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Journal of The Association of Physicians of India Vol. 64 July 2016 89 Pheochromocytoma Presenting with Acute Abdomen RM Suresh 1 , HC Lokesh 2 , BS Harsha 2 , Sri S Chandana 3 1 Professor and Head, 2 Sr. Resident, 3 Intern, Department of General Medicine, Hassan Institute of Medical Sciences, Hassan, Karnataka Received: 17.08.2015; Revised: 30.09.2015; Accepted: 23.10.2015 Introduction Pheochromocytomas are tumours of the adrenal medulla arising from the chromaffin cells. Less commonly, chromaffin cell tumors also arise in extra-adrenal sites (paragangliomas). They are neuroendocrine tumors which lead to a variety of systemic manifestations owing to their ability to secrete and release catecholamines. The classical presentation is constituted by the triad of episodic headache, palpitations and diaphoresis associated with labile hypertension. Other manifestations include, postural hypotension, visual disturbances, fever, tremors, nausea, weakness, pallor, anxiety, a sense of impending doom, chest pain, and very rarely, pain abdomen. They may occur either sporadically or as a component of heritable syndromes (in about 25-33% of the cases) like MEN (Multiple Endocrine Neoplasia) 2A and investigations were duly ordered. No abnormalities were detected on plain erect abdominal radiography and abdomino-pelvic ultrasound. The case was subsequently referred to the physician. On examination, the patient was febrile and looked anxious. His pulse was bounding with a rate of about 130 beats per minute. His blood pressure recordings were fluctuating. The initial recording yielded a reading of 90/70 mm Hg. A subsequent reading after 15 minutes was 210/120 mm Hg. The patient was duly shifted to the ICU. Precordial examination revealed a heaving apical impulse with a loud second heart sound. ECG showed features of severe LVH with no signs suggestive of ischemic heart disease. The Creatine Kinase MB value was within normal limits. A subsequent 2D echocardiogram showed severe concentric left ventricular hypertrophy with mild mitral regurgitation and aortic regurgitation. An fundoscopy was performed and features suggestive of Grade-3 Hypertensive Retinopathy were found. The investigations obtained are shown in Table 1. In view of the swinging blood pressures, florid hypertensive features and other constitutional signs, pheochromocytoma was suspected. An abdominal computerized tomograph (CT) with contrast study revealed a solid well-circumscribed heterogeneous mass lesion measuring 4.7cm x 3.5cm x 4.5cm with areas of necrosis, with no evidence of calcification or hemorrhage in the left suprarenal area (Figure 1). A subsequent 24 hour urine metanephrines assay yielded a high value of 650µg / 24hours (normal value: <350µg/ 24 hours), 1 confirming the suspicion of pheochromocytoma. A diagnosis of ‘Left Adrenal Pheochromocytoma’ was made. The Abstract Pheochromocytoma, a neuroendocrine tumor of the adrenal medulla, arising from chromaffin cells, usually presents with the clinical triad of paroxysmal headache, profuse sweating and palpitations, associated with labile hypertension. Here, we present the case of an adult male with an unusual manifestation of pheochromocytoma in the form of acute pain abdomen with nausea and abdominal guarding, mimicking acute peritonitis. He had fluctuating blood pressure recordings. On subsequent investigation, a mass lesion in the left suprarenal area on an abdominal CT scan and a 24-hour urinary metanephrine assay confirmed the diagnosis of pheochromocytoma. 2B, Neurofibromatosis 1 and VHL (von Hippel Lindau) syndrome. The tumours are popularly said to follow a ‘rule of tens’: ~10% are extra-adrenal, ~10% are bilateral, ~10% are malignant, ~10% can recur after surgical resection, ~10% are found in children, ~10% are familial, ~10% are not associated with hypertension, ~10% contain calcification. Case Report A 40 year-old male patient, farmer by occupation, visited the ER with complaints of sudden onset of pain in abdomen associated with profuse sweating and nausea. On examination, abdominal guarding was found. The case was initially seen by a surgeon. Acute peritonitis was suspected and Fig. 1: CECT abdomen showing a solid well-circumscribed heterogenous mass Table 1: Blood investigations Hemoglobin: 10.2 g/dl Bleeding time: 1 min 50 sec Cloing time: 3 min 55 sec RBC count: 5.07x10 6 cells/µL WBC count: 6.3x10 3 cells/ µL Platelet count: 84,000 cells/ µL RBS: 98 mg/dl Blood urea: 38 mg/dl Serum creatinine: 1.0 mg/dl Serum sodium: 123 mmol/L Serum potassium: 3.1 mmol/L Serum chloride: 107 mmol/L Serum inorganic phosphate: 3.4 mg/dl Total calcium: 9.8 mg/dl

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Journal of The Association of Physicians of India ■ Vol. 64 ■ July 2016 89

Pheochromocytoma Presenting with Acute AbdomenRM Suresh1, HC Lokesh2, BS Harsha2, Sri S Chandana3

1Professor and Head, 2Sr. Resident, 3Intern, Department of General Medicine, Hassan Institute of Medical Sciences, Hassan, KarnatakaReceived: 17.08.2015; Revised: 30.09.2015; Accepted: 23.10.2015

Introduction

Pheochromocytomas are tumours of the adrenal medulla arising from the chromaffin cells. Less commonly, chromaffin cell tumors also arise in extra-adrenal sites (paragangliomas). They are neuroendocr ine tumors which lead to a variety of systemic manifestations owing to their ability to secrete and release catecholamines. The classical presentation is constituted by the triad of episodic headache, palpitations and diaphoresis associated with labile hypertension.

Other mani fes ta t ions inc lude , p o s t u r a l h y p o t e n s i o n , v i s u a l disturbances, fever, tremors, nausea, weakness, pallor, anxiety, a sense of impending doom, chest pain, and very rarely, pain abdomen.

They may occur either sporadically or as a component of heritable syndromes (in about 25-33% of the cases) like MEN (Multiple Endocrine Neoplasia) 2A and

investigations were duly ordered. No abnormalities were detected on plain erect abdominal radiography and abdomino-pelvic ultrasound. The case was subsequently referred to the physician.

On examination, the patient was febrile and looked anxious. His pulse was bounding with a rate of about 130 beats per minute. His blood pressure recordings were fluctuating. The initial recording yielded a reading of 90/70 mm Hg. A subsequent reading after 15 minutes was 210/120 mm Hg. The patient was duly shifted to the ICU.

Precordial examination revealed a heaving apical impulse with a loud second heart sound. ECG showed features of severe LVH with no signs suggestive of ischemic heart disease. The Creatine Kinase MB value was within normal limits. A subsequent 2D echocardiogram showed severe concentric left ventricular hypertrophy with mild mitral regurgitation and aortic regurgitation.

An fundoscopy was performed and features suggestive of Grade-3 Hypertensive Retinopathy were found.

The investigations obtained are shown in Table 1.

In view of the swinging blood pressures, florid hypertensive features a n d o t h e r c o n s t i t u t i o n a l s i g n s , pheochromocytoma was suspected.

A n a b d o m i n a l c o m p u t e r i z e d tomograph (CT) with contrast study revealed a solid well-circumscribed heterogeneous mass lesion measuring 4.7cm x 3.5cm x 4.5cm with areas o f necros is , wi th no evidence of calcification or hemorrhage in the left suprarenal area (Figure 1).

A s u b s e q u e n t 2 4 h o u r u r i n e metanephrines assay yielded a high value of 650µg / 24hours (normal value: <350µg/ 24 hours),1 confirming the suspicion of pheochromocytoma.

A d i a g n o s i s o f ‘ L e f t A d r e n a l Pheochromocytoma’ was made. The

AbstractPheochromocytoma, a neuroendocrine tumor of the adrenal medulla, arising from chromaffin cells, usually presents with the clinical triad of paroxysmal headache, profuse sweating and palpitations, associated with labile hypertension. Here, we present the case of an adult male with an unusual manifestation of pheochromocytoma in the form of acute pain abdomen with nausea and abdominal guarding, mimicking acute peritonitis. He had fluctuating blood pressure recordings. On subsequent investigation, a mass lesion in the left suprarenal area on an abdominal CT scan and a 24-hour urinary metanephrine assay confirmed the diagnosis of pheochromocytoma.

2B, Neurofibromatosis 1 and VHL (von Hippel Lindau) syndrome.

The tumours are popularly said to follow a ‘rule of tens’: ~10% are extra-adrenal, ~10% are bilateral, ~10% are malignant, ~10% can recur after surgical resection, ~10% are found in children, ~10% are familial, ~10% are not associated with hypertension, ~10% contain calcification.

Case Report

A 40 year-old male patient, farmer by occupation, visited the ER with complaints of sudden onset of pain in abdomen associated with profuse sweating and nausea. On examination, abdominal guarding was found. The case was initially seen by a surgeon. Acute peritonitis was suspected and

Fig. 1: CECT abdomen showing a solid well-circumscribed heterogenous mass

Table 1: Blood investigations

Hemoglobin: 10.2 g/dlBleeding time: 1 min 50 secClotting time: 3 min 55 secRBC count: 5.07x106 cells/µLWBC count: 6.3x103 cells/ µLPlatelet count: 84,000 cells/ µLRBS: 98 mg/dlBlood urea: 38 mg/dlSerum creatinine: 1.0 mg/dlSerum sodium: 123 mmol/LSerum potassium: 3.1 mmol/LSerum chloride: 107 mmol/LSerum inorganic phosphate: 3.4 mg/dlTotal calcium: 9.8 mg/dl

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Journal of The Association of Physicians of India ■ Vol. 64 ■ July 201690

patient was started on oral Prazosin and subsequently on Propranolol. Further surgical intervention was planned.

The patient was further evaluated for syndromic forms of pheochromocytoma. No clinical features or family history suggestive of features of Multiple Endocr ine Neoplas ia 2A and 2B, Neurofibromatosis-1 or von Hippel Lindau disease were found. The thyroid function tests of the patient were within normal limits (T3 - 61.09 mg/dl, T4 - 7.12 µg/dl, TSH - 1.53µIU/ml). No skin or ocular features of the aforementioned syndromes were encountered . Endolymphat i c sac tumor, a feature of von Hippel Lindau disease, was not found on otological examination.

Discussion

T h e m a n i f e s t a t i o n s o f pheochromocytoma may vary from an asymptomat ic s ta te to a l i f e -threatening emergency. The condition can mimic primary cardiovascular, gastrointest inal and neurological disorders owing to the effect of elevated levels of catecholamines on the various systems. It has been rightly called ‘the great masquerader’.

I n t h i s p a t i e n t , w h o m a i n l y presented with acute severe abdominal pain, nausea, and local guarding, there were very few clinical pointers suggestive of the underlying condition. A high index of suspicion is therefore necessary in such situations, where labile hypertension, fever, tachycardia and diaphoresis are encountered.

Pheochromocytoma presenting de novo as abdominal pain is a relatively rare occurrence, reported in only a handful of studies.2-4

Pheochromocytoma may present as acute abdomen by various mechanisms which may be a direct result of changes in the tumor mass or a consequence of increased circulatory catecholamines.

Hemorrhage and necrosis in the tumor mass may be responsible for acute abdominal pain. This is the most likely mechanism in the case discussed above. Hemorrhagic necrosis may result in rupture and subsequent hemorrhagic shock. Also, it may further worsen the hemodynamic instability due to the sudden drop of circulatory catecholamines which often follows tumor necrosis.

The most catastrophic of changes in the tumor is the rupture of the pheochromocytoma. I t i s usual ly precipitated by increased intratumoral i n t r a va s c u l a r p r e s s u r e r e s u l t i n g from paroxysms of hypertension. This may cause intraperitoneal or retroperi toneal bleeding, causing marked hemodynamic instability. It is often lethal, owing to a low index of suspicion and dramatic clinical course. The presentation often mimics that of a ruptured aortic aneurysm.

Pheochromocytomas may a l so cause acute abdominal pain as a result of the effects of catecholamines o n t h e g a s t r o i n t e s t i n a l s y s t e m . Catecholamines cause relaxation of the intestinal smooth muscle (with a decrease in the frequency and intensity of peristalsis) , constrict ion of the pyloric sphincter and ileocecal valve, and vasoconstriction in the splanchnic circulation. This underlies the intestinal pseudo-obstruction, bowel ischemia and rarely, gastrointestinal perforation in pheochromocytoma, which may p r e s e n t a s a n a c u t e a b d o m i n a l e m e r g e n c y . T h e h e m o d y n a m i c instability that accompanies these presentations often leads the surgeon to perform an emergency surgery with insufficient investigations and an uncertain preoperative diagnosis. Such operative interventions are associated with a high mortal i ty rate in the setting of an unrecognized functional pheochromocytoma.

Handling the tumor inadvertently without the knowledge of its functional status can cause massive release of catecholamines into the circulation, precipitating cardiac arrhythmias and malignant hypertension. Peri-operative mortality often results from bleeding, severe post-operative hypertension, shock, acute pulmonary edema and multi-organ failure.5

Hence, it would be prudent to include pheochromocytoma in the differential diagnosis of an abdominal emergency a c c o m p a n i e d b y h e m o d y n a m i c instability.

Emergency surgical intervention must be restricted to patients who are unresponsive to maximal medical resuscitation.

T h e i m a g i n g a p p e a r a n c e s o f pheochromocytomas are varied with all imaging modalities, primarily due to the multiple pathologic processes that

they may undergo, such as hemorrhage, necrosis, calcification, fibrosis, lipid degenerat ion and cyst ic changes . Pheochromocytoma currently remains a true imaging chameleon, and its diagnosis should always be considered in the imaging evaluation of a patient with an adrenal mass.

R a d i o n u c l i d e s t u d i e s s u c h a s MIBG (meta-iodo-benzyl-guanidine) scintigraphy have great specificity in localisation, characterization and staging of pheochromocytomas. But their use is limited as they are expensive and time consuming.6

Demonstration of elevated plasma and urine levels of catecholamines or their metabolites, metanephrines, is the cornerstone for the diagnosis. Urinary 24-hour total metanephrine excretion level is the best single biochemical test for screening of pheochromocytoma.Conclusion

Complete surgical resect ion of pheochromocytoma prevents lethal hypertensive crises. It has to be borne in mind that this rare neuroendocrine tumor possesses the potential to mimic several conditions and its possibility should be enter ta ined whenever labile hypertension with associated constitutional features is encountered.

Judicious use of radio-imaging s t u d i e s a n d d e m o n s t r a t i o n o f an elevated 24 hour total urinary metanephrine level are useful in diagnosing this condition.Acknowledgements

We greatly acknowledge the faculty of the Department of General Surgery, Hassan Institute of Medical Sciences, Hassan, for their timely reference and subsequent follow-up of the patient.

References1. Jeyaraman K,  Natarajan V,  Thomas N,  et al. The role of

urinary fractionated metanephrines in the diagnosis of phaeochromocytoma. Indian J Med Res 2013; 137:316–323.

2. Counselman FL,  Brenner CJ,  Brenner DW. Adrenal pheochromocytoma presenting with persistent abdominal and flank pain. J Emerg Med 1991; 9:241-246.

3. Andersen PT, Baadsgaard SE, Larsen BP. Repetitive bleeding from a pheochromocytoma presenting as an abdominal emergency. Acta chirurgica Scandinavica 1986; 152:69-70.

4 Hatada T, Nakai T, Aoki I, et al. Acute abdominal symptoms caused by hemorrhagic necrosis of a pheochromocytoma: report of a case. Surg Today 1994; 24:363-7.

5. Kobayashi T, Iwai A, Takahashi R, et al. Spontaneous rupture of adrenal pheochromocytoma: Review and analysis of prognostic factors. J Surg Oncol 2005; 90:31-35.

6. Ilias I, Pacak K. Diagnosis, localization and treatment of pheochromocytoma in MEN 2 syndrome.  Endocrine Regulations 2009; 43:89-93.