Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours that
originate from chromaffin cells and occur in the adrenal medulla and in the sympathetic
or parasympathetic ganglia. Nearly 70% of PPGLs result from germline or somatic mutations
in a single driver gene. The aim of this study was to characterize the genetic background
and clinical characteristics related to genetic profile of patients with PPGLs from
Romania. We retrospectively retrieved data of 125 patients consecutively registered,
diagnosed with PPGLs in a tertiary referral center of endocrinology from Romania,
between 1976 and 2022. We identified 88 (70.4%) women, and 37 (29.6%) men, with a
mean age at diagnosis of 48.5 +/- 15 years. From these 125 patients, 80 (64%) were
submitted to the genomic study; 35% (n = 28) had a germline mutation (20 RET, 3 VHL,
1 SDHB, 1 NF1, 1 SDHD, 1 FANCA, 1 CASR) while 65% (n = 52) presented sporadic disease.
Patients with hereditary disease had significantly lower age at diagnosis comparing
to sporadic cases (37 +/- 15 vs. 49.9 +/- 12.2 years, p = 0.001). Bilateral tumors
developed in twelve patients from the hereditary group. Metastatic disease was described
in 4 out of 80 patients (2 of them with hereditary disease). Patients from sporadic
group tended to have a right lateralisation of the tumour compared to hereditary cases,
where the tumour was more often left sided. RET pathogenic variant (p.Cys634Trp) associated
with MEN2A syndrome was the most prevalent in Romanian population with PPGLs and could
be considered as a founder effect. Patients with hereditary disease are diagnosed
at a younger age and develop bilateral tumors more frequently compared to sporadic
cases.
