Multiple Endocrine Neoplasia type 2A (MEN-2a) is a rare disease associated with tumors of endocrine organs. Presentation most commonly is with medullary thyroid cancer and infrequently with other complaints. Pituitary adenoma has been seen coincidentally with this disease very rarely. Presented is a case of coincident MEN-2a with a symptomatic pituitary adenoma and an asymptomatic pheochromocytoma. A brief review is also provided.
Pheochromocytoma is a physiologically active tumor of the adrenal gland that occurs in isolation or in association with Multiple Endocrine Neoplasia type 2a (MEN-2a). Rarely is pheochromocytoma the presenting disease process in MEN-2a and even more rarely is it associated with pituitary macroadenoma. We present a case of MEN-2a presenting in a highly unusual manner that brings into question the need for more extensive workup prior to treatment for pheochromocytoma.
A 62-year-old white male presented with right abdominal and flank pain of gradual onset over several months. He had a history of hypertension controlled with atenolol only and had no history of paroxysmal hypertensive episodes. Workup revealed a 13 cm right adrenal mass by CT (Figure
CT of the abdomen showing an adrenal mass adherent to the IVC.
T2-Weighted MRI of the abdomen demonstrating high-attenuation characteristic of pheochromocytoma.
Open adrenalectomy was complicated with intraoperative hypertensive crisis, difficult exposure due to the size of the tumor, and ultimately right nephrectomy in order to facilitate removal of the tumor. Adherence to the inferior vena cava (IVC) necessitated partial resection of the IVC with primary closure. Once the tumor vasculature was isolated, hypotension ensued requiring pressor support. The patient remained intubated postoperatively and was extubated on postoperative day one. Later the same day, the patient complained of headache and left sided visual field loss. Exam confirmed left lateral hemianopsia. These findings were not present preoperatively based on history and physical exam.
MRI of the head was performed to evaluate visual field defect and a 1 cm pituitary macroadenoma was found compressing the optic chiasm (Figure
MRI of the brain showing pituitary macroadenoma compressing the optic chiasm.
Pathology of the adrenal specimen demonstrated pheochromocytoma with focal capsular penetration but tumor-free margins (Figure
Multiple Endocrine Neoplasia syndrome type 2a (MEN-2a) is an autosomal dominant hereditary syndrome caused by mutation of the tyrosine kinase RET proto-oncogene on chromosome 10q11.2. The hallmark of the disease is medullary thyroid cancer (MTC) which occurs in nearly 100% of cases [
Treatment of MTC is typically total thyroidectomy with bilateral neck dissection for lymphadenectomy. Screening for pheochromocytoma is performed yearly with urinary metanephrine assessment. Unilateral pheochromocytoma is commonly amenable to laparoscopic resection [
Surgery for large pheochromocytoma can be a difficult and dangerous task. Small series have shown little difference in complication rate between laparoscopic and open approach, however the risk of open conversion due to intraoperative bleeding increases for tumors greater than 6 cm [
Pheochromocytoma are most commonly sporadic, however 10–23% are associated with a familial syndrome. Workup with CT and/or MRI is recommended for staging and localization purposes. Scintigraphy using 131I-MIBG (metaiodobenzylguanidine) is useful to determine the location of occult lesions when CT or MRI are unproductive. There are currently no formal recommendations for workup of associated malignancies when there is no family history. Only 5% of patients with pheochromocytoma present without symptoms, however in patients with MEN-2a, 50% will be asymptomatic [
The RET proto-oncogene is a 21 exon gene encoding a tyrosine kinase receptor that is involved in transduction of growth and differentiation signals in developing tissues—particularly those of neural crest origin. RET is strongly associated with MEN-2a and patients with a RET mutation have a nearly 100% chance of developing MTC. Different point mutations in this gene are associated with varying penetrance of pheochromocytoma and hyperparathyroidism, lower age at onset of disease, and likelihood of metastatic disease at presentation. The mutation in the presented patient,
Pituitary adenoma is commonly associated with Multiple Endocrine Neoplasia type 1 (MEN 1), however is not associated with MEN-2a. In a recent review, Breckenridge et al. cited 25 cases of patients with pheochromocytoma and pituitary macroadenoma from 1964 to 2003 [
More recently, attention has been given to the entity of familial isolated pituitary adenoma (FIPA). Approximately 5% of pituitary adenomas are hereditary in nature but not associated with MEN 1 or Carney complex [
Overlap of pituitary adenoma with MEN-2a is a rare occurrence and it is unknown to be either sporadic or in association with another syndrome. An interplay between RET proto-oncogene and familial isolated pituitary adenoma may be involved. Asymptomatic pheochromocytoma has a high association with familial syndrome and may warrant further scrutiny. This case represents a truly unique presentation of this very rare phenomenon.