Peptidergic phenotypes of pheochromocytoma
Main Article Content
Abstract
Pheochromocytoma may present as either the classic catecholaminergic phenotype or as one of many kinds of peptidergic phenotypes, including’s Cushing syndrome, watery diarrhea, hypokalemia, and achlorhydria syndrome (WDHA), acromegaly, or humoral hypercalcemia, or a combination of both phenotypes. Cushing’s syndrome may be caused by a pheochromocytoma producing adrenocorticotropic hormone (ACTH) or one producing corticotropin-releasing hormone (CRH). WDHA can be caused by a pheochromocytoma producing vasoactive intestinal peptide (VIP). Acromegaly may be due to a pheochromocytoma producing growth hormone-releasing hormone (GHRH). Humoral hypercalcemia can be due to a pheochromocytoma producing parathyroid hormone-related peptide (PTHrP). -These findings strongly suggest that pheochromocytomas can produce and secrete many kinds of peptide hormones, reinforcing the multisecretory nature of chromaffin cells.
Knowledge of the clinical diversity of pheochromocytomas is important for both precise diagnosis and proper management. Complex clinical features among these cases may lead to the wrong diagnosis, such as an atypical overlap syndrome of multiple endocrine neoplasias. In the case of ectopic GHRH syndrome, unnecessary pituitary surgery may be performed because catecholaminergic features are scanty among patients with this syndrome.
Article Details
How to Cite
WATANABE, Masahiko.
Peptidergic phenotypes of pheochromocytoma.
Medical Research Archives, [S.l.], v. 5, n. 2, feb. 2017.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/997>. Date accessed: 17 nov. 2024.
Keywords
Pheochromocytoma; peptide hormone; CRH; ACTH; VIP; PTHrP
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
ALAM, M. J. 1994. Chronic refractory diarrhoea: a manifestation of endocrine disorders. Dig Dis, 12, 46-61.
ALEXANDRAKI, K. I. & GROSSMAN, A. B. 2010. The ectopic
ACTH syndrome. Rev Endocr Metab Disord, 11, 117-26.
ANDERSON, R. J., LUFKIN, E. G., SIZEMORE, G. W.,
CARNEY, J. A., SHEPS, S. G. & SILLIMAN, Y. E. 1981. Acromegaly and pituitary adenoma with phaeochromocytoma: a variant of multiple endocrine neoplasia. Clin Endocrinol (Oxf), 14, 605-12.
ASA, S. L., KOVACS, K., THORNER, M. O., LEONG, D. A., RIVIER, J. & VALE, W. 1985. Immunohistological localization of growth hormone-releasing hormone in human tumors. J Clin Endocrinol Metab, 60, 423-7.
BAYRAKTAR, F., KEBAPCILAR, L., KOCDOR, M. A., ASA, S. L., YESIL, S., CANDA, S., DEMIR, T., SAKLAMAZ, A., SECIL, M., AKINCI, B., YENER, S. & COMLEKCI, A. 2006. Cushing's syndrome due to ectopic CRH secretion by adrenal pheochromocytoma accompanied by renal infarction. Exp Clin Endocrinol Diabetes, 114, 444-7.
BERNARDI, S., GRIMALDI, F., FINATO, N., DE MARCHI, S., PROCLEMER, A., SABATO, N., BERTOLOTTO, M. & FABRIS, B. 2011. A pheochromocytoma with high adrenocorticotropic hormone and a silent lung nodule. Am J Med Sci, 342, 429-32.
BHANSALI, A., WALIA, R., RANA, S. S., DUTTA, P., RADOTRA, B. D., KHANDELWAL, N. & BHADADA, S. K. 2009. Ectopic Cushing's syndrome: experience from a tertiary care centre. Indian J Med Res, 129, 33-41.
BORSON-CHAZOT, F., GARBY, L., RAVEROT, G., CLAUSTRAT, F., RAVEROT, V. & SASSOLAS, G. 2012. Acromegaly induced by ectopic secretion of GHRH: a review 30 years after GHRH discovery. Ann Endocrinol (Paris), 73, 497-502.
BRENNER, N., KOPETSCHKE, R., VENTZ, M., STRASBURGER, C. J., QUINKLER, M. & GERL, H. 2008. Cushing's syndrome due to ACTH-secreting pheochromocytoma. Can J Urol, 15, 3924-7.
BRIDGEWATER, J. A., RATCLIFFE, W. A., BUNDRED, N. J. & OWENS, C. W. 1993. Malignant phaeochromocytoma and hypercalcaemia. Postgrad Med J, 69, 77-9.
CAREY, R. M., VARMA, S. K., DRAKE, C. R., JR., THORNER, M. O., KOVACS, K., RIVIER, J. & VALE, W. 1984. Ectopic secretion of corticotropin-releasing factor as a cause of Cushing's syndrome. A clinical, morphologic, and biochemical study. N Engl J Med, 311, 13-20.
CASSARINO, M. F., AMBROGIO, A. G., PAGLIARDINI, L., DE MARTIN, M., BARRESI, V., CAVAGNINI, F. & PECORI GIRALDI, F. 2012. ACTH-secreting pheochromocytoma with false-negative ACTH immunohistochemistry. Endocr Pathol, 23, 191-5.
CHEN, H., DOPPMAN, J. L., CHROUSOS, G. P., NORTON, J. A., NIEMAN, L. K. & UDELSMAN, R. 1995. Adrenocorticotropic hormone-secreting pheochromocytomas: the exception to the rule. Surgery, 118, 988-94; discussion 994-5.
COHADE, C., BROUSSAUD, S., LOUISET, E., BENNET, A., HUYGHE, E. & CARON, P. 2009. Ectopic Cushing's syndrome due to a pheochromocytoma: a new case in the post-partum and review of literature. Gynecol Endocrinol, 25, 624-7.
CONTRERAS, L. N., BUDD, D., YEN, T. S., THOMAS, C. & TYRRELL, J. B. 1991. Adrenal ganglioneuroma-pheochromocytoma secreting vasoactive intestinal polypeptide. West J Med, 154, 334-7.
COOPERMAN, A. M., DESANTIS, D., WINKELMAN, E., FARMER, R., EVERSMAN, J. & SAID, S. 1978. Watery diarrhea syndrome. Two unusual cases and further evidence that VIP is a humoral mediator. Ann Surg, 187, 325-8.
DANILOVIC, D. L., BRANDAO NETO, R. A., D'ABRONZO, H., MENEZES, M. R., LUCON, A. M. & MENDONCA, B. B. 2007. Ectopic ACTH syndrome caused by pheochromocytoma: computed tomography-guided percutaneous ethanol injection as an alternative treatment. J Endocrinol Invest, 30, 780-6.
ENDE, K., HENKEL, B., BRODHUN, M., SALOMON, C., LAUTEN, P., CONRAD, E., SEIFERT, M., STIER, A. & SCHARF, J. G. 2012. A 45-year-old female with hypokalemic rhabdomyolysis due to VIP-producing composite pheochromocytoma. Z Gastroenterol, 50, 589-94.
ENG, P. H., TAN, L. H., WONG, K. S., CHENG, C. W., FOK, A. C. & KHOO, D. H. 1999. Cushing's syndrome in a patient with a corticotropin-releasing hormone-producing pheochromocytoma. Endocr Pract, 5, 84-7.
FIEBRICH, H. B., BROUWERS, A. H., VAN BERGEIJK, L. & VAN DEN BERG, G. 2009. Image in endocrinology. Localization of an adrenocorticotropin-producing pheochromocytoma using 18F-dihydroxyphenylalanine positron emission tomography. The Journal of clinical endocrinology and metabolism, 94, 748-749.
FISHER, B. M., MACPHEE, G. J., DAVIES, D. L., MCPHERSON, S. G., BROWN, I. L. & GOLDBERG, A. 1987. A case of watery diarrhoea syndrome due to an adrenal phaeochromocytoma secreting vasoactive intestinal polypeptide with coincidental autoimmune thyroid disease. Acta Endocrinol (Copenh), 114, 340-4.
FLYNN, A., BENN, D., CLIFTON-BLIGH, R., ROBINSON, B., TRAINER, A. H., JAMES, P., HOGG, A., WALDECK, K., GEORGE, J., LI, J., FOX, S. B., GILL, A. J., MCARTHUR, G., HICKS, R. J. & TOTHILL, R. W. 2015. The genomic landscape of phaeochromocytoma. J Pathol, 236, 78-89.
FROHMAN, L. A., SZABO, M., BERELOWITZ, M. & STACHURA, M. E. 1980. Partial purification and characterization of a peptide with growth hormone-releasing activity from extrapituitary tumors in patients with acromegaly. J Clin Invest, 65, 43-54.
GEORGE, D. J., WATERMEYER, G. A., LEVIN, D., EPSTEIN, D., ROSS, I. L., SCHOLZ, B. U., SETSHEDI, M., LOCKETZ, M., DITTRICH, C., SHAW, J. & KRIGE, J. E. 2010. Composite adrenal phaeochromocytoma-ganglioneuroma causing watery diarrhoea, hypokalaemia and achlorhydria syndrome. Eur J Gastroenterol Hepatol, 22, 632-4.
IKUTA, S., YASUI, C., KAWANAKA, M., AIHARA, T., YOSHIE, H., YANAGI, H., MITSUNOBU, M., SUGIHARA, A. & YAMANAKA, N. 2007. Watery diarrhea, hypokalemia and achlorhydria syndrome due to an adrenal pheochromocytoma. World J Gastroenterol, 13, 4649-52.
ILIAS, I., TORPY, D. J., PACAK, K., MULLEN, N., WESLEY, R. A. & NIEMAN, L. K. 2005. Cushing's syndrome due to ectopic corticotropin secretion: twenty years' experience at the National Institutes of Health. J Clin Endocrinol Metab, 90, 4955-62.
ISIDORI, A. M., KALTSAS, G. A., POZZA, C., FRAJESE, V., NEWELL-PRICE, J., REZNEK, R. H., JENKINS, P. J., MONSON, J. P., GROSSMAN, A. B. & BESSER, G. M. 2006. The ectopic adrenocorticotropin syndrome: clinical features, diagnosis, management, and long-term follow-up. J Clin Endocrinol Metab, 91, 371-7.
IVANOVA, R. S. & DASHEV, G. I. 1990. Neuroendocrine features of adrenal pheochromocytomas: histological and immunocytochemical evaluation. Neoplasma, 37, 219-24.
JESSOP, D. S., CUNNAH, D., MILLAR, J. G., NEVILLE, E., COATES, P., DONIACH, I., BESSER, G. M. & REES, L. H. 1987. A phaeochromocytoma presenting with Cushing's syndrome associated with increased concentrations of circulating corticotrophin-releasing factor. J Endocrinol, 113, 133-8.
JIANG, J., ZHANG, L., WU, Z., AI, Z., HOU, Y., LU, Z. & GAO, X. 2014. A rare case of watery diarrhea, hypokalemia and achlorhydria syndrome caused by pheochromocytoma. BMC Cancer, 14, 553.
KAHN, M. T. & MULLON, D. A. 1964. PHEOCHROMOCYTOMA WITHOUT HYPERTENSION. REPORT OF A PATIENT WITH ACROMEGALY. Jama, 188, 74-5.
KIKUCHI, Y., WADA, R., SAKIHARA, S., SUDA, T. & YAGIHASHI, S. 2012. Pheochromocytoma with histologic transformation to composite type, complicated by watery diarrhea, hypokalemia, and achlorhydria syndrome. Endocr Pract, 18, e91-6.
KIMURA, S., NISHIMURA, Y., YAMAGUCHI, K., NAGASAKI, K., SHIMADA, K. & UCHIDA, H. 1990. A case of pheochromocytoma producing parathyroid hormone-related protein and presenting with hypercalcemia. J Clin Endocrinol Metab, 70, 1559-63.
LI, X. G., ZHANG, D. X., LI, X., CUI, X. G., XU, D. F., LI, Y., GAO, Y., YIN, L. & REN, J. Z. 2012. Adrenocorticotropic hormone-producing pheochromocytoma: a case report and review of the literature. Chin Med J (Engl), 125, 1193-6.
LIU, J., HEIKKILA, P., VOUTILAINEN, R., KARONEN, S. L. & KAHRI, A. I. 1994. Pheochromocytoma expressing adrenocorticotropin and corticotropin-releasing hormone; regulation by glucocorticoids and nerve growth factor. Eur J Endocrinol, 131, 221-8.
LOEHRY, C. A., KINGHAM, J. G. & WHORWELL, P. J. 1975. Watery diarrhoea and hypokalaemia associated with a phaeochromocytoma. Postgrad Med J, 51, 416-9.
MATTA, M. K., PROROK, J. J., TRIMPI, H. D., SHEETS, J. A., STASIK, J. J., JR. & KHUBCHANDANI, I. T. 1978. WDHA syndrome caused by pheochromocytoma: report of a case. Dis Colon Rectum, 21, 297-301.
MILLER, G. L. & WYNN, J. 1971. Acromegaly, pheochromocytoma, toxic goiter, diabetes mellitus, and endometriosis. Arch Intern Med, 127, 299-303.
MIRRAKHIMOV, A. E. 2015. Hypercalcemia of Malignancy: An Update on Pathogenesis and Management. N Am J Med Sci, 7, 483-93.
MULLER, O. A. & VON WERDER, K. 1992. Ectopic production of ACTH and corticotropin-releasing hormone (CRH). J Steroid Biochem Mol Biol, 43, 403-8.
MUMBY, C., DAVIS, J. R., TROUILLAS, J. & HIGHAM, C. E. 2014. Phaeochromocytoma and Acromegaly: a unifying diagnosis. Endocrinol Diabetes Metab Case Rep, 2014, 140036.
MUNE, T., KATAKAMI, H., KATO, Y., YASUDA, K., MATSUKURA, S. & MIURA, K. 1993. Production and secretion of parathyroid hormone-related protein in pheochromocytoma: participation of an alpha-adrenergic mechanism. J Clin Endocrinol Metab, 76, 757-62.
MYERS, J. H. & EVERSMAN, J. J. 1981. Acromegaly, hyperparathyroidism, and pheochromocytoma in the same patient. A multiple endocrine disorder. Arch Intern Med, 141, 1521-2.
NEWELL-PRICE, J., BERTAGNA, X., GROSSMAN, A. B. & NIEMAN, L. K. 2006. Cushing's syndrome. Lancet, 367, 1605-17.
NIGAWARA, K., SUZUKI, T., TAZAWA, H., FUNYU, T., YAGIHASHI, S., YAMAYA, K., TERAYAMA, Y. & YAMAGUCHI, K. 1987. A case of recurrent malignant pheochromocytoma complicated by watery diarrhea, hypokalemia, achlorhydria syndrome. J Clin Endocrinol Metab, 65, 1053-6.
NIJHOFF, M. F., DEKKERS, O. M., VLEMING, L. J., SMIT, J. W., ROMIJN, J. A. & PEREIRA, A. M. 2009. ACTH-producing pheochromocytoma: clinical considerations and concise review of the literature. Eur J Intern Med, 20, 682-5.
O'BRIEN, T., YOUNG, W. F., JR., DAVILA, D. G., SCHEITHAUER, B. W., KOVACS, K., HORVATH, E., VALE, W. & VAN HEERDEN, J. A. 1992. Cushing's syndrome associated with ectopic production of corticotrophin-releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma. Clin Endocrinol (Oxf), 37, 460-7.
ONOZAWA, M., FUKUHARA, T., MINOGUCHI, M., TAKAHATA, M., YAMAMOTO, Y., MIYAKE, T., KANAGAWA, K., KANDA, M. & MAEKAWA, I. 2005. Hypokalemic rhabdomyolysis due to WDHA syndrome caused by VIP-producing composite pheochromocytoma: a case in neurofibromatosis type 1. Japanese journal of clinical oncology, 35, 559-563.
OTSUKA, F., MIYOSHI, T., MURAKAMI, K., INAGAKI, K., TAKEDA, M., UJIKE, K., OGURA, T., OMORI, M., DOIHARA, H., TANAKA, Y., HASHIMOTO, K. & MAKINO, H. 2005. An extra-adrenal abdominal pheochromocytoma causing ectopic ACTH syndrome. Am J Hypertens, 18, 1364-8.
OZBAY, A., OBUKHAU, A., BUHL, L., BRONDT HARTLEV, L. & LOGSTRUP POULSEN, P. 2008. Adrenal pheochromocytoma producing vasoactive intestinal peptide and masking hypertension. Horm Res, 70, 188-92.
PAIS, S. O. 1978. Angiographic demonstration of a vasoactive intestinal polypeptide-secreting pheochromocytoma in a patient with WDHA syndrome. AJR Am J Roentgenol, 130, 172-4.
PREEYASOMBAT, C., SIRIKULCHAYANONTA, V., MAHACHOKELERTWATTANA, P., SRIPHRAPRADANG, A. & BOONPUCKNAVIG, S. 1992. Cushing's syndrome caused by Ewing's sarcoma secreting corticotropin releasing factor-like peptide. Am J Dis Child, 146, 1103-5.
QUARLES VAN UFFORD-MANNESSE, P., CASTRO CABEZAS, M., VROOM, T. M., VAN GILS, A., LIPS, C. J. & NIERMEIJER, P. 1999. A patient with neurofibromatosis type 1 and watery diarrhoea syndrome due to a VIP-producing adrenal phaeochromocytoma. J Intern Med, 246, 231-4.
ROTH, K. A., WILSON, D. M., EBERWINE, J., DORIN, R. I., KOVACS, K., BENSCH, K. G. & HOFFMAN, A. R. 1986. Acromegaly and pheochromocytoma: a multiple endocrine syndrome caused by a plurihormonal adrenal medullary tumor. J Clin Endocrinol Metab, 63, 1421-6.
ROUX, G., MARCHAL, G. & LOUBATIERES, R. 1955. [Not Available]. Mem Acad Chir (Paris), 81, 847-52.
RUGGERI, R. M., FERRAU, F., CAMPENNI, A., SIMONE, A., BARRESI, V., GIUFFRE, G., TUCCARI, G., BALDARI, S. &
TRIMARCHI, F. 2009. Immunohistochemical localization and functional characterization of somatostatin receptor subtypes in a corticotropin releasing hormone- secreting adrenal phaeochromocytoma: review of the literature and report of a case. Eur J Histochem, 53, 1-6.
SACKEL, S. G., MANSON, J. E., HARAWI, S. J. & BURAKOFF, R. 1985. Watery diarrhea syndrome due to an adrenal pheochromocytoma secreting vasoactive intestinal polypeptide. Dig Dis Sci, 30, 1201-7.
SAID, S. I. 1976. Evidence for secretion of vasoactive intestinal peptide by tumours of pancreas, adrenal medulla, thyroid and lung: support for the unifying APUD concept. Clin Endocrinol (Oxf), 5 Suppl, 201s-204s.
SAID, S. I. & MUTT, V. 1970a. Polypeptide with broad biological activity: isolation from small intestine. Science, 169, 1217-8.
SAID, S. I. & MUTT, V. 1970b. Potent peripheral and splanchnic vasodilator peptide from normal gut. Nature, 225, 863-4.
SALGADO, L. R., FRAGOSO, M. C., KNOEPFELMACHER, M., MACHADO, M. C., DOMENICE, S., PEREIRA, M. A. & DE MENDONCA, B. B. 2006. Ectopic ACTH syndrome: our experience with 25 cases. Eur J Endocrinol, 155, 725-33.
SALMI, J., PELTO-HUIKKO, M., AUVINEN, O., KARVONEN, A. L., SAARISTO, J., PARONEN, I., POYHONEN, L. & SEPPANEN, S. 1988. Adrenal pheochromocytoma-ganglioneuroma producing catecholamines and various neuropeptides. Acta Med Scand, 224, 403-8.
SASAKI, A., SATO, S., MURAKAMI, O., GO, M., INOUE, M., SHIMIZU, Y., HANEW, K., ANDOH, N., SATO, I., SASANO, N. & ET AL. 1987. Immunoreactive corticotropin-releasing hormone present in human plasma may be derived from both hypothalamic and extrahypothalamic sources. J Clin Endocrinol Metab, 65, 176-82.
SCHMID, K. W., DOCKHORN-DWORNICZAK, B., FAHRENKAMP, A., KIRCHMAIR, R., TOTSCH, M., FISCHER-COLBRIE, R., BOCKER, W. & WINKLER, H. 1993. Chromogranin A, secretogranin II and vasoactive intestinal peptide in phaeochromocytomas and ganglioneuromas. Histopathology, 22, 527-33.
SMITH, S. L., SLAPPY, A. L., FOX, T. P. & SCOLAPIO, J. S. 2002. Pheochromocytoma producing vasoactive intestinal peptide. Mayo Clin Proc, 77, 97-100.
STEWART, A. F. 2005. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med, 352, 373-9.
TAKEDA, K., HARA, N., KAWAGUCHI, M., NISHIYAMA, T. & TAKAHASHI, K. 2010. Parathyroid hormone-related peptide-producing non-familial pheochromocytoma in a child. Int J Urol, 17, 673-6.
TRUMP, D. L., LIVINGSTON, J. N. & BAYLIN, S. B. 1977. Watery diarrhea syndrome in an adult with ganglioneuroma-pheochromocytoma: identification of vasoactive intestinal peptide, calcitonin, and catecholamines and assessment of their biologic activity. Cancer, 40, 1526-32.
VAN DAM, P. S., VAN GILS, A., CANNINGA-VAN DIJK, M. R., DE KONING, E. J., HOFLAND, L. J. & DE HERDER, W. W. 2002. Sequential ACTH and catecholamine secretion in a phaeochromocytoma. European journal of endocrinology / European Federation of Endocrine Societies, 147, 201-206.
VAN EECKHOUT, P., SHUNGU, H., DESCAMPS, F. X., LANTHIER, P., CASTELAIN, T., SAEY, J. P., RETTMAN, R., DRESE, C. & COLIN, I. M. 1999. Acute watery diarrhea as the initial presenting feature of a pheochromocytoma in an 84-year-old female patient. Horm Res, 52, 101-6.
VERRUA, E., RONCHI, C. L., FERRANTE, E., FERRARI, D. I., BERGAMASCHI, S., FERRERO, S., ZATELLI, M. C., BRANCA, V., SPADA, A., BECK-PECCOZ, P. & LANIA, A. G. 2010. Acromegaly secondary to an incidentally discovered growth-hormone-releasing hormone secreting bronchial carcinoid tumour associated to a pituitary incidentaloma. Pituitary, 13, 289-92.
VIALE, G., DELL'ORTO, P., MORO, E., COZZAGLIO, L. & COGGI, G. 1985. Vasoactive intestinal polypeptide-, somatostatin-, and calcitonin-producing adrenal pheochromocytoma associated with the watery diarrhea (WDHH) syndrome. First case report with immunohistochemical findings. Cancer, 55, 1099-106.
VIEIRA NETO, L., TABOADA, G. F., CORREA, L. L., POLO, J., NASCIMENTO, A. F., CHIMELLI, L., RUMILLA, K. & GADELHA, M. R. 2007. Acromegaly secondary to growth hormone-releasing hormone secreted by an incidentally discovered pheochromocytoma. Endocr Pathol, 18, 46-52.
WAJCHENBERG, B. L., MENDONCA, B., LIBERMAN, B., ADELAIDE, M., PEREIRA, A. & KIRSCHNER, M. A. 1995. Ectopic ACTH syndrome. J Steroid Biochem Mol Biol, 53, 139-51.
WERMERS, R. A., FATOURECHI, V. & KVOLS, L. K. 1996. Clinical spectrum of hyperglucagonemia associated with malignant neuroendocrine tumors. Mayo Clin Proc, 71, 1030-8.
WHITE, A., RAY, D. W., TALBOT, A., ABRAHAM, P., THODY, A. J. & BEVAN, J. S. 2000. Cushing's syndrome due to phaeochromocytoma secreting the precursors of adrenocorticotropin. The Journal of clinical endocrinology and metabolism, 85, 4771-4775.
ALEXANDRAKI, K. I. & GROSSMAN, A. B. 2010. The ectopic
ACTH syndrome. Rev Endocr Metab Disord, 11, 117-26.
ANDERSON, R. J., LUFKIN, E. G., SIZEMORE, G. W.,
CARNEY, J. A., SHEPS, S. G. & SILLIMAN, Y. E. 1981. Acromegaly and pituitary adenoma with phaeochromocytoma: a variant of multiple endocrine neoplasia. Clin Endocrinol (Oxf), 14, 605-12.
ASA, S. L., KOVACS, K., THORNER, M. O., LEONG, D. A., RIVIER, J. & VALE, W. 1985. Immunohistological localization of growth hormone-releasing hormone in human tumors. J Clin Endocrinol Metab, 60, 423-7.
BAYRAKTAR, F., KEBAPCILAR, L., KOCDOR, M. A., ASA, S. L., YESIL, S., CANDA, S., DEMIR, T., SAKLAMAZ, A., SECIL, M., AKINCI, B., YENER, S. & COMLEKCI, A. 2006. Cushing's syndrome due to ectopic CRH secretion by adrenal pheochromocytoma accompanied by renal infarction. Exp Clin Endocrinol Diabetes, 114, 444-7.
BERNARDI, S., GRIMALDI, F., FINATO, N., DE MARCHI, S., PROCLEMER, A., SABATO, N., BERTOLOTTO, M. & FABRIS, B. 2011. A pheochromocytoma with high adrenocorticotropic hormone and a silent lung nodule. Am J Med Sci, 342, 429-32.
BHANSALI, A., WALIA, R., RANA, S. S., DUTTA, P., RADOTRA, B. D., KHANDELWAL, N. & BHADADA, S. K. 2009. Ectopic Cushing's syndrome: experience from a tertiary care centre. Indian J Med Res, 129, 33-41.
BORSON-CHAZOT, F., GARBY, L., RAVEROT, G., CLAUSTRAT, F., RAVEROT, V. & SASSOLAS, G. 2012. Acromegaly induced by ectopic secretion of GHRH: a review 30 years after GHRH discovery. Ann Endocrinol (Paris), 73, 497-502.
BRENNER, N., KOPETSCHKE, R., VENTZ, M., STRASBURGER, C. J., QUINKLER, M. & GERL, H. 2008. Cushing's syndrome due to ACTH-secreting pheochromocytoma. Can J Urol, 15, 3924-7.
BRIDGEWATER, J. A., RATCLIFFE, W. A., BUNDRED, N. J. & OWENS, C. W. 1993. Malignant phaeochromocytoma and hypercalcaemia. Postgrad Med J, 69, 77-9.
CAREY, R. M., VARMA, S. K., DRAKE, C. R., JR., THORNER, M. O., KOVACS, K., RIVIER, J. & VALE, W. 1984. Ectopic secretion of corticotropin-releasing factor as a cause of Cushing's syndrome. A clinical, morphologic, and biochemical study. N Engl J Med, 311, 13-20.
CASSARINO, M. F., AMBROGIO, A. G., PAGLIARDINI, L., DE MARTIN, M., BARRESI, V., CAVAGNINI, F. & PECORI GIRALDI, F. 2012. ACTH-secreting pheochromocytoma with false-negative ACTH immunohistochemistry. Endocr Pathol, 23, 191-5.
CHEN, H., DOPPMAN, J. L., CHROUSOS, G. P., NORTON, J. A., NIEMAN, L. K. & UDELSMAN, R. 1995. Adrenocorticotropic hormone-secreting pheochromocytomas: the exception to the rule. Surgery, 118, 988-94; discussion 994-5.
COHADE, C., BROUSSAUD, S., LOUISET, E., BENNET, A., HUYGHE, E. & CARON, P. 2009. Ectopic Cushing's syndrome due to a pheochromocytoma: a new case in the post-partum and review of literature. Gynecol Endocrinol, 25, 624-7.
CONTRERAS, L. N., BUDD, D., YEN, T. S., THOMAS, C. & TYRRELL, J. B. 1991. Adrenal ganglioneuroma-pheochromocytoma secreting vasoactive intestinal polypeptide. West J Med, 154, 334-7.
COOPERMAN, A. M., DESANTIS, D., WINKELMAN, E., FARMER, R., EVERSMAN, J. & SAID, S. 1978. Watery diarrhea syndrome. Two unusual cases and further evidence that VIP is a humoral mediator. Ann Surg, 187, 325-8.
DANILOVIC, D. L., BRANDAO NETO, R. A., D'ABRONZO, H., MENEZES, M. R., LUCON, A. M. & MENDONCA, B. B. 2007. Ectopic ACTH syndrome caused by pheochromocytoma: computed tomography-guided percutaneous ethanol injection as an alternative treatment. J Endocrinol Invest, 30, 780-6.
ENDE, K., HENKEL, B., BRODHUN, M., SALOMON, C., LAUTEN, P., CONRAD, E., SEIFERT, M., STIER, A. & SCHARF, J. G. 2012. A 45-year-old female with hypokalemic rhabdomyolysis due to VIP-producing composite pheochromocytoma. Z Gastroenterol, 50, 589-94.
ENG, P. H., TAN, L. H., WONG, K. S., CHENG, C. W., FOK, A. C. & KHOO, D. H. 1999. Cushing's syndrome in a patient with a corticotropin-releasing hormone-producing pheochromocytoma. Endocr Pract, 5, 84-7.
FIEBRICH, H. B., BROUWERS, A. H., VAN BERGEIJK, L. & VAN DEN BERG, G. 2009. Image in endocrinology. Localization of an adrenocorticotropin-producing pheochromocytoma using 18F-dihydroxyphenylalanine positron emission tomography. The Journal of clinical endocrinology and metabolism, 94, 748-749.
FISHER, B. M., MACPHEE, G. J., DAVIES, D. L., MCPHERSON, S. G., BROWN, I. L. & GOLDBERG, A. 1987. A case of watery diarrhoea syndrome due to an adrenal phaeochromocytoma secreting vasoactive intestinal polypeptide with coincidental autoimmune thyroid disease. Acta Endocrinol (Copenh), 114, 340-4.
FLYNN, A., BENN, D., CLIFTON-BLIGH, R., ROBINSON, B., TRAINER, A. H., JAMES, P., HOGG, A., WALDECK, K., GEORGE, J., LI, J., FOX, S. B., GILL, A. J., MCARTHUR, G., HICKS, R. J. & TOTHILL, R. W. 2015. The genomic landscape of phaeochromocytoma. J Pathol, 236, 78-89.
FROHMAN, L. A., SZABO, M., BERELOWITZ, M. & STACHURA, M. E. 1980. Partial purification and characterization of a peptide with growth hormone-releasing activity from extrapituitary tumors in patients with acromegaly. J Clin Invest, 65, 43-54.
GEORGE, D. J., WATERMEYER, G. A., LEVIN, D., EPSTEIN, D., ROSS, I. L., SCHOLZ, B. U., SETSHEDI, M., LOCKETZ, M., DITTRICH, C., SHAW, J. & KRIGE, J. E. 2010. Composite adrenal phaeochromocytoma-ganglioneuroma causing watery diarrhoea, hypokalaemia and achlorhydria syndrome. Eur J Gastroenterol Hepatol, 22, 632-4.
IKUTA, S., YASUI, C., KAWANAKA, M., AIHARA, T., YOSHIE, H., YANAGI, H., MITSUNOBU, M., SUGIHARA, A. & YAMANAKA, N. 2007. Watery diarrhea, hypokalemia and achlorhydria syndrome due to an adrenal pheochromocytoma. World J Gastroenterol, 13, 4649-52.
ILIAS, I., TORPY, D. J., PACAK, K., MULLEN, N., WESLEY, R. A. & NIEMAN, L. K. 2005. Cushing's syndrome due to ectopic corticotropin secretion: twenty years' experience at the National Institutes of Health. J Clin Endocrinol Metab, 90, 4955-62.
ISIDORI, A. M., KALTSAS, G. A., POZZA, C., FRAJESE, V., NEWELL-PRICE, J., REZNEK, R. H., JENKINS, P. J., MONSON, J. P., GROSSMAN, A. B. & BESSER, G. M. 2006. The ectopic adrenocorticotropin syndrome: clinical features, diagnosis, management, and long-term follow-up. J Clin Endocrinol Metab, 91, 371-7.
IVANOVA, R. S. & DASHEV, G. I. 1990. Neuroendocrine features of adrenal pheochromocytomas: histological and immunocytochemical evaluation. Neoplasma, 37, 219-24.
JESSOP, D. S., CUNNAH, D., MILLAR, J. G., NEVILLE, E., COATES, P., DONIACH, I., BESSER, G. M. & REES, L. H. 1987. A phaeochromocytoma presenting with Cushing's syndrome associated with increased concentrations of circulating corticotrophin-releasing factor. J Endocrinol, 113, 133-8.
JIANG, J., ZHANG, L., WU, Z., AI, Z., HOU, Y., LU, Z. & GAO, X. 2014. A rare case of watery diarrhea, hypokalemia and achlorhydria syndrome caused by pheochromocytoma. BMC Cancer, 14, 553.
KAHN, M. T. & MULLON, D. A. 1964. PHEOCHROMOCYTOMA WITHOUT HYPERTENSION. REPORT OF A PATIENT WITH ACROMEGALY. Jama, 188, 74-5.
KIKUCHI, Y., WADA, R., SAKIHARA, S., SUDA, T. & YAGIHASHI, S. 2012. Pheochromocytoma with histologic transformation to composite type, complicated by watery diarrhea, hypokalemia, and achlorhydria syndrome. Endocr Pract, 18, e91-6.
KIMURA, S., NISHIMURA, Y., YAMAGUCHI, K., NAGASAKI, K., SHIMADA, K. & UCHIDA, H. 1990. A case of pheochromocytoma producing parathyroid hormone-related protein and presenting with hypercalcemia. J Clin Endocrinol Metab, 70, 1559-63.
LI, X. G., ZHANG, D. X., LI, X., CUI, X. G., XU, D. F., LI, Y., GAO, Y., YIN, L. & REN, J. Z. 2012. Adrenocorticotropic hormone-producing pheochromocytoma: a case report and review of the literature. Chin Med J (Engl), 125, 1193-6.
LIU, J., HEIKKILA, P., VOUTILAINEN, R., KARONEN, S. L. & KAHRI, A. I. 1994. Pheochromocytoma expressing adrenocorticotropin and corticotropin-releasing hormone; regulation by glucocorticoids and nerve growth factor. Eur J Endocrinol, 131, 221-8.
LOEHRY, C. A., KINGHAM, J. G. & WHORWELL, P. J. 1975. Watery diarrhoea and hypokalaemia associated with a phaeochromocytoma. Postgrad Med J, 51, 416-9.
MATTA, M. K., PROROK, J. J., TRIMPI, H. D., SHEETS, J. A., STASIK, J. J., JR. & KHUBCHANDANI, I. T. 1978. WDHA syndrome caused by pheochromocytoma: report of a case. Dis Colon Rectum, 21, 297-301.
MILLER, G. L. & WYNN, J. 1971. Acromegaly, pheochromocytoma, toxic goiter, diabetes mellitus, and endometriosis. Arch Intern Med, 127, 299-303.
MIRRAKHIMOV, A. E. 2015. Hypercalcemia of Malignancy: An Update on Pathogenesis and Management. N Am J Med Sci, 7, 483-93.
MULLER, O. A. & VON WERDER, K. 1992. Ectopic production of ACTH and corticotropin-releasing hormone (CRH). J Steroid Biochem Mol Biol, 43, 403-8.
MUMBY, C., DAVIS, J. R., TROUILLAS, J. & HIGHAM, C. E. 2014. Phaeochromocytoma and Acromegaly: a unifying diagnosis. Endocrinol Diabetes Metab Case Rep, 2014, 140036.
MUNE, T., KATAKAMI, H., KATO, Y., YASUDA, K., MATSUKURA, S. & MIURA, K. 1993. Production and secretion of parathyroid hormone-related protein in pheochromocytoma: participation of an alpha-adrenergic mechanism. J Clin Endocrinol Metab, 76, 757-62.
MYERS, J. H. & EVERSMAN, J. J. 1981. Acromegaly, hyperparathyroidism, and pheochromocytoma in the same patient. A multiple endocrine disorder. Arch Intern Med, 141, 1521-2.
NEWELL-PRICE, J., BERTAGNA, X., GROSSMAN, A. B. & NIEMAN, L. K. 2006. Cushing's syndrome. Lancet, 367, 1605-17.
NIGAWARA, K., SUZUKI, T., TAZAWA, H., FUNYU, T., YAGIHASHI, S., YAMAYA, K., TERAYAMA, Y. & YAMAGUCHI, K. 1987. A case of recurrent malignant pheochromocytoma complicated by watery diarrhea, hypokalemia, achlorhydria syndrome. J Clin Endocrinol Metab, 65, 1053-6.
NIJHOFF, M. F., DEKKERS, O. M., VLEMING, L. J., SMIT, J. W., ROMIJN, J. A. & PEREIRA, A. M. 2009. ACTH-producing pheochromocytoma: clinical considerations and concise review of the literature. Eur J Intern Med, 20, 682-5.
O'BRIEN, T., YOUNG, W. F., JR., DAVILA, D. G., SCHEITHAUER, B. W., KOVACS, K., HORVATH, E., VALE, W. & VAN HEERDEN, J. A. 1992. Cushing's syndrome associated with ectopic production of corticotrophin-releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma. Clin Endocrinol (Oxf), 37, 460-7.
ONOZAWA, M., FUKUHARA, T., MINOGUCHI, M., TAKAHATA, M., YAMAMOTO, Y., MIYAKE, T., KANAGAWA, K., KANDA, M. & MAEKAWA, I. 2005. Hypokalemic rhabdomyolysis due to WDHA syndrome caused by VIP-producing composite pheochromocytoma: a case in neurofibromatosis type 1. Japanese journal of clinical oncology, 35, 559-563.
OTSUKA, F., MIYOSHI, T., MURAKAMI, K., INAGAKI, K., TAKEDA, M., UJIKE, K., OGURA, T., OMORI, M., DOIHARA, H., TANAKA, Y., HASHIMOTO, K. & MAKINO, H. 2005. An extra-adrenal abdominal pheochromocytoma causing ectopic ACTH syndrome. Am J Hypertens, 18, 1364-8.
OZBAY, A., OBUKHAU, A., BUHL, L., BRONDT HARTLEV, L. & LOGSTRUP POULSEN, P. 2008. Adrenal pheochromocytoma producing vasoactive intestinal peptide and masking hypertension. Horm Res, 70, 188-92.
PAIS, S. O. 1978. Angiographic demonstration of a vasoactive intestinal polypeptide-secreting pheochromocytoma in a patient with WDHA syndrome. AJR Am J Roentgenol, 130, 172-4.
PREEYASOMBAT, C., SIRIKULCHAYANONTA, V., MAHACHOKELERTWATTANA, P., SRIPHRAPRADANG, A. & BOONPUCKNAVIG, S. 1992. Cushing's syndrome caused by Ewing's sarcoma secreting corticotropin releasing factor-like peptide. Am J Dis Child, 146, 1103-5.
QUARLES VAN UFFORD-MANNESSE, P., CASTRO CABEZAS, M., VROOM, T. M., VAN GILS, A., LIPS, C. J. & NIERMEIJER, P. 1999. A patient with neurofibromatosis type 1 and watery diarrhoea syndrome due to a VIP-producing adrenal phaeochromocytoma. J Intern Med, 246, 231-4.
ROTH, K. A., WILSON, D. M., EBERWINE, J., DORIN, R. I., KOVACS, K., BENSCH, K. G. & HOFFMAN, A. R. 1986. Acromegaly and pheochromocytoma: a multiple endocrine syndrome caused by a plurihormonal adrenal medullary tumor. J Clin Endocrinol Metab, 63, 1421-6.
ROUX, G., MARCHAL, G. & LOUBATIERES, R. 1955. [Not Available]. Mem Acad Chir (Paris), 81, 847-52.
RUGGERI, R. M., FERRAU, F., CAMPENNI, A., SIMONE, A., BARRESI, V., GIUFFRE, G., TUCCARI, G., BALDARI, S. &
TRIMARCHI, F. 2009. Immunohistochemical localization and functional characterization of somatostatin receptor subtypes in a corticotropin releasing hormone- secreting adrenal phaeochromocytoma: review of the literature and report of a case. Eur J Histochem, 53, 1-6.
SACKEL, S. G., MANSON, J. E., HARAWI, S. J. & BURAKOFF, R. 1985. Watery diarrhea syndrome due to an adrenal pheochromocytoma secreting vasoactive intestinal polypeptide. Dig Dis Sci, 30, 1201-7.
SAID, S. I. 1976. Evidence for secretion of vasoactive intestinal peptide by tumours of pancreas, adrenal medulla, thyroid and lung: support for the unifying APUD concept. Clin Endocrinol (Oxf), 5 Suppl, 201s-204s.
SAID, S. I. & MUTT, V. 1970a. Polypeptide with broad biological activity: isolation from small intestine. Science, 169, 1217-8.
SAID, S. I. & MUTT, V. 1970b. Potent peripheral and splanchnic vasodilator peptide from normal gut. Nature, 225, 863-4.
SALGADO, L. R., FRAGOSO, M. C., KNOEPFELMACHER, M., MACHADO, M. C., DOMENICE, S., PEREIRA, M. A. & DE MENDONCA, B. B. 2006. Ectopic ACTH syndrome: our experience with 25 cases. Eur J Endocrinol, 155, 725-33.
SALMI, J., PELTO-HUIKKO, M., AUVINEN, O., KARVONEN, A. L., SAARISTO, J., PARONEN, I., POYHONEN, L. & SEPPANEN, S. 1988. Adrenal pheochromocytoma-ganglioneuroma producing catecholamines and various neuropeptides. Acta Med Scand, 224, 403-8.
SASAKI, A., SATO, S., MURAKAMI, O., GO, M., INOUE, M., SHIMIZU, Y., HANEW, K., ANDOH, N., SATO, I., SASANO, N. & ET AL. 1987. Immunoreactive corticotropin-releasing hormone present in human plasma may be derived from both hypothalamic and extrahypothalamic sources. J Clin Endocrinol Metab, 65, 176-82.
SCHMID, K. W., DOCKHORN-DWORNICZAK, B., FAHRENKAMP, A., KIRCHMAIR, R., TOTSCH, M., FISCHER-COLBRIE, R., BOCKER, W. & WINKLER, H. 1993. Chromogranin A, secretogranin II and vasoactive intestinal peptide in phaeochromocytomas and ganglioneuromas. Histopathology, 22, 527-33.
SMITH, S. L., SLAPPY, A. L., FOX, T. P. & SCOLAPIO, J. S. 2002. Pheochromocytoma producing vasoactive intestinal peptide. Mayo Clin Proc, 77, 97-100.
STEWART, A. F. 2005. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med, 352, 373-9.
TAKEDA, K., HARA, N., KAWAGUCHI, M., NISHIYAMA, T. & TAKAHASHI, K. 2010. Parathyroid hormone-related peptide-producing non-familial pheochromocytoma in a child. Int J Urol, 17, 673-6.
TRUMP, D. L., LIVINGSTON, J. N. & BAYLIN, S. B. 1977. Watery diarrhea syndrome in an adult with ganglioneuroma-pheochromocytoma: identification of vasoactive intestinal peptide, calcitonin, and catecholamines and assessment of their biologic activity. Cancer, 40, 1526-32.
VAN DAM, P. S., VAN GILS, A., CANNINGA-VAN DIJK, M. R., DE KONING, E. J., HOFLAND, L. J. & DE HERDER, W. W. 2002. Sequential ACTH and catecholamine secretion in a phaeochromocytoma. European journal of endocrinology / European Federation of Endocrine Societies, 147, 201-206.
VAN EECKHOUT, P., SHUNGU, H., DESCAMPS, F. X., LANTHIER, P., CASTELAIN, T., SAEY, J. P., RETTMAN, R., DRESE, C. & COLIN, I. M. 1999. Acute watery diarrhea as the initial presenting feature of a pheochromocytoma in an 84-year-old female patient. Horm Res, 52, 101-6.
VERRUA, E., RONCHI, C. L., FERRANTE, E., FERRARI, D. I., BERGAMASCHI, S., FERRERO, S., ZATELLI, M. C., BRANCA, V., SPADA, A., BECK-PECCOZ, P. & LANIA, A. G. 2010. Acromegaly secondary to an incidentally discovered growth-hormone-releasing hormone secreting bronchial carcinoid tumour associated to a pituitary incidentaloma. Pituitary, 13, 289-92.
VIALE, G., DELL'ORTO, P., MORO, E., COZZAGLIO, L. & COGGI, G. 1985. Vasoactive intestinal polypeptide-, somatostatin-, and calcitonin-producing adrenal pheochromocytoma associated with the watery diarrhea (WDHH) syndrome. First case report with immunohistochemical findings. Cancer, 55, 1099-106.
VIEIRA NETO, L., TABOADA, G. F., CORREA, L. L., POLO, J., NASCIMENTO, A. F., CHIMELLI, L., RUMILLA, K. & GADELHA, M. R. 2007. Acromegaly secondary to growth hormone-releasing hormone secreted by an incidentally discovered pheochromocytoma. Endocr Pathol, 18, 46-52.
WAJCHENBERG, B. L., MENDONCA, B., LIBERMAN, B., ADELAIDE, M., PEREIRA, A. & KIRSCHNER, M. A. 1995. Ectopic ACTH syndrome. J Steroid Biochem Mol Biol, 53, 139-51.
WERMERS, R. A., FATOURECHI, V. & KVOLS, L. K. 1996. Clinical spectrum of hyperglucagonemia associated with malignant neuroendocrine tumors. Mayo Clin Proc, 71, 1030-8.
WHITE, A., RAY, D. W., TALBOT, A., ABRAHAM, P., THODY, A. J. & BEVAN, J. S. 2000. Cushing's syndrome due to phaeochromocytoma secreting the precursors of adrenocorticotropin. The Journal of clinical endocrinology and metabolism, 85, 4771-4775.