Case Report

Portal vein thrombus and Liver failure in a patient with pheochromocytoma crisis

Abstract

A 51-year-old man with known pheochromocytoma refused surgical treatment over several years and subse- quently presented in catecholamine crisis with shock and multiple organ failure. Laboratory testing revealed liver failure with elevated Liver enzymes and coagulation abnormalities, and imaging showed ischemia of extended parts of the right liver lobe. It also revealed a large thrombus in the right portal vein, which together with severe arterial vasoconstriction impaired the dual Blood supply of the liver. The patient recovered after effective medical treatment and finally underwent surgical tumor resection. Thereafter, Antihypertensive treatment could be stopped. We present this exceptional case of adrenal crisis and discuss the mechanisms leading to liver failure in general and portal vein thrombosis in particular.

We present the case of a 51-year-old man who had hypertensive spells up to 280/150 mm Hg 40 years ago. At 11 years of age, a pheochromocytoma (24 g) was removed after explorative laparatomy. Follow-up for 12 years confirmed normal blood pressures, and the patient was considered cured. After years of remission, recurrent disease was diagnosed 4 years ago, as the patient had fatigue and hypertensive spells again. A computed tomographic scan revealed a tumor in the lower pelvis, and a biopsy confirmed recurrent pheochromocytoma. The patient refused surgical resection and he was treated with phenoxybenzamine, an ?- receptor blocker. In addition, the patient sought relief with Alternative medicine.

As fatigue progressed and jaundice occurred, he was seen by a general practitioner. The patient was normoten- sive and laboratory testing showed normal Creatinine levels (64 umol/L) and liver enzymes (aspartate aminotransferase, 25 U/L; alanine aminotransferase, 14 U/L). Two weeks later, the patient became confused and somnolent and he was brought to a local hospital. The initial blood pressure was 151/110 mm Hg. Examination revealed acute renal

and liver failure. Echocardiography showed a severely depressed left ventricular ejection fraction (LVEF) of less than 20%. Antihypertensive treatment with labetalol was started and the patient was transferred to our tertiary intensive care unit. The somnolent patient presented with clammy skin and severe peripheral cyanosis. He was afebrile. Blood pressure values were normal at that time, despite grossly elevated norepinephrine levels of 70 times the upper limits of normal. Intubation for airway protection was performed. Laboratory testing was remarkable for high liver enzymes and creatinine values, coagulation abnorm- alities, and elevated lactate levels (Table 1). The patient was anuric, and severely impaired kidney perfusion was seen by ultrasound. A computed tomographic scan confirmed a large abdominal tumor with central necrosis (Fig. 1). A portal vein thrombus with ischemia of extended parts of the right liver lobe was detected (Fig. 2).

Labetalol was stopped and replaced by IV phentolamine, a pure ?-blocker. Continuous renal replacement therapy was initiated. With normalization of the peripheral circulation, cardiac index increased substantially and lactate normalized. After 12 hours of treatment, echocardiography showed an improvement of the LVEF to 37%. As liver function ameliorated, anticoagulation was initiated for the portal vein thrombosis. Four days later, the patient was extubated and Oral medication begun. Efficient blood pressure control was achieved by doxazosine (10 mg BID), carvedilol (25 mg BID), lisinopril (30 mg OD), and nifedipine (60 mg OD). After 15 days in the intensive care unit and 22 days on the ward, the patient was discharged. Six weeks after the initial admission, he was scheduled for surgery. Preoperatively, an 18F-DOPA-PET scan did not show metastasis, and an embolization of the lesion was performed. The tumor was removed, and histology confirmed the diagnosis of a pheochromocytoma/paraganglioma. Postoperatively, LVEF recovered to more than 50% and the Antihypertensive medication could be stopped, while the patient still required intermittent hemodialysis.

Pheochromocytomas are rare tumors, occurring in 0.05% of the population [1]. They are the cause of secondary hypertension in less than 1% [2]. About 25% of the tumors are associated with Genetic disorders [3]. Although our patients’ family history was negative, the presentation in childhood (classic pheochromocytoma) and the extraadrenal

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Table 1 Patient characteristics on admission and after 36 hours

Parameters	On admission	After 36 h
Systolic blood pressure (mm Hg)	118	96
Diastolic blood pressure (mm Hg)	72	52
Mean blood pressure (mm Hg)	90	64
Heart rate (L/min)	88	88
Cardiac index (L min-1 m-2)	2.5	4.6
systemic vascular resistance	1964	1423
(dyn x s/cm5)
Creatine kinase (U/L)	5279	2838
Lactate dehydrogenase (U/L)	15202	7854
Aspartate transaminase (U/L)	9823	2250
Ammonia (umol/L)	49	16
Factor V (%)	34	52
Lactate (mmol/L)	3.9	1.6
Creatinine (mmol/L)	352	215

manifestation 40 years later would be consistent with a germline mutation in the gene encoding the B subunit of mitochondrial succinate dehydrogenase (SDH) [3]. How- ever, genetic testing was negative (Table 2).

Pheochromocytoma classically presents with recurrent headache, sweating, and tachycardia [4]. However, it can present with a wide variety of symptoms including shock [3]. Our case is not only remarkable for its initial presentation and recurrence 4 decades later but also for its most recent presentation with portal vein thrombosis.

We hypothesize that low blood flow as a result of the impaired LV function as well as Volume depletion secondary to vasoconstriction led to this complication. Case reports of venous thromboses in pheochromocytoma exist. However, they are associated with tumor invasion into blood vessels [5,6]. Paraneoplastic thrombophilia is uncommon in pheo- chromoytomas. Ischemia of parts of the right liver lobe with

Fig. 1 Computed tomographic scan of the pelvis on admission (64-slice, with contrast media). The arrows show a large pheochro- mocytoma (8 cm in diameter) with central necrosis (asterisk).

Fig. 2 Computed tomographic scan of the pelvis on admission (64-slice, with contrast media). The arrow in A shows the thrombus in the portal vein. Panel B shows ischemic areas in the right liver lobe.

subsequent liver failure is explained by interruption of the dual blood supply: the thrombus obstructed venous inflow whereas vasoconstriction impaired arterial liver perfusion. Liver function recovered remarkable quickly after restoration of arterial perfusion.

low cardiac output was caused by several consequences of the massive Catecholamine release [7]. First, a persistent overstimulation with epinephrine leads to down-regulation of cardiac ?₁ receptors [8,9] and to a switch from ?₁ to ?₂ signaling, resulting in negative inotropy [10]. Second, vasoconstriction increased afterload, which further impaired LV function. Finally, tachycardia can impair diastolic ventricular filling.

The case highlights that pheochromocytoma can induce multiple organ failure. Liver infarction developed because venous inflow was obstructed by a portal vein thrombus and arterial perfusion was severely impaired due to vasoconstriction. Effective ?-blocking treatment

Case Report

Table 2 Genetic testing for germline mutations

Gene	Exon	Mutation
VHL	Exon 1-3	None
SDHB	Exon 1-8	None
SDHD	Exon 1-4	None
RET	Exon 10,11,13	None
VHL, von Hippel-Lindau disease; SDHB, succinate dehydrogenase subunit B; SDHD, succinate dehydrogenase subunit D; RET, gene encoding for multiple endocrine neoplasia syndrome type 2.

improved the macro- and microcirculation resulting in an improvement of organ dysfunction in general and liver failure in particular.

Andreas E. Brauchlin MD Medical Intensive Care Unit University Hospital Zurich CH 8091 Zurich, Switzerland

Alain Rudiger MD Medical Intensive Care Unit University Hospital Zurich CH 8091 Zurich, Switzerland

E-mail address: [email protected]

Esther B. Bachli MD

Clinic for Internal Medicine

Uster Hospital CH 8610 Uster, Switzerland

Christoph Schmid MD Division of Endocrinology Diabetes and Clinical Nutrition University Hospital Zurich

CH 8091 Zurich, Switzerland

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Marco Maggiorini MD Medical Intensive Care Unit University Hospital Zurich CH 8091 Zurich, Switzerland

doi:10.1016/j.ajem.2008.09.002

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