Rupture of pheochromocytoma caused by phenoxybenzamine - A case report.

Introduction

Spontaneous rupture of adrenal pheochromocytoma is rare with few cases reported in literature.The exact mechanism of pheochromocytoma rupture is unknown, but a high intracapsular pressure caused by rapid growth of tumor or intratumoral hemorrhage may tear the capsule and also cause necrosis of tumor. The mechanism by which alpha adrenergic blockers can cause rupture of pheochromocytoma is discussed.

Case presentation

A 66 year old man presented with history of vague epigastric pain and paroxysms of severe head ache, palpitation, sweating and fainting. Serial blood pressure recordings revealed a very fluctuant blood pressure (range 240/120 to 120/80). Abdominal examination was fairly unremarkable. His hemoglobin and hematocrit were 16 gm/dl and 46% respectively and fasting blood sugar 171mg/dl. Plasma catecholamine, urine 24 hour metanephrines and VMA were within normal limits. Ultra sonogram and CT abdomen available at admission were reviewed. The inferior vena cava was found pushed anteriorly by the tumor and also that the right adrenal gland is not visualized separate from the tumor.

With a diagnosis of right adrenal pheochromocytoma patient was prepared for surgery by control of blood pressure by alpha adrenergic blocker (phenoxybenzamine), beta blockers and glycemic control by human actrapid insulin. On the preoperative day in the hospital patient had severe hypotension and asystole. Patient was resuscitated in ICU with intravenous crystalloids and noradrenalin infusion. Alpha and beta blockers were stopped. Patient stabilized. After a few hours patient experienced severe abdominal pain. Examination revealed tachycardia (110–120/minute) and blood pressure 120/80 mm Hg. Abdomen was guarded with diffuse tenderness.Hemoglobin dropped from 16 to 14 gm/dl. Ultrasonogram of abdomen was repeated which showed an hyperechoic tumor with free fluid in the peritoneum confirming the suspicion of ruptured pheochromocytoma. Patient was closely observed in intensive care unit and taken up for surgery at the scheduled time next day.

At surgery by a right thoraco-abdominal approach about 2 L of altered blood, clots and free tumor bits where found in the peritoneal cavity. A large tumor was found arising from the right adrenal with evidence of tumor necrosis, intratumoral bleed and capsular tear and intraperitoneal bleed. No ongoing active bleeding was encountered at surgery. The inferior vena cava was stretched over the tumor and compressed. Liver, left adrenal gland was unremarkable. Peritoneal lavage was done. Right adrenalectomy performed after Kocherisation of duodenum, mobilizing the right lobe of liver and separating the tumor from inferior vena cava (Fig. 1), thus completely removing the tumor (Fig. 2). The patient was hemodynamically stable throughout the procedure. Patient was shifted to intensive care unit and electively ventilated and extubated the next day. Patient had prolonged ascitic leak from drain due to hypoalbuminemia. Patient improved with intravenous albumin and active feeding. The patient underwent transurethral resection of prostate before discharge. On histopathological examination of the tumor confirmed it as pheochromocytoma. Patient at 8 years was asymptomatic and euglycemic without insulin/hypoglycemic agents with a hemoglobin of 13 gm% and normotensive.

Fig. 1

Operative photograph of the exposed right adrenal tumor (black arrow) with inferior vena cava stretched over it (white arrow).

Fig. 2

Removed specimen of right adrenal tumor.

Discussion

Alpha adrenergic blockers are the mainstay of treatment of hypertension due to pheochromocytoma. However it has been suggested that alpha adrenergic blockers can cause intratumoral hemorrhage and avascular necrosis. The effect is proposed to be due to lowered systemic BP causing the already precarious circulation within the tumor to become inadequate causing necrosis. Alpha adrenergic blockers cause vasodilatation flooding the already necrotic areas with blood causing progressive interstitial hemorrhage within the tumor and when the pressure inside the tumor increases rupture of the capsule and hemoperitoneum. This effect is clear in our case by the fact that when the patient had profound systemic hypotension most likely induced by the alpha adrenergic blocker patient probably developed massive necrosis and later while the patient became hemodynamically stable there was perfusion of this necrotic tumor resulting in intratumoral bleed and rupture and hemoperitoneum causing severe abdominal pain. The increased echogenicity of the tumor compared to previous scan and the hemoperitoneum are suggestive of that. Such a clear association between alpha adrenergic blocker and rupture of pheochromocytoma could not be identified in literature, though alpha-adrenergic blockers are reported to cause the complication. Most of the association of rupture of pheochromocytoma with alpha-blockers in literature is with phentolamine; its association with phenoxybenzamine couldn't be found elsewhere in literature.

Why the plasma and urine levels of catecholamines were normal in this case even before the patient developed this complication remains unclear. It was possible that progressive pheochromocytoma destruction caused by the necrosis led to a pronounced decrease in catecholamine production. This is again supported by the fact that in our case the tumor manipulation during surgery did not cause any significant fluctuation in blood pressure.

Surgical treatment of ruptured pheochromocytoma involves emergency or elective surgery. Emergency surgery is associated with high mortality, but no mortality has been reported in literature series with elective surgery.

Conclusion

Though alpha adrenergic blockers are indicated in the pre operative management of hypertension due to pheochromocytoma, one should always be cautious about the possible complication of necrosis, interstitial hemorrhage and rupture of the tumor. A high index of suspicion and prompt stabilization and surgical intervention can save the patient.