Malignant Pheochromocytoma: Chromaffin Granule Transmitters and Response to Treatment

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 36; no. 6; pp. 1045 - 1052
• Main Authors: Rao, Fangwen, Keiser, Harry R., O’Connor, Daniel T.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.12.2000; Hagerstown, MD Lippincott
• Subjects: Adolescent; Adrenal Gland Neoplasms - blood; Adrenal Gland Neoplasms - diagnosis; Adult; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - blood; Chemotherapy; Chromaffin Granules - metabolism; Chromogranin A; Chromogranins - blood; Female; Humans; Male; Medical sciences; Middle Aged; Outcome Assessment (Health Care); Pharmacology. Drug treatments; Pheochromocytoma - blood; Pheochromocytoma - diagnosis; Prognosis; Endocrinopathy; Epinephrine; Human; Pheochromocytoma; Prognosis; Catecholamine; Vincristine; Secretory tumor; Dacarbazine; Alkylating agent; Alkaloid; Chemotherapy; Cyclophosphamide; Oxazaphosphinane derivatives; Surgery; Nitrogen mustard; Norepinephrine; Combined treatment; Diagnosis; Antimitotic
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/01.HYP.36.6.1045

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 criteriaresponders (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.