Category: Adrenal Disorders

Monitor: 9

9 - SIMULTANEOUS OCCURRENCE OF SUCCINYL DEHYDROGENASE B MUTATION AND TUMOR PROTEIN P53 MUTATION IN A PATIENT WITH METASTATIC PHEOCHROMOCYTOMA

Saturday, Apr 27
10:00 AM – 10:30 AM

Objective : Pheochromocytomas are catecholamine-secreting neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla. Approximately 10 percent of the pheochromocytomas are malignant as defined by the presence of distant metastases. SDHB mutations are known to cause the development of pheochromocytomas and paragangliomas, which are more likely to be malignant than in other gene mutations. Germline mutations in TP53 occur in Li–Fraumeni syndrome, which is associated with an increased risk of developing various cancers, including adrenocortical carcinomas, at an early age. We describe a case of a metastatic malignant pheochromocytoma who was found to have both SDHB and TP53 mutations occurring together.


Methods : N/A


Results : N/A


Discussion : A 39-year-old male with a 3-year history of hypertension presented to the hospital with neck pain and a non-healing fracture of the cervical spine. MRI of the neck revealed a C3 vertebral body collapse and an underlying C3 lesion. Computed tomography (CT) of the thorax, abdomen, and pelvis showed multiple lesions in the axial and appendicular skeleton, a sternal body mass, bilateral pulmonary nodules, bilateral adrenal masses, and an aortocaval lymph node conglomerate. Serum epinephrine was 200 pg/ml (N 10-200), norepinephrine 28,241 pg/ml (N 80-520), and dopamine 250 pg/ml (N 0-20). He underwent biopsy of the protruding sternal mass which revealed metastatic pheochromocytoma. Genetic testing revealed both SDHB and TP53 mutations. He was started on alpha-, beta- and calcium channel blockers to control hypertension and tachycardia. Two months after the diagnosis, CT of the abdomen and pelvis showed progression of disease, with enlargement of the right adrenal mass as well as the aortocaval LN conglomerate, with mass effect on several surrounding structures. His plasma metanephrines were significantly elevated. He was started on systemic chemotherapy with Cyclophosphamide, Dacarbazine, and Vincristine. He required several antihypertensive medications, including metyrosine, to control his blood pressure and more specifically to prepare for chemotherapy.


Conclusion :

SDHB mutations are known to lead to the development of pheochromocytomas, however, to date, there are scarce and inconsistent data connecting TP53 gene mutation in the pathogenesis of such tumors. To our knowledge, this is the first reported case of these two gene mutations occurring together in the same individual. Our case demonstrates a highly aggressive clinical course of pheochromocytoma and raises the possibility that the simultaneous occurrence of these two mutations modified their clinical expression and the behavior of his tumor.

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Ewa Gniado

Endocrinology Fellow
University of Cincinnati Medical Center
Cincinnati, Ohio

Ewa Gniado, MD, is a second year fellow in the Endocrinology, Diabetes & Metabolism Fellowship Program at University of Cincinnati College of Medicine.

Sona Sharma

Associate Professor of Clinical Medicine
Division of Endocrinology, Diabetes and Metabolism University of Cincinnati College of Medicine

Sona Sharma, MD, is an attending physician in the Division of Endocrinology, Diabetes and Metabolism University of Cincinnati College of Medicine, with a special interest in adrenal gland disorders.

Colin Carracher

Assistant Professor
Division of Endocrinology Department of Internal Medicine UC College of Medicine

Colin Carracher, MD, is an assistant professor in the Internal Medicine Division of Endocrinology at the University of Cincinnati College of Medicine. He has a special interest in diabetes technology and adrenal disorders.