(Hypertension. 2000;36:1045.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Malignant Pheochromocytoma
Chromaffin Granule Transmitters and Response to Treatment
From the Department of Medicine and Center for Molecular Genetics (F.R., D.T.O.), University of California, San Diego; the National Heart, Lung, and Blood Institute (H.R.K.), Bethesda, Md; and the VA San Diego Healthcare System (F.R., D.T.O.), San Diego, Calif.
Correspondence to Daniel T. O’Connor, MD, Department of Medicine and Center for Molecular Genetics (9111H), University of California, San Diego, 3350 La Jolla Village Dr, San Diego, CA 92161. E-mail doconnor{at}ucsd.edu
Abstract—Chromaffin granule transmitters such as chromogranin A and catecholamines have been used in the diagnosis of pheochromocytoma, but the diagnostic and prognostic value of chromogranin A have not been explored in malignant pheochromocytoma. We evaluated these transmitters in patients with pheochromocytoma (n=27), both benign (n=13) and malignant (n=14). Patients with benign pheochromocytoma were studied before and after surgical excision (n=6), whereas patients with malignant pheochromocytoma were evaluated before and after combination chemotherapy with regular cycles of cyclophosphamide/dacarbazine/vincristine (nonrandomized trial in n=9). During treatment, patient responses to chemotherapy were divided according to anatomic and clinical criteria: responders (n=5) versus nonresponders (n=4). Plasma chromogranin A rose progressively (P<0.0001) from control subjects (48.0±3.0 ng/mL) to benign pheochromocytoma (188±40.5 ng/mL) to malignant pheochromocytoma (2932±960 ng/mL). Parallel changes were seen for plasma norepinephrine (P<0.0001), though plasma epinephrine was actually lower in malignant than benign pheochromocytoma (P=0.0182). In bivariate analyses, chromogranin A, norepinephrine, and epinephrine discriminated between pheochromocytoma and control subjects (all P<0.0001), whereas in a multivariate analyses, norepinephrine was the best discriminator (P=0.011). Chromogranin A was significantly different in benign versus malignant pheochromocytoma on both bivariate (P=0.0003) and multivariate (P=0.011) analyses. After excision of benign pheochromocytoma, chromogranin A (P=0.028), norepinephrine (P=0.047), and epinephrine (P=0.037) all fell to values near normal. During chemotherapy of malignant pheochromocytoma (n=9), plasma chromogranin A (P=0.047) and norepinephrine (P=0.02) fell but not epinephrine. In 5 responders to chemotherapy, there were significant declines in chromogranin A (P=0.03) and norepinephrine (P=0.03) but not epinephrine; in 4 nonresponders, none of the transmitters changed. Plasma chromogranin A varied longitudinally with tumor response and relapse. We conclude that plasma chromogranin A is an effective tool in the diagnosis of pheochromocytoma, and markedly elevated chromogranin A may point to malignant pheochromocytoma. During chemotherapy of malignant pheochromocytoma, chromogranin A can be used to gauge tumor response and relapse.
Key Words: plasma • chromogranins • norepinephrine • epinephrine
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