Pheochromocytoma and intestinal ganglioneuromatosis are rare entities associated with Multiple Endocrine Neoplasia Type 2B (MEN2B) [1]. Rare complications of each pathology include colonic pseudo-obstruction and ischemia [1,2], bowel perforation is even more rare [3–9]. Pheochromocytomas are rare tumors derived from neural crest cells often found in the adrenal glands that secrete catecholamines [2]. Intestinal ganglioneuromatosis is a benign disorder resulting in proliferative lesions of the enteric nervous system [1]. MEN2B is an autosomal dominant genetic disorder which leads to the development of endocrine tumors [2]. This is the first case report of colonic perforation where all 3 pathologies were observed concurrently.

A 54-year-old man presented to a tertiary center Emergency Department with a 2-day history of diffuse abdominal pain and syncope. He was in shock, he had a heart rate of 146 beats per minute, a blood pressure of 82/33 mmHg, an oxygen saturation of 91% (room air), 26 respirations per minute, and he was afebrile. He showed signs of peritonitis on abdominal exam, and a chest x-ray revealed significant pneumoperitoneum suggesting a perforated viscus. He was booked for emergency surgery.

The patient did not report a medical or surgical history. However, an electronic chart (within the same hospital system) was found, prior to surgery, which revealed a recent admission for colonic pseudo-obstruction and metabolic derangements, and a 3.8 × 2.5 cm mass on the left adrenal gland. During this admission, he was cared for in the Department of Endocrinology where the pheochromocytoma could be investigated. To diagnose the adrenal tumor, 24-hour urine metanephrines were measured and showed significantly high levels [14 μmol/day (normal 0.3–2 μmol/day)]. The additional findings of suspicious thyroid nodules with elevated calcitonin levels [1,425 ng/L (normal < 10 ng/L)], mucosal neuromas, and marfanoid body habitus, raised the suspicion of MEN2B involvement. The patient did not attend outpatient follow up appointments to confirm this diagnosis.

At the present admission, the patient received fluid resuscitation and broad-spectrum antibiotics, and this was followed by surgery. The exploratory laparotomy revealed gross fecal contamination, the colon was dilated to 10 cm, and had a redundant, leathery texture. Dark pigmentation was noted that resembled melanin, the appearance of staining coated the visceral and parietal peritoneum (Figure 1). The stomach, duodenum, and small bowel appeared otherwise normal. A 1 cm colonic defect was identified at the rectosigmoid junction. The post-induction arterial blood gas test showed severe metabolic acidosis (pH 6.93, pCO₂ 28 mmHg, HCO₃ 10 mmol/L and base excess −22 mmol/L). Intraoperatively, the patient received ringer’s lactate, D50, sodium bicarbonate, and calcium gluconate. He remained tachycardic (heart rate of 120 beats per minute) and normotensive (mean arterial pressure > 65 mmHg) throughout the surgery and was without vasopressor support. Given the pathological appearance of the entire colon and the redundant mesentery, a total abdominal colectomy was performed using an energy device to precisely cut and seal the blood vessels during dissection. The terminal ileum and rectal stump were left in discontinuity. The abdomen was washed out and a temporary abdominal closure device (AbThera) was placed. The total operative time was 32 minutes. The patient was transferred to the Intensive Care Unit. His hemodynamic and metabolic profiles improved rapidly. He was brought back into surgery 36 hours later for a second look laparotomy, washout, creation of an end ileostomy, and abdominal closure. Once more, his tissues had the same darkened appearance, but otherwise appeared healthy. The adrenal mass was left in situ for outpatient evaluation and treatment (outside of this acute presentation).

Postoperatively, he experienced recurrent supraventricular tachycardia requiring chemical and electrical cardioversions. These episodes were thought to be attributed to his pheochromocytoma, and ceased after treatment with an alphablocker (terazosin), and then with a beta-blocker (metoprolol) to control the heart rhythm. Despite his severe metabolic acidosis and labile heart rate, he required minimal vasopressor support. His hospital stay involved the Departments of General Surgery, Critical Care, Infectious Diseases, and Endocrinology. He remained in hospital for 9 weeks due to a high-output ileostomy, and electrolyte abnormalities, and he received physical rehabilitation. He was discharged home on postoperative Day 62 at baseline functional status from his index operation.

Histopathology from the specimen revealed bowel perforation arising in a background of diffuse intestinal ganglioneuromatosis, without evidence of malignancy or dysplasia. A referral for genetic testing for MEN2B was requested at the time of discharge, and at the time of reporting, was still pending.

This case report describes a medically complex patient presenting with bowel perforation where the inciting cause was not clear at the time of surgery. The patient’s medical history offered many possible contributing factors that may have led to his acute presentation. These included colonic pseudo-obstruction, pheochromocytoma, and a histology finding of diffuse intestinal ganglioneuromatosis in the bowel specimen. While pheochromocytomas and MEN2B are uncommon conditions, they are well-documented pathologies in which bowel perforation can occur. The detection of intestinal ganglioneuromatosis in this patient was particularly unusual and has scarcely been reported in bowel perforation, adding a layer of complexity to this case.

Pheochromocytomas are rare tumors derived from neural crest cells often found in the adrenal glands. These catecholamine secreting tumors elicit symptoms in the patient including hypertension, tachycardia, and diaphoresis [2]. Approximately 30% of pheochromocytomas are associated with genetic syndromes, most commonly MEN2, Von Hippel-Lindau, and Neurofibromatosis 1 [10]. In rare circumstances, pheochromocytoma can affect the gastrointestinal (GI) system. Several case reports have described pheochromocytoma presenting as pseudo-obstruction or bowel perforation in a mixture of pediatric and adult populations [1]. The proposed mechanism initiated by the pheochromocytoma is the inhibition of colonic motility via excessive sympathetic stimulation and splanchnic vasoconstriction (through excessive catecholamine activation of alpha 1, alpha 2, and beta 2 adrenergic receptors) [1]. Paradoxically, certain prokinetics, such as 5-HT4 receptor agonists including metoclopramide, should be avoided in patients with pheochromocytoma and pseudo-obstruction. It is thought that a hypertensive crisis can be induced (due to catecholamine release), and this exacerbates colonic ischemia (a phenomenon that has been reported twice before in similar situations) [5,7].

Intestinal ganglioneuromatosis is a rare benign disorder causing proliferative lesions of the enteric nervous system [11]. Ganglioneuromas are more commonly found in the adrenal glands, however, when found in the GI tract, the extent of involvement can vary widely. Generally, intestinal ganglioneuromatosis is categorized into 3 subtypes: polypoid ganglioneuroma, ganglioneuromatosis polyposis, and diffuse ganglioneuromatosis [12]. While generally asymptomatic, a patient with ganglioneuromatosis can present with GI symptoms including a change in bowel habits, abdominal pain, strictures, and pseudo-obstruction. Bowel perforation in these patients is postulated to be secondary to colonic distension from pseudo-obstruction or transmural ulceration from the lesions. Symptomatic lesions are typically identified in childhood [1,11,13–15], although case reports in adults have been described [5,15]. When intestinal ganglioneuromatosis is identified, it is almost exclusively in patients with genetic conditions such as MEN2B [2].

MEN2B is an autosomal dominant genetic disorder arising from germline mutations in the rearranged during transfection proto-oncogene which lead to endocrine tumors. It is the rarest of the MEN syndromes with an estimated prevalence of 0.9–1.7 per million [16]. MEN2B is a clinical diagnosis in patients with medullary thyroid carcinomas, mucosal neuromas, and marfanoid body habitus [2]. Compared with MEN2 Subtype A, MEN2 Subtype B may lead to the development of pheochromocytoma and/or intestinal ganglioneuromatosis, which is present in approximately 50%, and 40% of MEN2B patients, respectively [2,16]. As such, MEN2B patients may present with GI symptoms including pseudo-obstruction, primarily in early childhood [17].

This case report details a patient who presented to hospital in critical condition with features highly suggestive of untreated MEN2B. Whilst the association between pheochromocytoma and colonic pseudo-obstruction leading to bowel perforation is rare, it is well documented in endocrinology literature [7]. Currently, there are no existing surgical guidelines or recommendations addressing bowel perforation in the context of pheochromocytoma or intestinal ganglioneuromatosis. A literature review identified 6 documented cases of bowel perforation due to pheochromocytoma, and the mortality rate was 50% [3–8]. Notably, these studies did not report histological evidence of intestinal ganglioneuromatosis in the examined specimens (Table 1 [3–8]). Bowel perforation in the setting of intestinal ganglioneuromatosis is more unique. To date, only 1 such case has been published, it was in a 15 year old patient with a perforated splenic flexure requiring a left hemicolectomy [9] (no adult cases have been reported). As with bowel perforation in pheochromocytoma, there are no guidelines on the surgical management for this pathology. In this case report of pan-colonic dilation and a rectosigmoid perforation, a total abdominal colectomy was chosen based on the standard management of toxic megacolon in the setting of colonic pseudo-obstruction and pathological appearance of the entire colon intraoperatively [18].

In conclusion, a very rare case has been described of a patient with both pheochromocytoma and intestinal ganglioneuromatosis who presented in extremis with colonic pseudo-obstruction and a rectosigmoid perforation.

Although pheochromocytoma is a rare, but well-described risk factor for bowel perforation in patients with MEN2B, the potential role of intestinal ganglioneuromatosis cannot be overlooked as a contributing factor. This patient’s survival was largely attributed to early recognition of his medical comorbidities associated with MEN2B, early involvement of subspecialized consultant services, and the crucial role of endogenous catecholamine release in maintaining adequate organ perfusion during his critical state.