Adrenal—Incidentals, Pearls, PitfallsAdrenal—Incidentals, Pearls, Pitfalls

Clive Grant, MDClive Grant, MDMayo ClinicMayo Clinic

DisclosuresDisclosures

None

Adrenal CaseAdrenal Case

HPIHPI• 55 y/o female55 y/o female• 1 yr ago: L mast, – SLN for 3.5 cm infiltrating 1 yr ago: L mast, – SLN for 3.5 cm infiltrating

ductal carcinoma; ER, PR +ductal carcinoma; ER, PR +• 4 cycles AC chemotherapy; Tam4 cycles AC chemotherapy; Tam• Energy and WBC (2,600) did not return to nlEnergy and WBC (2,600) did not return to nl• Home MD further investigatedHome MD further investigated

Adrenal: Patient Eval Adrenal: Patient Eval

Meds: TamoxifenMeds: TamoxifenPSH: 2 back operations; appyPSH: 2 back operations; appyPMH: Well except breast CaPMH: Well except breast CaExam: VS nl Wt 120 lbsExam: VS nl Wt 120 lbs• Chest: mast site negChest: mast site neg• Nodes: all negNodes: all neg• Abd, pelvis: negAbd, pelvis: neg

Labs: Lytes, glu, Cr, LFTs, CXR nlLabs: Lytes, glu, Cr, LFTs, CXR nl

CT ImagingCT Imaging

CT: 6 cm mass replacing R adrenal. L adrenal nl; no hepatic masses; no abdominal lymphadenopathy

Adrenal Mass: EvaluationAdrenal Mass: Evaluation

What further testing?What further testing?• Serum, urine aldosteroneSerum, urine aldosterone• AM, PM cortisolAM, PM cortisol• 24-hr urine 24-hr urine ““mets and catsmets and cats””• 1 mg overnight dex suppression1 mg overnight dex suppression• CT-directed biopsyCT-directed biopsy• Bone scanBone scan• PET scanPET scan

Adrenal Mass: TestingAdrenal Mass: Testing

TestTest• AldoAldo• CortisolCortisol• PheoPheo• Dex suppDex supp• BxBx

• Bone scanBone scan• PET scanPET scan

ResultsResults• Not DoneNot Done• NormalNormal• NormalNormal• Not DoneNot Done• Small sample: positive for Small sample: positive for

malignancy, c/w breast camalignancy, c/w breast ca• No metsNo mets

PET ScanPET Scan

No abnormal uptake

except a large mass in the

right adrenal gland,

consistent with

malignancy.

Adrenal Mass: ManagementAdrenal Mass: Management

Options?Options?

1.1. Switch to different br ca drugSwitch to different br ca drug

2.2. Laparoscopic adrenalectomyLaparoscopic adrenalectomy

3.3. Open anterior adrenalectomyOpen anterior adrenalectomy

4.4. Right adrenal radiationRight adrenal radiation

Adrenal Cancer: Adrenal Cancer: TreatmentTreatment

SurgicalSurgical

• Open anterior right total adrenalectomyOpen anterior right total adrenalectomy

PathologyPathology

• 7.5 cm, 115 gm adrenocortical carcinoma; 7.5 cm, 115 gm adrenocortical carcinoma; no extra-adrenal invasionno extra-adrenal invasion

Adrenal IncidentalomaAdrenal IncidentalomaObjectivesObjectives

Following this presentation, you shouldFollowing this presentation, you should• Understand the definition and frequency Understand the definition and frequency

of adrenal incidentaloma of adrenal incidentaloma • Be prepared to evaluate an incidentaloma Be prepared to evaluate an incidentaloma

and make management recommendationsand make management recommendations• Understand the pitfalls and nuances of Understand the pitfalls and nuances of

the management algorithmthe management algorithm

Adrenal IncidentalomaAdrenal IncidentalomaDefinitionDefinition

Criteria1 cm diameter

• Well defined

Exclude

• Suspected hormonal hyperfunction

• Prior/concurrent malignancy

• Localized tumor symptoms/signs

• Constitutional symptoms of malignancy

Criteria1 cm diameter

• Well defined

Exclude

• Suspected hormonal hyperfunction

• Prior/concurrent malignancy

• Localized tumor symptoms/signs

• Constitutional symptoms of malignancy

Adrenal IncidentalomaAdrenal IncidentalomaHistoricalHistorical

Autopsy series

• 1.4-15% incidence

• Average size 1 cm

• Frequency increases with age

Problem recognition

• 1982 Geelhoed, 20 patients

• 1983 Prinz, 9 patients

Autopsy series

• 1.4-15% incidence

• Average size 1 cm

• Frequency increases with age

Problem recognition

• 1982 Geelhoed, 20 patients

• 1983 Prinz, 9 patients

Adrenal IncidentalomaAdrenal IncidentalomaNl Anatomy, Early CTNl Anatomy, Early CT

Nl adrenalsNl adrenals Incidentaloma, 1983Incidentaloma, 1983

Adrenal IncidentalomaAdrenal IncidentalomaAge DependenceAge Dependence

0

1

2

3

4

5

6

7

8

Pat

ien

ts, %

0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79

Age, yrs

Adrenal IncidentalomaAdrenal IncidentalomaAlgorithmAlgorithm

Adrenal tumorAdrenal tumor

ScreenScreen ExciseExciseObserveObserve

AssessmentAssessmentfor malignancyfor malignancy

Evaluation forEvaluation forhyperfunctionhyperfunction

Adrenal IncidentalomaAdrenal IncidentalomaEndocrine HyperfunctionEndocrine Hyperfunction

Possible Occult Functioning TumorsPossible Occult Functioning Tumors

• PheochromocytomaPheochromocytoma

• AldosteronomaAldosteronoma

• CushingCushing’’s adenomas adenoma

Adrenal IncidentalomaAdrenal IncidentalomaPheochromocytomaPheochromocytoma

IncidentalomasIncidentalomas• 5.1% prove to be pheochromocytomas5.1% prove to be pheochromocytomas• 7% pts with pheos have nl 24-hr urinary 7% pts with pheos have nl 24-hr urinary

fractionated fractionated catecholaminescatecholamines• 7% have nl 24-hr urinary total 7% have nl 24-hr urinary total

metanephrinesmetanephrines• 99%99% of of functioningfunctioning pheos have increased pheos have increased

levels of one or both of above levelslevels of one or both of above levels

24 hr urinary mets and cats

Adrenal IncidentalomaAdrenal IncidentalomaPrimary AldosteronismPrimary Aldosteronism

ScreeningScreening

• Most frequent cause of 2º hypertensionMost frequent cause of 2º hypertension

• Morning Morning PAC/PRAPAC/PRA

– On any antihypertensive except On any antihypertensive except spironolactonespironolactone

– Ratio of Ratio of 20 and a PAC of 15 ng/dL is 20 and a PAC of 15 ng/dL is positivepositive

Adrenal Incidentaloma Adrenal Incidentaloma Preclinical CushingPreclinical Cushing’’s Syndrome (PCSs Syndrome (PCS))

DefinitionDefinition

• Pts who lack typical signs/sxs of Pts who lack typical signs/sxs of

hypercortisolism having an incidentaloma hypercortisolism having an incidentaloma

with autonomous cortisol secretionwith autonomous cortisol secretion

• Pts may exhibit side effects of Pts may exhibit side effects of

endogenous cortisol secretionendogenous cortisol secretion

Adrenal IncidentalomaAdrenal IncidentalomaFrequency--PCSFrequency--PCS

Study Group--Italian Soc EndocrinologyStudy Group--Italian Soc Endocrinology• 786 patients786 patients• 49 (6.2%) with PCS49 (6.2%) with PCS

Continuum of glucocorticoid autonomyContinuum of glucocorticoid autonomy• Most adrenal adenomas have functional Most adrenal adenomas have functional

autonomyautonomy• PCS may develop over extended period (1.7-10 PCS may develop over extended period (1.7-10

yrs) yrs) repeat hormonal screening at 1-yr F/Urepeat hormonal screening at 1-yr F/U

Adrenal IncidentalomaAdrenal IncidentalomaEvaluation--PCSEvaluation--PCS

Laboratory CriteriaLaboratory Criteria

• 1-mg dex suppression test1-mg dex suppression test

– 8 AM cortisol level > 5 8 AM cortisol level > 5 g/dLg/dL

– Confirm with 2-day low-dose dex Confirm with 2-day low-dose dex

suppression testsuppression test

• ACTH assays--most not sensitive enoughACTH assays--most not sensitive enough

Adrenal IncidentalomaAdrenal IncidentalomaAdvantages vs DisadvantagesAdvantages vs Disadvantages

•Op mort/morb•XS surg for

benign lesions

•Op mort/morb•XS surg for

benign lesions

Risk of malignancy

Risk of malignancy

ExcisionExcision ObservationObservation

Adrenal IncidentalomaAdrenal IncidentalomaMalignant PotentialMalignant Potential

Potential Distinguishing CriteriaPotential Distinguishing Criteria

• Mass SizeMass Size

• Imaging phenotypeImaging phenotype

• Image-guided needle biopsyImage-guided needle biopsy

–MetastasisMetastasis

– InfectionInfection

• Iodocholesterol scintigraphyIodocholesterol scintigraphy

Adrenal IncidentalomaAdrenal IncidentalomaImaging PhenotypeImaging Phenotype

CT characteristicsCT characteristics• Density--Hounsfield scaleDensity--Hounsfield scale• 0 = water 1,000 = bone -1,000 = air0 = water 1,000 = bone -1,000 = air• -20 to -150 = adipose-20 to -150 = adipose• 20 to 50 = kidney20 to 50 = kidney• If adrenal is < 10, nearly 100% benign If adrenal is < 10, nearly 100% benign

adenomaadenoma• IV contrast:IV contrast:• Modest enhancementModest enhancement• Rapid washoutRapid washout

Adrenal IncidentalomaAdrenal IncidentalomaExampleExample

Adrenal IncidentalomaAdrenal IncidentalomaExampleExample

Precontrast Postcontrast

Report: 2.8 cm, precontrast 22-28 HU, immediate Report: 2.8 cm, precontrast 22-28 HU, immediate postcontrast 32-38 HU; Delayed 56-60 HU--postcontrast 32-38 HU; Delayed 56-60 HU--NotNot diagnostic for adenoma (Pathology: adrenal adenoma)diagnostic for adenoma (Pathology: adrenal adenoma)

Adrenal IncidentalomaAdrenal Incidentaloma Imaging PhenotypeImaging Phenotype

CT Characteristics (contCT Characteristics (cont’’d)d)• ShapeShape–Smooth, round/oval vs IrregularSmooth, round/oval vs Irregular

• TextureTexture–Homogeneous vs heterogeneousHomogeneous vs heterogeneous

• LateralityLaterality–Uni- vs bilateralUni- vs bilateral

• OtherOther–Hemorrhage, necrosis, calcificationsHemorrhage, necrosis, calcifications

Adrenal IncidentalomaAdrenal IncidentalomaCharacteristicsCharacteristics

AdenomaAdenoma• Size--small, typically Size--small, typically 3 cm 3 cm• Shape--round to oval, smooth marginsShape--round to oval, smooth margins• Texture--homogeneous, low densityTexture--homogeneous, low density• Laterality--solitary, unilateralLaterality--solitary, unilateral• Contrast enhancement--limitedContrast enhancement--limited• MR imaging--isointense to liver on T2-weighted imageMR imaging--isointense to liver on T2-weighted image• Necrosis, hemorrhage, CaNecrosis, hemorrhage, Ca2+2+--rare--rare• Growth--usually stable, very slow growthGrowth--usually stable, very slow growth

Adrenal IncidentalomaAdrenal IncidentalomaCharacteristicsCharacteristics

MRI: MRI: Typical appearance of Typical appearance of ““in phasein phase”” and and ““out of out of phasephase”” cuts with signal drop cuts with signal drop out typical for benign out typical for benign adenomaadenoma

Adrenal DisordersAdrenal DisordersBenign Nonfunctioning AdenomaBenign Nonfunctioning Adenoma

Adrenal IncidentalomaAdrenal Incidentaloma Imaging PhenotypeImaging Phenotype

Imaging: >25 HU precontrast; enhancing rimImaging: >25 HU precontrast; enhancing rimSurgical Dx: Surgical Dx: pheochromocytomapheochromocytoma

Adrenal IncidentalomaAdrenal IncidentalomaCharacteristicsCharacteristics

PheochromocytomaPheochromocytoma• Size--large, typically > 3 cmSize--large, typically > 3 cm• Shape--round, oval, clear marginsShape--round, oval, clear margins• Texture--inhomogeneous with cystic areasTexture--inhomogeneous with cystic areas• Laterality--solitary, unilateralLaterality--solitary, unilateral• Contrast enhancement--vascular, markedContrast enhancement--vascular, marked• MR--markedly hyperintense on T2MR--markedly hyperintense on T2• Necrosis, hemorrhage, CaNecrosis, hemorrhage, Ca2+2+--hemorrhage and cystic --hemorrhage and cystic

necrosis commonnecrosis common• Growth--usually slowGrowth--usually slow

Adrenal IncidentalomaAdrenal IncidentalomaPheochromocytomaPheochromocytoma

““IncidentalIncidental”” pheo pheo Typical pheoTypical pheo

Adrenal IncidentalomaAdrenal IncidentalomaCharacteristicsCharacteristics

Adrenocortical carcinomaAdrenocortical carcinoma• Size--large, typically > 4 cmSize--large, typically > 4 cm• Shape--irregular, unclear marginsShape--irregular, unclear margins• Texture--inhomogeneous, mixed densitiesTexture--inhomogeneous, mixed densities• Laterality--solitary, unilateralLaterality--solitary, unilateral• Contrast enhancement--vascular, markedContrast enhancement--vascular, marked• MR--hyperintense on T2MR--hyperintense on T2• Necrosis, hemorrhage, CaNecrosis, hemorrhage, Ca2+2+--common--common• Growth--rapidGrowth--rapid

Adrenal IncidentalomaAdrenal IncidentalomaExamplesExamples

Adrenal IncidentalomaAdrenal IncidentalomaCharacteristicsCharacteristics

MetastasisMetastasis• Size--variable, frequently < 3 cmSize--variable, frequently < 3 cm• Shape--oval to irregular, unclear marginsShape--oval to irregular, unclear margins• Texture--inhomogeneousTexture--inhomogeneous• Laterality--often bilateralLaterality--often bilateral• Contrast enhancement--vascular, enhancement tumor Contrast enhancement--vascular, enhancement tumor

rimrim• MR--hyperintense on T2MR--hyperintense on T2• Hemorrhage/cystic necrotic areas commonHemorrhage/cystic necrotic areas common• Growth--usually slowGrowth--usually slow

Adrenal IncidentalomaAdrenal Incidentaloma Imaging PhenotypeImaging Phenotype

Surgical Dx:Surgical Dx:Metastatic colon Metastatic colon carcinomacarcinoma

CharacteristicsCharacteristics•HeterogeneousHeterogeneous•Irregular borderIrregular border•Enhancing rimEnhancing rim

Adrenal IncidentalomaAdrenal IncidentalomaUnusual TumorsUnusual Tumors

Tb, AddisonTb, Addison’’ssMalignant fibrous Malignant fibrous

histiocytomahistiocytoma

Adrenal IncidentalomaAdrenal IncidentalomaUnusual TumorsUnusual Tumors

Cystic large cell lymphoma of adrenalCystic large cell lymphoma of adrenal

Adrenal IncidentalomaAdrenal IncidentalomaUnnecessary SurgeryUnnecessary Surgery

1 2 3 4 5 6 7 8 9 10 110

10

20

30

40

%%

Size of tumor (cm)Size of tumor (cm)

(115) (115)

(65)

(22)(12) (4)

(3) (1)

32%

6%

12%

Malignant tumors

Adrenal IncidentalomaAdrenal IncidentalomaAlgorithmAlgorithm

Based on observations:Based on observations: 10% incidentalomas hyperfunctional, 10% incidentalomas hyperfunctional,

autonomousautonomous

• < 5% adrenocortical carcinomas< 5% adrenocortical carcinomas

• 95% adrenocortical cancers > 4 cm95% adrenocortical cancers > 4 cm

• 95% cortical adenomas < 5 cm95% cortical adenomas < 5 cm

• Imaging phenotype very helpfulImaging phenotype very helpful

• FNA rarely indicatedFNA rarely indicated

Adrenal IncidentalomaAdrenal IncidentalomaAlgorithmAlgorithm

H & P24-hr urine mets, cats1-mg overnight DST

If BP: PAC/PRA

Nonfunctional,< 4 cm

Functioning mass,> 4 cm

Surgicalresection

Repeat imagingNo change--observe

If > 1cmIf > 1cm

sizesize

Imaging phenotype

Benign Suspicious

Thank

you