The answer is B. (Chaps. 328, 331) After an ACTH-producing tumor is removed from the pituitary, the patient will have adrenal insufficiency and require glucocorticoids for a year. Normal ACTH-producing pituitary cells have atrophied but do eventually recover to function normally. The patient should have been started on glucocorticoids the time of surgery with a slow taper over a period of months. The choice of dexamethasone as the glucocorticoid would allow accurate assessment of the hypothalamic-pituitary-adrenal axis in the immediate postoperative setting. Prednisone could be initiated in place of dexa- methasone after testing is completed. It would be very unusual to remove enough normal ACTH-producing pituitary cells to cause adrenal insufficiency while leaving enough TSH- producing cells to maintain normal thyroid function. XII-75. The answer is D. (Chaps. 328, 331. Oldfield, N Engl J Med 325:897, 1991.) Pituitary tumors suppress with high-dose dexamethasone and are more common than adrenal and ectopic tumors. Suppression is defined as a Ͼ90% decrease in the 24-h urine free cortisol on the second day. However, some ectopic ACTH-producing tumors, particularly carci- noids, also are suppressed with high-dose dexamethasone. The next step in localizing the tumor is the performance of a petrosal sinus catheterization. Concomitant administration of CRH during this procedure will increase its accuracy. If peripheral ACTH levels are more than double central levels, the tumor is most likely ectopic. If, however, the central ACTH levels are more than double the peripheral levels, the tumor is more likely to be pituitary in origin. If testing suggests a pituitary origin, an MRI with and without gadolin- ium is warranted. If testing suggests an ectopic source, locating the tumor can be difficult. One might start with a fine-cut CT scan of the lungs. Octreotide scans sometimes may be helpful in locating ectopic tumors. If the 24-h urine free cortisol had not suppressed, one would expect the tumor to be either adrenal or ectopic in origin. XII-76. The answer is D. (Chap. 330) The contrast used in catheterization procedures contains iodine. Iodine tends to worsen hyperthyroidism caused by autonomous nodules, whereas it inhibits the release of thyroid hormone in patients with autoimmune thyroid disease such as Graves’ disease and Hashimoto’s thyroiditis. Iodine-containing medications sometimes are used in the treatment of Graves’ disease. If a patient is known to have an autonomous nodule, he or she should receive an antithyroid drug such as methimazole or propylthio- uracil before undergoing catheterization. Further, the antithyroid medication should be continued for at least 2 weeks after the procedure. XII-77. The answer is E. (Chap. 330) This entity of self-induced thyrotoxicosis is most com- monly seen in medical and paramedical personnel and in those with easy access to thyroid hormone. Weight loss induction is one motivation for taking the unprescribed thyroid hormone in supraphysiologic doses. The patient’s thyroid is suppressed because of nega- tive feedback. Therefore, the 24-h radioactive iodine uptake is low, as in thyroiditis. This entity can be distinguished from thyroiditis by the presence of a low thyroglobulin. Graves’ disease and toxic multinodular goiters cause an elevated 24-h radioactive iodine uptake. XII-78. The answer is B. (Chaps. 28, 333. Ferris et al, N Engl J Med 341:667 – 678, 1999.) Preventing diabetic retinopathy is the most effective approach toward the preservation of vision. The Diabetes Control and Complications Trial (DCCT) studied 1441 patients with type 1 diabetes. Approximately 50% of these patients had mild to moderate nonprolifer- ative retinopathy at baseline. The patients were randomly assigned to receive either inten- sive or conventional therapy and were followed for a mean of 6.5 years. Improved glycemic control produced a remarkable reduction not only in the rate of the development of reti- nopathy but also in the progression of already established mild to moderate retinopathy. It should be noted that better control of hyperglycemia lowers but does not eliminate the XII. E NDOCRINE AND M ETABOLIC D ISORDERS — A NSWERS 323 risk of retinopathy and other complications of diabetes mellitus. Several studies suggest that the treatment of hypertension may also slow the progression of diabetic retinopathy. This may not be a specific class effect as patients treated with both captopril, an ACE inhibitor, and atenolol showed equal benefits towards the reduction of progressive reti- nopathy. In addition, reduction in the serum lipid concentration may also slow the pro- gression of diabetic retinopathy. The use of aspirin has little or no effect on diabetic retinopathy. Although smoking cessation clearly decreases the risk of cardiovascular mor- bidity in patients with diabetes mellitus, it is unclear whether this prevents the progression of diabetic retinopathy. XII-79. The answer is D. (Chap. 339. Chandrasekharappa, Science 276:404, 1997.) MEN I is characterized by hyperparathyroidism, pancreatic islet cell tumors, and pituitary tumors. The hyperparathyroidism can be particularly difficult to manage, as it usually is caused by four-gland hyperplasia and recurs after surgery. Hyperparathyroidism is the most common manifestation of the syndrome. Most individuals are affected by age 40. Islet cell tumors are the second most common manifestation of MEN I. Pituitary tumors occur in more than half of MEN I patients. The most common type of pituitary tumor found in this population is a prolactinoma. The gene implicated in the pathogenesis of MEN I has been cloned. It is located on chromosome 11 and has been named MENIN. MEN I is inherited in an autosomal dominant fashion. A c-RET proto-oncogene mutation has been identified in 93 to 95% of patients with MEN II, not in those with MEN I. XII-80. The answer is B. (Chap. 333) The mainstay of therapy for diabetic ketoacidosis (DKA) is insulin and intravenous fluids. DKA cannot be reversed without insulin. The usual fluid deficit is 3 to 5 L, and both salt solutions and free water are needed. Because glucose levels drop more quickly than ketones disappear from the plasma, it is usually necessary to give intravenous dextrose when the blood glucose level drops below about 14 to 16.7 mmol/L (250 to 300 mg/dL). This allows continued administration of insulin to clear the ketones from the blood. Although the serum potassium concentration is high, there is a total body patassium deficit of several hundred millimoles. The potassium con- centration will drop quickly as the pH rises, causing potassium to enter cells. Bicarbonate therapy is not recommended unless the arterial pH falls below 7.10 or 7.00 because the rapid alkalinization may impair oxygen delivery to tissues and impair left ventricular func- tion. In addition, insulin therapy is effective in reversing the acidemia without the assist- ance of bicarbonate therapy. XII-81. The answer is C. (Chap. 339. Neufeld et al, Medicine 60:355 – 362, 1981.) Polyglan- dular autoimmune syndrome type II (Schmidt’s syndrome) is characterized by lymphocytic infiltration of the adrenal and thyroid glands along with type 1 diabetes mellitus in about half of affected families. Hypogonadism is also common. A few patients develop transient hypoparathyroidism caused by antibodies that compete with parathyroid hormone for bind- ing to the parathyroid receptor. Mucocutaneous candidiasis does not occur as part of this syndrome. Instead, it occurs in most patients with polyglandular autoimmune syndrome type I. Patients who are found to have hypothyroidism should first be checked for adrenal insufficiency prior to the initiation of thyroid replacement medication. XII-82. The answer is E. (Chaps. 28, 333. Ferris et al, N Engl J Med 341:667 – 678, 1999.) Blindness resulting from proliferative diabetic retinopathy continues to be a growing health epidemic. The use of retinal photocoagulation can effectively treat neovascular changes to the retina and can even reverse the development of macular edema. The diabetic retinop- athy study enrolled 1742 patients with severe nonproliferative or proliferative diabetic retinopathy. Patients were randomly assigned to treat only one eye with photocoagulation; the other eye received no treatment. After a 5-year follow-up, a 50% reduction in severe visual loss in the eyes that had received photocoagulation as compared to the eyes that received no photocoagulation suggested that photocoagulation can reduce the development of severe diabetic retinopathy. The timing of this therapy is somewhat debatable. The XII. E NDOCRINE AND M ETABOLIC D ISORDERS — A NSWERS 324 Early Treatment Diabetic Retinopathy Study (ETDRS) enrolled 3711 patients with either nonproliferative or early proliferative diabetic retinopathy. Again, only one eye was treated, and there was a significant reduction in the progression of diabetic retinopathy in the treated eye. It was determined that aspirin or other antiplatelet therapy was ineffective in reducing the progressive retinal changes. This patient already has excellent glycemic control with the use of metformin; it is unclear whether or not more aggressive treatment with insulin would be more effective as the DCCT trial analyzed only patients with type 1 diabetes mellitus. XII-83. The answer is D. (Chap. 354) Generalized lipodystrophy is characterized by loss of body fat and metabolic abnormalities, including insulin resistance, hyperglycemia, hyper- triglyceridemia, and a high metabolic rate despite normal thyroid function. The congenital form is autosomal recessive, while the acquired form often develops after an illness such as measles, chickenpox, whooping cough, or infectious mononucleosis. Other abnormal- ities associated with this disorder include paradoxical fatty engorgement of the liver and enlarged kidneys and genitalia. Mental retardation is seen in about half the congenital cases. Linear growth is accelerated in the first few years of life, but epiphyses close early so that the final height is usually normal. A few patients will develop hypertrophic car- diomyopathy, but it rarely leads to heart failure. Fatty liver has been noted during infancy and can lead to cirrhosis and its complications. XII-84. The answer is D. (Chaps. 75, 334, 340) Less than 5% of cases of DKA are accom- panied by severe phosphorus deficiency, though serum inorganic phosphorus often falls after therapy for DKA is initiated as phosphorus is shifted into cells. Patients who present in DKA with hypokalemia and hypophosphatemia are more likely to be severely potas- sium- and phosphorus-depleted and probably will require treatment with phosphorus. Such a patient usually has been sick for many days, has maintained a good fluid intake, and has not had significant vomiting. The insulin deficiency and metabolic acidosis mobilize in- tracellular phosphate stores, and the patient excretes the phosphorus briskly for days before presentation. XII-85. The answer is A. (Chap. 330. Hermus, Huysmans, N Engl J Med 338:1438 – 1447, 1998.) A clinically solitary thyroid nodule is a discrete swelling within an otherwise palpably normal thyroid gland. With time, many solitary thyroid nodules may enlarge, shrink, or eventually disappear spontaneously. However, most do not change appreciably. The majority of these nodules are benign colloid nodules. Other causes of benign solitary nodules are thyroid adenomas, cysts, and thyroiditis. Approximately 5% of all solitary thyroid nodules are thyroid carcinomas. Fine-needle aspiration biopsy is indicated in all patients with solitary thyroid nodules and is especially helpful in patients with no other obvious signs of carcinoma. When this technique is used, approximately 70% of nodules are found to be cytologicaly benign. The false-negative rate is Ͻ5%. Approximately 4% of these lesions are found to be malignant. In the remaining patients, an indeterminate finding is made. This is typically due to the insufficient number of follicular cells recovered in order to make a definitive diagnosis. In these patients thyroid scintigraphy with iodine 123 (or iodine 131) should demonstrate a hyperfunctioning nodule. Autonomously func- tioning nodules are rarely malignant. A negative iodine 123 thyroid scintigraph should be followed up with surgery. XII-86. The answer is A. (Chap. 51. Lue, N Engl J Med 342:1802– 1813, 2000.) Androgens increase libido, but their exact role in erectile dysfunction remains unclear. Individuals with castrate levels of testosterone can still achieve erections from visual or sexual stimuli. Increased prolactin levels decrease libido by suppressing gonadotropins-releasing hormone (GnRH), which indirectly leads to a decreased serum testosterone level. Patients with diabetes mellitus have reduced amounts of nitric oxide synthase in both endothelial and neural tissues. Psychogenic erectile dysfunction is caused by a psychogenic stimulus to the sacral cord which inhibits reflexogenic responses. In addition, excess sympathetic stim- XII. E NDOCRINE AND M ETABOLIC D ISORDERS — A NSWERS 325 ulation may cause increased penile smooth muscle tone. Among the antihypertensive agents, the thiazide diuretics and beta blockers have been implicated most frequently. Calcium channel blockers and angiotensin-converting enzymes are less frequently sited. Alpha blockers are less likely to be associated with erectile dysfunction. XII-87. The answer is B. (Chap. 51. Lue, N Engl J Med 342:1802 – 1813, 2000; Goldstein et al, Sildenafil Study Group, N Engl J Med 338:1397–1404, 1998.) Sildenafil has been proven effective in the treatment of erectile dysfunction. Sildenafil is a selective inhibitor of cyclic GMP – specific phosphodiesterase type V. This is the predominant isoenzyme which metabolizes cyclic GMP in the corpus cavernosum. The mechanism by which cyclic GMP stimulates relaxation in the smooth muscles remains to be elucidated. Sildenafil has no effect on libido or sexual performance. Sildenafil is effective in the management of erectile dysfunction from a broad range of causes. These include psychogenic, diabetic, vasculogenic, postradical prostatectomy, and spinal cord injury. The onset of action is ϳ60 to 90 min; reduced initial doses should be considered for patients who are elderly or who have renal insufficiency. In addition, patients taking nitrates for coronary disease should avoid sildenafil. Side effects associated with sildenafil include headaches, facial flushing, dyspepsia, and nasal congestion. In addition, ϳ7% of men may experience a transient altered color vision (blue halo effect). XII-88. The answer is A. (Chaps. 155, 333. Joshi et al; N Engl J Med 341:1906 – 1912, 1999.) This patient has malignant external otitis, which usually is caused by Pseudomonas ae- ruginosa. It tends to occur in older patients with diabetes mellitus who present with severe ear pain, drainage, fever, leukocytosis, and soft tissue swelling around the ear. The facial nerve is paralyzed in about 50% of cases, and this subset carries a poor prognosis with a 50% mortality rate. A mound of granulation tissue is usually present at the junction of the osseous and cartilaginous portions of the ear. The treatment of choice is a 6-week course of ticarcillin or carbenicillin plus tobramycin. In addition, surgical debridement is often necessary. CT of the mastoid or temporal bone typically reveals bony erosions and new bone formation, while the floor of the skull may have soft tissue densities associated with areas of cellulitis. XII-89. The answer is E. (Chaps. 128, 333. Joshi et al, N Engl J Med 341:1906–1912, 1999.) Necrotizing fasciitis is caused by mixed aerobic-anaerobic bacteria. Infection typically begins in a breach in the integrity of a mucus membrane barrier, such as the mucosa of the gastrointestinal or genitourinary tract. The portal can be a malignancy, hemorrhoid, or fissure. Other predisposing factors include peripheral vascular disease, diabetes mellitus, or immunosuppression from chemotherapy. Leakage into the perineal area results in a syndrome called Fournier’s gangrene. This is characterized by massive tissue swelling of the scrotum and penis with extension into the perineum or the abdominal wall and anterior portion of the lower extremities. A cutaneous wound or eschar is often noted. Crepitus is a useful finding but is noted in only half of the cases. Soft tissue gas may be detected more frequently by plain radiography than by clinical examination. Emergency evaluation and treatment of necrotizing fasciitis are imperative. Both clindamycin and penicillin are used secondary to the possibility of clindamycin resistance and the potentially life-threatening nature of this infection. Prompt aggressive surgical debridement is crucial in decreasing mortality. XII-90. The answer is A. (Chap. 341. Strewler, N Engl J Med 342:177 – 185, 2000.) The secretion of parathyroid hormone – related protein is the predominant cause of hypercal- cemia in patients with cancer. Among patients with solid tumors and hypercalcemia, ϳ80% have increased levels of parathyroid hormone – related protein. Parathyroid hormone – re- lated protein increases both bone and renal tubular resorption of calcium. Both parathyroid hormone – related protein and parathyroid hormone have phosphaturic action. In addition to the humeral effects, parathyroid hormone – related protein can also induce local oste- olysis around bone metastases. Parathyroid hormone – related protein is found in many XII. E NDOCRINE AND M ETABOLIC D ISORDERS — A NSWERS 326 tissues in both fetuses and adults, including epithelia, mesenchymal tissues, endocrine glands, and the central nervous system. Gene-knockout models in mice have suggested that parathyroid hormone – related protein is critical for embryonic development. A ho- mozygous null mutation of the parathyroid hormone – related protein in mice reveals severe defects in the development of cartilage. The domain of the protein that is homologous between the parathyroid hormone and the parathyroid hormone – related protein is amino acids 1–13 of the amino portion of the protein. XII-91. The answer is A. (Chap. 328) Medications are important causes of hyperprolactine- mia. Drugs implicated in hyperprolactinemia include dopamine-blocking drugs (e.g., phe- nothiazines, butyrophenones, metoclopramide, resperidone) and dopamine-depleting drugs (e.g., methyldopa and reserpine). In addition, chronic cocaine use can cause hyperprolac- tinemia. Severe primary hypothyroidism can cause hyperprolactinemia either through the increase in the thyroid-releasing hormone (TRH) level or through a decrease in dopamin- ergic tone. Therefore, levothyroxine would not be expected to cause hyperprolactinemia. Glucocorticoids and cigarette use do not cause elevations of the serum prolactin level. XII-92. The answer is B. (Chap. 334) Drugs are important causes of hypoglycemia. Insulin, sulfonylureas, disopyramide, and pentamidine all cause hypoglycemia through hyper- insulinemia. Sulfonamides and salicylates may interact with the sulfonylurea receptor. Thiazides can cause an exacerbation of glucose intolerance and worsen hyperglycemia. Beta agonists such as epinephrine and calcium channel blockers have no effect on serum glucose levels. Acetaminophen when taken in normal dosages does not affect the serum glucose concentration; however, an overdose causing hepatic damage could lead to severe hypoglycemia. XII-93. The answer is D. (Chaps. 52, 336) The luteal phase of the menstrual cycle follows ovulation and is characterized by an increase in progesterone secretion by the corpus luteum. With anovulatory cycles, the corpus luteum does not form and progesterone levels remain low. Furthermore, with anovulatory cycles, the characteristic surge of LH and FSH at midcycle is absent and menses are usually painless. Irregular estrogen breakthrough bleeding that occurs with anovulatory cycles is the consequence of persistent ovarian estradiol secretion and an absence of luteal-phase progesterone secretion. XII-94. The answer is C. (Chap. 341) Familial hypocalcemia, short stature, and abnormalities of the metacarpal and metatarsal bones are characteristic features of congenital pseudo- hypoparathyroidism (Albright’s hereditary osteodystrophy). The underlying defect is renal resistance to the action of parathyroid hormone, caused in many patients by a mutation in a guanyl-nucleotide-binding protein. Although plasma levels of parathyroid hormone are elevated, urinary cyclic AMP is low, and there is a diminished response of urinary cyclic AMP to the exogenous administration of the hormone. The basal ganglia are frequently calcified. No antibodies to parathyroid tissue can be demonstrated, and unlike the situation in idiopathic hypoparathyroidism, the frequency of monilial infection is not increased. Hypothyroidism is common in persons with pseudohypoparathyroidism; it is usually a result of resistance to TSH resulting from the same defect in membrane adenylate cyclase activity that causes resistance to parathyroid hormone. As with true hypoparathyroidism, patients have low calcium and high phosphate levels. XII-95. The answer is B. (Chap. 77. Rosenbaum et al, N Engl J Med 337:396– 407, 1997; Calle et al, N Engl J Med 341:1097– 1105, 1999.) Obesity is the most common and costly nutritional problem in the United States and affects approximately one-third of all adults. A BMI Ͼ 28 is associated with the risk of morbidity such as stroke, ischemic heart dis- ease, or diabetes mellitus that is three to four times the risk in the general population. A central distribution of body fat is associated with a higher risk of morbidity and mortality than a more peripheral distribution of body fat. Obesity in childhood appears to increase the risk of subsequent morbidity, whether or not obesity persists into adulthood. The risk XII. E NDOCRINE AND M ETABOLIC D ISORDERS — A NSWERS 327 associated with a high BMI is greater for whites than for blacks. With the exception of a few single-gene disorders that result in obesity (e.g., Prader-Willi syndrome), obesity is probably due to subtle alterations between multiple genetic and environmental factors that favor the net deposition of calories as fat. XII-96. The answer is C. (Chap. 343. Delmas, Meunier, N Engl J Med 336:558 – 566, 1997.) Paget’s disease of the bone is characterized by a localized increase in bone remodeling. This leads to marked bone hypertrophy as well as abnormal bone structure. Patients often present with pain and bone deformities. If the skull is affected, it may be grossly enlarged with irreversible hearing loss. Fractures are often noted and may be secondary to only minimal trauma. Complications resulting from nerve entrapment may be serious, especially if the spine is affected. The most characteristic feature of Paget’s disease noted radiograph- ically is the localized enlargement of bone. Other radiographic features include cortical thickening and sclerotic changes. Radionucleotide bone scanning is the most reliable means of identifying Paget’s lesions. Serum alkaline phosphatase concentrations may be markedly elevated, and urinary hydroxyproline excretion is usually increased. Patients with Paget’s disease who have bone pain or articular pain may benefit from therapy with acetaminophen and nonsteroidal anti-inflammatory drugs. In addition patients should receive antiresorptive therapy. An oral bisphosphonate, such as alendronate, should be the first choice of therapy. Intravenous pamidronate is an alternative if the patient’s long-term compliance with oral treatment is doubtful. XII-97. The answer is A. (Chap. 328) The development of a pituitary adenoma in a patient who has undergone bilateral adrenalectomy for the treatment of Cushing’s disease is termed Nelson’s syndrome. This disorder is characterized by hyperpigmentation, erosion of the sella turcica, and high plasma ACTH levels. Because of adrenalectomy, urinary 17- ketosteroid excretion usually is low; plasma cortisol levels are determined by the regimen of replacement therapy. These tumors can cause significant mass effects such as bitemporal hemianopia from optic chiasm compression or oculomotor nerve palsy from cavernous sinus invasion. XII-98. The answer is B. (Chap. 337) Pathologic gynecomastia develops when the effective testosterone-to-estrogen ratio is decreased owing to diminished testosterone production (as in primary testicular failure) or increased estrogen production. The latter may arise from direct estradiol secretion by a testis stimulated by LH or hCG or from an increase in peripheral aromatization of precursor steroids, most notably androstenedione. Elevated androstenedione levels may result from increased secretion by an adrenal tumor (leading to an elevated level of urinary 17-ketosteroids) or decreased hepatic clearance in patients with chronic liver disease. A variety of drugs, including diethylstilbestrol, heroin, digitalis, spironolactone, cimetidine, isoniazid, and tricyclic antidepressants, also can cause gyne- comastia. In the case presented in the question, the history of paternity and the otherwise normal physical examination indicate that a karyotype is unnecessary, and the bilateral breast enlargement essentially excludes the presence of carcinoma and thus the need for biopsy. The presence of a low LH and testosterone suggests either estrogen or hCG pro- duction. Given the presence of a normal testicular exam, a primary testicular tumor is not suspected. Carcinoma of the lung or germ cell tumors can each produce hCG, causing gynecomastia. XII-99. The answer is E. (Chap. 333. Atkinson, Maclaren, N Engl J Med 331:1428 – 1436, 1994.) There is considerable disagreement regarding the genetics of diabetes mellitus, but certain aspects appear to be clear-cut. Genetic factors are probably permissive for the development of type 1 (immune-mediated) and are related more directly to the develop- ment of type 2 (non-immune-mediated) diabetes. The genetic locus for diabetes appears to be located near the HLA genes on the sixth chromosome. The presence of HLA antigen B8 or B15 increases the risk for developing type 1 diabetes nearly threefold, antigens DR3 and DR4 fourfold to fivefold, and antigen combinations (e.g., B8/B15) up to tenfold. XII. E NDOCRINE AND M ETABOLIC D ISORDERS — A NSWERS 328 However, homozygosity for a high-risk allele (e.g., DR3/DR3) does not increase the risk further. Evidence implicates positions 45 and 57 of the DQ chain as having importance ␤ in determining genetic susceptibility to type 1 diabetes. The concordance rate for mono- zygotic twins under 40 years of age is Ͻ50%. Pedigree analysis has shown a very low prevalence of vertical transmission for type 1 diabetes. The onset of juvenile diabetes has a seasonal variation and may follow mumps, hepatitis, or coxsackievirus infections, among others. These infections in genetically predisposed persons are theorized to produce an immune response with the development of cytotoxic islet cell antibodies, which complete the destruction of the beta cells. This theory would explain why circulating anti-islet cell antibodies are usually detectable soon after the onset of type 1 diabetes. In some cases anti-islet cell antibodies have been demonstrated in twins of diabetics destined to develop the disease even before glucose tolerance became abnormal. XII-100. The answer is B. (Chaps. 7, 333) The occurrence of hyperglycemic ketoacidosis or hyperglycemic hyperosmolar coma is diagnostic of diabetes mellitus. Similarly, persistent fasting hyperglycemia [glucose concentration Ͼ7.8 mmol/L (140 mg/dL)], even if it is asymptomatic, has been recommended by the National Diabetes Data Group as a criterion for the diagnosis of diabetes. However, abnormal glucose tolerance — whether after eating or after a standard “glucose tolerance test” — can be caused by many factors (e.g., anxiety, infection or other illness, lack of exercise, or inadequate diet). Similarly, glycosuria may have renal as well as endocrinologic causes. Therefore, these two conditions cannot be considered diagnostic of diabetes. Gestational diabetes is diagnosed in women between the twenty-fourth and twenty-eighth weeks of gestation, first using a 50-g oral glucose load if the 1-h glucose level Ͼ7.8 mmol/L (140 mg/dL); a 100-g oral glucose test is performed after an overnight fast. Gestational diabetes is initially treated with dietary measures; if the postprandial glucose level remains elevated, insulin therapy is often started. About 30% of women with gestational diabetes will eventually develop true dia- betes mellitus. XII-101. The answer is C. (Chap. 333) Diabetic, hyperosmolar, nonketotic coma is a medical emergency that usually occurs as a complication of maturity-onset diabetes. Typically, affected persons are elderly (often living alone or in a nursing home), have a history of recent stroke or infection, and are unable to drink sufficient water to balance urinary fluid losses. These factors combine to cause sustained hyperglycemic diuresis with profound volume depletion and decreased urine output. Presenting features often include signs of circulatory compromise as well as central nervous system manifestations ranging from confusion or seizures to coma. Ketoacidosis is absent, perhaps because the concentration of portal-vein insulin is high enough to prevent full activation of hepatic ketogenesis. Serum levels of free fatty acids are generally lower than in diabetic ketoacidosis, and although hypertonicity is marked, measured serum sodium concentration is kept from being significantly elevated by the profound hyperglycemia. Infections are common, and disseminated intravascular coagulation can occur as a result of elevated plasma viscosity (both bleeding and in situ thrombosis have been reported). Although the administration of free water eventually becomes necessary, the treatment of salt deficits has the highest initial therapeutic priority. Several liters of isotonic saline should be given over the first 2 h, followed by half-normal saline and then a 5% glucose solution when blood glucose levels approach normal. Hypotonic fluids should not be used initially because most of the water enters the intracellular compartment, possibly leading to cerebral edema, rather than re- maining in the plasma and interstitial spaces, where it is needed to support the circulation. Insulin also is required, but usually in lower doses than in patients with diabetic ketoaci- dosis. XII-102. The answer is A. (Chap. 333. Flier, Diabetes 41:1207, 1992.) Chronic insulin resis- tance is defined as a need for more than 200 units of insulin per day for several days in the absence of infection or ketoacidosis. This definition was based on the assumption that the normal human pancreas produces this much insulin daily; in fact, normal daily insulin [...]... The initial symptom of optic neuropathy due to glaucoma is loss of central vision XIII-31 A 65-year-old man with a long-standing history of hypertension complains of recurrent 30-min episodes of right arm weakness occasionally associated with difficulty speaking The results of his neurologic examination at this time are normal Cerebral angiography reveals 80% stenosis of the left internal carotid artery... majority of XX males have a fragment of the Y chromosome translocated to one of the X chromosomes The management of XX male syndrome is similar to that of Klinefelter syndrome XII-1 09 The answer is C (Chaps 340, 341) Vitamin D toxicity generally occurs after chronic ingestion of large doses of vitamin D2 or D3 (usually in excess of 50,000 to 100,000 IU daily for months) Ingestion of a single large dose of. .. numbers of insulin receptors or the presence of anti-insulin-receptor anti-bodies is playing a role in her insulin resistance XII-103 The answer is A (Chap 333 Ritz, Orth, N Engl J Med 341:1127 – 1133, 199 9.) Approximately 40% of patients with type 1 diabetes mellitus sustain diabetic nephropathy The progression of renal disease is markedly accelerated by hypertension, and even mild degrees of hypertension... XIII-21 Which of the following would help exclude the diagnosis of seizure in a patient with sudden loss of consciousness? (A) A brief period of tonic-clonic movements at the time of falling (B) An aura of a strange odor before falling (C) Sudden return to normal mental function upon awakening, though with a feeling of physical weakness (D) Urinary incontinence (E) Laceration of the tongue XIII-22... the left motor strip Cerebral embolism XIII-25 A 1 9- year-old man has had an 8-year history of recurrent episodes of loss of conscious activity that last for seconds to several minutes Sometimes he has as many as 100 of these lapses The patient regains awareness of his environment very quickly There is no major motor manifestation during the episodes or a period of confusion afterward The patient’s neurologic... A hallmark of diabetic nephropathy is the presence of so-called macroproteinuria (excretion of Ͼ0.55 g/d), and once this phase is reached, there is a steady decline in renal function So-called microalbuminuria, the excretion of 0.03 to 0.3 g/d of albumin, is also statistically predictive of the progression of renal disease In contrast, nocturia is usually a manifestation of undertreatment of diabetes... well as exhibiting a bizarre stooped posture Which of the following would be the best approach to reverse these troublesome neurologic symptoms? (A) (B) (C) (D) (E) Administration of benztropine Administration of oxazepam Administration of propranolol Administration of levodopa-carbidopa (Sinemet) Reduction of the dose of chlorpromazine XIII-46 A 42-year-old man who has had difficulty concentrating on... Chromosomal abnormalities can be identified in approximately one-half of patients (C) A myelomeningocele is the most common type of spina bifida (D) Spina bifida occulta occurs most often at L1 or L2 (E) Spina bifida is more common in blacks XIII-86 A 64-year-old attorney with a 10-year history of adult-onset diabetes mellitus presents with the complaint of chronic burning dysesthesia in the feet This symptom... left ptosis is seen The skin of the face is dry bilaterally The remainder of the neurologic examination is normal The first step in the workup should be (A) (B) (C) (D) (E) cerebral MRI ultrasound study of the carotid arteries chest x-ray ophthalmology consultation blood glucose determination Questions XIII -9 1 to XIII -9 2 A 28-year-old woman presents to your clinic complaining of blurred vision and left... expansion of a trinucleotide repeat (C) There is an abnormal accumulation of metabolites of prion protein (D) There is destruction of the lower motoneuron (E) There are large intracytoplasmic inclusions throughout the neuroaxis, called Lewey bodies XIII-51 A 45-year-old man complains of severe right arm pain He gives a history of having slipped on the ice and 340 XIII NEUROLOGIC DISORDERS — QUESTIONS XIII-51 . while the floor of the skull may have soft tissue densities associated with areas of cellulitis. XII- 89. The answer is E. (Chaps. 128, 333. Joshi et al, N Engl J Med 341: 190 6– 191 2, 199 9.) Necrotizing. calcium and high phosphate levels. XII -9 5 . The answer is B. (Chap. 77. Rosenbaum et al, N Engl J Med 337: 396 – 407, 199 7; Calle et al, N Engl J Med 341:1 097 – 1105, 199 9.) Obesity is the most common and. embolism XIII-25. A 1 9- year-old man has had an 8-year history of recurrent episodes of loss of conscious activity that last for seconds to several minutes. Sometimes he has as many as 100 of these