The patient is a Nepalese-speaking female in her 50s with no known medical history who presents to the Emergency Department with nausea, vomiting, and diarrhea for the past three days. She describes numerous episodes of non-bloody, non-bilious vomiting associated with persistent nausea throughout this time. She also endorses countless episodes of loose, watery stools which are also non-bloody. She does note some mild, crampy abdominal pain which is greatest in the epigastric region and primarily occurs just prior to her episodes of diarrhea.
On the day of presentation she became diaphoretic with her symptoms, so her family encouraged her to come to the ED for evaluation. She denies any fevers, chest pain, shortness of breath, dysuria, or sick contacts. She has occasionally had similar episodes of vomiting and diarrhea over the past several months. She also endorses occasional diffuse headaches over the past few months that usually respond to Tylenol. She also denies weight loss, fevers or other constitutional symptoms.
Of note, the patient states that she is from Nepal and just moved to the United States two weeks prior to her ED visit. She has spent the past 20 years of her life in a refugee camp in Nepal and has not visited a doctor during this time. She has not yet established care with a primary physician in the U.S.
Vitals: T 36.5 HR: 82BP: 138/103 RR: 15 SpO2 98% on RA
Physical Exam: The patient is a thin female who appears uncomfortable. HEENT exam is unremarkable, and mucous membranes are moist. The patient’s pulmonary and cardiovascular exams are normal. Abdominal exam reveals a soft, non-distended abdomen with active bowel sounds, mild periumbilical tenderness but no rebound, guarding or peritoneal signs. She is mildly diaphoretic, but the remainder of her musculoskeletal and skin exams are normal. She is awake, alert and oriented with a non-focal neurologic exam.
CT Abdomen/Pelvis: 5.2 cm left adrenal neoplasm is incompletely characterized. Central area of low attenuation could represent necrosis or fat. Recommend enhanced abdominal MRI for further evaluation. Diffuse osteopenia.
CXR: Large right lung apex opacity, likely a combination of right upper lobe atelectasis and neoplasm. Findings likely reflect an endobronchial obstructing right upper lobe mass.
This patient presented with nausea, vomiting and abdominal pain and was found to have both a lung mass and an adrenal mass. In a woman who had recently immigrated from a refugee camp in Nepal, there was significant concern for tuberculosis or malignancy. She was admitted to the hospital for several days, and was seen by both the pulmonary and infectious disease services. Ultimately, it was felt that her lung findings were residual architectural changes from a previous tuberculosis exposure, and active tuberculosis was ruled out. She was ultimately discharged with plans for outpatient work-up of what was felt to be an incidentally found adrenal mass.
However, she returned to the hospital several weeks later for hypovolemic shock presumed to be due to her persistent, profound diarrhea. She was admitted to the MICU and underwent an extensive work-up for an infectious cause of her symptoms, including intestinal biopsies to evaluate for GI tuberculosis, all of which were unremarkable.
The patient then began developing progressive weight loss and sweating, and was eventually seen by endocrinology who sent urine metanephrine levels given her known adrenal mass. These resulted with values greater than 10 times the upper limit of normal and she was ultimately diagnosed with a pheochromocytoma. She was started on alpha-blocking medications and six weeks later underwent uncomplicated surgical removal of the mass. She has been doing well since the procedure with near complete resolution of her symptoms and follows regularly with her primary care physician.
Incidental findings are not uncommon in the Emergency Department given the frequency of advanced imaging performed as part of diagnostic workups. Adrenal incidentalomas are defined as adrenal masses that are incidentally discovered on abdominal imaging performed for reasons other than suspected adrenal dysfunction. The prevalence of such adrenal lesions ranges between 1.4-2.9% on autopsy with an increase in frequency with advanced age. Nearly half of these masses are benign adenomas, and they often play no role in the reason for the Emergency Department visit. Nonetheless, these lesions can be malignant or secretory lesions, as in the above patient, which may actually contribute to the ultimate diagnosis. In this category of more ominous adrenal lesions, pheochromocytomas are still exceedingly rare, comprising only 8% of all adrenal masses.
During embryogenesis, neural crest cells migrate to the sympathetic chain and the adrenal medulla, resulting in chromaffin cells which are responsible for secreting the catecholamines epinephrine, norepinephrine, and small amounts of dopamine. Pheochromocytomas are catecholamine-secreting neoplastic versions of these cells.
The clinical manifestations of such tumors are highly variable as they have varying degrees of catecholamine secretion and receptor response, yet the overall mortality from these tumors is about 15%. Many patients may be completely asymptomatic for years prior to a formal diagnosis, but some will experience the classic paroxysms of headaches, diaphoresis, and palpitations in the setting of a significantly elevated blood pressure. Weight loss and intermittent episodes of significant anxiety are also commonly reported.
There are case reports of pheochromocytomas secreting vasoactive intestinal peptide (VIP) in addition to catecholamines. These patients often present with profound watery diarrhea in addition to the typical symptoms, which may explain the initial clinical presentation of the above patient. If catecholamine secretion is severe, the patient’s presentation may be life-threatening, and the need to rapidly identify the correct diagnosis even more crucial. Acute cardiomyopathy, hypertensive emergency, significant hyperthermia, and shock are just some of the various clinical presentations of patients with these lesions.
This diagnosis should be considered in the Emergency Department whenever a patient with a known adrenal incidentaloma presents with the characteristic symptoms of a pheochromocytoma. The triad of headache, diaphoresis, and palpitations has a positive likelihood ratio of 6.3, regardless of the presence of hypertension, and may be a useful clue in making the diagnosis. Patients with severe hypertension or hemodynamic instability with no apparent etiology or hypertension that worsens with administration of beta-blockers should also prompt consideration of the diagnosis. Those with familial syndromes such as neurofibromatosis and multiple endocrine neoplasia are particularly susceptible to developing these as well.
Laboratory data may reveal hyperglycemia, hypercalcemia, and erythrocytosis. While urine metanephrines are not a routine Emergency Department test, an abdominal CT often is. The literature suggests that in unstable patients in whom pheochromocytoma is even suspected, an abdominal CT is an acceptable diagnostic tool, as patients with neoplasms secreting enough catecholamines to cause hemodynamic instability will have radiographic evidence of the lesion. While is not a diagnosis that is typically made in the Emergency Department, early workup may help expedite discovery of the diagnosis if there is a high enough index of suspicion.
Hemodynamically stable patients with suspected pheochromocytoma are appropriate for outpatient work-up, while more unstable patients will benefit from inpatient diagnostic testing and management of their symptoms. These patients should be admitted to a medicine service who can manage the various consulting teams that will be necessary, from endocrinology for symptom control to urology for tumor removal. The treatment of these lesions primarily involves managing the severe hypertension until surgical removal of the mass can be performed. Alpha blockade with agents such as phentolamine or terazosin is the primary treatment. Beta blockers are contraindicated for these patients because they may worsen hypertension due to the unopposed alpha effects of the circulating catecholamines.
There is no specific blood pressure target for these patients, and pheochromocytoma-mediated hypertension should be managed in the ED similarly to other patients with hypertensive emergency. There is very little data on initiation of alpha blockade for treatment of pheochromocytoma in the Emergency Department. However, the US Endocrine Society guidelines indicate that patients with known pheochromocytomas should receive initiation of alpha blockade as soon as possible, regardless of the presenting blood pressure. This is to help mitigate the unpredictable possibility of developing hypertensive crisis in these patients.
Therefore, it would be appropriate to start a low-dose alpha blocker in the ED when this diagnosis is made. Given the chronic vasoconstriction due to catecholamine excess, fluid resuscitation is also important, as many of these patients are hypovolemic. Optimization of hemodynamics with these interventions should be undertaken prior to surgical intervention, as it leads to improved post-surgical morbidity and mortality.
Ultimately, this is a rare diagnosis which can lead to any number of presenting complaints in the Emergency Department. It has an overall mortality of 15%, although this can be improved by earlier diagnosis. As such, the next time an adrenal incidentaloma is buried in the radiology read of an abdominal CT scan, consider adding pheochromocytoma to your differential diagnosis.
Authored by Jessica Merriam, MD Posted by Grace Lagasse, MD
- Aron D, Terzolo M, Cawood T. Adrenal incidentalomas. Endocrinology & Metabolism, 2012; 26: 69-82.
- Amar L and Eisenhofer G. Diagnosing phaeochromocytoma/paraganglioma in a patient presenting with critical illness: biochemistry versus imaging. Clinical Endocrinology, 2015; 83:298-302.
- Pourian M, Mostafazadeh D, Soltani I. Does this patient have pheochromocytoma? A systematic review of clinical signs and symptoms. Journal of Diabetes and Metabolic Disorders, 2015; 15: 11.
- Vidt D. Emergency room management of hypertensive urgencies and emergencies. The Journal of Clinical Hypertension, 2001; 3: 151-164.
- Vara Luiz H, Tanchee M, Pavlatou M, Yu R, et al. Are patients with hormonally functional phaeochromocytoma and paraganglioma initially receiving a proper adrenoceptor blockade? A retrospective cohort study. Clinical Endocrinology, 2016; 85: 62-69.