P-635: AT2 receptor stimulation may halt progression of pheochromocytoma

A 32-year old man had a left adrenal pheochromocytoma (pheo) removed in 1984. In 1997 he represented with hypertension and history of recent pheo in a niece. His plasma norepinephrine was elevated 2-fold (1.7 ng/L). A CT scan showed a 1.5 cm adenoma in the right adrenal, but plasma epinephrine was normal, and no hot spots were found on 123I-mIBG scan or selective venous sampling. Blood pressure was controlled by phenoxybenzamine, but there was a progressive increase in plasma norepinephrine to 3.3 ng/L. Over the next two years, the adrenal adenoma also grew in size, but remained negative on mIBG and octreotide scans. Additional therapy with irbesartan was started in 1999 on the theoretical basis that the reflex increase in plasma angiotensin II (AII) levels would stimulate the AT2 receptors on the pheo; activation of these receptors in the PC12 pheo cell line stimulates apoptosis and inhibits proliferation. After 1999, plasma norepinephrine remained stationary, and the adrenal adenoma stopped growing. In 2004, two PET scans were performed, with 18F-FDG, and 18F-FDOPA. The second of these showed an isolated hot-spot, superimposed on the area of the adrenal ‘adenoma’, and the patient awaits laparoscopic right adrenalectomy. We have similarly used high-dose candesartan in another patient to halt progression, over two years, of a carcinoid tumor, measured by CT scanning and 24h urine 5HIAA excretion. Therapy with candesartan has recently commenced in a third patient, with inoperable malignant pheo. We present these case histories in order to provoke discussion and encourage other investigators to observe the influence of angiotensin receptor blockade upon neuroendocrine tumor size and secretion, when surgery is not immediately possible. A randomised controlled trial can follow replication of our favorable reports.