Endocrine Abstracts

Context: Pheochromocytoma and Paragangliomas (PPGL) are rare neuroendocrine tumors with a strong genetic background. In this report, our objectives are to understand the molecular genetics and the genotype/phenotype correlation of these tumors in the highly consanguineous population of Saudi Arabia.

Patients and methods: We studied 88 patients with PPGL and no known family history of these tumors. We extracted DNA from peripheral leucocytes and performed PCR-based Sanger sequencing of RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, MAX and/or TMEM127. The order in which these genes were selected was based on the clinical phenotype following the Endocrine Society guidelines. When no genetic alteration was found, whole exome sequencing was performed. The clinical phenotype was correlated with the underlying mutations.

Results: Of the 88 patients included in this report, 30 (34%) were males, 58 (66%) were females with a median age of 43.5 years (interquartile range 26-53.7). No mutation was found in 42 patients (47.7%). The other 46 patients (52.3%) had an underlying PPGL-predisposing genetic mutations. The most commonly mutated gene was SDHB (11/88), followed by SDHD (8/88), RET (6/88) and SDHC (3/88). There was a tendency for more locally invasive and metastatic PPGL in the patients with underlying genetic alterations, especially SDHB mutations, but this did not reach statistical significance. Although the majority of patients achieved cure (60.5%), 26 patients (29.5%) had persistent/recurrent disease. There was no difference in the final outcome between those with underlying genetic mutations and those without mutations.

Conclusions: In this study, 52.6% of PPGL carry underlying genetic mutations. SDHB is the most commonly mutated and associated with higher risk of locally invasive and distant metastases. There is tendency towards locally invasive and distant metastases in those carrying underling mutations but the final outcome was similar between those with and those without underlying mutations.