Poster Presentation ESA-SRB-APEG-NZSE 2022

SDHB mutation presenting with multifocal paraganglioma in a young woman (#331)

David Je 1 , Joanne Campbell 1
  1. Endocrinology, Launceston General Hospital, Launceston, Tasmania, Australia

Background:

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours (NET) arising from adrenal medulla chromaffin cells and extramedullary neural crest cells1. We report the case of a woman with multifocal paraganglioma due to SDHB mutation, and her carrier daughter found to have an Organ of Zuckerkandl paraganglioma during long-term screening.

 

Case history:

A 34 year old female with no significant medical history presented with one year history of headaches, tinnitus, syncope, vomiting and unintentional weight loss. Her father had a neck paraganglioma excised 7 years ago. Para-aortic and bladder masses were found on computed tomography and biopsies confirmed paraganglioma. Magnetic resonance imaging showed a 13x16x35mm base of neck tumour. Normetadrenaline was elevated (11,000pmol/L; reference <900). All three lesions were MIBG avid. Partial cystectomy and excision of the para-aortic lesion confirmed NET on histology. Skull base lesion was treated with stereotactic radiotherapy.

 

Results:

Genetic testing confirmed a diagnosis of SDHB mutation related multifocal paraganglioma. Yearly plasma metanephrines were negative and periodic positron emission tomography (PET) showed diminishing activity in the base of skull lesion. SDHB mutation was found in her sister (asymptomatic), nephew (who had paraganglioma surgically removed), son and daughter (age 9 and 11 years). Annual plasma metanephrine screening in the daughter became elevated (9730pmol/L; reference <550) at age 19 years. A PET avid Organ of Zukerkandl mass (55x45mm) was removed laparoscopically, confirming paraganglioma.  

 

Conclusion:

Up to 40% of PPGL arise from germline mutations and approximately 20% of PPGL patients carry a germline mutation in an SDHx gene2. The first international consensus (2021) on screening and follow-up of asymptomatic SDHx mutation carriers recommended that children and adults should be regularly screened clinically, biochemically and with imaging according to the proposed protocol2. Surveillance improves outcomes for SDHB mutation carriers, with evidence for smaller tumours, reduced risk of metastases and lower mortality3.

  1. Cerqueira, A., Seco, T., Costa, A., Tavares, M., & Cotter, J. (2020). Pheochromocytoma and Paraganglioma: A Review of Diagnosis, Management and Treatment of Rare Causes of Hypertension. Cureus, 12(5), e7969. https://doi.org/10.7759/cureus.7969
  2. Amar, L., Pacak, K., Steichen, O., Akker, S. A., Aylwin, S., Baudin, E., Buffet, A., Burnichon, N., Clifton-Bligh, R. J., Dahia, P., Fassnacht, M., Grossman, A. B., Herman, P., Hicks, R. J., Januszewicz, A., Jimenez, C., Kunst, H., Lewis, D., Mannelli, M., Naruse, M., … Lussey-Lepoutre, C. (2021). International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers. Nature reviews. Endocrinology, 17(7), 435–444. https://doi.org/10.1038/s41574-021-00492-3
  3. Davidoff, D. F., Benn, D. E., Field, M., Crook, A., Robinson, B. G., Tucker, K., De Abreu Lourenco, R., Burgess, J. R., & Clifton-Bligh, R. J. (2022). Surveillance Improves Outcomes for Carriers of SDHB Pathogenic Variants: A Multicenter Study. The Journal of clinical endocrinology and metabolism, 107(5), e1907–e1916. https://doi.org/10.1210/clinem/dgac019