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Life-Threatening Events in Patients with Pheochromocytoma

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Life-Threatening Events in Patients with Pheochromocytoma A Riester and others Life-threatening events in 173:6 757–764 Clinical Study pheochromocytoma Life-threatening events in patients with pheochromocytoma Anna Riester, Dirk Weismann1, Marcus Quinkler2, Urs D Lichtenauer3, Sandra Sommerey4, Roland Halbritter5, Randolph Penning6, Christine Spitzweg7, Jochen Schopohl, Felix Beuschlein and Martin Reincke Medizinische Klinik und Poliklinik IV, Klinikum der Universita¨ tMu¨ nchen, Ludwig-Maximilians-Universita¨ t, Ziemssenstr. 1, D-80336 Munich, Germany, 1Medizinische Klinik und Poliklinik I, Universita¨ tsklinikum Wu¨ rzburg, Correspondence Wu¨ rzburg, Germany, 2Endokrinologie in Charlottenburg, Berlin, Germany, 3Helios Klinik Schwerin, Schwerin, should be addressed Germany, 4Chirurgische Klinik und Poliklinik – Innenstadt, Klinikum der Universita¨ tMu¨ nchen, Ludwig-Maximilians- to M Reincke Universita¨ tMu¨ nchen, Munich, Germany, 5Facharztpraxis, Pfaffenhofen, Germany, 6Institut fu¨ r Rechtsmedizin and Email 7Medizinische Klinik und Poliklinik II, Klinikum der Universita¨ tMu¨ nchen, Ludwig-Maximilians-Universita¨ t, Munich, martin.reincke@ Germany med.uni-muenchen.de Abstract Objective: Pheochromocytomas are rare chromaffin cell-derived tumors causing paroxysmal episodes of headache, palpitation, sweating and hypertension. Life-threatening complications have been described in case reports and small series. Systematic analyses are not available. We took an opportunity of a large series to make a survey. Design and methods: We analyzed records of patients diagnosed with pheochromocytomas in three geographically spread German referral centers between 2003 and 2012 (nZ135). Results: Eleven percent of the patients (ten women, five men) required in-hospital treatment on intensive care units (ICUs) due to complications caused by unsuspected pheochromocytomas. The main reasons for ICU admission were acute catecholamine induced Tako-Tsubo cardiomyopathy (nZ4), myocardial infarction (nZ2), acute pulmonary edema (nZ2), cerebrovascular stroke (nZ2), ischemic ileus (nZ1), acute renal failure (nZ2), and multi organ failure (nZ1). One patient required extracorporeal membrane oxygenation due to a hypertensive crisis with lung edema occurring during delivery European Journal of Endocrinology (nZ1). Two patients died of refractory shock and pheochromocytomas were found postmortem. Two patients were treated by emergency surgery. Compared to pheochromocytoma patients without life-threatening events (nZ120), patients with complications had a significant larger maximal tumor diameter (7.0 vs 4.5 cm, P!0.01), higher levels of catecholamines (20- vs ninefold upper limit of normal, P!0.01), and tended to be younger (42 vs 51 years, PZ0.05). Conclusion: Although pheochromocytomas are rare, they are likely to be associated with a life-threatening situation. Clinicians have to be aware of these situations and perform a timely diagnosis. European Journal of Endocrinology (2015) 173, 757–764 Introduction Pheochromocytomas and paragangliomas are rare severity of these classical symptoms is highly variable catecholamine-secreting tumors of chromaffin cell origin, (1, 2). In fact, up to 30% of the tumors are found which derive from the adrenal medulla or the extra- incidentally (3) and autopsy studies indicate that many adrenal sympathetic or parasympathetic nervous system. tumors are not identified during a lifetime (4, 5, 6). The Clinically, pheochromocytomas present with symptoms prevalence of pheochromocytomas in patients with associated with catecholamine excess, typically resulting hypertension is in the range of 0.6% (7). Pheochromo- in paroxysmal hypertension and the triad of headache, cytomas can also present with life-threatening compli- sweating, and palpitation. However, the presence and cations resulting in acute end organ damage (8, 9). www.eje-online.org Ñ 2015 European Society of Endocrinology Published by Bioscientifica Ltd. DOI: 10.1530/EJE-15-0483 Printed in Great Britain Downloaded from Bioscientifica.com at 09/25/2021 02:20:49PM via free access Clinical Study A Riester and others Life-threatening events in 173:6 758 pheochromocytoma Manipulation of the tumor during surgery or when intra- (nZ20), from January 2008 to December 2012. A shorter abdominal pressure increases (for example, during preg- time period for the Charite´ University was chosen as only nancy or vaginal delivery) can be a trigger that causes during this time a complete documentation of all cases of catecholamine release resulting in severe clinical con- pheochromocytomas can be ensured. All 135 patients who sequences. However, the real incidence of life-threatening underwent pheochromocytoma surgery during this period complications is unknown. Indeed, lack of any mortality is were included. Patients with repeated surgery due to usually reported in the vast majority of series, and most relapse of malignant pheochromocytomas were included life-threatening complications appear as anecdotal case only for the first episode. We collected data of demo- reports in the literature. To our knowledge only two graphics, duration of hospitalization, symptoms, pre- systematic studies have addressed this issue, thereby operative catecholamine levels, tumor histology, genetics, providing the basis of a better judgment of this situation surgical treatment, and outcome. The patients were (10, 11). In 2013, Scholten et al. (11) published a divided into two groups based on the presence or absence retrospective comprehensive study analyzing the perio- of life-threatening complications in their clinical course. perative management of pheochromocytoma crisis and A life-threatening complication was defined as a medical recommended an elective adrenalectomy after cardiovas- condition, requiring intensive care unit (ICU) admission cular stabilization and a-blockade; 137 patients from one most likely attributed to a catecholamine release of a United States center were included and zero mortality was hitherto undiagnosed pheochromocytoma or paragan- reported. In the same year, Giavarini et al. (10) presented a glioma (pheo complication). According to this definition, retrospective study including 140 patients with pheochro- in the three referral centers 15 out of 135 patients had a mocytoma from a French center. They found catechol- life-threatening event. Patients who underwent elective amine-induced cardiomyopathy in 11% of the patients surgery due to uncomplicated pheochromocytomas and recommend screening for pheochromocytoma in (nZ120) served as a control group (pheo control). patients with acute heart failure without evidence of Preoperative diagnosis was established by elevated valvular or coronary heart disease. Based on a review of plasma or urine catecholamines in combination with a 106 cases published between 2008 and 2013, Withelaw positive tumor localization in computed tomography et al. (12) recently proposed a subclassification of (CT), magnetic resonance imaging (MRI), metajodobenzyl- pheochromocytoma crisis with ‘type A crisis’ charac- guanidin (MIBG) scintigraphy, or F-DOPA-PET-CT scan terized by a limited crisis with hemodynamic instability (positron emission tomography). For comparability, the and end organ damage or dysfunction and ‘type B crisis’ highest level of catecholamines measured in an individual European Journal of Endocrinology defined as an extensive crisis with sustained hypotension patient in urine or plasma was expressed as fold of upper (shock) and multi-organ dysfunction (two or more organ limit of normal (ULN). The tumor size was determined systems). either by pathology or by radiographic imaging, because In the current study, we took the opportunity of three tumor diameter in pathology was not provided consist- pheochromocytoma databases of referral hospitals in ently due to the retrospective design of the study. Munich, Wu¨rzburg, and Berlin. Pooled data analysis Mortality was defined as death during hospitalization. revealed a high incidence of complications. Using this The clinical presentation of each patient prior to admis- data set we investigated clinical presentation and outcome sion was assessed. Hypertension was defined either as of patients with life-threatening events causally in treatment with antihypertensive medication or a pre- comparison to patients who underwent adrenalectomy viously documented elevated blood pressure above for uncomplicated pheochromocytoma in the same 140/90 mmHg. Paroxysmal hypertension, sweating, pallor, time period. and palpitation were counted as pheochromocytoma specific symptoms. Malignancy was defined as the presence of distant metastases in organs other than Subjects and methods sympathetic tissues (i.e., bone, liver, lung) (13). We reviewed the records of patients with pheochromo- cytomas in three German tertiary referral centers: the Ethical information University Hospital of the Ludwig-Maximilians-Universi- ta¨t, Munich (nZ72) and University Hospital Wu¨rzburg Due to the retrospective character of the study, informed (nZ43) from January 2003 to December 2012 and the consent of the patients was not requested in accordance University Hospital of the Charite´ University, Berlin with German regulations. www.eje-online.org Downloaded from Bioscientifica.com at 09/25/2021 02:20:49PM via free access European Journal of Endocrinology Table 1 Characteristics of patients presented with life-threatening complications due to pheochromocytoma. Clinical Study Severe hypotension ULN Type B: End organ damage and (catechol- Cardiac Cardiac epinephrine Type A: extensive comorbidities during
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