Pheochromocytoma imaging with an unremarkable biochemical evaluation

Issue: November 2008

ByStephanie L. Lee, MD, PhD, ECNU

ByBeth M. Kaplan, MD

Patient is a 65-year-old white man with a past medical history significant for severe coronary artery disease, arrhythmias, hypertension, hyperlipidemia, anxiety and type 2 diabetes. He was referred to the endocrine clinic for the evaluation of a right adrenal nodule. The adrenal mass was found incidentally on an abdominal CT performed as part of an evaluation for epigastric pain caused by peptic ulcer disease.

Stephanie L. Lee

Beth Kaplan

The patient had an extensive history of CAD with myocardial infarctions complicated by arrhythmias at the ages of 30 and 57. At the time of his last MI, nine months prior to presentation, a coronary artery stent was placed. His family history was negative for early CAD or endocrine disorders. His medications included multiple antihypertensive agents including: Lisinopril 5 mg, Imdur 30 mg, Norvasc 10 mg, and Atenolol 50 mg. He was taking other medications including: Diazapam 10 mg, Metformin 500 mg, Protonix 40 mg, Avodart 0.5 mg, Crestor 10 mg and ASA 325 mg daily.

He reported fatigue, occasional lightheadedness when standing and frequent palpitations over the past few years; he denied headache, sweating, tremors, weight changes, “spells,” chest pain or dyspnea on exertion. His blood pressure was at goal on his antihypertensive regimen.

On physical exam, his BP was 119/70 mmHg with a pulse of 56 and he was not orthostatic by heart rate or BP. His weight was 95 kg and BMI 29.4. His cardiac exam was significant for bradycardia with a II/VI murmur at the base; he had bilateral trace pretibial edema. Thyroid, pulmonary, abdominal and neurologic exams were normal.

Twenty-four hour urine collection for catecholamines revealed an minimally elevated norepinephrine 144 (normal 15-100 mcg/24 hr) with normal epinephrine 12 (normal 2-24 mcg/24 hr) and dopamine 268 (52-480 mcg/24 hr) levels. Urine metanephrines were normal with a normetanephrines 446 (normal 44-540 mcg/24 hr) and metanephrines 61 (normal 26-230 UG/24 hr). Plasma normetanephrine levels were minimally elevated at 164 pg/ml (normal <148). The patient was not on any medications that would cause false elevations of catecholamines or metanephrines. The testing was done using high performance liquid chromatography with tandem mass spectroscopy.

Abdominal CT at an outside facility revealed a 1.9 cm x 1.9 cm right adrenal nodule which measured 15 Hounsfield units on non-contrast CT and avidly enhanced to greater than 100 Hounsfield units on both the arterial and portal venous phases (Figure 1). The CT images were unavailable at the time of presentation and therefore an MRI was done to further evaluate the right adrenal mass. The scan revealed a T2 hyperintense, T1 hypointense right adrenal lesion (Figure 2). Finally, the patient had a 123-I-Metaiodobenzylguanidine (MIBG) study to further evaluate his adrenal mass. It showed a single focus of abnormal uptake inferior to the left lobe of the liver that correlated with the patient’s right adrenal nodule and was consistent with a functional pheochromocytoma (Figure 3).

Figure 1. Axial CT scan of the abdomen showing a pheochromocytoma
Figure 1: Axial CT scan of the abdomen showing a pheochromocytoma. A. The pheochromocytoma (red arrow) located superior to the right adrenal gland has high 15 Hounsfield units density on the non-contrast. B. The pheochromocytomas (blue arrow) markedly enhances after intravenous contrast administration (Hounsfield units >100).

Figure 2. Coronal images of a MRI of a pheochromocytoma
Figure 2. Coronal images of a MRI of a pheochromocytoma. A. The pheochromocytoma (red arrow) is dark on a T1-weighted image. B. The pheochromocytoma (blue arrow) is hyperintense (compared to liver) on the T2-weighted image.

CT scans have a sensitivity of 93% to 100% of detecting an adrenal pheochromocytoma but the sensitivity falls to 90% with extra-adrenal pheochromocytomas. Its specificity however is poor, and has been reported to be as low as 50% in some studies because of adrenal “incidentalomas.” This patient’s adrenal CT scan was suggestive of a pheochromocytoma including high Hounsfield units density pre-contrast with a >10 Hounsfield units and marked enhancement of the Hounsfield units density with IV contrast. In addition, a delay in contrast washout of <50% at 10 minutes is typical of a pheochromocytoma. MRI is similar in sensitivity to CT scans for detecting adrenal pheochromocytomas, however, more sensitive than CT scans for detecting extra-adrenal tumors. Like CT scan, the specificity has been reported to be as low as 50%. This patient’s adrenal MRI scan was highly suggestive of a pheochromocytoma with a high signal intensity (hyperintense compared to liver) on T2 weighted images. 123-I-MIBG is taken up into the pre-synaptic adrenergic tissue in a manner similar to norepinephrine. Therefore uptake into the adrenal gland of this agent has a high 95 to 100% specificity for pheochromocytoma detection but its sensitivity has been reported to be 77% to 90%. The MIBG is not as sensitive as a CT or MRI scans and therefore cannot be used to exclude the presence of a pheochromocytoma. But in this case, the patient was at high risk for surgery because of his recent myocardial infarction and with his minimally abnormal biochemical studies, the functional accumulation of MIBG confirmed the diagnosis of a pheochromocytoma prior to surgery. Generally, significantly positive biochemical tests plus confirmation of an adrenal mass with a high T2 signal on a MRI scan or marked enhancement after IV contrast on a CT scan is sufficient to go forward with surgery.

Figure 3. MIBG scintigraphy scan of a pheochromocytoma
Figure 3. MIBG scintigraphy scan of a pheochromocytoma. MIBG accumulation (red arrow) in a right pheochromocytoma is located inferior to the left lobe of the liver in the posterior view. Right panel: anterior view. Left panel: posterior view.

The patient was started on an alpha blockade with Terazosin and continued his Atenolol and other hypertensive medications. One week prior to surgery he was started on Demser, which blocks the rate limiting enzyme in the biosynthetic pathway of catecholamines to deplete the pheochromocytoma of catecholamine stores. He underwent a laparoscopic right adrenalectomy without complications. The pathology revealed a right 2.2 cm pheochromocytoma with positive staining for NSE, chromogranin and synaptophysin. Plasma metanephrines and 24 hour urine metanephrines and catecholamines one month after surgery returned to normal.

Stephanie L. Lee, MD, PhD, is an Associate Chief in the Section of Endocrinology, Diabetes and Nutrition and an Associate Professor of Medicine at Boston Medical Center.

Beth Kaplan, MD, is a Fellow in Endocrinology in the Section of Endocrinology, Diabetes and Nutrition at Boston Medical Center.

For more information:

Francis IR, Korobkin M. Pheochromocytoma. Radiol Clin North Am. 1996;34:1101-1112.

Pacak, K, Linehan, WM, Eisenhofer, G, et al. Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Intern Med. 2001;134:314-329.

Quint LE, Glazer GM, Francis IR, et al. Pheochromocytoma and paraganglioma: comparison of MR imaging with CT and I-131 MIBG scintagraphy. Radiology. 1987;165:89-93.

Sawka A, et al. The Economic Implications of Three Biochemical Screening Algorithms for Pheochromocytoma. J Clin Endo Metab. 2004;89:2859-2866.