1. Adrenal Masses: Differential Dx and Work-up Sara Faber August 4, 2008

2. Why should we care? ► Autopsy studies demonstrate ~9% of people have a 2 mm – 4 cm mass at time of death. ► More recent studies have shown that up to 5% of CT scans performed for various reasons reveal adrenal lesions.

3. Approach to the Adrenal Mass ► Functional versus Non-functional? ► Malignant versus Benign? ► Most masses are nonfunctional and only 1 in 4000 is malignant.

4. Non-functional and Benign Diagnosis No. (%) of Lesions Adenoma788 (75) Myelolipoma68 (6) Hematoma47 (4) Cyst13 (1) Pheochromocytoma3 (0.3) Macronodular Hyperplasia1 (0.1) Adrenal Cortical Neoplasm of unknown malignant potential1 (0.1) Presumed benign by imaging/clinical stability128 (12) Total1049 (100)

5. What if there’s suspicion of functionality or malignancy? ► Functional tumors:  Adrenal Medullary Tumors: ► Pheochromocytoma ► Childhood tumors: ganglioneuromas, neuroblastomas  Adrenal Cortical Tumors: ► Cortisol-secreting adenoma ► Aldosteronoma ► Carcinoma ► Known history of malignancy  Adrenal glands are common sites of metastasis

6. Pheochromocytoma ► Epi:  Rare: 3-4 diagnoses/million in the US  25% diagnosed incidentally by imaging ► Signs/Symptoms: HTN, tachycardia, palpitations, sweating, HA, tremor ► Labwork demonstrates:  Elevated plasma fractionated metanephrines  24 hour urine: elevated fractionated catecholamines and their metabolites: metanephrines and vanillylmandelic acid (VMA) ► For the boards: assoc with AD syndromes MEN I & II; type 1 neurofibromatosis; von Hippel Lindau; Sturge Weber

7. Cortisol-secreting Adenoma: the sweet part ► Epi: F > M; ages 30-50s ► Signs/Symptoms:  May lead to clinical or sub-clinical Cushing’s syndrome  Most commonly: obesity, HTN, glucose intolerance or DMII, hypercholesterolemia ► Labwork demonstrates:  Failed dex suppression test (cortisol can be monitored with diurnal bloodwork for inpts or saliva for outpts)  Low DHEA-sulfate (increased cortisol suppresses pituitary-adrenal axis)  Elevated 24 hour urinary cortisol

8. Aldosteronomas: the salty part ► Epi:  <1% of incidentalomas, more often L than R  F > M, age 30-40 ► Signs/Symptoms:  Most often, patients are not hypoK  Therefore, screen all HTN pts with incidental mass ► Labwork reveals:  Increased serum aldosterone  Decreased plasma renin activity

9. Adrenal Cortical Carcinoma: the sex hormones ► Epi:  Rare: 0.02% of cancers, 0.3 cases/million worldwide  F > M; two age peaks: M; two age peaks: <5yo & 40-50s ► Signs/Symptoms:  Androgen excess is most common  virilization  Cushing’s syndrome also seen ► Labwork demonstrates:  Elevated DHEA-sulfate and androstendedione  Failed dex suppression

10. So, what to do with adrenal masses? ► Previously, histopathology was gold standard ► Currently, various imaging techniques are regarded as ideal, due to ease:  CT with or without contrast (83% accurate in diagnosing malignancy)  Chemical shift MRI (94% accurate)  Norcholesterol scintigraphy (92% accurate)

11. Additional recommendations ► Labwork  FOR ALL MASSES: Dex suppression test, plasma-free metanephrines to determine functionality  In HTN pts, measure serum K+ and plasma aldosterone/renin activity ► Monitor with physical exam, bloodwork and 2 imaging studies 6 months apart.

12. Size matters… ► NIH recommendation for adrenal masses:  If mass > 6 cm  surgery.  If mass < 4 cm  monitor (bloodwork and imaging)  If 4-6 cm, decision may be based upon imaging findings and bloodwork results.

13. References ► Song, et al. The Incidental Adrenal Mass on CT: Prevalence of Adrenal Disease in 1,049 Consecutive Adrenal Masses in Patients with No Known Malignancy. AJR 2008; 190: 1163-1168. ► Lumachi, et al. High risk of malignancy in patients with incidentally discovered adrenal masses: accuracy of adrenal imaging and image- guided fine needle aspiration cytology. Tumori 2007; 93(3): 269-274. ► NIH state-of-the-science statement on management of the clinically inapparent adrenal mass (“incidentaloma”). NIH Consens State Sci Statements 2002; 19(2): 1-25. ► Kuruba, et al. Current management of adrenal tumors. Curr Opin in Onc 2008; 20(1): 34-46. ► Cotran, et al. Robbins Pathologic Basis of Disease, 6 th ed. WB Saunders Company, Philadephia, PA. 1999.