Endocrine Abstracts

Introduction: It is known that phaeochromocytoma penetrance in MEN2A syndrome steadily increases with age. In general, MEN2A related pheochromocytomas (PHEOs) have a benign evolution; however, some of them have an aggressive behaviour despite the same genetic background as the benign forms.

Aim: To evaluate potential factors that may influence PHEO penetrance and tumor dimensions (age at diagnosis, MTC aggressiveness or genetic status).

Material and Methods: Patients with PHEOs in MEN2A syndrome were retrospectively retrieved from the database of a Tertiary Reference Centre from Romania. Genetic status, age at diagnosis, tumor dimensions, localisation, and the presence of other syndromic components were collected.

Results: Twenty-two patients from fifteen families were included in this study. Fourteen patients (63.6%) were women and 8 (36.4%) were men. Mean age for diagnosis was 36.6±2.8 years. Mean tumour diameter was 46.4±3.5 mm. Eighteen patients (12 families) had a pathogenic variant of exon 11 [p.Cys634Trp (55.5%), p.Cys634Arg/Tyr (22.2%/16.6%); p.Asp631Tyr (5.5%)] while 4 ( 3 families) of them had a pathogenic variant (PV) of exon 10 [p.Cys618Arg (75%), and p.Cys618Tyr (25%)]. Mean age in families with exon 11 was lower (35.6±2.9 years) than in exon 10 (41±9.2 years). Mean tumor diameter was non-significantly higher in exon 11 PV than in exon 10 (48±4 vs 38±5.8). In 3 patients PHEO was the first manifestation of the syndrome all with PV of exon 11, while in 4 CMT was the first manifestation of the disease. In other 15 patients CMT and PHEO were simultaneously diagnosed. Patients with exon 10 had a more aggressive form of CMT than those with exon 11. Regarding PHEO localisation, 31.8% (n=7) were right sided, 27.3% (n=6) were left sided, and 40.9% (n=9) presented bilateral PHEOs, four synchronous and five metachronous. Patients with bilateral disease tended to have a familial lateralisation pattern. Regarding tumor natural evolution, maximal tumor diameter did not correlate to age of diagnosis in any of the families.

Conclusion: Exon 11 mutation is the most frequently reported in MEN2A related PHEOs. p.Cys634Trp is the most pathogenic variant of exon 11, while in exon 10 was p.Cys618Arg. Patients with mutation in exon 11 tended to develop PHEOs in younger age than those with mutation in exon 10, and to have more rapidly evolving tumors. MTC was more aggressive in patients with exon 10 mutations. PHEOs in MEN2A tended to have a familial lateralisation pattern.