A patient with a large recurrent pheochromocytoma demonstrating the pitfalls of diagnosis


Background. A 59-year-old man presented for a follow-up, 6 years after surgery for a large pheochromocytoma. He had suffered from diabetes mellitus, hypertension and abdominal pain in the right flank region. Previous postoperative follow-up did not reveal tumor recurrence.

Investigation. Measurement of plasma free metanephrine and normetanephrine by high-performance liquid chromatography and radioimmunoassay; 123I-metaiodobenzylguanidine (MIBG) scintigraphy; hybrid 123I-MIBG single-photon emission CT (SPECT)–CT; MRI; testing for plasma norepinephrine and epinephrine; intraoperative ultrasonography; histological staining for chromogranin A and synaptophysin; and postoperative 18F-dihydroxyphenylalanine (DOPA) PET scan.

Diagnosis. Recurrent pheochromocytoma.

Management. Laparotomy with tumor resection. Reduction of antihypertensive medications. Further follow-up by MRI, hybrid 123I-MIBG SPECT–CT and testing for plasma catecholamines and free metanephrines.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: 123I-metaiodobenzylguanidine scintigraphy in the case patient.
Figure 2: 123I-metaiodobenzylguanidine (MIBG) scintigraphy with single-photon emission CT (SPECT)–CT in the case patient.
Figure 3
Figure 4: Histology and immunhistochemistry of tissue samples taken at the second surgery of the case patient.


  1. 1

    Lenders, J. W., Eisenhofer, G., Mannelli, M. & Pacak, K. Phaeochromocytoma. Lancet 366, 665–675 (2005).

  2. 2

    Thompson, L. D. Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases. Am. J. Surg. Pathol. 26, 551–566 (2002).

  3. 3

    Eisenhofer, G. et al. Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location by use of plasma free metanephrines. Clin. Chem. 51, 735–744 (2005).

  4. 4

    Eisenhofer, G. et al. Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results. J. Clin. Endocrinol. Metab. 88, 2656–2666 (2003).

  5. 5

    Thouënnon, E. et al. Identification of potential gene markers and insights into the pathophysiology of pheochromocytoma malignancy. J. Clin. Endocrinol. Metab. 92, 4865–4872 (2007).

  6. 6

    Sawka, A. M. et al. A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma. BMC Endocr. Disord. 4, 2 (2004).

  7. 7

    Pacak, K. et al. A “pheo” lurks: novel approaches for locating occult pheochromocytoma. J. Clin. Endocrinol. Metab. 86, 3641–3646 (2001).

  8. 8

    Peaston, R. T., Graham, K. S., Chambers, E., van der Molen, J. C. & Ball, S. Performance of plasma free metanephrines measured by liquid chromatography-tandem mass spectrometry in the diagnosis of pheochromocytoma. Clin. Chim. Acta 411, 546–552 (2010).

  9. 9

    Unger, N. et al. Diagnostic value of various biochemical parameters for the diagnosis of pheochromocytoma in patients with adrenal mass. Eur. J. Endocrinol. 154, 409–417 (2006).

  10. 10

    Pillai, D. & Callen, S. Pilot quality assurance programme for plasma metanephrines. Ann. Clin. Biochem. 47 (Pt 2), 137–142 (2010).

  11. 11

    Algeciras-Schimnich, A., Preissner, C. M., Young, W. F. Jr, Singh, R. J. & Grebe, S. K. Plasma chromogranin A or urine fractionated metanephrines follow-up testing improves the diagnostic accuracy of plasma fractionated metanephrines for pheochromocytoma. J. Clin. Endocrinol. Metab. 93, 91–95 (2008).

  12. 12

    Qin, Y., Buddavarapu, K. & Dahia, P. L. Pheochromocytomas: from genetic diversity to new paradigms. Horm. Metab. Res. 41, 664–671 (2009).

  13. 13

    Majumdar, S. et al. Compound heterozygous mutation with a novel splice donor region DNA sequence variant in the succinate dehydrogenase subunit B gene in malignant paraganglioma. Pediatr. Blood Cancer 54, 473–475 (2010).

  14. 14

    Bausch, B., Borozdin, W. & Neumann, H. P. Clinical and genetic characteristics of patients with neurofibromatosis type 1 and pheochromocytoma. N. Engl. J. Med. 354, 2729–2731 (2006).

  15. 15

    Ricketts, C. J. et al. Tumor risks and genotype–phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD. Hum. Mutat. 31, 41–51 (2010).

  16. 16

    Lloyd, R. V. Adrenal cortical tumors, pheochromocytomas and paragangliomas. Mod. Pathol. 24 (Suppl. 2), S58–S65 (2011).

  17. 17

    Morimoto, R. et al. Immunohistochemistry of a proliferation marker Ki67/MIB1 in adrenocortical carcinomas: Ki67/MIB1 labeling index is a predictor for recurrence of adrenocortical carcinomas. Endocr. J. 55, 49–55 (2008).

  18. 18

    Fiebrich, H. B. et al. 6-[F-18]Fluoro-L-dihydroxyphenylalanine positron emission tomography is superior to conventional imaging with 123I-metaiodobenzylguanidine scintigraphy, computer tomography, and magnetic resonance imaging in localizing tumors causing catecholamine excess. J. Clin. Endocrinol. Metab. 94, 3922–3930 (2009).

  19. 19

    Bhatia, K. S. et al. Reznek RH. 123I-metaiodobenzylguanidine (MIBG) scintigraphy for the detection of adrenal and extra-adrenal phaeochromocytomas: CT and MRI correlation. Clin. Endocrinol. (Oxf.) 69, 181–188 (2008).

  20. 20

    Jacobson, A. F., Deng, H., Lombard, J., Lessig, H. J. & Black, R. R. 123I-meta-iodobenzylguanidine scintigraphy for the detection of neuroblastoma and pheochromocytoma: results of a meta-analysis. J. Clin. Endocrinol. Metab. 95, 2596–2606 (2010).

  21. 21

    Timmers, H. J. et al. Comparison of 18F-fluoro-L-DOPA, 18F-fluoro-deoxyglucose, and 18F-fluorodopamine PET and 123I-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma. J. Clin. Endocrinol. Metab. 94, 4757–4767 (2009).

  22. 22

    Havekes, B. et al. New imaging approaches to phaeochromocytomas and paragangliomas. Clin. Endocrinol. (Oxf.) 72, 137–145 (2010).

  23. 23

    Huang, H. et al. Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine: recommendation from a 22-year follow-up of 18 patients. Cancer 113, 2020–2028 (2008).

  24. 24

    Amar, L. et al. Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. J. Clin. Endocrinol. Metab. 92, 3822–3828 (2007).

  25. 25

    Gao, B. et al. Development and validation of pheochromocytoma of the adrenal gland scaled score for predicting malignant pheochromocytomas. Urology 68, 282–286 (2006).

  26. 26

    Gao, B. et al. A logistic regression model for predicting malignant pheochromocytomas. J. Cancer Res. Clin. Oncol. 134, 631–634 (2008).

  27. 27

    Shen, W. T., Sturgeon, C., Clark, O. H., Duh, Q. Y. & Kebebew, E. Should pheochromocytoma size influence surgical approach? A comparison of 90 malignant and 60 benign pheochromocytomas. Surgery 136, 1129–1137 (2004).

  28. 28

    Strong, V. E. et al. Prognostic indicators of malignancy in adrenal pheochromocytomas: clinical, histopathologic, and cell cycle/apoptosis gene expression analysis. Surgery 143, 759–768 (2008).

  29. 29

    Pohlink, C. et al. Does tumor heterogeneity limit the use of the Weiss criteria in the evaluation of adrenocortical tumors? J. Endocrinol. Invest. 27, 565–569 (2004).

  30. 30

    Wilhelm, S. M., Prinz, R. A., Barbu, A. M., Onders, R. P. & Solorzano, C. C. Analysis of large versus small pheochromocytomas: operative approaches and patient outcomes. Surgery 140, 553–559; discussion 559–60 (2006).

Download references


Written consent for publication was obtained from the patient.

C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

Author information

J. Singer, C. A. Koch, G. Eisenhofer, M. Seiwerts, G. Borte, K. Schierle and R. Paschke researched the data for the article. J. Singer, C. A. Koch, W. Kassahun, P. Lamesch, G. Eisenhofer, M. Seiwerts, G. Borte and R. Paschke provided a substantial contribution to discussions of the content. J. Singer, C. A. Koch and R. Paschke wrote the article. All authors reviewed and/or edited the manuscript before submission.

Correspondence to Jörg Singer.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Singer, J., Koch, C., Kassahun, W. et al. A patient with a large recurrent pheochromocytoma demonstrating the pitfalls of diagnosis. Nat Rev Endocrinol 7, 749–755 (2011). https://doi.org/10.1038/nrendo.2011.132

Download citation

Further reading