Adrenal Incidentaloma: Work up and Management No Conflicts to Declare Quan-Yang Duh Professor of Surgery University of California, San Francisco UCSF Postgraduate Course in Endocrine & Breast Surgery March 6, 2015 Surgical Approach to Adrenal “Incidentaloma” Incidentalomas: Objectives � Work up for incidental adrenal tumors “Adrenal incidentalomas are tumours of the adrenal gland that are discovered incidentally � Evaluating and treating functioning tumors when imaging studies are done for purpose � Pheochromocytoma other than searching for adrenal pathology.” � Hypercortisolism and hyperaldosteronism � Evaluating and treating adrenal malignancy 1-5% of abdominal imaging studies identify � metastasis unanticipated adrenal tumor � adrenocortical cancer � Techniques and results of adrenalectomy Geelhoed GW, Druy EM. Surgery 92: 866-874, 1982 Duh QY. Br J Surg 89:1347, 2002 1
(Relative) Contraindications for Indications for Adrenalectomy Laparoscopic Adrenalectomy � Hypersecretion of hormones � Large adrenal tumors � Local symptoms � What is “large”? > 6-15 cm? � Cancers or potential cancers � > 8 cm for right, > 10 cm for left � Uncertain diagnosis � Adrenocortical carcinomas � Not for obviously invasive cancers. � Start laparoscopic then convert as needed? All adrenalectomy can be performed by laparoscopy EXCEPT… � Technical limitations � Risks of inadequate/inappropriate resection (cancer) 500 Laparoscopic Adrenalectomies Most Adrenal Incidentalomas are Non- functioning Adenomas UCSF,1993 to 2009: Diagnoses � Hyperaldosteronism N=161 32% � Patient selection (retrospective, prospective, population based) influences prevalence of � Pheochromocytoma N=117 23% incidentaloma � Cushing N=82 16% � 1% at age 30, 4% at age 60, 7% at age 70 � Cortical tumors N=41 8% � Patient selection also influences the � Metastases N=42 8% prevalence of surgical disease (e.g., � Others N=57 11% functioning or suspicious tumors) � 7-30% of operated, 1-10% of pheos or ACC 2
Swedish Prospective Multicenter Study Western Sweden Adrenal Study Group Population : Incidentaloma for Adrenal Incidentaloma � 381 patients, 33 hospitals, 1996-2001 � Population 1.7 millions, 18 months, 19 radiology Depts, consecutive, prospective � 164 men, 217 women, age 64 (18-84), 3 (1-20) cm � 34,044 scans, 534 assessed (1.6 %) � Operative criteria: � > 3-4 cm or hypersecreting hormone � 226 pts included, 15 operated (6.6%) � 85/381 (22%) operated � 3 aldo, 1 pheo, 1 metastasis � 10 non-functioining large adenoma (>3 cm) � 20 (5%) hypersecreting benign tumors (15 pheos) � No additional disease diagnosed at 2 yr f/u � 14 (4%) malignant (10 adrenal cortical ca) � 10 (4-16) cm Muth A, et al. Br J Sur; 2011;98:1383-91 B Bulow & B Ahren (Lund): J Intern Med. 2002;252:239-46. NIH State-of-the-Science Conference on Biochemical Diagnosis of Pheochromocytoma: Which test is best? the Clinically Inapparent Adrenal Mass � 1-mg Dex suppression � Plasma metanephrines � Plasma free metanephr � Best negative predictive v � Resect all pheo, clinical � More false positives Cushing, aldo and others � Screen familial disease � Surgery or observation for � Urinary metanephrines subclinical Cushing � Best positive predictive v � Resect > 6 cm � Fewer false positives � Observe < 4 cm � All other patients � Q 6 m imaging x 2 � (CT/MRI characteristics) � Q y hormonal study x 4 Lenders et al: JAMA 287: 1427, 2002 NIH Consens State Sci Statements. 2002 Feb 4-6;19(2):1-25 3
Pheochromocytoma: Localizing Studies Germ-line Mutations are Common CT MRI MIBG (not a “10% tumor”, 1/3 hereditary) � If multifocal, 84% � If < 18 year- old, 59% � If Extra- adrenal, 93% � 66/271 (24%) of non-syndromic pheo � 30 VHL, 13 RET, 11 SDHD, 12 SDHB Malignant or metastatic Best for surgical planning Planning for I131 Tx Neumann et al: NEJM 346: 1459, 2002 Pheochromocytoma Crisis Is Not a Cushing’s Syndrome: Surgical Emergency Laboratory Diagnosis � Low-dose dexamethasone suppression � 25 /137 (18%) UCSF pheo presented in crisis � 1 mg dexamethasone PO at 11 PM � Alpha-adrenergic blockade at least 10 days � 8 AM plasma cortisol (nl < 5 mcg/dL vs 1.8) � 10 urgent, 15 elective, no emergency operation � Mid-night salivary cortisol level � No death � normal < 550 ng/dL � 24 hr urine free cortisol � 33/97 pheo crisis pts had emergency operations � Central obesity � nl 5-50 mcg/24 hr � Death 6/33 vs 0/64 (emergent vs urgent/elective) � Moon facies � Plasma ACTH � Intraop complications 80% vs 42% � Supraclavicular � “Subclinical Cushing’s” � Postop complications 71% vs 33 % fat pad � Dexamethasone not suppressible � Purple Striae � Post resection Addisonian crisis Scholten, et al: J Clin Endocrinol Metab 98:581-591, 2013. Shen WT, et al: Arch Surg.141:771, 2006 4
Incidentaloma with Subclinical Cushing’s Aldosteronoma: CT scan Resect or Observe? � 1- 2 cm � Randomized, 45 patients, 7.7 (2-15) years, Padua. � Incidentaloma < 3.5 cm, no overt disease, but � No contralateral abnl abnormal Dex-suppression. � Adrenal protocol � 23 Lap adrenalectomy � Diabetes : 62.5% (5/8) normalized or improved � Without and with contrast � Hypertension: 67% (12/18) � Thin cut (2.5 mm or less) � Hyperlipidemia: 37.5% (3/8) � Low Hounsfield U � Obesity: 50% (3/6) � Osteoporosis did not improve. � < 10 pre-contrast � 22 Non-surgical: No improvement � Early washout of � 3 crossed over to adrenalectomy (tumor grew to > 3.5 cm) contrast Toniato A, et al: Ann Surg 249:388-391, 2009 Laboratory Diagnosis: 1 o hyperaldo Role of Adrenal Vein Sampling � High plasma aldosterone (PA) � If relying on CT scan alone � > 20 ng/dL (adenoma), 12-20 (hyperplasia) � 22% would have been exclude for adrenalectomy � off meds (spironolactone, diuretic, ACE inhibitors, etc) (bilateral normal or bilateral nodular) � on high salt diet (>120 mEq/d x 4d) � Low plasma renin activity (PRA) � 25% would have unnecessary or inappropriate � < 0.5 ng/ml/hr (wrong side) adrenalectomy � High PA/PRA ratio (> 20-30) � “AVS is an essential diagnostic step in most � Adenomas higher (25-100), hyperplasia (15-25) patients to distinguish between unilateral and � Elevated 24 hour urinary aldosterone bilateral adrenal aldosterone hypersecretion” � Less commonly used WF Young, et al. Surgery 136:1227, 2004 Founders JW, et al. JCEM 93:3266, 2008 5
A Clinical Prediction Score to Diagnose Incidentaloma: Unilateral Primary Aldosteronism Avoid FNA � 100% specific for APA if typical adenoma � Mayo clinic, 1995- >0.8 cm and K < 3.5 or Cr Clr >100 2005, 20 FNA � 14 complications � 6 hematoma � 5 incorrect dx � 2 recurrences Vanderveen KA, et al (Thompson GB), Surgery; 2009; 146:1158-66 Kupers EM, et al. J Clin Endocrinol Metab 97:3530-7, 2012 Adrenal Incidentaloma as Presentation of Resection for Isolated Adrenal Metastasis Unknown Primary Cancer is very Rare � MSK 1995-2006 � Retrospective review 1715 patients referred for evaluation of suspected unknown primary � Median survival 30 months cancer,1639 had cancer. � 17% local recurrence � Adrenal involved at presentation in 95 (5.8%). � 31 lap vs. 63 open � Op time: 175 min vs. 208 min � Involved only adrenal in 4 patients (0.2%). � EBL: 106 ml vs 749 ml � All large (> 6 cm), symptomatic, 3/4 bilateral. � Hosp: 2.8 d vs. 8.0 d � NO TURE INCIDENTALOMA � Fewer complications Strong VE, et al. Ann Surg Oncol 14: 3392, 2007 Lee J, et al (MD Anderson): Surgery 1998; 124:1115-22. Duh QY. Ann Surg Oncol 14:3288, 2007 6
Is size the best Predictor for the risk of Adrenocortical Carcinoma: Imaging Adrenal Cortical Cancer? 30% � CT findings � Central necrosis � Cortical adenoma 25% � Irregularity � Homogeneous 20% � HU > 20 � Pre-contrast < 10 HU � Rapid wash-out � Invasion (liver, IVC) 15% � Carcinoma, mets, 10% pheochromocytoma � Heterogeneous 5% � Pre-contrast > 20 HU � Slow wash-out 0% < 4 cm 4-6 cm > 6 cm NIH Consens State Sci Statements. 2002 Feb 4-6;19(2):1-25 Laparoscopic compared to Open Laparoscopic Adrenalectomy: Size Matters (UCSF, 1993-2011) Adrenalectomy: more positive margin and tumor rupture, earlier recurrence � 523 patients, 563 adrenalectomies � Aldo180, pheo 123, Cushing 85, mets 44, others 91 � Smaller (< 3 cm) vs Larger ( ≥ 3 cm) tumors � op time 2.29 hr vs 3.07 hr � EBL 44 ml vs 97 ml � Intraop complication 2% vs 10% � Postop complications 14% vs 24 % � Hospital stay 1.6 days vs 2.5 days Miller BS, et al: World J Surg 34:1380-1385, 2010. 7
Management of Adrenal Bilateral Incidentalomas Incidentalomas � 15-20% of � Work up of adrenal tumors incidentalomas � R/O pheo (metanephrines), Cushing (Dex-sup.) � 4 times more � no FNA likely to have � When to operate subclinical � Functioning tumors, isolated metastases Cushing � Large (> 5-6 cm) and increased risk of cancer � 4 times less � How to operate likely to have � Laparoscopic (retroperitoneal vs transabdominal) Pheos � Open resection for cancer Pasternak JD, et al: Pacific Coast Surgical Association, 2015 8
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