Endocrine Abstracts

Introduction: Germline mutations in succinate dehydrogenase complex (SDHx) are a risk factor for developing Pheochromocytoma (Pheo) and/or Paragangliomas (PGL) (named together PPGL), being responsible for approximately 30% of cases. The precise genotype-phenotype correlations and best management strategies are still uncertain.

Objective: To characterize the clinical features and genotype-phenotype associations in a group of SDHx-mutated PPGL patients.

Methods: Retrospective analysis of all germline SDHx-mutated PPGL cases followed in a reference centre.

Results: Total PPGL patients with SDHx-mutation: 30 (16 female). SDHB-related: 18(60%); SDHD-related: 9(30%); SDHC-related: 3(10%). Mean age at diagnosis: 36,8±15,4 years. Median follow-up: 94,8 months. Twenty nine patients had symptoms at diagnosis. Cathecholamine secretion was detected in 9(30%). Nine cases (30%) were malignant. Anatomical distribution: SDHB: 9 head and neck PGL (HNPGL), 5 Pheo and 5 thoraco-abdominal PGL (TAPGL) cases; SDHD: 9 HNPGL, 1 Pheo and 1 TAPGL cases. All SDHC were single non-metastatic HNPGL. Malignancy: SDHB=44,4%; SDHD=11,1%. Multiple PPGL: SDHB=16,7%; SDHD=55,6%. Family history of SDHx-related PPGL was present in 20%. Deletions in SDHB exon-1 were the most frequent genetic defect. Complete resection was achieved in 7(33,3%) and pre-surgery vascular embolization was performed in 10(47,6%) of HNPGL patients. Radiotherapy was used in 12(40%) patients (mainly unresectable HNPGL) achieving partial response/stabilization. 177Lu-DOTATOC or 131I-MIBG were used in 4. Overall, remission was observed in 33,3%, stable disease in 53% and progression in 13,3% of patients. Related morbidity was observed in 66,6% of patients, and one death occurred.

Conclusion: SDHC and SDHD patients are prone to develop single and multiple HNPGL, respectively, and SDHB patients carry increased risk of malignancy, as suggested in other studies. SDHB patients and HNPGL had the worse prognosis, the former related to malignancy, and the last to cranial nerve deficits, unresectable disease and multimodality interventions. Radiotherapy represented a good alternative in unresectable HNPGL.