Background: Pheochromocytoma occurs in nearly 50% of MEN 2A (multiple endocrine neoplasia, type 2A) cases. Many issues related to this tumor are still the subject of debate: the diagnostic management in patients who have had positive genetic study results (RET mutation), variations related to mutation, the best surgical option, and the real relapse rate during long-term follow-up. The aim of this study is to present our experience with this unusual disease, looking for answers to some of these questions.
Patients and methods: Of 169 patients belonging to 19 MEN 2A families, 54 (32%) presented with pheochromocytoma. The following variables have been studied: (1) clinical and diagnostic data [age, mutation, clinical features, results of catecholamines and catabolites in a 24-h urine sample, computerized tomography (CT) scan and iodine-131 meta-iodobenzylguanidine (MIBG) scintigraphy results, and the means of diagnostic, clinical, or genetic screening]; (2) surgical treatment; and (3) follow-up and recurrence. The mean follow-up time was 92.5 months (range: 12-120 months).
Results: The mean age of the 54 patients was 37.9 years (range: 14-71 years); 33 were women. Most (96.3%) mutations were found in exon 11. The most frequent mutations were Cys634Tyr (in 33 cases [61.1%]) and Cys634Arg (in 14 [25.9%]). The diagnosis of pheocromocytoma was made after the diagnosis of MTC in 26 cases (48.2%), simultaneously in 21 (38.9%), and prior in the 7 remaining cases (12.9%). At the time of diagnosis 28 patients (51.8%) were asymptomatic and 26 (48.2%) had clinical features related to pheochromocytoma. In 6 patients (11.1%), the values of catecholamines and catabolites in urine were normal. In the cases with high values, the most useful isolated determination was that of metanephrines (82%), followed by adrenaline (76%). The CT scan did not provide a correct diagnosis in 6 patients with bilateral lesions, and one patient with a bilateral tumor was not diagnosed by MIBG. The combination of CT scan and MIBG diagnosed 100% of cases. The pheochromocytoma was bilateral in 27 cases, with a total number of 81 pathological glands detected. A laparascopic approach was used in 30 cases and a laparotomy in 24. The mean tumor size was 4.5 cm (range: 1-18 cm). Five patients with unilateral resection relapsed (18.5%), and the mean relapse time was 43.2 months (range: 12-120 months). There was a greater frequency of pheochromocytoma in those subjects who had the Cys634Arg mutation (p < 0.03). In addition, the Cys634Arg mutation is more frequent in bilateral cases. There are no prognostic factors for recurrence.
Conclusions: Pheochromocytoma in MEN 2A is related to the type of mutation, which can be early onset and is frequently asymptomatic. Its diagnosis requires catecholamines determinations as well as a CT scan. Correct diagnosis of bilaterality is established by CT and MIBG. Laparoscopic adrenalectomy is the treatment of choice.