ADRENAL INCIDENTALOMAS: ANALYSIS OF 126 CASES

Chin Med Sci JVol.18,No. 4December 2003P. 226 -230CHINESEMEDICAL SCIENCESJOURNALADRENAL INCIDENTALOMAS: ANALYSIS OF 126 CASES .R3Li Hanzhong'*(李汉忠)，Yan Weigang'(严 维刚), Zeng Zhengpei?( 曾正陪)，Xiao He'(肖河)， Feng Chao'(冯 超) and Wang Huijun'(王 惠君)'Department of Urology ，'Department of Endocrinology, Peking Union Medical College Hospital,CAMS & PUMC, Beijing 100730Key words adrenal incidentaloma; diagnosis; treatmentPurpose. To evaluate the diagnosis and treatment of adrenal incidentalomas.Methods. One hundred and twenty -six patients with incidentalomas were analyzed， among them 98underwent operation.Resuls. Eighty eight of the adrenal incidentalomas were discovered by ultrasound. Of all the typesof adrenal incidentalomas. 52 (41.3%) of them were adenomas; 43 (34.1%) were hypersecretory adrenaltumors, including 29 pheochromoeytomas, 9 primary aldosteronisms, 1 adrenogenitol syndrome combinedwith adrenal adenoma， 2 Cushing's ayndrome combined with adenomas and 2 Cushing's syndrome com-bined with nodular bhyperplasias. All nonhypersecretory adrenal adenomas were under 6 cm, and all adrenal carcinomas were above 6 cm.Conclusions. To search forquite essential in the proccess o[ diagnosing adrenal incidentalomas. For nonhypersecretory adrenal adeno-nas， the size of tumor is the most important index in determining whether the tunor is benign or malig-nant and whether the tumor needs to be treated with operation.Adrenal masses discovered by imaging techniquesraphy (CT) and magnetic resonance imaging (MRI).for reasons unrelated to adrenal diseases are called aThe current prevalence of unsuspected adrenal massesdrenal incidentalomas(1-3). Incidentaloma is a defi-is approximately 1% to 5% in abdominal CT scannition，not a diagnosis. The detection of more inci-series(4,5). In fact， the incidence of adrenal nod-dentalomas is expected as the use of abdominal imag-les at autopsy is as high as 32% among patientsing increases， such as ultrasound, computed tomog- without premortem suspicion of adrenal disease(6).MATERIALS AND METHODSReceived for publication April 8, 2003.Corresponding author. Phone:010- 65296035; Fax:65296035;From 1990 to 2002，879 patients with adrenalE-milvwgemailbox@sina.com中国煤化工HCNMHGVol. 18, No, 4CHINESE MEDICAL SCIENCES JOURNAL227tumors were admited to our hospital， among them .were bilaleral pheochromocytomas; 1 was combined126 were adrenal ineidentalomas. The case historieswith adenomas; 2 were malignant pheochromocytomas.of the 126 patients were reviewed. Of them, 64 wereSeven had no histories of hypertension. Measurementmales and 62 were females.Their age were 9 ~74of 24 -hour urinary catecholamine was performedned inyears old (median age 53). Adrenal masses wereall patients and 26 of them were high and othersbilateral in 8 and unilateral in 118,of which 4were normal. Ffeen of the 29 patients were per-were on the left side and 71 were on the right side.forned with 川-MIBG scintigraphy， except 2 malig-Ninety-eight (77.8%) of the 126 patients were per-nant pheochromocytomas, all the others were positive.formed operations.Hormonal study was performed in all patients andTable 1. Detailed cases, percenages of rvurious adrenalincidentalomas and percentages appeared inincluded 24- -hour urinary free cortisol, serum free cor-literaturetisol, supine and upright position of plasma aldos-terone and plasma renin activity ，serum testosterone ,CategoriesCases % % in literature(3)17-hydroxyprogesterone (17-0HP)， 24-hour urinaryPheochromocytoma223.015-23cathecolamines and plasma cathecolamines. Ultrasound,malignantCT，MRI and 3I -metaiodobenzylquanidine (" -benign .22MIBC) scintigraphy were performed.Ganglioneuromas.60~-6Medullary neurofibroma0.8RESULTSAdrenocortical rarrinoma2.1.2-11Adenoma2 41.336-94Eighty(63.5%) of the 126 adrenal ineidentalomasCushing's syndromewere discovered by routine physical examination， a-Primary aldosteronismsmong which 67 by ulrasound and 13 by CT. TheAdrenogenitol syndromether 46 (36.5%) were discovered during the imag-Nonhypersecretory40ing performed for extra- -adrenal complaints, of whichNolular hyperplasia3.27~1721 were discovered by ultrasound， 24 by CT and 1Adrenal metastases7.0-21by abdomen plain film. Fifty -seven (45.2%) of thelyst4-22126 had hypertension histories and 15 (11.9%) withEpidermoid eystxhistories of extra -adrenal malignancy. Table 1 listsMyelolipoma5.67~15he numbers and percentages of various diagnoses ofLipoma0.0-11the histopathologic features. Except for 14 nonhyper-Hemangiomasecretory adenomas ，7 adrenal metastases, 4 pheochro-Fibroxanthomemocytomas，2 nodular hyperplasias and 1 myelolipo-Total126ma that were not performed operations, the others alla: No report in the literalurehad histopathologic diagnoses.Of the 43 (34.1%) hyperseeretory adrenal inci-AIl of the 9 primary aldosteronisms patients haddenlalomas, 29 were pheochromocytomas， 12 werehypertension histories before operation and 6 of themadenomas (including 9 primary aldosteronisms， 2had hypokalemia histories. Suppressed plasma reninCushing's syndrome and 1 adrenogenitol syndrome),activity and elevated plasma aldosterone were foundand the other 2 were nodular bhypeplasias (both ofin all cases.Subtle hypercortisolism were found in 2 Cush-them had Cushing's syndromes). .Of the 29 pheochromocytomas, 2 were associateding's syndrome patients with incidental adrenal ade-with medullary thyroid carcinoma and were. diagnosednomas. Though they had no typical manifestation ofas Muliple Endocrine Neoplasia type II (MENI); 2Cushielevated 24- -hour中国煤化工"THCNMHG228CHINESE MEDICAL SCIENCES JOURNALDecember 2003urinary free cortisol and serum free cortisol levels,Twenty -8ix nonhypersecretory tumor patients were fol-and unsuppressbility of cortisol in overnight dexam-lowed and 4 of them died for reasons unrelated toethasone suppression tests was found in the 2 cases.he primary tumor.A female adrenogenitol syndrome patient had themanifestation of subtle vifilim. Elevated blood testosteoneDISCUSSIONand nomal blood 17-0HP were found.Of the 4 nodular hypeplasia patients， 2 pre-The use and sometines abuse of abdominalsented with elevated 24 -hour urinary free cortisolimaging procedures have greatly increased the discov-levels and 2 with normnal 24-hour urinary free corti- ery rate of adrenal ineidentalomas. Of the 126 asol levels.drenal incidentaloma patients admitted to our hospitalAl1 of the 9 adrenal metastases had known ma-rom 1990 to 2002， 17 (13.5%) were admited tlignancies. The primary malignancies originated from .our hospital from 1990~1994， 40 (31.7%) fromliver, stomach, pancreas, kidney， lung and pleura.1995-2008 and 69 (54.8%) from 1999 ~2002. MostAll of the3adrenocortical carcinomas were of the masses were discovered during the routinenonhypersecretory.Except for the above mentioned,physical examination， so routine physical examinationthe rest adrenal incidentalomas were all nonhyper~is an important method in discovering adrenal inci-secretory.dentalomas.Ninety. -eight of the 126 cases were perormedThough adrenal incidentalomas are discovered byoperations.Pathology of 98 adrenal incidentalomasimaging techniques for reasons unrelated to adrenalshowed that the maximum diamneters were from 0.6 diseases, we found that some diseases such as extra-:m to 19 cm.The maximum diameter of the 3 aadrenal malignancy and hypertension might be relat-drenocortical carcinomas was 19 cm，19 crm and 7ed to adrenal masses. For example, we found 2 pa-cm; the maximum diameter of the 2 adrenal metas-tients diagnosed as MENII were of pheochromocy-tases was 12 cm and 6 cm;the maximum diameterstomas as well as medullary thyroid carcinomas. Theof 25 pheochromoc.ytomas were from 2 cm to 18 cm;adrenal glands are highly vascular organs and there-that of the 2 Cushing' s syndrome with incidental afore common sites of metastases from exlra -adrenaldrenal adenornas were 10 cm and 3.1 cm; that of malignancy. We found all of the 9 adrenal metastasesthe 1 adrenogenitol syndrome was 4 cm;that of thepatients had known extra -adrenal malignancy， but9 primary aldosteronisms were from 0.6 cm to 3.8 cm;only 6 extra-adrenal malignancies were found in thethat of the 28 nonhypersecretory adenomas was fronother 117 adrenal incidentalomas. In patients with1.0cmto5.8cm..known malignancy， 8% to 38% have adrenal metas-Average period of follow -up was 49 months tases at autopsy.Conversely, in patients with no(range 1~147 months). Follow- up was available forknown primary malignancy， the overall rate for dis-16 in the 28 patients who were not perforned opera-covering a metastatic adrenal malignancy is low (7).tions. Ten nonhypersecretory adenomas patients were We found 57 (45.0%) of the 126 adrenal inciden-followed, 8 of them were alive and disease free (onetalomas patients and 11 (27%) of the 40 nonhyper-of them developed to be Cushing's syndrome after 96secretory adenomas had hypertension histories.Thmonths) and 2 died for reasons unrelated to the pri-prevalence of hypertension in patients with adrenalmary tumor. One pheochromocytomas patient died andincidentalomas is higher than in general populationthe other three lost follow -up. Five adrenal metastasis[20% in North America (3) and 7.7% in China].patients died for disease. Of 98 patients that were Some cases of incidentally discovered adrenal massesperformed operations, 62 were followed. Thirty-six ofre adrenocortical adenomas secreting cortisol at athe 43 hypersecretory tumors were followed and 26ate not sufficient to cause overt Cushing syndrome;were alive and disease free and the other 10 died.中国煤化工rome By delintion,THCNM HGVol. 18, No. 4CHINESE MEDICAL SCIENCES JOURNAL229the 24-hour urinary cortiso excretion is most ofenexeretion has the highest sensitivity in the diugnosisnormal. The best diagnostie approach is the overnightf phenochromocytomna (13). Our research obviously1.0 mg dixamethasone suppression test (8,9). Thisshows thatcompared with phenochromnocytomas,test is mandatory, since surgical removal of an undi-Cushing’syndrorme and adrenogenitol syndrome wereagnosed“pre-toxic" adrenocortical incidentalomas marare in the adrenal incidentalomas. One of the mainprecipitate an acute adrenal insufficiency crisis. Thereasons lies in that they had typical symptoms and .occuTrence of Cushing syndrome in such patients issigns.about 10% altr 10 years，emphasizing the need forMoreover, we found that all the 9 primary al-long- term follow- -up(3).dosteronisms had hypertension histories， but only 6Table 1 gives the number and percentage of allof them had hypokalemia history. So we think thakinds of incidentalomas, and reports of the literaturesthe absence of hypertension makes aldosteronism an(3). As other reports stated， we found the mostunlikely possibility ，although "normotensive primarypopular adrenal incidentalomas is adenoma. Exceptaldosteronism” has been reported， but normokalemiafor nodular hyperplasias， all the other adrenal inci-does not exclude aldosteronism because a significantdentalomas comply with the reports of literatures. Wenumber of patients who sustain aldosteronism arealso discovered some rare adrenal incidentalomas suchnormokalemic(14).a8 hemangioma， fibroxanthoma， epidermoid cyst andTo decide whether an adrenal incidentaloma ismedullary fbroneuromas.malignant or not is the second step for the clinician.Endocrine evaluation is the first step in evaluat-In patients with simple cysts ，adrenal hemorrhageing adrenal incidentalomas. Most frequently adrenaland myelolipoma， CT and MRI can provide accurateincidentalomas are nonhypersecretary adenomas ，ruttissue characterization. But it is difficul lo differenti-some may retain minor endocrine abnormalities oate nonbypersecretory adenomnas from adrenocorticalsubclinical hyperfunction. We found 4 Cushing's syn-careinomas. We found the maximum diameters of thedrome patients with no typical symptoms and signs ,26 nonhypersecrelory adenomas that were performedbut they had elevated 24 -hour urinary free cortisoloperations were all less than 6cm，but 3 adrenocorti-levels. Subelinical hypersecretion of cortisol occurs incal carecinomas were all larger than 6cm，thus we10%~15% of patients with adrenal incidentalomas inconclude that the size of the mass is one of the mostthe reports of the literatures(10,11).important factors in deciding tumor' s malignancy. TheMost of the 43 hypersecretory adrenal inciden-probability of an adrenal mass being malignant hastalomas were pheochromocytomas and primary aldos-been shown to increase significantly with its size. Weteronisms. They had been treated as primary hyper-recommend that a mass larger than 6 cm should betension for long period of time until they were dis-surgically removed. A 'small' lesion that bears allcovered by imaging techniques.The reason was thethe imaging fealures in favor of benignity should althey had no typical characleristic symptoms. Somethe most be followed. Only 5% of incidentalomaspatients do not have hypertensive symptoms and maysized less than 3cm may be malignant(15). Lesion ofeven be hypotensive, especially in the case of pre-"intermediary”size (3~6 cm) with benign imagingdominant epinephrine secretion. Several series havefeatures may be simply followed. When a doubt re-reported that as many as 76% of pheochromocytomasmains concerning their benignity， further evaluationare not diagnosed until after death (12). Althoughis necessary. Terzolo， et al.(16) found that the tu-phenochromocytoma is rare in hypertensive patients,nor diameter was highly correlated with the risk ofwe strongly recommend that a hormonal screening e-cancer; a cutoff at 5em had a sensitivity of 93%valuation be performed in all patients to exclude the with a sperifecity of 64% in discriminating betweenpresence of this potentially lethal condition. Measure-benign and malignant cortical lesions. But the choicement of 24 -hour uninary catecholamine or metanephrineof中国煤化工i all dehaedTYHCNMHG230CHINESE MEDICAL SCIENCES JOURNALDecember 2003and management strategies based on adrenal mass 6. Jenkins PI，Chew SL，Lowe DC，el al: Adrenocorti-size alone are neither sensitive nor specific,andcotrophin -independent unilateral macronodualr adrenal hy-tend to miss smaller and perhaps more surgically a-pemplasia occurring with myelolipoma: an unusual cause ofCushing's syndrome. Clin Endocrinol 1994; 41: 827 -38.menable lesions. Besides the size， malignancy hadother features to judge，such as irregular shape and7. Lim P0，Rodgers P，Cardale K, et al. Potentially highprevalence of primary aldosteronism in a primary- carepopu-thick margins; necrosis; low lipid content; high denlation. Lancet 1999; 353: 40-7.sity on CT scan and high, nonhomogenous increase 8. Barouz, Cuiban D, Maroufi A. et a. Orenight dexam.after contrast injection， and high T2- weighted signalethasone suppression test: comparison of plasma and sali-on MRI scan. Tumor progression shows mass enlarge-ary cortisol measurement for the screening of Cushing'sment and images of malignancy. We found 1 adreno-syndrome. Eur J Endocrinol 1996; 134: 93-6.cortical carcinoma， 12cm in CT scan in 1995 and 18 cm9. Tsuboi Y, Ishikawa SE, Fujsawa C, et al. Possible pre-Cushing' s syndrome due to an adrenal adenoma incidenta-3 years later, the histological tumor size was 19 cm.ly discovered. Endocrine J 1995; 42: 509- 16.Management of adrenal incidentalomas needs CT or10. Baron L, Boscaro M. Diagnosis and management of adrenalMRI and hormnonal investigation in order to detect ma-incidentalomas. J Urol 2000; 163: 398- 6. .lignancy and subelinical hypersecretory syndromes. Sub-11. Rossi R. Tauchmanova L， Luciano A, et al. Subclinicalclinical functional adrenal masses, single adrenal metas-Cushing's syndrome in patients with adrenal incidentaloma;tasis and primary nonhypersecretory tumors sized 6 cmclinical and biochemical features. J Cin Endocrinol Metabare treated by surgery.A close morpho-functional fol2000; 85(4): 1440-9.low-up is indicated for primary adrenal incidentalomas12. Kjellman M，Holst M，Backdahl M, et al. No overrepre-sentation of congenital adrenal hyperplasia in patients withwhen nonhypersecretory and smaller than 3~6 cm.adrenacortical tumours. Clin Endocrinol 19; 46: 29.13. Bitter DA. Ross Ds. 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