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Journal of Endocrinological Investigation

, Volume 28, Issue 4, pp 175–179 | Cite as

Intrahepatic cholestasis as a paraneoplastic syndrome associated with pheochromocytoma

  • C. H. Chung
  • C. H. Wang
  • C. Y. Tzen
  • C. P. LiuEmail author
Case Report

Abstract

Pheochromocytoma is a rare tumor of chromaffin cells that secrete catecholamines and several cytokines. The clinical manifestations are protean and may include hypertension, weight loss, sweating, palpitation, headache, anxiety, tremor, nausea, vomiting, and hypercalcemia. The tumor can mimic many unrelated diseases, leading to significant delay and difficulty in diagnosis. We report a case of a 37-yr-old male admitted with jaundice, dark urine, fever, and signs of a systemic inflammatory response. Abdominal computed tomography revealed a heterogeneously enhancing tumor between the pancreatic tail and left kidney. There was no evidence of obstruction to bile flow, neoplastic involvement of the liver or bile ducts, or infectious etiology. The tumor was removed and found to be a pheochromocytoma. Immunohistochemical analysis revealed the presence of interleukin-1β in the tumor cells. After surgery, the jaundice resolved without further treatment, leading us to the conclusion that it was a paraneoplastic phenomenon possibly related to interleukin-1β production. We suggest that occult pheochromocytoma should be added to the differential diagnosis of unexplained intrahepatic cholestasis.

Key-words

pheochromocytoma cholestasis paraneoplastic syndrome IL-1β fever 

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References

  1. 1.
    White A, Ray DW, Talbot A, Abraham P, Thody AJ, Bevan JS. Cushing’s syndrome due to phaeochromocytoma secreting the precursors of adrenocorticotropin. J Clin Endocrinol Metab 2000, 85: 4771–5.PubMedGoogle Scholar
  2. 2.
    Venihaki M, Gravanis A, Margioris AN. KAT45 human pheochromocytoma cell line. A new model for the in vitro study of neuro-immuno-hormonal interactions. Ann N YAcad Sci 1998, 840: 425–33.Google Scholar
  3. 3.
    Boccara G, Mann C, Guillon G. Secretion of vasopressin from a human pheochromocytoma. Ann Intern Med 1998, 128: 1049.PubMedCrossRefGoogle Scholar
  4. 4.
    Drenou B, Le Tulzo Y, Caulet-Maugendre S, et al. Pheochromocytoma and secondary erythrocytosis: role of tumor erythropoietin secretion. Nouv Rev Fr Hematol 1995, 37: 197–9.PubMedGoogle Scholar
  5. 5.
    Bridgewater JA, Ratcliffe WA, Bundred NJ, Owens CW. Malignant phaeochromocytoma and hypercalcaemia. Postgrad Med J 1993, 69: 77–9.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Al-Dawoud A, Murray WR, Allison MC. Focal pancreatic infarction in pheochromocytoma Dig Dis Sci 1993, 38: 1338–41.PubMedCrossRefGoogle Scholar
  7. 7.
    Gokce O, Gokce C, Gunel S, et al. Pheochromocytoma presenting with headache, panic attacks and jaundice in a child. Headache 1991, 31: 473–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Ramakrishnan R, Werbeck J, Khurana KK, Khan SA. Expression of interleukin-6 and tumor necrosis factor alpha and histopathologic findings in painful and nonpainful breast tissue. Breast J 2003, 9: 91–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Young Jr WF. Pheochromocytoma: 1926–1993. Trends Endocrinol Metab 1993, 4: 122–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Young Jr WF, Maddox DE. Spells: in search of a cause. Mayo Clin Proc 1995, 70: 757–65.PubMedCrossRefGoogle Scholar
  11. 11.
    Borsch G, Wegener M, Wedmann B, Kissler M, Glocke M. Clinical evaluation, ultrasound, cholescintigraphy, and endoscopic retrograde cholangiography in cholestasis: a prospective comparative clinical study. J Clin Gastroenterol 1988, 10: 185–90.PubMedCrossRefGoogle Scholar
  12. 12.
    Pascanen PA, Partanen K, Pikkarainen P, Alhava E, Pirinen A, Janatuinen E. Diagnostic accuracy of ultrasound, computed tomography, and endoscopic retrograde cholangiopancreatography in the detection of obstructive jaundice. Scand J Gastroenterol 1991, 26: 1157–64.CrossRefGoogle Scholar
  13. 13.
    Richter WO, Schwandt P. Serious side effect of nifedipine. Arch Intern Med 1987, 147: 1852.PubMedCrossRefGoogle Scholar
  14. 14.
    Schwartz MS, Frank MS, Yanoff A, Morecki R. Atenolol-associated cholestasis. Am J Gastroenterol 1989, 84: 1084–6.PubMedGoogle Scholar
  15. 15.
    Moseley RH. Sepsis-associated cholestasis. Gastroenterology 1997, 112: 302–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Stern H. Cytomegalovirus and EB virus infections of the liver. Br Med Bull 1972, 28: 180–5.PubMedGoogle Scholar
  17. 17.
    Fuhrman SA, Gill R, Horwitz CA, et al. Marked hyperbilirubinemia in infectious mononucleosis: analysis of laboratory data in seven patients. Arch Intern Med 1987, 147: 850–3.PubMedCrossRefGoogle Scholar
  18. 18.
    Gordon DL, Atamian SD, Brooks MH, et al. Fever in pheochromocytoma Arch Intern Med 1992, 152: 1269–72.PubMedCrossRefGoogle Scholar
  19. 19.
    Summerskill WHJ, Shorter RG. Progressive hepatic failure: its association with undifferentiated renal tumor. Arch Intern Med 1967, 120: 81–4.PubMedCrossRefGoogle Scholar
  20. 20.
    Watterson J, Priest JR. Jaundice as a paraneoplastic phenomenon in a T-cell lymphoma. Gastroenterology 1989, 97: 1319–22.PubMedGoogle Scholar
  21. 21.
    Yalcin S, Kars A, Sokmensuer C, Atahan L. Extrahepatic Hodgkin’s disease with intrahepatic cholestasis: report of two cases. Oncology 1999, 57: 83–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Tiede DJ, Tefferi A, Kochhar R, Thompson GB, Hay ID. Paraneoplastic cholestasis and hypercoagulability associated with medullary thyroid carcinoma: resolution with tumor debulking. Cancer 1994, 73: 702–5.PubMedCrossRefGoogle Scholar
  23. 23.
    Fukumoto S, Matsumoto T, Harada S, Fujisaki J, Kawano M, Ogata E. Pheochromocytoma with pyrexia and marked inflammatory signs: a paraneoplastic syndrome with possible relation to interleukin-6 production. J Clin Endocrinol Metab 1991, 73: 877–81.PubMedCrossRefGoogle Scholar
  24. 24.
    Minetto M, Dovio A, Ventura M, et al. Interleukin-6 producing pheochromocytoma presenting with acute inflammatory syndrome. J Endocrinol Invest 2003, 26: 453–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Alheim K, Andersson C, Tingsborg S, Ziolkowska M, Schultzberg M, Bartfai T. Interleukin 1 expression is inducible by nerve growth factor in PC12 pheochromocytoma cells. Proc Natl Acad Sci USA 1991, 88: 9302–6.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Bornstein SR, Ehrhart-Bornstein M, Gonzalez-Hernandez J, Schroder S, Scherbaum WA. Expression of interleukin-1 in human pheochromocytoma. J Endocrinol Invest 1996, 19: 693–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Kontogeorgos G, Scheithauer BW, Kovacs K, Horvath E, Melmed S. Growth factors and cytokines in paragangliomas and pheochromocytomas, with special reference to sustentacular cells. Endocr Pathol 2002, 13: 197–206.PubMedCrossRefGoogle Scholar
  28. 28.
    Whiting JF, Green RM, Rosenbluth AB, Gollan JL. Tumor necrosis factor-alpha decreases hepatocyte bile salt uptake and mediates endotoxin-induced cholestasis. Hepatology 1995, 22: 1273–8.PubMedGoogle Scholar
  29. 29.
    Green RM, Whiting JF, Rosenbluth AB, Beier D, Gollan JL. Interleukin-6 inhibits hepatocyte traurocholate uptake and sodium-potassium-adenosine triphosphatase activity. Am J Physiol 1994, 267: G1094–100.PubMedGoogle Scholar
  30. 30.
    Geier A, Dietrich CG, Voigt S, et al. Effects of proinflammatory cytokines on rat organic anion transporters during toxic liver injury and cholestasis. Hepatology 2003, 38: 345–54.PubMedCrossRefGoogle Scholar
  31. 31.
    Jones A, Selby PJ, Viner C, Hobbs S, Gore ME, McElwain TJ Tumor necrosis factor, cholestatic jaundice, and chronic liver disease. Gut 1990, 31: 938–9.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Fisher B, Keenan AM, Garra BS, et al. Interleukin-2 induces profound reversible cholestasis: A detailed analysis in treated cancer patients. J Clin Oncol 1989, 7: 1852–62.PubMedGoogle Scholar
  33. 33.
    Reichen J, Simon FR. Cholestasis. In: Arias IM, Boyer JL, Fausto N, Jakoby WB, Schachter DA, Shafritz DA eds. The Liver: Biology and Pathobiology, 3rd ed. New York: Raven Press Ltd. 1994, 1291–325Google Scholar
  34. 34.
    Erlinger S. Cholestasis. In: Schiff ER, Sorrell MF, Maddrey WC eds. Schiff’s Diseases of the Liver, 8th ed. Philadelphia: Lippincott-Raven Publishers. 1999, 611–29.Google Scholar
  35. 35.
    Elferink RO. Cholestasis. Gut 2003, 52(Suppl 2): ii42–8.PubMedCentralPubMedGoogle Scholar
  36. 36.
    Kullak-Ublick GA, Stieger B, Meier PJ. Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 2004, 126: 322–42.PubMedCrossRefGoogle Scholar
  37. 37.
    Hartmann G, Cheung AK, Piquette-Miller M. Inflammatory cytokines, but not bile acids, regulate expression of murine hepatic anion transporters in endotoxemia. J Pharmacol Exp Ther 2002, 303: 273–81.PubMedCrossRefGoogle Scholar
  38. 38.
    Kleemann R, Gervois PP, Verschuren L, Staels B, Princen HM, Kooistra T. Fibrates down-regulate IL-1-stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFkappa B-C/EBP-beta complex formation. Blood 2003, 101: 545–51.PubMedCrossRefGoogle Scholar
  39. 39.
    Yeh ET. CRP as a mediator of disease. Circulation 2004, 109(21 Suppl 1): II11–4.PubMedGoogle Scholar
  40. 40.
    Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N EnglJ Med 1999, 340: 448–54.CrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2005

Authors and Affiliations

  • C. H. Chung
    • 1
  • C. H. Wang
    • 1
  • C. Y. Tzen
    • 2
  • C. P. Liu
    • 3
    Email author
  1. 1.Division of Endocrinology and Metabolism, Department of MedicineMackay Memorial Hospital, Mackay Medicine, Nursing and Management CollegeTaipeiTaiwan
  2. 2.Department of PathologyMackay Memorial Hospital, Mackay Medicine, Nursing and Management CollegeTaipeiTaiwan
  3. 3.Division of Infectious Diseases, Department of Medicine and Department of Medical ResearchMackay Memorial HospitalTaipeiTaiwan

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