1. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Approach to the Incidental Adrenal Nodule Author: Andrew Hope, MD Editor: Amy Shaheen, MD, Assistant Professor of Clinical Medicine Duke University Medical Center

2. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Definition & Incidence Definition: –A lesion incidentally discovered radiographically measuring >1cm. Incidence: –At autopsy 9% of normotensive patients, and 12% of hypertensive pts, will have a 2-4cm adrenal mass. –On CT scan, 0.4% of live patients will have >1cm “incidentaloma”

3. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Differential Diagnosis Benign (70% of time in non-known CA pts) –Adenoma –Myelolipoma –Adrenal cysts –Hematoma Malignant –Pheochromocytoma –Metastases –Adrenal cortical carcinoma –Ganglioneuroma

4. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Approach to excluding malignancy 1) Evaluate patient risk factors: Patients with history of known cancer will have malignancy 75% of time. Otherwise, age, race, most other patient characteristics not known to be predictive of malignancy.

5. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Radiographic characteristics of lesion 2) Examine Radiographic characteristics of lesion: There are a host of CT and MR imaging characteristics that help distinguish among benign adenomas, adrenocortical CA, pheochromocytoma, cysts, and hematomas. Some of them are listed here, although clearly a radiologist’s assistance will be needed to make the diagnosis (as long as we order the right test—according to NIH guidelines, CT and MRI are equivalent in evaluation of adrenal mass):

6. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Features of benign adenoma Features of benign adenoma: Round, homogeneous density; sharp margination; size<4cm; low unenhanced attenuation; limited enhancement with IV contrast on CT; isointensity with liver both T1 and T2 on MR; chemical shift c/w lipid on MR

7. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Features of Adrenocortical CA Features of adrenocortical CA: Irregular shape; inhomogeneous density 2/2 tumor necrosis; tumor calcification; diameter>4cm; unilateral; high unenhanced CT attenuation; inhomogeneous enhancement with CT contrast; hypointensity c/w liver T1 MR, high/intermed T2 MR; evidence of invasion/metastasis

8. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Features of pheochromocytoma Features of pheochromocytoma: –Enhancement with CT contrast; high signal on T2 MR; cystic/hemorrhagic changes; variable size, bilateral

9. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Features of metastatic lesions Features of metastatic lesions: –Irregular shape, inhomogeneous; often bilateral; high unenhanced CT attenuation; enhancement with contrast on CT; isointensity with liver T1 MR and high/intermed intensity T2 Note: Adrenal cysts, hemorrhage, myelilopoma are distinguished with other characteristics

10. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Hypersecreting lesions 3) Perform hormonal evaluation for hypersecreting lesions. (this should be done in all patients) –Cortisol-secreting tumors (10% of cases, 5-8% are subclinical Cushing’s). Clinical features: obesity, hypertension, glucose intolerance, hypercholesterolemia All pts with adrenal mass should have 1mg dexamethasone suppression test performed (NIH consensus guidelines)

11. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Pheochromacytoma, Aldosteronoma Pheochromocytoma (3-10% of adrenal masses). Plasma free metanephrines should be sent in all pts with adrenal mass (NIH consensus guidelines). This test is 99% sensitive and 90% specific for pheo. Alternatively, a 24 hr urine could be collected for metanephrines, vanillylmandelic acid (VMA), and free catecholamines Aldosteronoma (rare, <1%). Patients with adrenal incidentaloma and hypertension should be evaluated with plasma aldosterone and renin, even if not hypokalemic (NIH guidelines). Summary: all patients need 1mg dexamethasone suppression test and plasma free metanephrines. Add plasma rennin/aldo if hypertension present.

12. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Further Studies FNA. This is useful only to distinguish metastatic lesions from adrenal tumors. For example, a case series found that 2/3 of lung cancer patients with adrenal masses had a benign adrenal lesion.

13. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Surgery vs. Conservative follow up 4) Decide surgery vs. conservative follow up. Criteria for surgery: –Size Over 6 cm  surgery. Less than 4 cm  clinical follow up. 4-6 cm  consider in context of other features of patient and mass. Functional tumors. –Clinically apparent cortisol-secreting tumors  surgery. Subclinical cortisol-secreting tumors  “data insufficient” for recommendation, i.e. refer to specialist –Pheochromocytoma, dx supported by lab findings.  surgery

14. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Follow up for unresected adrenal masses Follow up for unresected adrenal masses: –Imaging. A repeat imaging study (CT or MR) should be performed 6-12 months after the initial study to evaluate change in size. Adrenocortical CA is rapidly growing, and this interval is sufficient to detect the size change. –Hormonal evaluation. Pts should have yearly 1mg overnight dexamethasone suppression tests and urine or plasma metanephrine measurement for 4 years. This practice rules out the development of a hypersecreting tumor.

15. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Question (1) A 42 y/o woman presents for evaluation of a 2.8-cm left adrenal mass. She was seen in the ER 1 week ago for abdominal pain. CT scan shows only the adrenal mass. Physical examination, vital signs, and review of systems are all normal. Medical history and family history are unremarkable.

17. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Correct Answer rationale C) The first step in management is an evaluation of serum and urine hormone levels to determine whether the mass is functional or nonfunctional. If it is nonfunctional, follow-up CT and repeat hormone testing at 6-12 months are indicated to ensure the mass is not enlarging or beginning to produce hormones. At 2.8 cm, the mass has a low malignant or functional potential, and therefore there is no immediate indication for removal of the mass, biopsy, or further imaging. (MKSAP-13)

18. Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services Duke Internal Medicine Residency Curriculum Adrenal Nodules: Sources NIH Consensus Panel, “Management of the Clinically Inapparent Adrenal Mass”, NIH Consensus and State-of-the-Science Statements, 2002: Volume 19, no. 2 UTDOL, 2005