Oral Presentation ESA-SRB 2023 in conjunction with ENSA

Performance of genetic testing for phaeochromocytoma & paraganglioma: 15-year experience at a large tertiary referral centre. (#129)

Simon Ryder 1 2 , Emma Duncan 3 , David Pattison 1
  1. Royal Brisbane & Womens Hospital, Queensland Health, Brisbane, QLD, Australia
  2. Logan Hospital, Meadowbrook, QLD, Australia
  3. King's College, London, United Kingdom

Phaeochromocytomas and paragangliomas (PPGL) are highly heritable tumours and germline testing is recommended for all individuals with PPGL. However, traditional clinical approaches may preclude optimal PPGL management. We assessed the use of genetic testing in PPGL management in a tertiary centre with 15 years of access to germline testing.

This retrospective cohort study included 110 probands diagnosed with a first presentation of PPGL between 2005-19. The primary outcome was the proportion of individuals referred for genetic testing within 12 months of diagnosis. Univariate and multivariate analyses were performed, examining genetic testing rates over time and factors potentially influencing the use of genetic testing.

48/110 (44%) individuals diagnosed with PPGL did not undergo genetic testing or counselling. Genetic testing rates improved between 2014-19, compared with two prior five-year tertiles (p=0.009). On univariate analysis, factors associated with genetic testing including endocrinologist involvement, younger age,  a positive family history, a personal history of a tumour associated with a hereditary PPGL syndrome, bilateral PC, and presence of synchronous PPGL. On logistic regression, individuals with endocrinologist involvement were more likely to undertake genetic testing (OR=10.9, 95% CI [3.4, 43.7]) and increasing age was associated with a lower likelihood of genetic testing (p=0.008). Of 54 individuals who underwent germline testing, 15 (28%) were found to have a pathogenic variant. Pathogenic variants were more likely in extra-adrenal (1/4, 25%) or head and neck PGL (11/23, 48%) than in individuals with PC (3/27, 11%, p=0.006). Although there was a suggestive trend, there was no significant difference in the detection of pathogenic variants between older individuals (>50 years) (5/27, 19%) and younger individuals (<50 years) (10/27, 37%, p=0.13).

This study supports the use of genetic testing in all individuals with PPGL but gaps exist in clinical practice. Broader education is needed to optimise use of personalised medicine approaches.

  1. Pacak K, Eisenhofer G, Ahlman H, et al. Pheochromocytoma: recommendations for clinical practice from the First International Symposium. October 2005. Nat Clin Pract Endocrinol Metab. 2007;3(2):92-102.
  2. Lenders JW, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(6):1915-1942.
  3. Ryder, S, Love, A, Duncan, E. and Pattison, D. PET detectives: Molecular imaging for phaeochromocytomas and paragangliomas in the genomics era. Clinical Endocrinology. 2021;95:13-28.