Originally derived from the neural crest, pheochromocytomas are neuroendocrine tumors of the adrenal medulla that arise from chromaffin cells. These tumors may be sporadic or hereditary, manifesting as part of a genetic syndrome such as Multiple Endocrine Neoplasia type 2, Von Hippel-Lindau disease, and Neurofibromatosis Type 1. The annual incidence of a pheochromocytoma is 2 to 9.1 per million adults and, when sporadic, commonly become apparent at 30–50 years old [2]. In our case, although only 84 common genes were evaluated, genetic evaluation revealed no mutation suggestive of hereditary pheochromocytoma. Moreover, unlike our case, hereditary pheochromocytomas are reported to occur at younger ages with smaller sized tumors, and, when compared to sporadic pheochromocytomas, are more often asymptomatic [3].

Although only estimated to occur in 24% of pheochromocytoma patients, the tumor’s secretion of catecholamines give rise to the classic triad of palpitations, diaphoresis, and headache [4]. Additional symptoms may include hypertension which can be refractory to treatment, flushing, abdominal pain, and hyperglycemia, as our patient demonstrated on initial presentation in diabetic ketoacidosis. In rare occasions, patients can present with “pheochromocytoma crisis” in cardiogenic shock, resulting in multiple organ failure. Furthermore, our patient had post-operative transient adrenal insufficiency. Adrenal insufficiency can develop following unilateral adrenalectomy in cases of overt or subclinical Cushing’s syndrome because of suppression of cortisol production from the contralateral adrenal gland [5]. This patient did not have evidence of cortisol hyper-secretion preoperatively. The incidence of adrenal insufficiency followed unilateral adrenalectomy for pheochromocytoma has not been reported in the medical literature, but it is thought to be rare [6].

Adrenal tumors are commonly benign. Conversely, adrenocortical carcinoma is a rare malignant adrenal mass that produces steroids and androgens. It has also been described in few cases to mimic pheochromocytomas [7]. In addition, the reported prevalence of malignant pheochromocytomas, defined by metastasis into non-chromaffin cells, ranges between 5 and 26% [8]. Local invasion does not diagnose malignancy. Surgery plays a critical role in malignant pheochromocytoma, as a possible curative treatment by adrenalectomy. Genetic testing of the SDHB mutation as part of pathologic analysis after resection gives additional information regarding the patient’s predisposition to developing pheochromocytomas, or in the case of malignant masses, prognosis, since shorter survival has been associated with positive SDHB mutations [3]. In our case, there was no signs of metastasis in anatomical and functional imaging, and SDHB mutation was also negative.

Minimally invasive surgery with laparoscopic adrenalectomy is preferred for smaller pheochromocytomas due to lower rates of intraoperative hemodynamic instability, less intraoperative blood loss, and shorter postoperative hospital stays [9]. However, the 2014 Endocrine Society Clinical Practice Guideline recommends open adrenalectomy for pheochromocytomas > 6 cm given high probability of a malignant functional tumor. Furthermore, complex anatomy can negatively impact the success of laparoscopic surgery. In the presented case, the final greatest dimension of tumor was 12.6 cm and concomitant pelvic horseshoe kidney and retro-aortic left adrenal vein were present. To our knowledge, this is the first case reporting a giant pheochromocytoma (12 cm in size) with a simultaneous horseshoe kidney. Previously few case reports demonstrated their co-existence, albeit all pheochromocytomas treated were smaller, 3 and 5 cm respectively [10, 11]. Horseshoe kidneys are rare entities, found in approximately 0.25% of the population and have a male predominance. Renal vein anomalies have an incidence reported in up to 23% of patients with horseshoe kidneys [12], as was identified in our patient with a retro-aortic renal vein. Given the patient’s anatomic variations and very large tumor size, an open radical surgical resection with adequate exposure was of paramount importance.

The additional challenge of adrenalectomy for pheochromocytoma is perioperative hemodynamic instability in the form of both severe hypertension and hypotension. Hypertension is observed with manipulation or palpation of the pheochromocytoma. Conversely, extreme hypotension arises upon interruption of the vessels leading to a sudden decrease in catecholamine secretion. Hypotension is further exacerbated by decreased vascular volume by intraoperative blood loss. In a study of 67 patients who underwent surgery for pheochromocytoma, changes in blood pressure greater than 30% of the patient’s pre-operative mean arterial pressure were observed in 97% of patients, with 36% experiencing hypertension and 93% experiencing hypotension [13]. Five or more episodes of severe hypotension correlated with longer stays in the intensive care unit due to the increased risk of the patient’s developing end-organ failure [13]. Intra-operatively, the individual patient’s course remains unpredictable and requires close monitoring by the anesthesiologist. Few factors, including tumor size, selective alpha-blockade, and operative approach, have been associated with intraoperative hemodynamic stability [14].

Thorough pre-surgical planning and close coordination among urologist, anesthesiologist, endocrinologist and other surgical teams are essential to prevent severe perioperative complications. Moreover, Abdou et al. reported a challenging case of a 5.5 cm left adrenal mass and horseshoe kidney, which failed surgical resection twice previously. The first attempted laparoscopic surgery was aborted due to severe adhesions, whereas the second attempted open surgery was aborted due to severe bleeding [11]. Only after a preoperative coil embolization of three large feeding arteries arising from the left renal artery and supplying the left adrenal mass, they could resect the mass in the third attempted open surgical resection successfully, with significantly low blood loss, 250 ml. Although pre-operative embolization could have potentially reduced the blood loss in our case, embolization is not without risks as it can precipitate hypertensive crisis, thus its role in treatment of pheochromocytoma still remains controversial. Furthermore, although the 3 cm splenic laceration was quite small, due to massive fluid shifts during the case, control of the bleeding was difficult and hemostasis could not be achieved sufficiently, therefore we elected for a splenectomy. Although, current literature suggested that immunization might be effective even in the immediate perioperative time for postsplenectomy infection prophylaxis [15], given the proximity of the giant adrenal mass to the spleen and complexity of the anatomy in this presented case, a preoperative vaccination at least 2 weeks prior to the planned surgery could have been performed instead.

To our knowledge, this is the first case report describing a giant pheochromocytoma with a concurrent horseshoe kidney. She also had several additional anatomical variations, including the retro-aortic left renal vein, and congested left ovarian vein, complicating an already surgically challenging procedure. Wide resection of the highly aggressive adrenal tumor was required due to the symptomatic mass caused by catecholamine overproduction and the possibility of malignancy. The surgical principles of gentle retraction of the adrenal mass and early control of adrenal vein to prevent bursts of catecholamine release may not be easily feasible for complex large pheochromocytoma cases with anatomical anomalies. Nonetheless, with detailed anatomic studies, thorough pre-operative planning, multiple provider collaboration, and meticulous intraoperative monitoring, it is possible to minimize complications and achieve successful outcomes.