Endocrine Abstracts

Background: Malignant paragangliomas are rare. Predictors of malignant potential include high levels of normetadrenaline and/or dopamine, and the presence of a germline mutation in the succinate dehydrogenase B gene (SDHB). Prognosis is poor and treatment options are limited, with only short-term responses observed after ¹³¹I-MIBG therapy or chemotherapy.

Aim: To report response to the oral tyrosine kinase inhibitor sunitinib.

Case report: A 29-year-old gentleman presented with abdominal pain. Ultrasound showed a peri-adrenal mass, later confirmed as a paraganglioma of the organ of Zuckerkandl based on raised 24 h urinary normetadrenaline and CT confirmation. The tumour was successfully excised and post-operative metanephrines and MRI were normal. Genetic testing demonstrated a heterozygous frame shift mutation in exon 4 of the SDHB gene. Normal whole body MRI and metanephrines were reported at 1 year, but 16 months after surgery he re-presented with back pain. MRI revealed a 10×6 cm sacral mass. Repeat urine collection showed pure dopamine elevation, and repeat ¹²³I-MIBG confirmed poor avidity. Surgical review offered no potential for resection, and chemotherapy was not pursued in view of relatively poor response rates to treatment. Ultrasound showed high vascularity, hence treatment with sunitinib was started. Repeat CT at 6- and 12-months confirmed partial radiological and complete biochemical response to therapy; surgical resection is now being reconsidered.

Conclusions: To our knowledge, this is one of the first cases to confirm a partial response to sunitinib in a metastatic SDHB-related paraganglioma.It illustrates i) that the presence of a germline SDHB mutation, low avidity on ¹²³I-MIBG scintigraphy and dopamine secretion are all features of malignant disease, ii) that tumour surveillance in asymptomatic carriers should occur at least annually, and iii) that sunitinib may offer hope for the treatment of metastatic phaeochromocytoma and paraganglioma, including a possible neoadjuvant role in preparation for surgery.