Pheochromocytoma Crisis Presenting with Cardiogenic Shock

e-Herz: Case study

Herz 2014 · 39:156–160 Y.S. Chatzizisis1 · A. Ziakas1 · C. Feloukidis1 · D. Paramythiotis2 · S. Hadjimiltiades1 · DOI 10.1007/s00059-013-3778-2 A. Iliadis3 · G. Basdanis2 · I. Styliadis1 Received: 21 February 2012 1 First Department of Cardiology, AHEPA University Hospital, Aristotle University Medical School, Thessaloniki Revised: 27 January 2013 2 Accepted: 8 February 2013 Propedeutic Surgery Department, AHEPA University Hospital, Published online: 14 March 2013 Aristotle University Medical School, Thessaloniki © Urban & Vogel 2013 3 Department of Pathology, AHEPA University Hospital, Aristotle University Medical School, Thessaloniki

e-Herz Pheochromocytoma crisis presenting with cardiogenic shock

Pheochromocytoma is a neuroendocrine ers of myocardial necrosis (troponin, CK- This abrupt fluctuation of blood pres- tumor composed of chromaffin cells that MB, LDH, SGOT) and left ventricular sure raised the suspicion of pheochro- secrete catecholamines [1]. It can be clin- dysfunction (BNP) were unremarkable. mocytoma, which was further support- ically silent but occasionally may present The following day the patient com- ed by the markedly elevated vanillylman- with hypertension when catecholamine plained of intense chest pain with dia- delic acid in urine (42 mg/24 h, normal: release is triggered by exogenous stimu- phoresis and signs of peripheral hypoper- 4–7 mg/24 h) and by abdominal comput- li [2, 3]. In this report, we describe a case fusion. His vital signs were: blood pres- ed tomography (CT) that demonstrated a of pheochromocytoma crisis presenting sure, 65/40 mmHg on both arms; heart large (7.1×6.6 cm), heterogeneous, left su- with cardiogenic shock and we discuss rate, 126 beats/min; respiratory rate, prarenal mass (. Fig. 2). the diagnostic and therapeutic challenges. 26 breaths/min with oxygen saturation The patient was started on proprano- at 90%; and body temperature, 36.3°C. lol i.v. and subsequently on labetalol i.v. Case report EKG showed transient ST elevations in that effectively increased the blood pres- all precordial leads V1–V6 (. Fig. 1). On sure to normal levels and also controlled A 55-year-old man was admitted to our the basis of the clinical and EKG find- the heart rate (. Fig. 3). Intravenous flu- department with diffuse abdominal pain ings, the initial differential diagnosis in- ids and phenoxybenzamine 10 mg qd per and vomiting. His past medical history cluded acute coronary syndrome vs. aor- os were also commenced. The following was notable for non-Hodgkin’s lympho- tic dissection and the patient was trans- day the patient was asymptomatic with ma treated with chemotherapy 15 years ferred to the coronary care unit for fur- well-controlled blood pressure and heart previously. Over the last 3 years, he had ther management. A transthoracic echo- rate. Two weeks after combined treatment headaches characterized by increasing cardiogram showed normal biventricu- with phenoxybenzamine 10 mg qd per os frequency and severity. The headaches lar size and systolic function without ev- and propranolol 40 mg b.i.d. per os, the were attributed to anxiety disorder and idence of regional wall motion abnor- patient underwent surgical tumor resec- the patient was started on mirtazapine. malities, normal biatrial size, and mild tion (. Fig. 4a). Mirtazapine was interrupted by the pa- calcific aortic stenosis. Urgent coronary Immunostaining of the resected tumor tient 20 days before his admission to our angiography demonstrated normal ar- with chromogranin-A and CD56 (neural department. On admission, the patient’s teries and aortography showed no evi- cell adhesion molecule, N-CAM), which blood pressure was 155/90 mmHg. Phys- dence of aortic dissection. The renal ar- is a marker of neuroendocrine activity, ical examination revealed mild abdom- teries were normal on angiography. Of confirmed the diagnosis of pheochromo- inal distention. The rest of the physical note, during the first contrast injec- cytoma. Histopathology showed areas of examination and the psychiatric evalua- tion the patient complained of worsen- extensive tumor necrosis as shown on the tion were unremarkable. Initial laborato- ing chest pain and his blood pressure CT scan. The Pheochromocytoma of the ry tests demonstrated leukocytosis (WBC raised abruptly from 80/50 mmHg to Adrenal Gland Scaled Score (PASS) [4] =19,200/μl, 78% neutrophils) and hyper- 204/102 mmHg and then returned back was greater than 4 suggestive of aggres- glycemia (glucose =294 mg/dl). All the to the baseline 70/45 mmHg; heart rate sive tumor behavior (. Fig. 4b, c, d). The other laboratory results, including mark- remained increased at 130 beats/min. patient was discharged uneventfully with-

156 | Herz 1 · 2014 Fig. 1 8 EKG showed mild ST elevation in leads V1–V6

out any medication 10 days after the oper- ation and he remained normotensive and asymptomatic in the ensuing months.

Discussion

Pheochromocytoma is a rare catecholamine-producing tumor of chromaffin Fig. 2 9 Abdominal cells. Usually it presents with the classic computed tomogra- triad of headache, palpitations, and dia- phy scan demonstrat- phoresis [5]. Chest pain, abdominal pain ed a large (7.1×6.6 cm) left-sided, heteroge- with nausea, vomiting, and diarrhea are neous adrenal mass also frequent symptoms, as in our pa- (yellow arrow) with a tient. Psychiatric disorders may also oc- hypodense central ar- cur that can be easily misdiagnosed as ea likely represent- anxiety or somatization disorders as ini- ing necrosis or hemor- rhage (white arrow) tially happened in our case [6]. Weight loss or unexpected development of dia- 300 mmHg betes mellitus could also be associated with pheochromocytoma [7]. Cardiovas- cular manifestations of pheochromocytoma include hypertension, arrhythmia,

150 mmHg transient left ventricular apical balloon- ing, acute myocardial infarction, conges- tive heart failure, dilated cardiomyopathy, and aortic dissection [8]. The patient may even present with ischemic EKG chang- 0 mmHg es. Catecholamines may alter ion trans-

150 bpm port across cell membranes, thereby leading to ischemic EKG changes [9]. In ad- dition, during a pheochromocytoma crisis, the supply–demand mismatch caused by the catecholamine-driven tachycardia 100 bpm may precipitate true ischemia, leading to EKG abnormalities even in the absence of coronary atherosclerosis [10]. There have been reported cases of pheochromocytoma patients presenting 50 bpm with takotsubo syndrome with normal 12 pm 8 pm 4 am 12 pm coronary arteries, regional wall motion abnormalities, and troponin leak [11, 12, Fig. 3 8 Blood pressure and heart rate waveforms showed marked fluctuations during the first 24 h. 13]. In contrast to these cases, there was Gradual stabilization of blood pressure and heart rate was achieved with administration of proprano- no evidence of takotsubo-like myocardi- lol i.v and labetalol i.v. al response in our patient. The ST elevations were transient and brief and there

Herz 1 · 2014 | 157 e-Herz: Case study Abstract · Zusammenfassung

was no troponin leak or left ventricular show that mirtazapine can inhibit vari- Herz 2014 · 39:156–160 dysfunction. ous catecholamine transporters, there- DOI 10.1007/s00059-013-3778-2 © Urban & Vogel 2013 The most profound effect of the cate- by increasing the synaptic cleft that sub- cholamine surge in the current case was sequently increases the likelihood of ad- Y.S. Chatzizisis · A. Ziakas · C. Feloukidis · a marked, transient, peripheral vasodila- renergic receptor activation. Theoretical- D. Paramythiotis · S. Hadjimiltiades · tion resulting in cardiogenic shock. Al- ly, mirtazapine could accentuate the cate- A. Iliadis · G. Basdanis · I. Styliadis though pheochromocytoma usually in- cholamine surge in the presence of pheo- Pheochromocytoma duces hypertension, 20% of the patients chromocytoma. However, unlike most crisis presenting with may present with hypotension and 2% conventional antidepressants, clinically cardiogenic shock with cardiogenic shock [2]. Several mech- used doses of mirtazapine have no appre- Abstract anisms are responsible for the reduction ciable affinity for the serotonin, norepi- Pheochromocytoma is a catecholamine-se- of peripheral resistances by pheochromo- nephrine, or dopamine transporters and creting tumor of the adrenal glands whose cytoma. The predominant catecholamine have minimal effect as a reuptake inhib- typical presentation includes the triad of secretion appears to play a key role. Epi- itor of these neurotransmitters [17] Ap- headache, palpitations, and diaphoresis. nephrine- or dopamine-secreting pheo- proximately 10% of pheochromocyto- Pheochromocytoma crisis is an urgent med- chromocytomas may manifest with hy- mas are malignant. The diagnosis of ma- ical condition whose diagnosis and manage- potension, since epinephrine acts most- lignant pheochromocytoma can be made ment constitute a challenge for physicians. We present the case of a 55-year-old man ly on β2-adrenergic receptors located on only in the presence of metastases [18]. who developed cardiogenic shock in the set- smooth muscle cells of the peripheral ar- Although there are no specific metabol- ting of a pheochromocytoma crisis. After sta- teries, whereas norepinephrine-secreting ic, radiologic, or histopathologic features bilizing blood pressure with combined ad- tumors may present with hypertension of malignant pheochromocytoma, there ministration of α- and β-blockers, the tumor was surgically removed. Our diagnostic and secondary to the α1-adrenergic receptor- are several postoperative features that de- therapeutic challenges are discussed. mediated peripheral vasoconstriction [7, termine the likelihood of malignancy or 14]. In the current case, we did not assess recurrence, such as a PASS greater than Keywords directly the catecholamine levels during 4, increased tumor weight, high periop- Pheochromocytoma · Cardiogenic shock · the cardiogenic shock and therefore only erative dopamine levels, and postopera- Catecholamines · Adrenergic blockers · assumptions can be made regarding the tive persistent hypertension [19]. Patients Surgery predominant secretion by the tumor. An with these characteristics should have imbalance in catecholamine secretion by more thorough follow-up. In our case the the tumor in favor of epinephrine could tumor appeared to be benign despite hav- Phäochromozytomkrise likely explain the clinical events in our ing indirect markers of malignancy (e.g., mit kardiogenem Schock case. PASS >4 with tumor necrosis, increased Zusammenfassung Intriguingly, during the coronary an- tumor weight). The benign nature of the Ein Phäochromozytom ist ein katecholamin- giography, the patient’s blood pressure tumor was supported by the absence of sezernierender Tumor der Nebennieren, des- status altered abruptly from hypotension clear tissue invasion on CT and macro- sen typische Symptomatik aus der Trias von Kopfschmerzen, Herzklopfen und Schweiß to severe hypertension. It is most likely scopically during the resection, as well as ausbrüchen besteht. Die Phäochromozytom- that contrast injection triggered hyper- by the uneventful postoperative course of krise ist ein medizinischer Notfall, dessen Di- tension [15]. Fluctuation of blood pres- our patient. However, given the increased agnostik und Behandlung eine Herausforde- sure in pheochromocytoma is quite rare PASS our patient continues to be followed rung für Ärzte darstellt. Wir präsentieren den and is believed to be associated with tu- up. Fall eines 55-jährigen Mannes, der während mors that primarily secrete epinephrine The therapeutic management of a einer phäochromozytombedingten Krise ein- en kardiogenen Schock entwickelte. Nach [3]. Although the precise mechanism of pheochromocytoma has two major ob- Stabilisierung des Blutdrucks mit kombinier this hemodynamic instability remains jectives: (a) to control the pheochromo- ter Verabreichung von α-und β-Blockern unclear, baroreflex failure appears to play cytoma crisis in order to prevent ma- wurde der Tumor operativ entfernt. Unsere a key role [16]. jor and potentially lethal cardiovascular diagnostischen und therapeutischen Ansätze Our patient was treated with mir- complications, such as myocardial inju- werden vorgestellt und diskutiert. tazapine because of a suspected anxiety ry and malignant arrhythmias, and (b) Schlüsselwörter disorder. The medication was interrupt- to prepare the patient for surgical inter- Phäochromozytom · Kardiogener Schock · ed abruptly by the patient without any vention. In the present case, in the set- Katecholamine · Adrenozeptorenblocker · medical consultation. The interaction of ting of severe hypotension, we decided to Chirurgie mirtazapine with pheochromocytoma- administer propranolol i.v. However, ad- secreted catecholamines could be con- ministration of a nonselective β-blocker, sidered. Mirtazapine is a noradrener- like propranolol, would induce hy- gic and specific serotonergic antidepres- pertension without prior α-blockade sant that is primarily used for the treat- [20]. This occurs because nonselective ment of depression. Experimental data β-blockers antagonize the catecholamine

158 | Herz 1 · 2014 Fig. 4 9 a Macroscop- ic appearance of the resected tumor. b H&E stain- ing showed nests of tumor cells (zellballen) surround- ed by a discontinuous lay- er of sustentacular cells and fibrovascular stroma. There were blood vessels sur- rounding tumor nests that were composed of round- to-oval cells. There was evidence of extensive tumor necrosis. c Immunostaining for chromogranin-A was positive in pheochromocytoma cells. d CD56 (neural cell adhesion molecule, N- CAM) immunostaining was positive in pheochromocytoma cells, as well as in normal cortical cells of the zona glomerulosa but not in cells of the zona fasciculata or zona reticularis

β2-mediated vasodilation while leaving ment of pheochromocytoma [24]. With Corresponding address the α-mediated vasoconstriction intact, regard to the preoperative preparation, it thereby resulting in increased vascular is advisable that the patient remains as- Y.S. Chatzizisis resistance, hypertension, and increased ymptomatic and normotensive for at least First Department of Cardiology, cardiac afterload. For this reason, we al- 7–14 days before the surgery, as long as AHEPA University Hospital, so used labetalol hydrochloride, which is this is clinically feasible [25]. It has been Aristotle University Medical School 1 Stilponos Kyriakidi Street, a combination of α1-adrenergic and non- recommended that the following criteria 54636 Thessaloniki selective β-adrenergic receptor blocking should be met prior to tumor removal: (a) Greece agent [21]. Even though labetalol has been blood pressure less than 160/90 mmHg [email protected] used in the treatment of pheochromocy- for 24 h before surgery, (b) no postural toma crisis, it is not yet recommended as hypotension, (c) absence of ST or T ab- Conflict of interest. On behalf of all authors, the cor- first-line treatment because it has weak normalities for 1 week, and (d) no more responding author states that there are no conflicts α-blocking activity [21, 22]. Moreover, than one premature ventricular contrac- of interest. labetalol reduces significantly the uptake tion every 5 min [26]. of metaiodobenzylguanidine (MIBG), References and therefore, it needs to be interrupt- Conclusion 1. Pacak K, Lineham WM, Eisenhofer G et al (2001) ed about 2 weeks before MIBG uptake Recent advances in genetics, diagnosis, localiza- scanning [23]. In our case we switched tion, and treatment of pheochromocytoma. Ann labetalol to phenoxybenzamine, a long- In conclusion, in the current report we Intern Med 134:315–329 present a case of a pheochromocyto- 2. Bergland BE (1989) Pheochromocytoma present- acting, noncompetitive, irreversible ing as shock. Am J Emerg Med 7:44–48 α-adrenergic blocking agent, which is the ma crisis presenting with transient car- 3. Magnano AR, Bai D, Bloomfield DM (2002) Images mainstay of therapy in pheochromocyto- diogenic shock due to catecholamine in cardiovascular medicine. Cyclic tachycardia and (most likely epinephrine) surge. Admin- hypotension. Circulation 106:e1-e2 ma. Because of its noncompetitive block- 4. Lester DR, Thompson MD (2002) Pheochromocy- ade effect, it is more difficult for the cir- istration of propranolol, labetalol, and toma of the Adrenal Gland Scale Score (PASS) to culating catecholamines secreted by the phenoxybenzamine was effective in sta- separate benign from malignant neoplasms. Am J bilizing the blood pressure prior to sur- Surg Pathol 26:551–566 pheochromocytoma to overcome the 5. Karagiannis A, Mikhailidis DP, Athyros VG, Harsou- blocking effects of phenoxybenzamine. gical resection of the tumor. Early recog- lis F (2007) Pheochromocytoma: an update on ge- Collectively, the most effective pharma- nition of the tumor is crucial, as pheo- netics and management. Endocrine-Related Can- chromocytoma patients presenting with cer 14:935–956 cological approach to pheochromocyto- 6. Gillmer RE (1972) Pheochromocytoma-an in- ma crisis should involve the administra- shock may have a poor prognosis. teresting psychiatric presentation. S Afr Med J tion of an α-blocker for a few days fol- 46:174–176 7. Benowitz NL (1988) Pheochromocytoma-recent lowed by a β-blocker. advances in diagnosis and treatment. West J Med As in our case, surgical resection of the 148:561–567 tumor is the only effective radical treat-

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