Campbell-Walsh Urology, 11th Edition

PART XI

The Adrenals

65

Pathophysiology, Evaluation, and Medical Management of Adrenal Disorders

Alexander Kutikov; Paul L. Crispen; Robert G. Uzzo

Questions

  1. At birth the adrenal cortex:
  2. is completely developed.
  3. weighs half as much as the adrenal cortex in adults.
  4. is composed of fetal and adult components.
  5. will continue to enlarge until 12 months of age.
  6. is composed of a single histologic zone.
  7. Adrenal rest tissue within the testis can mimic testicular cancer in patients with:
  8. neuroblastoma.
  9. pheochromocytoma.
  10. primary aldosteronism.
  11. congenital adrenal hyperplasia.
  12. cryptorchidism.
  13. In cases of renal agenesis, the ipsilateral adrenal gland is typically:
  14. absent.
  15. in the normal location.
  16. located at the level of the eighth thoracic vertebral body.
  17. located at the level of the first lumbar vertebral body.
  18. at a location dependent on the cause of renal agenesis.
  19. The most abundant product of the adrenal cortex is:
  20. mineralocorticoids.
  21. glucocorticoids.
  22. adrenal androgens.
  23. catecholamines.
  24. adrenocorticotropic hormone (ACTH).
  25. Aldosterone synthase (CYP11B2) is unique to:
  26. the zona glomerulosa.
  27. the zona fasciculata.
  28. the zona reticularis.
  29. the adrenal medulla.
  30. the distal renal tubule.
  31. The only zone of the adrenal cortex that does not atrophy upon pituitary failure is:
  32. the zona glomerulosa.
  33. the zona fasciculata.
  34. the zona reticularis.
  35. the adrenal medulla.
  36. none of the above.
  37. Presence of the phenylethanolamine-N-methyltransferase (PNMT) enzyme in the adrenal medulla is significant because:
  38. the enzyme catalyzes degradation of catecholamines to metanephrines.
  39. the enzyme catalyzes conversion of catecholamines to vanillylmandelic acid (VMA).
  40. the enzyme converts tyrosine to dopamine.
  41. the enzyme catalyzes the conversion of norepinephrine to epinephrine.
  42. all of the above.
  43. Metanephrines:
  44. refers to the term used for catecholamines and their byproducts.
  45. refers to the combined term for methylated metabolites of norepinephrine (normetanephrine) and epinephrine (metanephrine).
  46. refers to precursors to normetanephrines.
  47. are rarely helpful in establishing a diagnosis of pheochromocytoma.
  48. refers to the term used to describe epinephrine and norepinephrine in the context of pheochromocytoma symptomatology.
  49. The term free metanephrines:
  50. is interchangeable with the term total metanephrines.
  51. is interchangeable with the term fractionated metanephrines.
  52. refers to normetanephrine and metanephrine that are not conjugated by a sulfate moiety.
  53. refers to normetanephrine and metanephrine that are not bound to albumin.
  54. refers to all of the above.
  55. The most common cause of Cushing syndrome (exclusive of exogenous steroid intake) is:
  56. Cushing disease.
  57. a cortisol-producing adrenal adenoma.
  58. ectopic ACTH production by a lung malignancy.
  59. an adrenal carcinoma.
  60. a pheochromocytoma.
  61. What common urologic ailment can be found in up to 50% of patients with Cushing syndrome?
  62. Testicular cancer
  63. Torsion of the appendix testis
  64. Urolithiasis
  65. Fournier gangrene
  66. Stress urinary incontinence
  67. How does one perform a low-dose dexamethasone suppression test (LDDST)?
  68. Admit the patient and measure serum cortisol levels every 6 hours while the patient is on a dexamethasone drip.
  69. Measure the patient's saliva cortisol level at midnight.
  70. Obtain a 24-hour urine cortisol measurement after the patient receives 1 mg of dexamethasone with the first void.
  71. Have the patient take 10 mg of dexamethasone at 11 pmand measure urinary cortisol the next morning.
  72. Have the patient take 1 mg of dexamethasone at 11 pmand measure serum cortisol the next morning.
  73. The adrenal surgeon plays no role in the management of Cushing disease.
  74. True
  75. False
  76. What percentage of patients presenting with primary aldosteronism are hypokalemic?
  77. 5% to 12%
  78. 9% to 37%
  79. 33% to 50%
  80. 55% to 75%
  81. 63% to 91%
  82. Elevated aldosterone in patients with familial hyperaldosteronism type I is mediated by:
  83. renin.
  84. sodium.
  85. angiotensin II.
  86. cortisol.
  87. ACTH.
  88. What percentage of patients with a positive screening test will be diagnosed with primary aldosteronism after confirmatory testing?
  89. 2% to 10%
  90. 20% to 40%
  91. 30% to 50%
  92. 50% to 70%
  93. 75% to 90%
  94. What is the most common subtype of primary aldosteronism?
  95. Idiopathic hyperplasia
  96. Aldosterone-producing adenoma
  97. Unilateral adrenal hyperplasia
  98. Familial hyperaldosteronism type I
  99. Adrenocortical carcinoma
  100. The primary determinant of potentially surgically correctable primary aldosteronism is:
  101. blood pressure.
  102. patient age.
  103. demonstration of lateralized aldosterone secretion.
  104. response to medical therapy.
  105. plasma aldosterone levels.
  106. Which class of antihypertensives is contraindicated during the evaluation of primary aldosteronism?
  107. Calcium channel blockers
  108. Alpha blockers
  109. Beta blockers
  110. Aldosterone-receptor blockers
  111. Angiotensin-converting enzyme inhibitors
  112. What percentage of patients with incidental adrenal masses prove to have pheochromocytoma?
  113. 1%
  114. 5%
  115. 10%
  116. 25%
  117. 35%
  118. What subtype is assigned to patients with a von Hippel-Lindau (VHL)mutation and a history of pheochromocytoma but no other stigmata of the VHL syndrome?
  119. Type 1
  120. Type 2A
  121. Type 2B
  122. Type 2C
  123. None of the above
  124. What genetic abnormality is strongly linked with malignant pheochromocytoma?
  125. RETmutation
  126. VHLmutation
  127. SDHBmutation
  128. SDHDmutation
  129. All of the above
  130. What test is considered the cornerstone for modern pheochromocytoma biochemical testing?
  131. Plasma catecholamines
  132. Plasma-free metanephrines or fractionated urinary metanephrines
  133. Vanillylmandelic acid testing
  134. Fasting morning urinary norepinephrine
  135. Adrenal vein sampling for catecholamines
  136. With regard to preoperative pheochromocytoma blockade, β-blockers should be started:
  137. 2 weeks prior to adrenalectomy.
  138. at least several days prior to α-blockers.
  139. to control tachycardia and arrhythmias that can result upon initiation of α blockade.
  140. in conjunction with metyrosine.
  141. never, because β-blockers can be lethal in patients with pheochromocytomas.
  142. Patients with adrenal crisis can exhibit all of the following symptoms EXCEPT:
  143. hypotension unresponsive to fluid resuscitation.
  144. abdominal pain.
  145. nausea.
  146. fever.
  147. priapism.
  148. All of the following lesions can be extra-adrenal EXCEPT:
  149. myelolipoma.
  150. ganglioneuroma.
  151. aldosteronoma.
  152. pheochromocytoma.
  153. oncocytoma.
  154. A 25-year-old woman is diagnosed with a left adrenal mass, with abundant stippled calcifications, that exhibits imaging features inconsistent with adrenal adenoma. The patient complains of a severe bout of diarrhea that started approximately 8 months ago. Adrenalectomy reveals a ganglioneuroma. At her postoperative visit she is grateful, because her gastrointestinal (GI) complaints vanished following surgery. The substance responsible for diarrhea in this patient is most likely:
  155. metanephrine.
  156. epinephrine.
  157. norepinephrine.
  158. VMA.
  159. vasoactive intestinal polypeptide (VIP).
  160. What percentage of adrenal cysts is associated with malignancy in surgical series?
  161. 1%
  162. 3%
  163. 7%
  164. 12%
  165. 15%
  166. Adrenocortical carcinoma in children:
  167. has a more favorable 5-year survival rate compared with adults.
  168. uses the same pathologic staging system as adults.
  169. is rarely associated with virilization.
  170. has equal female and male incidence in children older than 10 years.
  171. is frequently metastatic to the central nervous system.
  172. The most common hormone secreted by adrenocortical carcinoma is:
  173. aldosterone.
  174. testosterone.
  175. dehydroepiandrosterone (DHEA).
  176. cortisol.
  177. androstenedione.
  178. The Weiss criteria for identifying malignant adrenal tumors should be applied with caution in tumors with:
  179. necrosis.
  180. high mitotic index.
  181. inferior vena cava (IVC) invasion.
  182. liver metastasis.
  183. oncocytic features.
  184. In patients presenting with metastatic adrenocortical carcinoma, the systemic agent of choice is:
  185. valrubicin.
  186. mitotane alone or in combination with additional cytotoxic agents.
  187. gemcitabine and cisplatin.
  188. docetaxel (Taxotere).
  189. bleomycin, etoposide, and cisplatin.
  190. In the treatment of pathologically localized adrenocortical carcinoma:
  191. adjuvant radiation therapy decreases systemic progression.
  192. complete surgical resection offers the best chance of cure.
  193. increased Ki-67 expression has been associated with improved survival.
  194. the tumor's functional status is an independent predictor of survival.
  195. adjuvant therapy with mitotane has no proven benefit.
  196. A 50% false-positive rate can be seen during low-dose dexamethasone suppression testing in:
  197. men with testicular cancer.
  198. women taking oral contraceptives.
  199. men with history of orchiopexy.
  200. patients with brain malignancy.
  201. patients with pheochromocytoma.
  202. The adrenal gland should be resected whenever one performs a radical nephrectomy.
  203. True
  204. False
  205. What common over-the-counter medication can produce a false-positive result during plasma free metanephrine testing?
  206. Ibuprofen
  207. Aspirin
  208. Omeprazole
  209. Diphenhydramine
  210. Acetaminophen
  211. A 55-year-old woman presents for the evaluation of an adrenal mass. Past medical history is significant for severe hypertension requiring four oral medications for adequate blood pressure control. A noncontrast computed tomography (CT) scan of the abdomen reveals a 3-cm left adrenal mass, with an average attenuation of 7 Hounsfield units (HU). Appropriate initial screening should include:
  212. free-fractionated plasma metanephrines, plasma aldosterone concentration, and plasma renin activity.
  213. low-dose dexamethasone suppression test and serum catecholamines.
  214. late-night salivary cortisol test, plasma aldosterone concentration, plasma renin activity, and plasma free metanephrines.
  215. plasma aldosterone concentration and plasma renin activity.
  216. 24-hour urinary-fractionated metanephrines and serum cortisol concentration.
  217. A 62-year-old man presents for postoperative surveillance of renal cell carcinoma. Three years prior, a right nephrectomy was performed for T2N0M0 grade III clear cell renal cell carcinoma. A current abdominal CT scan reveals a 3.5-cm right adrenal mass with an average attenuation of 32 HU prior to contrast administration. A CT washout study is performed, and absolute percent washout is calculated to be 52%. No other suspicious lesions are noted within the chest, abdomen, or pelvis. The next step in management should be:
  218. observation.
  219. adrenalectomy.
  220. percutaneous biopsy.
  221. initiation of an oral tyrosine kinase inhibitor.
  222. assessment of the adrenal tumor's functional status.
  223. A 58-year-old woman has been diagnosed with primary aldosteronism based on appropriate screening and confirmatory testing. A CT scan of the abdomen reveals a 1.0-cm left adrenal mass. Adrenal vein sampling is performed with the results outlined below. Results of adrenal vein sampling:

Right cortisol gradient 2.7:1

Left cortisol gradient 3.4:1

Aldosterone ratio (left:right) 2.5:1

The next step in management would be:

  1. Repeat adrenal vein sampling with ACTH stimulation
  2. Counseling for left adrenalectomy
  3. Counseling for right adrenalectomy
  4. Initiation of medical management based on diagnosis of bilateral adrenal hyperplasia
  5. 131I-Iodomethyl-norcholesterol (NP-59) scintigraphy to confirm lateralization
  6. A 43-year-old woman undergoes an uneventful right laparoscopic adrenalectomy for a 4.5-cm pheochromocytoma. The pathology report states that the lesion is benign and that the margins are negative. On postoperative day 1, she is ready for discharge and wants to know if any additional follow-up is necessary. You inform her that the following is required:
  7. Consideration of genetic screening
  8. Repeat metabolic testing in 2 weeks
  9. Cross-sectional imaging in 6 months
  10. Biochemical testing in 6 months and then lifelong biochemical testing
  11. All of the above

Pathology

  1. A 60-year-old woman is noted to have a 4-cm left adrenal mass on an abdominal CT scan. The endocrine workup is negative, and the mass is excised laparoscopically. The pathology depicted in Figure 65-1is reported as a myolipoma. The next step in management is:

FIGURE 65-1 (From Bostwick DG, Cheng L. Urologic surgical pathology. 2nd ed. Edinburgh: Mosby; 2008.)

  1. no additional therapy is indicated because this is a benign tumor.
  2. ask the pathologist to grade the tumor.
  3. the patient should receive mitotane.
  4. the patient should be followed carefully for development of hypertension.
  5. a metaiodobenzylguanidine (MIBG) scan should be obtained.
  6. A 45-year-old man has an incidentally discovered 6-cm adrenal mass. Hormonal workup is negative. The mass is laparoscopically removed. The pathology is depicted in Figure 65-2and is read as adrenal corticocarcinoma. On separate stains the lesion stains positive for Ki-67. The next step in management is:

FIGURE 65-2 (From Bostwick DG, Cheng L. Urologic surgical pathology. 2nd ed. Edinburgh: Mosby; 2008.)

  1. request a pathologic grade.
  2. stain for catecholamines.
  3. inquire as to whether any fat was observed in the specimen.
  4. short-term follow-up with imaging.
  5. adjuvant mitotane.

Imaging

  1. See Figure 65-3. A 42-year-old man with lung cancer has this CT scan. The right adrenal nodule has attenuation measurements of 7 HU. The most likely diagnosis is:

FIGURE 65-3

  1. adrenal adenoma.
  2. adrenal metastasis.
  3. indeterminate adrenal nodule.
  4. pheochromocytoma.
  5. adrenal myelolipoma.

Answers

  1. c. Is composed of fetal and adult components.The adrenal gland weighs twice as much as the adult gland and begins to atrophy at birth. Development of the gland continues during the first 3 years of life, with the zona reticularis developing last.
  2. d. Congenital adrenal hyperplasia.Testicular adrenal rests must be remembered when evaluating patients with congenital adrenal hyperplasia and testicular masses to avoid an unnecessary orchiectomy.
  3. b. In the normal location.Reports of adrenal agenesis are extremely rare.
  4. c. Adrenal androgens.Although adrenal androgens are arguably the least physiologically significant compounds produced by the adrenals, the glands produce more than 20 mg of these compounds per day. Meanwhile, only 100 to 150 mcg/day of aldosterone and approximately 10 to 20 mg/day of cortisol are produced by the glands.
  5. a. The zona glomerulosa. The zona glomerulosa cells are the sole source of aldosterone in humans.
  6. a. The zona glomerulosa. Production of aldosterone in the zona glomerulosa is primarily regulated by angiotensin II through the renin-angiotensin-aldosterone system and potassium levels.Elevation of ACTH can also increase aldosterone secretion, but this is a much less potent stimulus. Therefore, in pituitary failure, when ACTH levels fall, the zona glomerulosa fails to atrophy.
  7. d. The enzyme catalyzes the conversion of norepinephrine to epinephrine.PNMT is virtually unique to the adrenal medulla (the brain and organ of Zuckerkandl also express the protein). Therefore the presence of PNMT results in epinephrine being virtually a unique product of the adrenal gland.
  8. b. Refers to the combined term for methylated metabolites of norepinephrine (normetanephrine) and epinephrine (metanephrine).The enzyme catechol-O-methyltransferase catalyzes the methylation of norepinephrine to normetanephrine and epinephrine to metanephrine. The term normetanephrines is not used.
  9. c. Refers to normetanephrine and metanephrine that are not conjugated by a sulfate moiety.Free metanephrines are unsulfonated normetanephrine and metanephrine, whereas total metanephrines refers to both conjugated and free compounds. The term fractionated metanephrines refers to laboratory reports that differentiate between metanephrine and normetanephrine concentrations (i.e., instead of only reporting metanephrine concentration, state the concentration of metanephrine and normetanephrine separately).
  10. a. Cushing disease. Cushing disease, which describes overproduction of ACTH by the pituitary, accounts for some 70% of endogenous Cushing syndrome.
  11. c. Urolithiasis. Urolithiasis is seen in up to 50% of patients with Cushing syndrome; therefore stone formers with cushingoid features deserve a hypercortisolemia workup. The astute urologist should also remember that Cushing patients can also exhibit hypogonadal hypogonadism and should have a low threshold for a hypercortisolism workup in men with low testosterone and low gonadotropin levels.
  12. e. Have the patient take 1 mg of dexamethasone at 11 pmand measure serum cortisol the next morning. Despite its intimidating name and rather complex physiologic underpinnings, the test is remarkably simple to administer. Write the patient a prescription for 1 mg of dexamethasone and ask that it be taken by mouth at 11 pm. The next morning, determine the patient's serum cortisol level. If the cortisol level is 5 mcg/dL or higher (i.e., not suppressed), then the patient likely has hypercortisolemia. Be aware that women on birth control will have false-positive results.
  13. b. False.ACTH-secreting pituitary adenomas are treated with transsphenoidal surgical resection. However, a cure is seen in only 60% to 80% of patients. Among those who are cured, there is approximately 25% relapse. One option for patients who are refractory to neurosurgical treatment is a bilateral adrenalectomy. However, this treatment should not be performed hastily. It is crucial that a thoughtful multidisciplinary decision be made. Up to 30% of patients with Cushing disease who undergo bilateral adrenalectomy may develop Nelson syndrome—progressive growth of the pituitary adenoma causing increased intracranial pressure and compression of the ocular chiasm.
  14. b. 9% to 37%. Although hypokalemia has been classically described as a common finding in primary aldosteronism, only 9% to 37% of newly diagnosed patients are hypokalemic.
  15. e. ACTH.Because of the chimeric fusion of the promoter region of 11β-hydroxylase and the coding region of aldosterone synthase, aldosterone production is mediated by ACTH in familial hyperaldosteronism type I.
  16. d. 50% to 70%.Fifty percent to 70% of patients with a positive screening test will be diagnosed with primary aldosteronism following confirmatory testing.
  17. a. Idiopathic hyperplasia.This subtype of primary aldosteronism accounts for approximately 60% of cases.
  18. c. Demonstration of lateralized aldosterone secretion.Lateralization of aldosterone secretion is the primary determinant of successful surgical treatment of primary aldosteronism.
  19. d. Aldosterone-receptor blockers.Aldosterone-receptor blockers (spironolactone and eplerenone) are contraindicated during the evaluation of primary aldosteronism. Patients requiring these agents for blood pressure control should be transitioned to other medications during testing for at least 6 weeks.
  20. b. 5% (approximately).Incidentally discovered lesions account for 10% to 25% of all pheochromocytomas.
  21. d. Type 2C.Type 1 = VHL patient with no evidence or family history of pheochromocytoma. Type 2 patients are those with evidence or family history of pheochromocytoma. Type 2 is further subdivided. Type 2A = patients with concomitant RCC; type 2B = no evidence of renal malignancy; type 2C = patients with pheochromoctyoma and evidence of a VHL gene mutation but no other stigmata of VHL.
  22. c. SDHBmutation. Patients with multiple endocrine neoplasia (types 2A and 2B) possess a mutation in the RET proto-oncogene. Approximately half of these patients develop pheochromocytoma, but only about 3% of those with pheochromocytoma exhibit malignant potential. Ten percent to 20% of patients with VHL develop pheochromocytomas, but only 5% of those with pheochromocytoma have malignant disease. Pheochromocytoma among patients with neurofibromatosis type 1 is rare (1%), but malignant disease can be seen in more than 10%. Familial paraganglioma syndrome type 4 (SDHB mutation) carries the highest risk of malignancy (30% to 50%) among patients with the condition who develop pheochromocytoma (≈ 20%). Its pathologic cousin, familial paraganglioma syndrome type 1 (SDHD mutation), carries a negligible risk (< 3%) of malignancy among patients who develop pheochromocytomas (≈ 20%).
  23. b. Plasma-free metanephrines or fractionated urinary metanephrines.Methylated metabolites of catecholamines are known as metanephrines. Therefore normetanephrine (from norepinephrine) and metanephrine (from epinephrine) are collectively known as metanephrines. The vast majority of methylation occurs within the adrenal medulla or pheochromocytoma, when present. Because this conversion of catecholamines to metanephrines is an uninterrupted process within pheochromocytomas, testing for these compounds is a much more sensitive means of tumor detection than the measurement of catecholamine levels, which may be paroxysmal. Furthermore, measurement of levels of metanephrines is rather specific. Controversy exists regarding whether measurement of plasma-free metanephrines versus fractionated urinary metanephrine should be used as the initial test. The term "free" indicates that the metanephrines being measured are not conjugated by a sulfate moiety, whereas the term "fractionated" simply indicates that normetanephrine and metanephrine levels are reported as separate values.
  24. c. To control tachycardia and arrhythmias that can result upon initiation of α blockade. Beta-blockade should never be started prior to appropriate α blockade.In the absence of α blockade, β antagonists cause a potentiation of the action of epinephrine on the α1 receptor, due to blockade of the arteriolar dilation at the β2 receptor. Nevertheless, β blockade is at times necessary to control reflex tachycardia and arrhythmias that can result from α blockade.
  25. e. Priapism.Patients with adrenal crisis are easily misdiagnosed with an acute abdomen. Children can exhibit hypoglycemic seizures. Persistent painful erections are generally not associated with adrenal insufficiency.
  26. c. Aldosteronoma.All listed lesions, other than an aldosterone-producing adenoma, can develop outside of the adrenal gland.
  27. e. Vasoactive intestinal polypeptide (VIP). Ganglioneuromas are rare lesions that can arise in the adrenal glands and can secrete VIP, causing profound diarrhea in some patients.Nevertheless, most ganglioneuromas are asymptomatic.
  28. c. 7%.In a meta-analysis accounting for 515 adrenal cysts, the incidence of associated adrenal malignancy was 7%.
  29. a. Has a more favorable 5-year survival rate compared with adults.The 5-year survival rate in children with adrenal cortical carcinoma is 54% compared with only 20% to 47% in adults.
  30. d. Cortisol.Up to 74% of functional adrenocortical tumors produce excess cortisol.
  31. e. Oncocytic features.The Weiss criteria should be applied with caution in pediatric cases and in those with oncocytic features.
  32. b. Mitotane alone or in combination with additional cytotoxic agents.Mitotane has adrenolytic activity and is the first-line agent of choice in patients with metastatic adrenocortical carcinoma. The addition of streptozotocin or etoposide, doxorubicin, and cisplatin to mitotane is potentially beneficial and is currently being investigated in a randomized trial.
  33. b. Complete surgical resection(including en bloc resection of locally advanced disease) offers the best chance of cure. Adjuvant radiation therapy has demonstrated a decreased rate of local recurrence but has not been shown to improve overall survival. Adjuvant mitotane therapy has been shown to significantly improve recurrence-free and overall survival. A tumor's functional status has not been consistently demonstrated to impact survival.
  34. b. Women taking oral contraceptives.The urologist must be aware that the low-dose dexamethasone suppression test can yield as high as a 50% false-positive rate in women using oral contraceptives, because the contraceptives increase total (but not bioavailable) cortisol levels by raising the patient's cortisol-binding globulin concentrations.
  35. b. False.The classic description by Robson in the 1950s suggested that radical nephrectomy should include adrenalectomy. Today, however, adrenalectomy is believed to be necessary only for large (T2) upper pole tumors, in cases in which an abnormality in the gland can be seen on preoperative imaging and in cases in which a vein thrombus is present to the level of the adrenal gland.
  36. e. Acetaminophen.Prior to plasma-free metanephrine testing, ideally patients should not consume food or liquids after midnight. Caffeinated beverages, especially, must be avoided. Acetaminophen can produce a false-positive result due to cross reactivity in the assay and should be stopped for at least 5 days prior to testing. Tricyclic antidepressants and phenoxybenzamine should also be stopped, because these have been shown to be responsible for false-positive results (Eisenhofer et al, 2003).* Usual antihypertensive therapy can be continued. Although β blockade can potentially result in a false-positive test result, the current recommendation is to stop the medication only on repeat testing (Eisenhofer et al, 2003). Ideally, the serum sample should be drawn in the supine position following at least 20 minutes of supine rest. Position is especially important if a positive result has been obtained and confirmatory testing is being performed.
  37. c. Late-night salivary cortisol test, plasma aldosterone concentration, plasma renin activity, and plasma-free metanephrines. All patients presenting with an adrenal mass should be evaluated for cortisol and catecholamine hypersecretion.Given the patient's history of hypertension, evaluation of primary aldosteronism should also be undertaken. Choice c is the best answer.
  38. e. Assessment of the adrenal tumor's functional status.Although there is a high probability that the adrenal lesion, in this case, represents a recurrence of the patient's renal cell carcinoma, the functional status of the adrenal mass should be assessed. A pheochromocytoma may always be lurking.
  39. b. Counseling for left adrenalectomy.Both the right and left cortisol gradients suggest proper catheter placement for adrenal vein sampling. The aldosterone ratio of 2.5:1 demonstrates left lateralization of autonomous aldosterone secretion, and counseling for left adrenalectomy is appropriate.
  40. e. All of the above.The patient is less than 50 years old; therefore genetic screening is recommended. Up to 25% of patients who appear to have sporadic pheochromocytoma on presentation turn out to have germline mutations upon genetic testing. Repeat metabolic testing at 2 weeks after resection is prudent. Most experts recommend additional biochemical testing at 6 months, followed by annual lifelong screening. More than 15% of patients will demonstrate recurrence of pheochromocytoma in the first 10 years after a successful resection. Recurrent disease has been reported more than 15 years following adrenalectomy; therefore lifelong annual biochemical screening is advised. Although cross-sectional imaging is not absolutely required in the face of a negative biochemical workup, most surgeons obtain at least one study at some point during the postoperative follow-up.

Pathology

  1. a. No additional therapy is indicated because this is a benign tumor.This is a benign myolipoma. Notice that it consists of fat mixed with hematopoietic elements.
  2. d. Short-term follow-up with imaging.The marked nuclear variability, increased mitotic figures, and positive staining for Ki-67 all strongly suggest adrenal corticocarcinoma. No further pathologic information is necessary. These patients have a high risk of developing metastatic disease, at which time mitotane would be considered.

Imaging

  1. a. Adrenal adenoma.Adrenal nodules that are less than 10 HU in density are almost always benign nodules, most often adrenal adenomas.

Chapter review

  1. The right adrenal gland is triangular in shape; the left is crescent shaped.
  2. The zona glomerulosa secretes mineralocorticoids, the zona fasciculata secretes glucocorticoids, and the zona reticularis secretes sex steroids.
  3. The production of cortisol is circadian, with the peak occurring in the early morning and the nadir at 11:00 pm.
  4. Adrenal androgens are under the control of ACTH.
  5. Ectopic ACTH production almost always originates from malignant tissue.
  6. Renin release is stimulated by low renal perfusion pressure, increased renal sympathetic nervous activity, and low sodium.
  7. Mineralocorticoid production results in sodium retention and volume expansion initially; however, with continued production, the kidney escapes from the sodium-retentive action of the hormone.
  8. Sodium loading reduces endogenous aldosterone and renin production in those patients who do not have autonomous aldosterone secretion from aldosterone producing tumors.
  9. The predictors of persistent hypertension following adrenalectomy for primary aldosteronism include (1) age older than 50 years, (2) the requirement for more than two antihypertensive agents preoperatively, (3) a first-degree relative with hypertension, (4) prolonged duration of hypertension prior to adrenalectomy, and (5) renal insufficiency.
  10. Ki-67 staining of adrenal tissue is perhaps the best indicator of malignancy.
  11. Chromogranin A elevation in the serum has been used as a confirmatory test in patients with pheochromocytoma.
  12. Restoration of intravascular volume is the most important component of preoperative preparation in patients with pheochromocytoma.
  13. The most frequent cause of adrenal insufficiency in the United States is autoimmune adrenalitis; in developing countries, it is tuberculosis.
  14. Patients with congenital adrenal hyperplasia have a high risk for developing benign adrenal corticoadenomas.
  15. The Weiss criteria distinguish benign from malignant adrenal tumors. The presence of three or more of the Weiss criteria is associated with malignancy. When oncocytic features are present, the criteria should be used with caution.
  16. An attenuation of less than 10 Hounsfield units on unenhanced CT scan is strongly suggestive of an adrenal adenoma.
  17. There are four histologic types of adrenal cysts: (1) pseudocyst, (2) endothelial, (3) epithelial, and (4) parasitic.
  18. Positron emission tomography (PET) scan is the preferred imaging modality for pheochromocytoma.
  19. Pheochromocytomas recur in up to 16% of patients who have had a complete surgical resection; 50% of the recurrences are malignant.
  20. Metastases to the adrenal are common.
  21. Production of aldosterone in the zona glomerulosa is primarily regulated by angiotensin II through the renin-angiotensin-aldosterone system and potassium levels.
  22. Epinephrine is virtually a unique product of the adrenal gland, and when it is the dominant catechol produced by a tumor, an adrenal origin is suggested.
  23. Cushing disease is a result of an overproduction of ACTH by the pituitary. It accounts for some 70% of endogenous Cushing syndrome.
  24. Urolithiasis is seen in up to 50% of patients with Cushing syndrome.
  25. Up to 30% of patients with Cushing disease who undergo bilateral adrenalectomy may develop Nelson syndrome—progressive growth of the pituitary adenoma causing increased intracranial pressure and compression of the ocular chiasm.
  26. Although hypokalemia has been classically described as a common finding in primary aldosteronism, only 9% to 37% of newly diagnosed patients are hypokalemic.
  27. Conversion of catecholamines to metanephrines is an uninterrupted process within pheochromocytomas; testing for these compounds is a much more sensitive means for tumor detection than the measurement of catecholamine levels, which may be paroxysmal.
  28. Ganglioneuromas are rare lesions that can arise in the adrenal glands and can secrete the vasoactive intestinal polypeptide (VIP), causing profound diarrhea in some patients.
  29. All patients presenting with an adrenal mass should be evaluated for cortisol and catecholamine hypersecretion.

* Sources referenced can be found in Campbell-Walsh Urology, 11th Edition, on the Expert Consult website.