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Horm Metab Res 2009; 41(4): 333-338
DOI: 10.1055/s-0028-1103300
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Overexpression of Protein Kinase C-δ Plays a Crucial Role in Interleukin-6-Producing Pheochromocytoma Presenting with Acute Inflammatory Syndrome: A Case Report

H. Tokuda 1 , 2 , T. Hosoi 3 , K. Hayasaka 4 , K. Okamura 5 , N. Yoshimi 6 , O. Kozawa 2
  • 1Department of Clinical Laboratory, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu Aichi, Japan
  • 2Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan
  • 3Department of Advanced Medicine, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu Aichi, Japan
  • 4Department of Clinical Radiology and National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu Aichi, Japan
  • 5Department of Intensive Care, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu Aichi, Japan
  • 6Tumor Pathology, University of the Ryukyus Faculty of Medicine, Okinawa, Japan
Further Information

Publication History

received 04.07.2008

accepted 03.11.2008

Publication Date:
01 December 2008 (online)

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Abstract

Pheochromocytomas are tumors that may produce a variety of substances in addition to catecholamines. To date, among several cases of systemic inflammatory syndrome associated with interleukin-6 (IL-6) secretion, IL-6-producing pheochromocytomas, have been reported. However, the mechanism underlying IL-6 oversecretion in these cases has not yet been clarified. This report describes a patient with pheochromocytoma who exhibited pyrexia and marked inflammatory signs including C-reactive protein elevation. The inflammatory symptoms were easily controlled by the administration of loxoprofen, a nonsteroidal anti-inflammatory drug. The plasma concentration of IL-6 and 11-d-TXB2, a stable metabolite of thromboxane A2 (TXA2), were significantly elevated in parallel with an elevation of norepinephrine in the samples obtained by selective venous sampling. A left adrenalectomy was performed, and the acute inflammatory symptoms naturally diminished without loxoprofen. Cultured tumor cells obtained from the resected specimen spontaneously released IL-6, and indomethacin inhibited the IL-6 release. According to a cDNA microarray analysis, mRNA of protein kinase C-δ (PKC-δ), prostaglandin D synthase, and arachidonate release-relating enzymes were significantly overexpressed in the tumor tissue in comparison to the adjacent nontumor tissue. The constitutive phosphorylation of PKC-δ was observed in the tumor tissue. These results strongly suggest that the systemic inflammatory syndrome in IL-6-producing pheochromocytoma, at least in part, is caused by the overexpression of PKC-δ, resulting in an excess of arachidonate derivatives such as prostaglandins.

Key words

adrenal mass - cytokines - pheochromocytoma

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Correspondence

H. Tokuda

Department of Clinical Laboratory

National Hospital for Geriatric Medicine

National Center for Geriatrics and Gerontology

Obu Aichi 474-8511

Japan

Phone: +81/562/46 23 11

Fax: +81/562/46 83 96

Email: tokuda@ncgg.go.jp