Management of Functioning and Nonfunctioning Tumors of the Adrenal Gland

Transcription

1 GENERAL SURGERY BOARD REVIEW MANUAL PUBLISHING STAFF PRESIDENT, GROUP PUBLISHER Bruce M. White EXECUTIVE EDITOR Debra Dreger SENIOR EDITOR Miranda J. Hughes, PhD ASSISTANT EDITOR Rita E. Gould EDITORIAL ASSISTANT Kara V. Warner EXECUTIVE VICE PRESIDENT Barbara T. White, MBA PRODUCTION DIRECTOR Suzanne S. Banish PRODUCTION ASSOCIATES Tish Berchtold Klus Mary Beth Cunney ADVERTISING/PROJECT MANAGER Patricia Payne Castle NOTE FROM THE PUBLISHER: This publication has been developed without involvement of or review by the American Board of Surgery. Endorsed by the Association for Hospital Medical Education The Association for Hospital Medical Education endorses HOSPITAL PHYSICIAN for the purpose of presenting the latest developments in medical education as they affect residency programs and clinical hospital practice. Management of Functioning and Nonfunctioning Tumors of the Adrenal Gland Series Editor and Contributing Author: Christopher R. McHenry, MD, FACS, FACE Associate Professor of Surgery, Case Western Reserve University School of Medicine, Director, Division of General Surgery, MetroHealth Medical Center, Cleveland, OH Contributing Author: Debra J. Graham, MD, FACS Assistant Professor of Surgery, Case Western Reserve University School of Medicine, Chief, Surgical Service, Cleveland VA Medical Center, Cleveland, OH Table of Contents Preface ii Introduction Case Patient Imaging Therapeutic Options Operative Approaches Summary Points Board Review Questions Detailed Answers References Cover Illustration by Joe Wilder, MD Copyright 2001, Turner White Communications, Inc., 125 Strafford Avenue, Suite 220, Wayne, PA , All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, electronic, photocopying, recording, or otherwise, without the prior written permission of Turner White Communications, Inc. The editors are solely responsible for selecting content. Although the editors take great care to ensure accuracy, Turner White Communications, Inc., will not be liable for any errors of omission or inaccuracies in this publication. Opinions expressed are those of the authors and do not necessarily reflect those of Turner White Communications, Inc. General Surgery Volume 7, Part 3 i

2 GENERAL SURGERY BOARD REVIEW MANUAL Preface Hospital Physician s General Surgery Board Review Manual is a study guide intended to help candidates prepare for the written board certification examination. The manual consists of 4 publications focusing on selected topics. Space will not permit an exhaustive review; however, Volume 7 targets several of the more commonly encountered conditions or topics in general surgery. Included in this list are: Part 1 The Parathyroid Glands and Hyperparathyroidism: II Part 2 Diagnosis of Tumors of the Adrenal Gland Part 3 Management of Tumors of the Adrenal Gland Part 4 Gastrointestinal Carcinoid Tumors Board examination candidates will find this manual to be a concise review of some of the essential and wellrecognized aspects of these topics. Each manual includes a case study that highlights the clinical presentation, diagnostic evaluation, treatment, and follow-up of a representative patient. The case-based format presents the information in a logical fashion, including important elements of the history and physical examination, etiology, diagnosis, and management. This manual has been developed without the involvement of or review by the American Board of Surgery. It is based on the Series Editor s and Contributing Authors clinical experience, awareness of new developments in the field of general surgery, and knowledge of basic components of education contained in our residency training program. This board review manual program is not comprehensive and should be viewed as a supplement to other preparatory material for board certification. The Editors wish all candidates success on the examination. Christopher R. McHenry, MD, FACS, FACE Associate Professor of Surgery Case Western Reserve University School of Medicine Director, Division of General Surgery MetroHealth Medical Center Cleveland, OH ii Hospital Physician Board Review Manual

3 GENERAL SURGERY BOARD REVIEW MANUAL Management of Functioning and Nonfunctioning Tumors of the Adrenal Gland Series Editor and Contributing Author: Christopher R. McHenry, MD, FACS, FACE Associate Professor of Surgery Case Western Reserve University School of Medicine Director, Division of General Surgery MetroHealth Medical Center Cleveland, OH Contributing Author: Debra J. Graham, MD, FACS Assistant Professor of Surgery Case Western Reserve University School of Medicine Chief, Surgical Service Cleveland VA Medical Center Cleveland, OH I. INTRODUCTION This review describes the various imaging modalities available to aid in diagnosing and localizing adrenal masses; it is the second half of a 2-part review on tumors of the adrenal gland. Indications for operation and selection of an appropriate operative approach are also discussed. Sample board review questions and answers are included for self-assessment at the end of this review. The initial evaluation of the patient with an adrenal mass, presented in the first half of this review ( Diagnosis of Functioning and Nonfunctioning Tumors of the Adrenal Gland in the Hospital Physician General Surgery Board Review Manual, Volume 7, Part 2), describes confirming the diagnosis and determining the functional status of the lesion using biochemical and nuclear medicine studies. II. CASE PATIENT 1 PRESENTATION Patient 1 is a 61-year-old man who presents with a 7 to 10 day history of continuous right-sided abdominal pain radiating to his back. He denies any associated symptoms, such as nausea, vomiting, change in bowel habits, hematuria, headache, palpitations, or diaphoresis. His medical history is pertinent for resection of the upper lobe of his left lung (10 months before this presentation) because of a Mycobacterium avium intracellulare complex infection that was resistant to antibiotic treatment. Within the excised specimen, a poorly differentiated bronchogenic carcinoma was incidentally found. Nine peribronchial and mediastinal lymph nodes were resected, but not one was involved with tumor. Patient 1 also has a history of chronic obstructive pulmonary disease, benign prostatic hypertrophy, and a 50 pack-year smoking history. His family medical history is unremarkable. A review of systems is pertinent only for a 5-lb. weight loss during the past month, which he attributes to a reduced appetite secondary to his abdominal pain. DIAGNOSTIC TESTING Physical examination reveals a blood pressure of 145/66 mm Hg, heart rate of 75 bpm, and temperature of 36.8 C. He has no obvious features consistent with Cushing s syndrome (CS). He has no palpable adenopathy. His abdomen is soft and nontender with no palpable masses or organomegaly. He has a healed left thoracotomy scar. A computed tomograph of the abdomen reveals a large, rounded, well-defined, hypodense right adrenal mass that measures cm (Figure 1). The General Surgery Volume 7, Part 3 1

4 III. IMAGING Figure 1. Computed tomograph of the abdomen from patient 1 demonstrating a large, complex, cystic, and solid right adrenal mass (A) compressing the inferior vena cava (arrow). mass is predominantly cystic; however, multiple vague enhancing areas within the mass are suggestive of solid regions. The mass is displacing the right lobe of the liver and the right kidney. It is also compressing the inferior vena cava. Laboratory studies reveal: a potassium of 4.2 meq/l, a hemoglobin of 11.3 gm/dl, a hematocrit of 34.1%, and a normal 24-hour urine for vanillylmandelic acid (VMA) and metanephrines. Given patient 1 s known history of bronchogenic carcinoma, it is felt that his mass most likely represents metastatic disease. Positron emission tomography (PET) is performed after intravenous administration of 12 mci of fluorine-18 fluorodeoxyglucose (FDG). This scan confirms the presence of a large right adrenal mass with no other focal accumulation of FDG. The clinical impression is that this large adrenal mass represents a solitary metastasis. Patient 1 undergoes a right adrenalectomy through an open, anterior, transperitoneal approach. Exploration of the abdomen reveals no other site of metastatic disease. A right adrenalectomy is completed along with removal of a small segment of the right hemidiaphragm that is adherent to the mass. Patient 1 s postoperative course is uneventful. The final pathology of the right adrenal mass is metastatic carcinoma involving the adrenal gland with extensive necrosis and cyst formation. The histologic appearance of the tumor is similar to patient 1 s lung tumor, which was resected 10 months previously. Postoperatively, he is treated with 4 cycles of paclitaxel and carboplatin. At his 12-month follow-up visit, he is doing well without problems. A follow-up PET scan did not show new disease. Adrenal imaging is an important step in the evaluation of patients with adrenal disease, and, in the case of incidentalomas, prompts the diagnostic work-up. In both adrenocorticotrophic hormone (ACTH) independent CS and hyperaldosteronism, the distinction between bilateral glandular hyperplasia and unilateral adenoma is essential to determining appropriate therapy. Pheochromocytomas may be multiple, bilateral, or extra-adrenal, and accurate localization is important in the selection of operative approach. Tumor size and likelihood of malignancy also affect therapeutic decision making. COMPUTED TOMOGRAPHY Computed tomography (CT) is most commonly used in the evaluation of the adrenal mass. Certain lesions such as cysts, hematomas, and myelolipomas can be diagnosed by CT criteria alone. 1 Adrenal myelolipomas are benign adrenal neoplasms consisting of fat and immature myeloid tissue. Differentiation between cortical adenomas, pheochromocytomas, adrenocortical carcinomas, and metastatic lesions is not entirely possible using CT. Several criteria aid in the differentiation between benign and malignant (Table 1); however, they do not completely or accurately distinguish benign from malignant masses. 1 In an effort to more accurately distinguish benign from malignant masses (most commonly metastases to the adrenal gland), several authors have examined the use of CT attenuation values expressed in Hounsfield units (HU). Benign adenomas generally have lower attenuation values than do other adrenal lesions. Boland and colleagues 2 reported a series of patients with 46 adenomas and metastases and found that on noncontrasted CT scans they could accurately distinguish adenomas from metastases using a threshold of 13 HU. When intravenous contrast was used, all metastases and only 1 of 23 adenomas had attenuation values greater than 24 HU on 15-minute delayed images. In a series including all types of adrenal lesions, a nonenhanced attenuation value of 18 HU was shown to separate adenomas from nonadenomas with a sensitivity of 85% to 93% and a specificity of 92% to 100%. 3,4 Threshold values of 30 HU to 40 HU have been reported for delayed contrast CT scans with sensitivity and specificity of 95% to 100% and 100%, respectively. 3,5 Nonetheless, no contrasted or noncontrasted attenuation threshold value is uniformly accepted as diagnostic of a benign adenoma Hospital Physician Board Review Manual

5 MAGNETIC RESONANCE IMAGING As with CT, magnetic resonance imaging (MRI) provides anatomic information and may provide clues regarding whether a lesion is benign or malignant. In general, adenomas are hypointense relative to the liver, metastases and primary cortical carcinomas are of intermediate intensity, and pheochromocytomas are hyperintense on T2-weighted images. 1,6 In a series of patients with 81 adrenal masses reported by Doppman and colleagues, 6 all lesions had similar intensities on T1-weighted images. T2-weighted images are more useful because adenomas had a lesion to liver signal intensity (SI) ratio of less than 1.4; however, metastases and primary carcinomas has SI ratios between 1.2 and 2.8. The overlap group included 22% of lesions, but all lesions with SI ratios less than 1.2 were benign adenomas. Pheochromocytomas were characteristically bright, with SI ratios greater than 3. The single cyst in the series also had a SI ratio greater than 3 but could be clearly distinguished by ultrasound and CT characteristics. Contrast enhancement patterns may distinguish benign from malignant lesions. Several authors have reported that adenomas exhibit only mild enhancement with gadolinium and rapid washout, whereas malignancies show strong enhancement and slow washout. 1,7 Alterations in MRI technique have also been used. MRI with chemical shift imaging is most promising and has been shown to differentiate adenomas from nonadenomas with a sensitivity of 94% to 100% and a specificity of 100%. 8,9 In a recent series of 134 adrenal masses imaged using MRI and also assessed by histology, MRI diagnoses were in conflict with histologic diagnoses in only 12 (9%) cases. 10 However, 4 malignant lesions incorrectly identified as benign among these 12. Diagnostic accuracy was reported as 94% for adenomas, 98.5% for pheochromocytomas, 98.5% for adrenocortical carcinomas, 96% for metastases, and 100% for cysts. POSITRON EMISSION TOMOGRAPHY PET using FDG has been reported to successfully distinguish between benign and malignant adrenal tumors. In a series of 27 patients including 17 with metastases and 10 with adenomas, no malignancies were missed; however, there were 2 false-positive results. 11 In a second series of 24 patients, all lesions were correctly classified as benign or malignant by PET. 12 SCINTIGRAPHY Scintigraphic studies provide information regarding function but do not provide accurate anatomic information. Scintigraphy using 131 I-6β-iodomethyl- Table 1. Characteristics of Benign and Malignant Adrenal Lesions Using Computed Tomography Characteristic Benign Malignant Margin Sharp Irregular Shape Round, smooth Lobulated or irregular Size < 5 cm > 5 cm Consistency Homogenous Inhomogeneous Change over time No growth Growth Enhancement with contrast No Yes Calcification No Yes Evidence of invasion or spread No Yes Data from Newell-Price J, Trainer P, Besser M, Grossman A. The diagnosis and differential diagnosis of Cushing's syndrome and pseudo- Cushing's states. Endocr Rev 1998;19: norcholesterol (NP-59) is useful in the evaluation of cortical lesions. The tracer is taken up via lowdensity lipoprotein receptors on adrenal cell membranes. 1 Scanning is usually done 5 to 7 days after tracer administration. Three patterns of uptake are described: concordant, where there is increased uptake on the side of the known lesion; discordant, where there is decreased or no uptake on the side of the lesion; and nonlateralizing, where uptake is equal bilaterally. Concordant uptake is seen with adenomas and hyperplasia and the rare functioning adrenocortical carcinomas. Discordant uptake results from destructive or space-occupying lesions including metastases, cysts, hematomas, medullary tumors, and most adrenocortical carcinomas. A nonlateralizing scan suggests a periadrenal mass or may result from lesions smaller than 2 cm, which may not be detected by scanning. NP-59 scintigraphy is very dependent on lesion size, providing a correct diagnosis in only 52% of lesions less than 1 cm, 89% of lesions between 1 and 2 cm, and 100% of lesions larger than 2 cm I (or 123 I)-metaiodobenzylguanidine (MIBG) scintigraphy is useful in the diagnosis and localization of pheochromocytomas. The tracer is similar in structure to norepinephrine and is taken up by adrenergic tissue via a similar mechanism. The tracer is not taken up in significant amounts in normal adrenal tissue but is concentrated in both benign and malignant pheochromocytomas over 72 hours. During this same time period, General Surgery Volume 7, Part 3 3

6 IV. THERAPEUTIC OPTIONS A B Figure 2. Identification of pheochromocytoma. (A) MIBG scan demonstrating intense uptake in the left adrenal gland (arrow). (B) Large pheochromocytoma (P) of the left adrenal gland corresponding to the area of increased uptake on the MIBG scan. MIBG = 131 I (or 123 I)-metaiodobenzylguanidine. background activity decreases in the salivary glands, liver, spleen, and urinary bladder. 14 Thus, later imaging is used because of improved resolution. Sensitivity and specificity are reported to be 87% and 96%, respectively. 1,15,16 MIBG scanning is used to confirm the diagnosis of pheochromocytoma and to rule out multiple, bilateral, or extra-adrenal tumors (Figure 2). A proposed role in screening is not widely accepted. Therapeutic use in recurrent malignant pheochromocytoma has been reported, with transient responses in 60% of patients. 17 MEDICAL MANAGEMENT Adrenalectomy is the treatment of choice for functioning adrenal tumors and offers the only hope of survival in patients with adrenocortical carcinoma. Preoperative preparation is particularly important for pheochromocytomas, with α-blockade to control hypertension and β- blockade to control heart rate and rhythm as described earlier. In patients with hypercortisolism from functioning adrenocortical carcinomas, the effects of cortisol may be controlled with mitotane or ketoconazole. 18 Both affect the normal adrenal gland as well as the tumor and produce adrenal insufficiency. All patients operated on for CS secondary to adrenal disease are treated with steroids perioperatively and postoperatively. In patients with primary aldosteronism who are poor candidates for operation or who refuse surgery, medical management of hypertension and hypokalemia with potassium-sparing diuretics and combination antihypertensive therapy can be successful. 19 Percutaneous ablation of small adrenocortical adenomas has been reported using CT-guided acetic acid injection, 20 although this technique is new and its role in the management of adrenal disease is yet to be defined. INCIDENTALOMAS Management of incidentalomas deserves special mention. All incidentalomas that prove to be functional on biochemical screening or that show characteristics of malignancy on imaging studies should be removed. Those that do not meet these criteria should be excised if they are larger than 4 cm. 21 Incidentalomas that are not removed require regular follow-up for signs of growth. Most authors recommend surveillance by CT for up to 2 years, 22 although there is no clear consensus. 21 Lesions that increase in size or exhibit other malignant characteristics should be removed. ADRENAL METASTASES Adrenalectomy for solitary adrenal masses is frequently done but remains a controversial issue. Although metastases may be indicators of widespread disease, increasing evidence suggests that resection of solitary metastases provides a survival advantage. A randomized trial of surgery in the treatment of isolated brain metastases reported by Patchell et al 23 (which included metastases from breast, melanoma, gastrointestinal, genitourinary, and lung cancers) showed a 4 Hospital Physician Board Review Manual

7 significant increase in survival time in those undergoing surgery. Based on this report and others showing prolongation of survival, resection of solitary brain metastases has become an accepted practice. This principle has since been applied to solitary adrenal metastases. Several series comparing adrenalectomy to chemotherapy for the treatment of isolated adrenal metastases have been reported. Luketich and Burt 24 compared outcomes using chemotherapy versus surgery in the treatment of adrenal metastases from non small cell lung cancers in 14 patients. Average survival in the surgically treated group was 31 months versus 8.5 months in the chemotherapy group. Similarly, Higashiyama and colleagues 25 showed a survival advantage for patients undergoing adrenalectomy. Long-term survivors have also been reported. 24,26 Based on these reports, adrenalectomy for isolated adrenal metastases should be considered. In patients with an adrenal incidentaloma and a known history of malignancy, PET should be performed to exclude other metastatic disease. If no other disease is identified, lesions larger than 4 cm should be removed. For smaller lesions, fine-needle aspiration should be used to distinguish between nonfunctioning adenomas and metastases. Small nonfunctioning adenomas may be observed; however, removal of solitary metastases should be considered. V. OPERATIVE APPROACHES ANATOMY The adrenal glands are located in the retroperitoneum bilaterally superior to the kidneys. The right gland lies posterior and lateral to the inferior vena cava. The left adrenal is just superior to the left renal vein, lateral to the aorta, and posterior to the tail of the pancreas. Arterial supply is derived from the inferior phrenic arteries superiorly, directly from the aorta medially, and from the renal arteries inferiorly. Venous drainage is via a single vein. On the left, the adrenal vein arises from the inferior portion of the gland and drains into the left renal vein. On the right, the adrenal vein is very short. It arises medially and drains directly into the posterior lateral aspect of the vena cava (Figure 3). ADRENALECTOMY Adrenalectomy may be performed using several approaches. Open transabdominal, posterior, and thoracoabdominal approaches have all been used with success, with the choice of approach being tailored to the characteristics of the lesion. More recently, laparoscopic approaches have been introduced, including a transabdominal lateral approach and a posterior retroperitoneoscopic approach. Before the introduction of laparoscopy, small (< 5 cm) benign lesions were most commonly removed using a posterior approach through the bed of the 11th or 12th rib because of the advantages of shorter hospital stays and decreased morbidity. Larger lesions, malignant tumors, and pheochromocytomas were approached anteriorly to allow abdominal exploration and wide excision as indicated. Many surgeons now use a laparoscopic approach for all adrenal masses except for those that are very large or malignant. Several authors have reported series comparing laparoscopic and open approaches to the adrenal gland. Thompson and colleagues 27 compared laparoscopic transabdominal adrenalectomy with open adrenalectomy via the posterior approach. Advantages identified for the laparoscopic approach included shorter length of stay, decreased time to return to normal activities, increased patient comfort and patient satisfaction, and a decreased incidence of wound-related complications. In this series, 54% of patients undergoing the open posterior approach reported late wound complications, including chronic pain, laxity of the oblique muscles, and flank numbness. Disadvantages of the laparoscopic approach included increased operating time (clearly related to the learning curve for this procedure) and slightly increased hospital costs. Similar results have been reported in retrospective studies comparing the laparoscopic approach with both the open anterior and open posterior approaches. 28,29 Given its advantages, many conclude that laparoscopic adrenalectomy should become the preferred approach for most adrenal masses Many surgeons believe that primary adrenal malignancies should still be removed using an open transabdominal approach. 29,31,32 A posterior laparoscopic approach has also been described. It involves balloon dissection of the retroperitoneal space, followed by introduction of trocars, and dissection of the gland. Although the retroperitoneal approach may be more difficult, it does offer some advantage in patients with previous abdominal surgery. 32,33 Adrenal sparing surgery, open or laparoscopic, has been advocated recently for patients with hereditary pheochromocytoma. The vasculature is preserved as much as possible, and the lesion is removed leaving a 1 to 2 mm rim of normal adrenal tissue. Hemorrhage is General Surgery Volume 7, Part 3 5

8 Right inferior phrenic v. Hepatic v. Diaphragm Right adrenal v. (to inferior vena cava) Right adrenal gland Right middle adrenal a. Right accessory adrenal v. (to right renal v.) Right renal a. Right renal v. Left inferior phrenic v. Left inferior phrenic a. Esophagus Left inferior phrenic a. and superior adrenal a. Left adrenal gland Right inferior phrenic a. Left middle adrenal a. Celiac trunk Left inferior adrenal a. Left adrenal v. Left gonadal a. and v. Right gonadal v. Right gonadal a. Right kidney Right ureter Inferior vena cava Superior mesenteric a. Left kidney Aorta Left ureter Figure 3. Normal anatomic features of the adrenal glands. a. = artery; v. = vein. (Adapted with permission from Gray W, Skandalakis JF. Atlas of surgical anatomy for general surgeons. Baltimore: Williams & Wilkins; 1985:273.) the major problem encountered during partial resection and can generally be controlled with bipolar coagulation or suturing. 34,35 The choice of procedure should be based on tumor characteristics and surgeon expertise. Small benign lesions have been frequently removed through an open posterior approach. Bilateral disease has also been treated this way, using bilateral incisions. These lesions are now frequently approached laparoscopically, including bilateral lesions, which are usually removed using separate lateral transabdominal laparoscopic approaches and repositioning the patient between the separate procedures. The open anterior approach has long been favored for large lesions, malignant lesions (where thorough exploration for metastatic disease and an extensive resection are often necessary), and pheochromocytomas (to allow evaluation for bilaterality and extra-adrenal disease). With the development of newer imaging modalities, particularly MIBG scintigraphy and MRI, the preoperative evaluation of pheochromocytomas is more complete and a more limited operative approach is possible. 36 Most adrenal masses can be approached safely and effectively laparoscopically; however, large lesions (> 8 to 10 cm), adrenocortical carcinomas, and malignant pheochromocytomas should still be approached using an open anterior technique. If the nature of the lesion is unclear preoperatively, many surgeons would begin with a laparoscopic approach and convert to an open approach if it is obvious on exploration that the lesion is malignant. VI. SUMMARY POINTS Biochemical screening is always the first step in the diagnosis of symptomatic patients with suspected adrenal disease. In patients with positive screening tests, the diagnosis is confirmed using a combination of specific biochemical tests and imaging modalities. 6 Hospital Physician Board Review Manual

9 Incidentally discovered adrenal masses are most often nonfunctioning adenomas and do not require treatment if small, although they should be followed to confirm that they are not changing. However, functioning adenomas, pheochromocytomas, carcinomas, and lesions larger than 4 cm should be removed. Benign and malignant adrenal tumors cannot be clearly distinguished based on cytology or histology; therefore, the only role for fine-needle aspiration in the diagnosis of adrenal masses is to rule out metastatic disease to the adrenal gland. Proper preoperative preparation is essential in the treatment of patients with pheochromocytoma, including treatment of hypertension with α-blockers, volume expansion, and control of heart rate and rhythm with β-blockers. Laparoscopic adrenalectomy is the preferred approach for most adrenal masses, although many authors feel that this approach should not be used for malignant adrenal tumors. BOARD REVIEW QUESTIONS Choose the single best answer for each question. 1. The preferred screening test for diagnosis of Cushing s syndrome (CS) is: A) The 1-mg overnight dexamethasone suppression test B) Serum cortisol levels (AM and PM) C) Random serum cortisol levels D) Spot urinary free cortisol E) The 8-mg dexamethasone suppression test 2. Primary hyperaldosteronism secondary to an aldosterone-producing adenoma is best distinguished from bilateral adrenal hyperplasia by: A) A high aldosterone level and suppressed plasma renin activity B) Postural testing C) Measurement of 18-hydroxycorticosterone D) Computed tomography (CT) E) Selective adrenal vein sampling of cortisol and aldosterone levels 3. A 44-year-old man has a 4-cm mass in the right adrenal gland that was incidentally discovered on an ultrasound examination obtained for evaluation of gallbladder disease. The mass is hyperintense on a T2-weighted MRI and has a lesion to liver signal intensity (SI) ratio of 3.5. The most likely diagnosis is: A) Adrenocortical carcinoma B) Pheochromocytoma C) Nonfunctioning adenoma D) Metastasis 4. Which incidentally discovered adrenal lesion can be definitively diagnosed using CT? A) Nonfunctioning adenoma B) Pheochromocytoma C) Myelolipoma D) Aldosterone-producing adenoma E) Metastasis 5. Nonoperative therapy is appropriate for which adrenal incidentaloma? A) A 6-cm nonfunctioning adrenal adenoma B) A functioning adrenal adenoma less than 2 cm C) A myelolipoma D) A 2-cm pheochromocytoma in an asymptomatic patient E) An adrenocortical carcinoma invading the diaphragm 6. The preferred operative approach for an 8-cm inhomogeneous adrenal mass with indistinct margins is: A) Open posterior B) Open transabdominal C) Laparoscopic transabdominal D) Laparoscopic posterior 7. The appropriate evaluation of a normotensive, normokalemic 32-year-old patient with an incidentally discovered 3.5-cm mass in the right adrenal gland and a normal physical examination includes: A) Urinary metanephrines and vanillylmandelic acid (VMA) B) Plasma renin activity and serum aldosterone levels C) Urinary free cortisol D) Fine-needle aspiration General Surgery Volume 7, Part 3 7

10 DETAILED ANSWERS 1. (A) The 1-mg dexamethasone suppression test. The 1-mg dexamethasone suppression test has a greater sensitivity and specificity for diagnosis of CS than measurement of serum cortisol levels alone. There is considerable overlap in AM and PM serum cortisol levels as well as random serum cortisol levels in patients with and without CS. A spot urinary free cortisol level is not of value; however, a 24-hour urinary free cortisol is quite sensitive. The high-dose dexamethasone suppression test is used to distinguish patients with Cushing s disease secondary to a pituitary adenoma from patients with an ectopic adrenocorticotrophic hormone (ACTH) producing tumor. 2. (E) Selective adrenal vein sampling of cortisol and aldosterone levels. A high aldosterone level and a suppressed plasma renin activity are found in both patients with an aldosterone-producing adenoma and patients with bilateral adrenal hyperplasia. Postural testing, measurement of 18-hydroxycorticosterone, and CT of the adrenal glands can be very helpful in distinguishing an aldosterone-producing adenoma from hyperplasia; however, they are not always accurate. The best test for distinguishing the 2 entities is selective sampling of cortisol and aldosterone from both adrenal veins and the vena cava. 3. (B) Pheochromocytoma. A lesion to liver SI ratio determined from T2-weighted MRI greater than 3 is most frequently seen in patients with pheochromocytoma or an adrenal cyst. A nonfunctioning adrenal adenoma has a SI ratio of less than 1.4, whereas primary carcinomas or metastases have SI ratios between 1.2 and (C) Myelolipoma. Certain adrenal lesions such as cysts, hematomas, and myelolipomas can be diagnosed by CT criteria alone. Adrenal myelolipomas are benign adrenal neoplasms consisting of fat and immature myeloid tissue. These lesions can be diagnosed based on the identification of areas of fat attenuation on CT. 5. (C) Myelolipoma. The indications for surgery in patients with adrenal incidentaloma include all functioning adrenal tumors (including pheochromocytomas), nonfunctioning adrenal tumors larger than 4 cm, adrenocortical carcinoma, and nonfunctioning adrenal adenomas less than 4 cm that have been documented to be increasing in size. Most patients with adrenal myelolipomas are asymptomatic and do not require operative treatment. Rarely, some patients may experience abdominal pain with very large myelolipomas. In such cases, adrenalectomy would be appropriate. 6. (B) Open transabdominal. An 8-cm inhomogeneous mass with indistinct margins most likely represents a malignant adrenal lesion. Most surgeons still approach these lesions using an open transabdominal approach. Posterior approaches do not allow thorough evaluation for extra-adrenal spread of the disease or wide exposure for an extensive resection. A transabdominal laparoscopic approach does allow for abdominal exploration for metastatic disease but may not allow for an extensive resection. 7. (A) Urinary metanephines and VMA. The absence of hypertension does not rule out the diagnosis of pheochromocytoma, and the long-term morbidity and mortality of a missed diagnosis warrants screening. Urinary metanephrines and VMA are the appropriate screening tests. Aldosteronoma is extremely uncommon in the absence of hypertension. In hypertensive patients, a normal serum potassium level excludes the diagnosis. Screening for cortisol hypersecretion is not necessary unless adrenalectomy is planned. Fine-needle aspiration has a limited role in the evaluation of adrenal masses and is only used to evaluate presumed metastases to the adrenal gland. REFERENCES 1. Francis IR, Gross MD, Shapiro B, et al. Integrated imaging of adrenal disease. Radiology 1992;184: Boland GW, Hahn PF, Pena C, Mueller PR. Adrenal masses: characterization with delayed contrast-enhanced CT. Radiology 1997;202: Szolar DH, Kammerhuber F. Quantitative CT evaluation of adrenal gland masses: a step forward in the differentiation between adenomas and nonadenomas? Radiology 1997;202: Korobkin M, Brodeur FJ, Yutzy GG, et al. Differentiation of adrenal adenomas from nonadenomas using CT attenuation values. AJR Am J Roentgenol 1996;166: Korobkin M, Brodeur FJ, Francis IR, et al. Delayed enhanced CT for differentiation of benign from malignant adrenal masses. Radiology 1996;200: Doppman JL, Reinig JW, Dwyer AJ, et al. Differentiation of adrenal masses by magnetic resonance imaging. Surgery 1987;102: Krestin GP, Steinbrich W, Friedmann G. Adrenal masses: evaluation with fast gradient-echo MR imaging and Gd-DTPA-enhanced dynamic studies. Radiology 1989; 171: Hospital Physician Board Review Manual

11 8. Tsushima Y, Ishizaka H, Matsumoto M. Adrenal masses: differentiation with chemical shift, fast low-angle shot MR imaging. Radiology 1993;186: Schwartz LH, Panicek DM, Doyle MV, et al. Comparison of two algorithms and their associated charges when evaluating adrenal masses in patients with malignancies. AJR Am J Roentgenol 1997;168: Heinz-Peer G, Honigschnabl S, Schneider B, et al. Characterization of adrenal masses using MR imaging with histopathologic correlation. AJR Am J Roentgenol 1999; 173: Erasmus JJ, Patz EF, McAdams HP, et al. Evaluation of adrenal masses in patients with bronchogenic carcinoma using 18F-fluorodeoxyglucose positron emission tomography. AJR Am J Roentgenol 1997;168: Boland GW, Goldberg MA, Lee MJ, et al. Indeterminate adrenal mass in patients with cancer: evaluation at PET with 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology 1995; 194: Kloos RT, Gross MD, Francis IR, et al. Incidentally discovered adrenal masses. Endocr Rev 1995;16: Shapiro B, Copp JE, Sisson JC, et al. Iodine-131 metaiodobenzylguanidine for the locating of suspected pheochromocytoma: experience in 400 cases. J Nucl Med 1985;26: Mozley PD, Kim CK, Mohsin J, et al. The efficacy of iodine-123-mibg as a screening test for pheochromocytoma. J Nucl Med 1994;35: Sisson JC, Frager MS, Valk TW, et al. Scintigraphic localization of pheochromocytoma. N Engl J Med 1981;305: Krempf M, Lumbroso J, Mornex R, et al. Use of m-[131i]iodobenzylguanidine in the treatment of malignant pheochromocytoma. J Clin Endocrinol Metab 1991; 72: Demeure MJ, Somberg LB. Functioning and nonfunctioning adrenocortical carcinoma: clinical presentation and therapeutic strategies. Surg Oncol Clin N Am 1998; 7: Ghose RP, Hall PM, Bravo EL. Medical management of aldosterone-producing adenomas. Ann Int Med 1999; 131: Liang HL, Pan HB, Kee YH, et al. Small functional adrenal cortical adenomas: treatment with CT-guided percutaneous acetic acid injection report of three cases. Radiology 1999;213: Graham DJ, McHenry CR. The adrenal incidentaloma: guidelines for evaluation and recommendations for management. Surg Oncol Clin N Am 1998;7: Copeland PM. The incidentally discovered adrenal mass. Ann Intern Med 1983;98: Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990;322: Luketich JD, Burt ME. Does resection of adrenal metastases from non small cell lung cancer improve survival? Ann Thorac Surg 1996;62: Higashiyama M, Doi O, Kodama K, et al. Surgical treatment of adrenal metastases following pulmonary resection for lung cancer: comparison of adrenalectomy with palliative therapy. Int Surg 1994;79: Twomey P, Montgomery C, Clark O. Successful treatment of adrenal metastases from large-cell carcinoma of the lung. JAMA 1982;248: Thompson GB, Grant CS, van Heerden JA, et al. Laparoscopic versus open posterior adrenalectomy: a casecontrol study of 100 patients. Surgery 1997;122: Prinz RA. A comparison of laparoscopic and open adrenalectomies. Arch Surg 1995;130: Staren ED, Prinz RA. Adrenalectomy in the era of laparoscopy. Surgery 1996;120: Brunt LM, Doherty GM, Norton JA, et al. Laparoscopic adrenalectomy compared to open adrenalectomy for benign adrenal neoplasms. J Am Coll Surg 1996;183: Acosta E, Pantoja JP, Gamino R, et al. Laparoscopic versus open adrenalectomy in Cushing s syndrome and disease. Surgery 1999;126: Duh QY, Siperstein AE, Clark OH, et al. Laparoscopic adrenalectomy. Comparison of lateral and posterior approaches. Arch Surg 1996;131: Fernandez-Cruz L, Saenz A, Benarroch G, et al. Laparoscopic unilateral and bilateral adrenalectomy for Cushing s syndrome. Transperitoneal and retroperitoneal approaches. Ann Surg 1996;224: Janetschek G, Finkenstedt G, Gasser R, et al. Laparoscopic surgery for pheochromocytoma: adrenalectomy, partial resection, excision of paragangliomas. J Urol 1998; 160: Neumann HP, Bender BU, Reincke M, et al. Adrenalsparing surgery for phaeochromocytoma. Br J Surg 1999; 86: Orchard T, Grant CS, van Heerden JA, Weaver A. Pheochromocytoma continuing evolution of surgical therapy. Surgery 1993;114: Copyright 2001 by Turner White Communications Inc., Wayne, PA. All rights reserved. General Surgery Volume 7, Part 3 9