Poster Presentation ESA-SRB Conference 2015

Characteristics, Diagnoses and Clinical and Genetic Outcomes of Patient Population Attending a Multidisciplinary Familial Endocrine Neoplasia Clinic (#245)

Emma Scott 1 , Lyndal Tacon 1 2 , Michael Field 3 , Ashley Crook 3 , Diana Benn 3 , Roderick Clifton-Bligh 1 2
  1. Department of Endocrinology, Royal North Shore Hospital, Sydney
  2. Kolling Institute of Medical Research, University of Sydney, Sydney
  3. Department of Cancer Genetics, Royal North Shore Hospital, Sydney

BACKGROUND
Heritable endocrine neoplasias include parathyroid and pituitary adenomas, phaeochromocytoma, paraganglioma and medullary thyroid cancer. Causative genes include RET, MEN1, NF1, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127 and MAX. As there are specific management guidelines for gene carriers2,3,4, appropriate screening of individuals is necessary. The Multidisciplinary Familial Endocrine Genetics Clinic was created to screen and manage affected patients.

METHODS
A retrospective audit of medical records was undertaken of all patients who had been referred to the Royal North Shore Hospital Multidisciplinary Familial Endocrine Neoplasia Clinic between April 2013 and May 2015. Patient characteristics and clinical and genetic diagnoses were assessed.

RESULTS
Sixty-eight new patients were referred, 21 (31%) male and 47 (69%) female. Age ranged between 12 to 83 years. The geographic referral area was predominantly across New South Wales, but also from the ACT and Queensland. Referral reasons included pre-existing paraganglioma (8, 11.7%) and phaeochromocytoma (7, 10.2%), affected family members (17, 25%), neuroendocrine tumours (4, 5.8%), medullary thyroid cancer (3, 4.4%), and adrenocortical cancer (3, 4.4%). Eleven asymptomatic individuals with an affected family member were diagnosed with a genetic mutation, (4 in SDHA, 6 in SDHB, one in SDHC). Genetic mutations in patients with paraganglioma and phaeochromocytoma include SDHA (n=3), SDHC (n=1), SDHD (n=2), NF1 (n=1), and pending (n=7) results. Genetic screening of four individuals with neuroendocrine tumours found one MEN1 gene deletion.

DISCUSSION
The spectrum of genetic mutations found in our audit are comparable to other studies: for instance, with SDH mutations accounting for 11%, and NF1 2% of the susceptibility genes in phaeochromocytoma and paraganglioma1. This clinic has facilitated identifying gene mutation carriers, who are being screened for phenotypic features, and this may reduce morbidity and mortality that would otherwise accompany delayed diagnosis.

  1. Gimenez-Roqueplo AP, Dahia PL, Robledo M. Update in the genetics of paraganglioma and pheochromocytoma and hereditary syndromes.Hormone & Metabolic Research 2012; 44:328-333.
  2. Gimenez-Roqueplo AP1, Caumont-Prim A, Houzard C, Hignette C, Hernigou A, Halimi P, Niccoli P, Leboulleux S, Amar L, Borson-Chazot F, Cardot-Bauters C, Delemer B, Chabolle F, Coupier I, Libé R, Peitzsch M, Peyrard S, Tenenbaum F, Plouin PF, Chatellier G, Rohmer V. Imaging work-up for screening of paraganglioma and pheochromocytoma in SDHx mutation carriers: a multicenter prospective study from the PGL.EVA Investigators. J Clin Endocrinol Metab. 2013;98(1):E162-73
  3. Karagiannis, A., Mikhailidis, D.P., Athyros, V.G., Harsoulis, F. Phaeochromocytoma: an update on genetics and management. Endocrine-Related Cancer 2007; 14: 935-956.
  4. Brandi, M.L., Gagel, R.F., Angeli, A., Bilezikian, J.P., Beck-Peccoz, P., Bordi, C., Conte-Devolx, B., Lombari, G., Mannelli, M., Pacini, F., Ponder, B.A.J., Raue, F., Skogseid, B., Tamburrano, G., Thakker, R.V., Thompson, N.W., Tomassetti, P., Tonelli, F., Wells, S.A., Marx, S.J. Guidelines for diagnosis and therapy of MEN Type 1 and Type 2. J Clin Endocrinol Metab. 2001; 86:5568-5671.