Poster Presentation ESA-SRB 2023 in conjunction with ENSA

SDHB and the pituitary: a tale beginning with one sibling (#306)

Annabelle Hayes 1 , Venessa Tsang 2 3 , Roderick Clifton-Bligh 2 3
  1. Department of Diabetes and Endocrinology, St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia
  2. Department of Endocrinology, Royal North Shore Hospital , Sydney, NSW, Australia
  3. University of Sydney, Sydney, NSW, Australia

Background: SDHx mutations are estimated to represent 20% of paraganglioma/phaeochromocytoma (PPGL) [1]. Their role in the 3PA syndrome comprising pituitary adenoma, paraganglioma and phaeochromocytoma has been more recently described and remains rare [2].

To date 38 pituitary tumours have been described in patients with confirmed germline SDHA, SDHB, SDHC, SDHD and SDHAF2 mutations [3]. Given the high frequency of pituitary tumours (occurring in up to 1 in 1000), their occurrence in the presence of SDHx mutations does not demonstrate causality. However, links have been established with immunohistochemistry staining, tumour genetic studies and 1H-MRS. SDHx associated pituitary tumours demonstrate aggressive behaviour and prolactinoma subtypes are often resistant to medical therapy [4].

Case: A 29-year-old man was found to carry an SDHB gene mutation via cascade genetic testing in 2015. His father had died secondary to metastatic PPGL. His sister, also an SDHB carrier, had undergone surgical resection of a non-functioning head and neck PPGL.

At diagnosis, urinary metanephrine, normetanephrine and dopamine levels were within normal range. Imaging demonstrated a suspicious mediastinal lesion which required two thoracotomies to resect. The tumour was histologically consistent with a paraganglioma with loss of SDBH immunohistochemical staining.

Routine MRI follow up for PPGL continued spanning from the base of skull to pelvis but did not image the pituitary. New headaches, weight gain and symptomatic hypogonadism led to the diagnosis of 18mm pituitary tumour in 2020 with hyperprolactinaemia. Serum prolactin responded well to dopamine agonist therapy but apoplexy and further tumour growth has prompted surgical intervention.

His sister is also currently being investigated for a pituitary tumour.

Conclusion: SDHx associated pituitary tumours represent a minority of all pituitary tumours but may provide insight into a subset of tumourogenesis with a more aggressive clinical course. Their contribution to the 3PA syndrome is increasingly recognized

  1. 1. Eisenhofer G, Klink B, Richter S, et al. Metabologenomics of Phaeochromocytoma and Paraganglioma: An Integrated Approach for Personalised Biochemical and Genetic Testing. Clin Biochem Rev. 2017;38(2):69-100.
  2. 2. Xekouki P, Brennand A, Whitelaw B, et al. The 3PAs: An Update on the Association of Pheochromocytomas, Paragangliomas, and Pituitary Tumors. Hormone and Metabolic Research. 2019 2019-07-01;51(07):419-436.
  3. 3. Branzoli F, Salgues B, MarjaĊ„ska M, et al. SDHx mutation and pituitary adenoma: can in vivo 1H-MR spectroscopy unravel the link? Endocrine-Related Cancer. 2023 2023-02-01;30(2).
  4. 4. Vasilev V, Daly AF, Zacharieva S, et al. Clinical and Molecular Update on Genetic Causes of Pituitary Adenomas. Hormone and Metabolic Research. 2020 2020-08-01;52(08):553-561.