SAT-222 Aggressive Phenotype Pheochromocytoma Associated with NF-1 and BRCA Mutation

Introduction Pheochromocytomas are catecholamine-secreting tumors of the adrenal medulla that occur sporadically or with familial association. Familial predilection occurs in those with multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis Type 1 (NF-1). To date, more than 21 gene mutations have been identified that are involved in the development of pheochromocytomas. However, co-existence of two different mutations such as NF-1 and BRCA gene mutations with pheochromocytoma has not been well described. Clinical Case A 40 year-old woman with NF-1 and recently diagnosed left breast invasive ductal carcinoma, estrogen positive, progesterone positive, HER-2 negative BRCA2 positive breast cancer and right breast lobular carcinoma in situ underwent staging CT scan. A 2.7 cm left adrenal incidentaloma with heterogeneous texture and 69–100 HU was discovered. Symptom review revealed chronic headaches and increasing frequency of anxiousness and irritability. She had no personal or family history of hypertension. Laboratory analysis showed elevated catecholamine levels included plasma normetanephrine of 2.8 nmol/L (normal <0.9), metanephrine of 0.9 nmol/L (normal <0.5), 24 hour urine metanephrine 498 mcg/24 hr (normal <180) and 24 hour urine normetanephrine of 1,152 mcg/24 hr (normal <451). Findings were consistent with adrenal pheochromocytoma. She was immediately started on phenoxybenzamine and encouraged to increase fluid intake to expand intravascular volume before surgery. She underwent laparoscopic left partial adrenalectomy fourteen days later. Surgical pathology revealed a 3.0 cm pheochromocytoma in a background of nodular hyperplasia of the medulla, described as an aggressive tumor phenotype based on morphological features. Conclusions It has been estimated that 1.5–14% of adrenal incidentalomas are pheochromocytomas. While only 3% of NF-1 patients have pheochromocytomas, 20–50% of NF-1 patients with concurrent hypertension have underlying chromaffin tumors. This association is significant when compared to the pheochromocytoma incidence of 0.1% in all hypertensive individuals. Interestingly, germline mutations of BRCA-1 associated protein-1 gene have been reported in patients with paragangliomas, therefore it may be plausible to consider interactions between NF-1 and breast cancer BRCA-2 gene mutations, resulting in an unusual and more aggressive pheochromocytoma phenotype, even when detected at an early stage, as in this case. It is also important to recognize and adequately treat pheochromocytoma prior to having surgery to avoid possible intraoperative hypertensive crisis, a concept that was underscored in this particular case when the patient was relatively asymptomatic and entirely normotensive preoperatively.