Endocrine Abstracts

Paragangliomas are rare neuroendocrine neoplasms that arise from chromaffin tissue commonly located in the adrenal medulla, pre-aortic and paravertebral sympathetic plexus or skull base. About 30% of paragangliomas have a genetic basis. They may be associated with autosomal dominant inheritance of variants in the gene encoding succinate dehydrogenase or may coexist in genetically determined endocrine syndromes. The study aim was to analyse clinical and molecular data of patients with extraadrenal paraganglioma from one clinical center in 2016-2021.

Materials and Methods: In all paraganglioma patients (29 cases), the age of diagnosis, clinical symptoms, location, 24-hour urinary fractionated metanephrines concentration, serum concentration of chromogranin A, the largest dimension of the lesion, and distant metastases were evaluated. Molecular analysis for pathogenic variants in SDHB, SDHC, SDHD, RET, MEN1, MAX, and VHL genes was performed using next-generation sequencing methods.

Results: 22 women and 7 men were enrolled. Patients were divided into four subgroups according to location, head and neck - 7 patients, thorax - 3 patients, abdomen - 15 patients, and pelvis - 4 patients. The median age of diagnosis for each group was: head and neck 62 years (range 43 - 70), chest 45 years (range 34 - 52), abdomen 58 years (range 18 - 73), pelvis 45.5 years (range 20 - 72). The most common symptom was hypertension, affecting 93.1% of the patients. Tachycardia was present in 27.6% of the study group. The study showed the highest urinary fractionated normetanephrine concentration in patients with paragangliomas with pelvic location (P=0.016)–median 6134.1 µg/24 h (range 1053.8 - 12650.9) [ref. range 88.0 - 440.0]. There was no significant difference in serum concentration of chromogranin A between groups. Molecular alterations within the genes analysed were found in 5 patients: 3 pathogenic variants within the SDHD gene were identified, 1 variant of uncertain significance (VUS) in SDHD and 1 VUS in SDHB, respectively. Molecular alterations were observed in 71.4% of patients with paragangliomas with head and neck localization and were not identified at other locations. Distant metastases were found in 14.3% of the patients in paragangliomas of the head and neck region, 33.3% of the thorax, 6.7% of the abdomen, and 25.0% of the pelvis.

Conclusions: The pelvic location of the paraganglioma was associated with a statistically higher urinary fractionated normetanephrine concentration. Pathogenic variants within the genes analysed found in the study group involved patients with localization in the head and neck region.