Adrenal Incidentalomas in the real worldAdrenal Incidentalomas in the real world

Brian R. Herts, MDBrian R. Herts, MDAssociate Professor of RadiologyAssociate Professor of Radiology

Head, Abdominal Imaging, Imaging Institute &Head, Abdominal Imaging, Imaging Institute &Staff, The Staff, The GlickmanGlickman Urological and Kidney Inst.Urological and Kidney Inst.

Cleveland ClinicCleveland Clinic

ObjectivesObjectives• 1. Define “adrenal incidentaloma”• 2. Review the differential diagnosis of

incidental adrenal lesions and the most common lesions

• 3. Provide a practical approach to using imaging studies to determine the most likely etiology of incidental adrenal lesions

Preface Preface -- Adrenal FactsAdrenal Facts……

•• Definition of an adrenal Definition of an adrenal incidentalomaincidentaloma•• Adrenal mass, typically > 1 cmAdrenal mass, typically > 1 cm•• Discovered by imaging performed for indication other than Discovered by imaging performed for indication other than

assessing for adrenal diseaseassessing for adrenal disease•• Should exclude staging evaluation of patients with cancerShould exclude staging evaluation of patients with cancer

•• Prevalence of unsuspected adrenal masses increases Prevalence of unsuspected adrenal masses increases with agewith age

•• Prevalence 0.2% Prevalence 0.2% -- 10% as age increases 2010% as age increases 20’’s to 70+ yrss to 70+ yrs•• Higher on autopsy studies, but typically includes all sizesHigher on autopsy studies, but typically includes all sizes

Etiologies of Etiologies of adrenalomasadrenalomas(i.e. should we be worried?)(i.e. should we be worried?)

•• Differential diagnosis of adrenal incidentalomasDifferential diagnosis of adrenal incidentalomas•• NonNon--hypersecretinghypersecreting benign cortical adenomas (majority)benign cortical adenomas (majority)•• HypersecretingHypersecreting adenomasadenomas

•• CortisolCortisol secreting adenomas, secreting adenomas, aldosteronomasaldosteronomas, , pheospheos•• Metastatic diseaseMetastatic disease•• Adrenal cortical carcinomaAdrenal cortical carcinoma•• MyelolipomaMyelolipoma•• Cysts Cysts •• HHemorrhageemorrhage

Adrenal adenomasAdrenal adenomas

•• 11--10% at autopsy, equal incidence in both genders10% at autopsy, equal incidence in both genders•• Most are less than 2 cmMost are less than 2 cm•• Estimated 15% are functional (excess glucocorticoids, Estimated 15% are functional (excess glucocorticoids,

mineralocorticoids)mineralocorticoids)•• Clinical / subClinical / sub--clinical Cushingclinical Cushing’’s, Conns, Conn’’s syndrome, s syndrome, PheoPheo

•• Lipid in adrenal adenomas are precursors to adrenal Lipid in adrenal adenomas are precursors to adrenal cortical hormonescortical hormones

•• LipidLipid--rich adrenal cortical adenomas are detected by rich adrenal cortical adenomas are detected by identifying identifying intracytoplasmicintracytoplasmic lipid content (70%)lipid content (70%)

•• LipidLipid--poor adrenal cortical adenomas do not have enough poor adrenal cortical adenomas do not have enough lipid content to be detected on imaging (30%) and are lipid content to be detected on imaging (30%) and are characterized by rapid washout compared with metastasescharacterized by rapid washout compared with metastases

Adrenal CarcinomaAdrenal Carcinoma

•• Rare Rare -- 44--12 cases / million 12 cases / million •• Prevalence increases with size Prevalence increases with size ……

•• ≤≤ 4 cm 4 cm -- 2%2%•• 4.1 4.1 -- 6 cm 6 cm -- 6%6%•• > 6 cm > 6 cm -- 25%25%

•• Poor prognosis Poor prognosis -- median survival 18 monthsmedian survival 18 months•• Therefore Therefore -- even though 75% of adrenal masses > 6 cm and > even though 75% of adrenal masses > 6 cm and >

90% of lesions 4 90% of lesions 4 -- 6 cm are not adrenal CA, Urologists and 6 cm are not adrenal CA, Urologists and general surgeons are overly cautiousgeneral surgeons are overly cautious

•• Most adrenal mass lesions > 4 cm that cannot be confirmed as Most adrenal mass lesions > 4 cm that cannot be confirmed as benign are resectedbenign are resected

•• So So …… #1: size is an important determinant of managing #1: size is an important determinant of managing adrenal incidentalomasadrenal incidentalomas

•• Cancers likely to metastasize to the adrenal glandsCancers likely to metastasize to the adrenal glands•• Either common cancers, or common to adrenalEither common cancers, or common to adrenal

•• Lung CA Lung CA •• Breast CA Breast CA •• LymphomaLymphoma•• Renal cell carcinomaRenal cell carcinoma•• GI tract: Esophageal, Gastric and ColonGI tract: Esophageal, Gastric and Colon

•• CA CA hxhx: estimated 75% of adrenal masses are metastases: estimated 75% of adrenal masses are metastases•• No CA No CA hxhx: metastases are extremely rare: metastases are extremely rare

•• 0 of 973 consecutive incidental adrenal masses (Song J, AJR 20080 of 973 consecutive incidental adrenal masses (Song J, AJR 2008))•• 1.5% of 342 patients, all lesions > 5 cm (Herrera MF, Surgery 191.5% of 342 patients, all lesions > 5 cm (Herrera MF, Surgery 1991)91)

•• So So …… #2: history of a malignancy#2: history of a malignancy is an important is an important determinant of managing adrenal incidentalomasdeterminant of managing adrenal incidentalomas

Metastatic diseaseMetastatic disease

Grossly fatty mass = Grossly fatty mass = MyelipomaMyelipoma

•• BBenignenign tumortumor--like like lesionlesion composed of mature composed of mature adiposeadipose tissue tissue and and haematopoietichaematopoietic elements in elements in variousvarious proportionsproportions

•• Asymptomatic and are not hormonally active Asymptomatic and are not hormonally active •• Unusually not treated (if very large may be resected for Unusually not treated (if very large may be resected for

bleeding risk)bleeding risk)

CT and MR imaging of CT and MR imaging of adrenalomasadrenalomas•• CT CT -- unenhanced and washout (as needed)unenhanced and washout (as needed)

•• LipidLipid--rich adenomas rich adenomas -- Unenhanced CTUnenhanced CT•• < 10 HU ~ meta< 10 HU ~ meta--analysis analysis senssens 71%, spec 98% for adenoma 71%, spec 98% for adenoma

(Boland) (Boland) •• LipidLipid--rich and lipid poor adenomas: Washout CTrich and lipid poor adenomas: Washout CT

•• Thin slice, unenhanced, PV phase and 10Thin slice, unenhanced, PV phase and 10--15 minute delay15 minute delay•• 50% and 60% absolute washout50% and 60% absolute washout

•• MR MR -- inin-- and opposedand opposed--phase imagingphase imaging•• Lipid rich adenomas Lipid rich adenomas -- signal dropout with opposedsignal dropout with opposed--phasephase

•• Gross fat (CT or MR)? Gross fat (CT or MR)? –– myelolipomamyelolipoma•• Note: appearance says Note: appearance says nothingnothing about adrenal excess functionabout adrenal excess function

•• So So …… #3: CT & MR appearance#3: CT & MR appearance is another important is another important determinant of managing adrenal incidentalomasdeterminant of managing adrenal incidentalomas

MR inMR in-- and opposedand opposed--phasephase

•• InIn--phase imaging: signal from Hphase imaging: signal from H-- atoms in water and lipid additiveatoms in water and lipid additive•• Opposed phase imaging: signal from HOpposed phase imaging: signal from H-- atoms in water and lipid are atoms in water and lipid are

diametrically opposed and subtract (waterdiametrically opposed and subtract (water--fat)fat)•• Relies on balance of both types of signalRelies on balance of both types of signal•• No MR criteria for lipidNo MR criteria for lipid--poor adenomaspoor adenomas

CT washoutCT washout

•• Unenhanced CT: if HU < 10, then stop = LipidUnenhanced CT: if HU < 10, then stop = Lipid--rich adenomarich adenoma•• Absolute washout: > 60% Absolute washout: > 60% c/wc/w adenoma (lipid poor) adenoma (lipid poor) -- spec 92%spec 92%

(delay (delay -- unenhanced) / (enhanced unenhanced) / (enhanced -- unenhanced)unenhanced)•• Relative washout: > 40% Relative washout: > 40% c/wc/w adenoma adenoma -- spec 92%spec 92%

(delay / enhanced)(delay / enhanced)

NIH Consensus NIH Consensus Conference Conference

Ann Intern Med 2003Ann Intern Med 2003

•• Exclude myelolipoma and cystExclude myelolipoma and cyst•• Recommended clinical evaluationRecommended clinical evaluation

•• 11--mg overnight mg overnight dexamethasonedexamethasone suppression test (suppression test (cushingcushing’’ss))•• Urinary or plasma metanephrines (Urinary or plasma metanephrines (pheopheo))•• If HTN If HTN -- serum K+ and serum K+ and aldosteronealdosterone -- plasma plasma reninrenin activity ratio (activity ratio (ConnConn))

•• Recommended imaging evaluationRecommended imaging evaluation•• NCCT density measurement or inNCCT density measurement or in-- opposed phase MRopposed phase MR•• Washout CT protocolWashout CT protocol

•• Recommended surgery for lesionsRecommended surgery for lesions•• Endocrine evidence of adrenal Endocrine evidence of adrenal hyperfunctionhyperfunction (some exceptions)(some exceptions)•• Tumors > 6 cm or Tumors > 6 cm or tumors 4tumors 4--6 cm6 cm if not closely followedif not closely followed

•• Recommended FNA Recommended FNA •• History of malignancy and negative imaging for adenoma, other History of malignancy and negative imaging for adenoma, other metsmets

Endocrinology Endocrinology perspective perspective

Endocrine Rev 2004Endocrine Rev 2004

ACR committee approachACR committee approach•• Step 1: exclude benign diseaseStep 1: exclude benign disease

•• MyelolipomaMyelolipoma•• Adenoma by CT or MRAdenoma by CT or MR

•• Step 2: size > 4 cmStep 2: size > 4 cm•• PET, FNAB or resectionPET, FNAB or resection

•• Step 3 Step 3 (<4 cm)(<4 cm): history & priors: history & priors•• Stable, no CA Stable, no CA HxHx -- benignbenign•• Indeterminate Indeterminate -- imageimage

•• Step 4: Adrenal CT or MRStep 4: Adrenal CT or MR•• Lipid rich / poor adenoma Lipid rich / poor adenoma -- ‘‘stopstop’’•• BxBx or PET or PET -- hxhx primaryprimary

•• Consider biochemical assayConsider biochemical assay

Practical (personal) approachPractical (personal) approach•• HistoryHistory -- What if any primary malignancy? What if any primary malignancy?

•• Endocrine issues Endocrine issues -- rarely available rarely available

•• AppearanceAppearance•• Trauma / hemorrhage, myelolipoma Trauma / hemorrhage, myelolipoma -- stopstop•• Heterogeneous, > 10 HU, older Heterogeneous, > 10 HU, older -- pursue pursue …… w/ imaging, PET or FNAB w/ imaging, PET or FNAB

depending on depending on hxhx, size & age, size & age

•• Size & AgeSize & Age•• Greater than 4 cmGreater than 4 cm

•• CA CA hxhx –– probable met. Workprobable met. Work--up w/ PET / FNAB if clinically relevantup w/ PET / FNAB if clinically relevant•• No CA No CA hxhx -- ““adrenal massadrenal mass”” -- biochemical assessment, resectionbiochemical assessment, resection

•• 22--4 cm 4 cm –– indeterminate range. Full workup, biochemistry, imagingindeterminate range. Full workup, biochemistry, imaging•• Small size (< 2 cm), young patient, no CA Small size (< 2 cm), young patient, no CA hxhx, stable, homogeneous, stable, homogeneous

•• Likely adenoma Likely adenoma -- ignore possibility of ignore possibility of metsmets / adrenal CA/ adrenal CA

•• Adenoma by imagingAdenoma by imaging (CT or MR)(CT or MR)•• suggest endocrine assessment suggest endocrine assessment -- exclude exclude hyperfunctionhyperfunction

Case 1Case 1

Case 2Case 2

Case 3Case 3

Case 4Case 4

ReferencesReferences•• Young WF. The incidentally discovered adrenal mass. NEJM Young WF. The incidentally discovered adrenal mass. NEJM

2007;356:6012007;356:601--610610• Boland GW et al. Characterization of adrenal masses using unenhanced

CT: an analysis of the CT literature. AJR 1998; 171(1):201-204•• Song et al. The incidental adrenal mass on CT: prevalence of adrSong et al. The incidental adrenal mass on CT: prevalence of adrenal enal

disease in 1,049 consecutive adrenal masses in patients with no disease in 1,049 consecutive adrenal masses in patients with no known known malignancy. AJR 2008;190:1163malignancy. AJR 2008;190:1163--11681168

•• GrumbachGrumbach MM et al. Management of the clinically MM et al. Management of the clinically inapparentinapparent adrenal adrenal mass. Ann Intern Med 2003;138:424mass. Ann Intern Med 2003;138:424--429429

•• MansmannMansmann G et al. The clinically G et al. The clinically inapparentinapparent adrenal mass: update in adrenal mass: update in diagnosis and management. Endocrine Rev 2004;25:309diagnosis and management. Endocrine Rev 2004;25:309--340340

•• KorobkinKorobkin M et al. Differentiation of adrenal adenomas from M et al. Differentiation of adrenal adenomas from nonadenomasnonadenomasusing CT attenuation values. AJR 1996;166:531using CT attenuation values. AJR 1996;166:531--536536

•• CaoiliCaoili EM et al. Adrenal masses: characterization with combined EM et al. Adrenal masses: characterization with combined unenhanced and delayed CT. Radiology 2002;222:629unenhanced and delayed CT. Radiology 2002;222:629--633 633

•• ACR Appropriateness criteria (draft March 2009)ACR Appropriateness criteria (draft March 2009)