Adrenal—Incidentals, Pearls, Pitfalls

1. Adrenal—Incidentals, Pearls, Pitfalls Clive Grant, MD Mayo Clinic

2. Disclosures None

3. Adrenal Case • HPI • 55 y/o female • 1 yr ago: L mast, – SLN for 3.5 cm infiltrating ductal carcinoma; ER, PR + • 4 cycles AC chemotherapy; Tam • Energy and WBC (2,600) did not return to nl • Home MD further investigated

4. Adrenal: Patient Eval • Meds: Tamoxifen • PSH: 2 back operations; appy • PMH: Well except breast Ca • Exam: VS nl Wt 120 lbs • Chest: mast site neg • Nodes: all neg • Abd, pelvis: neg • Labs: Lytes, glu, Cr, LFTs, CXR nl

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

6. Adrenal Mass: Evaluation • What further testing? • Serum, urine aldosterone • AM, PM cortisol • 24-hr urine “mets and cats” • 1 mg overnight dex suppression • CT-directed biopsy • Bone scan • PET scan

7. Test Aldo Cortisol Pheo Dex supp Bx Bone scan PET scan Results Not Done Normal Normal Not Done Small sample: positive for malignancy, c/w breast ca No mets Adrenal Mass: Testing

8. PET Scan No abnormal uptake except a large mass in the right adrenal gland, consistent with malignancy.

9. Adrenal Mass: Management • Options? • Switch to different br ca drug • Laparoscopic adrenalectomy • Open anterior adrenalectomy • Right adrenal radiation

10. Adrenal Cancer: Treatment • Surgical • Open anterior right total adrenalectomy • Pathology • 7.5 cm, 115 gm adrenocortical carcinoma; no extra-adrenal invasion

11. Adrenal IncidentalomaObjectives • Following this presentation, you should • Understand the definition and frequency of adrenal incidentaloma • Be prepared to evaluate an incidentaloma and make management recommendations • Understand the pitfalls and nuances of the management algorithm

12. Adrenal IncidentalomaDefinition • Criteria • 1 cm diameter • Well defined • Exclude • Suspected hormonal hyperfunction • Prior/concurrent malignancy • Localized tumor symptoms/signs • Constitutional symptoms of malignancy

13. Adrenal IncidentalomaHistorical • Autopsy series • 1.4-15% incidence • Average size 1 cm • Frequency increases with age • Problem recognition • 1982 Geelhoed, 20 patients • 1983 Prinz, 9 patients

14. Adrenal IncidentalomaNl Anatomy, Early CT Nl adrenals Incidentaloma, 1983

15. Adrenal IncidentalomaAge Dependence

16. Evaluation for hyperfunction Assessment for malignancy Adrenal IncidentalomaAlgorithm Adrenal tumor Screen Observe Excise

17. Adrenal IncidentalomaEndocrine Hyperfunction • Possible Occult Functioning Tumors • Pheochromocytoma • Aldosteronoma • Cushing’s adenoma

18. Adrenal IncidentalomaPheochromocytoma • Incidentalomas • 5.1% prove to be pheochromocytomas • 7% pts with pheos have nl 24-hr urinary fractionated catecholamines • 7% have nl 24-hr urinary total metanephrines • 99% of functioningpheos have increased levels of one or both of above levels 24 hr urinary mets and cats

19. Adrenal IncidentalomaPrimary Aldosteronism • Screening • Most frequent cause of 2º hypertension • Morning PAC/PRA • On any antihypertensive except spironolactone • Ratio of  20 and a PAC of 15 ng/dL is positive

20. Adrenal Incidentaloma Preclinical Cushing’s Syndrome (PCS) • Definition • Pts who lack typical signs/sxs of hypercortisolism having an incidentaloma with autonomous cortisol secretion • Pts may exhibit side effects of endogenous cortisol secretion

21. Adrenal IncidentalomaFrequency--PCS • Study Group--Italian Soc Endocrinology • 786 patients • 49 (6.2%) with PCS • Continuum of glucocorticoid autonomy • Most adrenal adenomas have functional autonomy • PCS may develop over extended period (1.7-10 yrs)  repeat hormonal screening at 1-yr F/U

22. Adrenal IncidentalomaEvaluation--PCS • Laboratory Criteria • 1-mg dex suppression test • 8 AM cortisol level > 5 g/dL • Confirm with 2-day low-dose dex suppression test • ACTH assays--most not sensitive enough

23. Adrenal IncidentalomaAdvantages vs Disadvantages • Op mort/morb • XS surg forbenign lesions Risk of malignancy Excision Observation

24. Adrenal IncidentalomaMalignant Potential • Potential Distinguishing Criteria • Mass Size • Imaging phenotype • Image-guided needle biopsy • Metastasis • Infection • Iodocholesterol scintigraphy

25. Adrenal IncidentalomaImaging Phenotype • CT characteristics • Density--Hounsfield scale • 0 = water 1,000 = bone -1,000 = air • -20 to -150 = adipose • 20 to 50 = kidney • If adrenal is < 10, nearly 100% benign adenoma • IV contrast: • Modest enhancement • Rapid washout

26. Adrenal IncidentalomaExample

27. Adrenal IncidentalomaExample Precontrast Postcontrast Report: 2.8 cm, precontrast 22-28 HU, immediate postcontrast 32-38 HU; Delayed 56-60 HU--Not diagnostic for adenoma (Pathology: adrenal adenoma)

28. Adrenal IncidentalomaImaging Phenotype • CT Characteristics (cont’d) • Shape • Smooth, round/oval vs Irregular • Texture • Homogeneous vs heterogeneous • Laterality • Uni- vs bilateral • Other • Hemorrhage, necrosis, calcifications

29. Adrenal IncidentalomaCharacteristics • Adenoma • Size--small, typically  3 cm • Shape--round to oval, smooth margins • Texture--homogeneous, low density • Laterality--solitary, unilateral • Contrast enhancement--limited • MR imaging--isointense to liver on T2-weighted image • Necrosis, hemorrhage, Ca2+--rare • Growth--usually stable, very slow growth

30. Adrenal IncidentalomaCharacteristics • MRI: Typical appearance of “in phase” and “out of phase” cuts with signal drop out typical for benign adenoma

31. Adrenal DisordersBenign Nonfunctioning Adenoma

32. Adrenal IncidentalomaImaging Phenotype Imaging: >25 HU precontrast; enhancing rim Surgical Dx: pheochromocytoma

33. Adrenal IncidentalomaCharacteristics • Pheochromocytoma • Size--large, typically > 3 cm • Shape--round, oval, clear margins • Texture--inhomogeneous with cystic areas • Laterality--solitary, unilateral • Contrast enhancement--vascular, marked • MR--markedly hyperintense on T2 • Necrosis, hemorrhage, Ca2+--hemorrhage and cystic necrosis common • Growth--usually slow

34. Adrenal IncidentalomaPheochromocytoma “Incidental” pheo Typical pheo

35. Adrenal IncidentalomaCharacteristics • Adrenocortical carcinoma • Size--large, typically > 4 cm • Shape--irregular, unclear margins • Texture--inhomogeneous, mixed densities • Laterality--solitary, unilateral • Contrast enhancement--vascular, marked • MR--hyperintense on T2 • Necrosis, hemorrhage, Ca2+--common • Growth--rapid

36. Adrenal IncidentalomaExamples

37. Adrenal IncidentalomaCharacteristics • Metastasis • Size--variable, frequently < 3 cm • Shape--oval to irregular, unclear margins • Texture--inhomogeneous • Laterality--often bilateral • Contrast enhancement--vascular, enhancement tumor rim • MR--hyperintense on T2 • Hemorrhage/cystic necrotic areas common • Growth--usually slow

38. Adrenal IncidentalomaImaging Phenotype • Characteristics • Heterogeneous • Irregular border • Enhancing rim Surgical Dx: Metastatic colon carcinoma

39. Adrenal IncidentalomaUnusual Tumors Malignant fibrous histiocytoma Tb, Addison’s

40. Adrenal IncidentalomaUnusual Tumors Cystic large cell lymphoma of adrenal

41. 32% (115) (115) 12% 6% (65) % Malignant tumors (22) (12) (4) (3) (1) 1 2 3 4 5 6 7 8 9 10 11 Size of tumor (cm) Adrenal IncidentalomaUnnecessary Surgery

42. Adrenal IncidentalomaAlgorithm • Based on observations: •  10% incidentalomas hyperfunctional, autonomous • < 5% adrenocortical carcinomas • 95% adrenocortical cancers > 4 cm • 95% cortical adenomas < 5 cm • Imaging phenotype very helpful • FNA rarely indicated

43. Functioning mass, > 4 cm Nonfunctional, < 4 cm Benign If > 1cm  size Suspicious Adrenal IncidentalomaAlgorithm H & P 24-hr urine mets, cats 1-mg overnight DST If  BP: PAC/PRA Imaging phenotype Surgical resection Repeat imaging No change--observe

44. Thank you