1. Introduction Pheochromocytomas are rare neuroendocrine tumors arising from catecholamine-producing cells in the adrenal medulla. Prevalence ranges from 0.1% to 0.6% in those undergoing screening for secondary hypertension 1. Pheochromocytomas have a highly variable clinical presentation and course. Most of the clinical signs and symptoms are due to the direct effects of secreted catecholamines 2. Hypertension, palpitations, anxiety, and headaches usually dominate the clinical presentation 2. Due to the rarity of this disorder and the potential for lethal cardiovascular complications, a high index of suspicion is required for diagnosis. Sometimes Hoofbeats are from Zebras: A Case Presentation to Demonstrate the Varied Clinical Manifestations of Pheochromocytomas Clinical Presentation and Course A 69-year-old female presented to the emergency department with the chief complaint of positional dizziness and palpitations. She had presented three years prior with a one-year history of intermittent dizziness and two episodes of syncope during micturition; she was found to have orthostatic hypotension that resolved with intravenous hydration and was discharged. During the current presentation, she was initially noted to be hypotensive and tachycardic with an electrocardiogram remarkable for atrial fibrillation with rapid ventricular response. Symptoms improved with intravenous hydration, and atrial fibrillation resolved fairly quickly with fluids and a diltiazem infusion. By the second day of admission, patient developed paroxysms of malignant hypertension with sinus tachycardia, anxiety, intermittent disorientation, and impulsivity as well as sporadic episodes of diaphoresis described as “hot flashes.” A nicardipine infusion was begun but intermittently stopped due to rapid fluctuations in blood pressure. Additional chart review revealed admission one month prior for pneumonia at which time she had undergone CT scan of the chest; an incidental 3.5-cm indeterminate lesion was noted on her left adrenal gland. Chart/Graph/Photo/Illustration Amy Swanson, MD, Sidney Palmer-Hill, MD course, cont. A work-up of secondary causes of hypertension was remarkable for significant elevations in serum metanephrines, normetanephrines, and urine catecholamines. Abdominal MRI was remarkable for a circumscribed mass with heterogeneous enhancement. PET CT demonstrated localized disease. Laparoscopic left adrenalectomy was performed after five days of sympathetic receptor blockade and intravenous fluid hydration. Intraoperatively, she became hypotensive after ligation of the main adrenal vein, which required phenylephrine infusion and ICU monitoring. Clinically, her mental status improved mildly, and her episodic symptoms resolved. Surgical pathology demonstrated a 3-cm pheochromocytoma confined within the adrenal gland capsule and surgical borders. Take Home Points There usually remains a delay of three years between initial symptoms and final diagnosis due to the non-specificity of symptoms 2. It has been reported that if headaches, palpitations, and sweating occur together, the specificity approaches 90% 2. Pheochromocytomas are commonly screened for in the evaluation of secondary hypertension. Hypertension is often paroxysmal on a background of sustained hypertension whereas others can have normal blood pressure between paroxysms 2. Hypertensive episodes can be severe and result in hypertensive emergencies, or blood pressure may be consistently normal 2. Recommendations regarding clinical testing for pheochromocytoma include screening for typical signs and symptoms if present and especially if paroxysmal, adrenal incidentaloma with or without hypertension, hereditary predisposition or syndromic features, or previous history 1. About 5% of all incidentalomas are pheochromocytomas 2. The initial testing recommended is the measurement of: – plasma free metanephrines (sensitivity 99%, specificity 89%) or –urinary fractionated metanephrines (sensitivity 97%, specificity 69%) 1. When there is clear biochemical evidence, imaging studies should be obtained, which include CT and MRI. Preferred management for local disease is laparoscopic resection preceded by 7-14 days of alpha-receptor blockade 1. Lifelong annual biochemical testing is recommended to assess for recurrent or metastatic disease 1. Conclusion This case illustrates several of the key clinical manifestations of pheochromocytomas, including: –syncope, –orthostatic hypotension, –dizziness, –hot flashes, –insomnia, –anxiety, –paroxysmal severe hypertension, –cardiac arrhythmia, –palpitations –delirium. The incidental CT findings helped guide the diagnostic approach; however, in any patient with paroxysms of similar symptoms, the diagnosis of pheochromocytoma should remain in the differential, and further evaluation considered. References 1.Lenders J, Quan-Yang D, Eisenhofer G, et al. Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014;99:1915-1942. 2.Lenders J, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. The Lancet. 2005;366:665-675. Data Review Plasma metanephrine, free 1.8 nmol/L (nl <.50) Plasma normetanephrine, free 9.1 nmol/L (nl <.90) Cortisol 18 mcg/dL (AM nl 4-19) Aldosterone, serum <4 ng/dL (nl <21) Renin activity, plasma 24 ng/mL/h (nl 0.6-3.0 ) TSH 3.01 (nl 0.3-5) Norepinephrine, urine 24h 752 mcg/24h (nl 15-80) Epinephrine, urine 24h 71 mcg/24h (nl<21) Dopamine, urine 24h 142 mcg/24h (nl 65-400) Metanephrine, urine, 24h 867 mcg/24h (<400) Normetanephrine, urine 24h 2745 mcg/24h (nl <900) CT Chest with Contrast (photo #1) Indeterminate 3.5 cm low-density rounded circumscribed structure left adrenal gland (48 Hounsfield units) MRI Abdomen w/wo Contrast 3.4 cm indeterminate left adrenal gland mass Tumor cells arranged in a zellballen fashion. Chromogranin A staining, which stains neuroendocrine markers. Tumor cells in the adrenal medulla with focal hemorrhage.