[I]Metaiodobenzylguanidine and [In]Octreotide Uptake in Benign and Malignant Pheochromocytomas*

Selecting the appropriate approach for resection and follow-up of pheochromocytomas (PCCs) is highly dependent upon reliable localization and exclusion of multifocal, bilateral, or metastatic disease. Metaiodobenzylguanidine (MIBG) scintigraphy was developed for functional localization of catecholamine-secreting tissues. Somatostatin receptor imaging (SRI) has a high sensitivity for localizing head and neck paragangliomas, but studies of intraabdominal PCCs are rare. In this study we review our experience of [I]MIBG and SRI, performed since 1983 and 1989, respectively, in the work-up of primary and recurrent PCCs. Scintigraphic results were correlated with catecholamine secretion, size and site, malignancy, associated tumor syndromes, and morphological features. [I]MIBG scans were performed in a total of 75 patients, in 70 cases before resection of primary PCCs and in 5 cases because of recurrent disease. Ninety-one PCCs were resected. The overall detection rates were 83.3% and 89.8% for PCCs larger than 1.0 cm. Multifocal disease was detected in 4 patients with [I]MIBG. [I]MIBG uptake correlated with greater size of PCC (r 5 0.33; P 5 0.008) and greater concentration of plasma epinephrine (r 5 0.32; P 5 0.006). [I]MIBG-negative PCCs (n 5 14) had significantly (P 5 0.01) smaller diameters than []MIBG-positive tumors. Furthermore, [I]MIBG uptake was significantly higher in unilateral (P 5 0.02), benign (P 5 0.02), sporadic (P 5 0.02), intraadrenal (P 5 0.02), and capsular invasive (P 5 0.03) PCCs than in bilateral, malignant, MEN2A/2B-related, extraadrenal, and noninvasive PCCs, respectively. The detection rate of SRI was only 25% (8 of 32) for primary benign PCCs. In 14 patients metastases occurred, which were effectively visualized with [I]MIBG in 8 of 14 cases. SRI was able to detect metastases in 7 of 8 cases, including 3 [I]MIBG-negative metastatic cases. In addition, [I]MIBG and SRI detected 2 recurrences. In conclusion, [I]MIBG uptake is correlated with the size, epinephrine production, and site of PCCs. Its role in bilateral and MEN2A/2B-related PCCs seems limited. In cases of recurrent elevation of catecholamines, localization of metastases and/or recurrence should be attempted with [I]MIBG scintigraphy. In suspicious metastatic PCCs, SRI might be considered to supplement [I]MIBG scintigraphy. (J Clin Endocrinol Metab 86: 685–693, 2001) D THE LAST 2 decades, management of pheochromocytomas (PCCs), catecholamine-secreting tumors arising from chromaffin cells of the sympatho-adrenal system, has substantially changed. The traditional concept of proper PCC surgery (1, 2), involving an extensive exploratory laparotomy to exclude occult foci in the contralateral adrenal gland or the retroperitoneal space, has gradually become a matter of debate (3, 4). With the introduction of less invasive procedures for resection of PCCs, such as unilateral approaches through a flank incision (3, 5), laparoscopy (6, 7), or retroperitoneoscopy (8, 9), accurate preoperative localization has become more important. Selecting the appropriate surgical approach, however, is highly dependent upon reliable exclusion of multifocal, bilateral, or metastatic disease. PCCs can occur in association with several hereditary tumor syndromes. Gene mutations responsible for Von HippelLindau disease (VHL) (10) and multiple endocrine neoplasia type 2A/2B (MEN2A/2B) (11, 12) can be identified, and detection of carriers of these syndromes has become possible. Improvements in detection techniques for catecholamines and emphasis on screening for hereditary cases have increased early stage diagnosis of PCCs and its preceding medullary hyperplasia. The radiopharmaceutical agent [I]metaiodobenzylguanidine ([I]MIBG), a guanethidine analog that is stored in sympatho-adrenal tissues, was developed for adrenal scintigraphy (13, 14). Recently, in a large European multicenter study, the sensitivity of [I]MIBG (n 5 160) to detect PCCs was 81% (4). Improvements in scintigraphic procedures may reduce false negative results. Labeling MIBG with I instead of I yielded superior imaging quality (15–17). However, 12.5% of PCCs still remained undetected in the largest published series to date (n 5 24 PCCs in 120 patients) (18). One could speculate that structural and functional differences in PCCs are responsible for diminished [I]MIBG uptake in different tumor types. However, potential clinical and morphological features that could influence [I]MIBG uptake in PCCs have Received May 5, 2000. Revision received July 26, 2000. Rerevision received October 9, 2000. Accepted November 2, 2000. Address all correspondence and requests for reprints to: Erwin van der Harst, M.D., Department of Surgery, Erasmus University Hospital, Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail: [email protected]. * This work was supported by a grant from the Jan Dekkerstichting en Dr Ludgardina Bouwmanstichting (Muiderberg, The Netherlands) and Stichting De Drie Lichten (Hilversum, The Netherlands). 0021-972X/01/$03.00/0 Vol. 86, No. 2 The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2001 by The Endocrine Society