Oral Presentation Asia Pacific Neuroendocrine Tumour Society 2018

Clinical, Genetic, and Molecular Characterizations of Pheochromocytoma in MEN2 (#4)

Rami Alrezk 1 , Melissa Gonzales 1 , Karel Pacak 1
  1. NIH, Germantown, MD, United States

Introduction:Pheochromocytomas and paragangliomas are neuroendocrine tumors of the adrenal medulla and extra-adrenal paraganglia, respectively. MEN2 is an autosomal dominant genetic condition caused by a mutation in the RET proto-oncogene

Aim: To characterize the clinical features of MEN2 patients, and to evaluate genotype-phenotype correlation 

Methods: We conducted a retrospective analysis of prospectively collected data after screening the protocol for patients with MEN2 and identified 43 patients to include in this study. Statistical analyses performed using descriptive statistics and Chi-Square test for association

Results: The study group consisted of 43 patients with MEN2 associated PHEO, 27 of which were confirmed through genetic testing to have the mutation in the RET proto-oncogene. 51.85% (14/27) of patients with germline RET+ MEN2 mutations showed the change in exon 11. In exon 11, the most frequent DNA changes at 18.52% each (5/27) were in c.1900 from T>C and c.1901 from G>A. No genotype-phenotype association was detected. Average age at diagnosis is 35, bilateral pheochromocytoma was found in 38.9% (14/36), extraadrenal Pheochromocytoma in 30.8%. 18F-DOPA PET/CT had Sensitivity: 90.91%, specificity: 33.33%, PVV: 83.33%, NPV: 50%, while 131I-mIBG scans have Sensitivity: 83.33%, specificity: 100%, PPV: 100%, NPV: 40%. Noradrenergic profile found in 13.51% (5/37) of patients; and adrenergic in 23.33% (7/30) of patients, while mixed biochemical profile was found in only 6% of patients (2/30). 40% (16/40) of patients were reported to have MTC, of which 68.75% (11/16) had metastatic MTC. Using Chi-Square test, DNA sequence was not associated with early diagnosis with X2 =10.9, corresponding with P-Value=0.36. or bilateral adrenal disease with X2 =17.7, corresponding with P-Value=0.08. or extra-adrenal disease with X2 =16.9 with P-Value=0.15

Conclusion: In this study, we present descriptive characterizations of Pheochromocytoma in MEN2. F-Dopa found to be an excellent functional imaging modality for diagnosing Pheo in MEN2. No genotype-phenotype correlation was found

  1. Thosani S, Ayala-Ramirez M, Palmer L, Hu MI, Rich T, Gagel RF, Cote G, Waguespack SG, Habra MA, Jimenez C. The characterization of pheochromocytoma and its impact on overall survival in multiple endocrine neoplasia type 2. J Clin Endocrinol Metab. 2013;98(11):E1813–E1819.
  2. Pacak K, Eisenhofer G, Ilias I. Diagnosis of pheochromocytoma with special emphasis on MEN2 syndrome. Hormones (Athens) 2009;8(2):111–116.