Abstract
Using specific immunoradiometric assays, we evaluated the clinical usefulness of chromogranin A and the α-subunit of glycoprotein hormones in neuroendocrine tumours of neuroectodermic origin. The serum α-subunit of glycoprotein hormones was only slightly increased in 2 out of 44 medullary thyroid carcinoma or phaeochromocytoma patients with increased calcitonin or 24-hour urinary metanephrine levels. Serum chromogranin A was increased in 12 of 45 (27%) medullary thyroid carcinoma patients with an elevated calcitonin level and in 4 of 16 medullary thyroid carcinoma patients (25%) with an undetectable calcitonin level, in 5 of 7 phaeochromocytoma patients with increased urinary catecholamine and metabolite excretion, and in 2 of 3 patients with a non-functioning phaeochromocytoma. During follow-up, the course of chromogranin A was found to parallel that of tumour burden and/or 24-hour urinary metanephrine in 5 phaeochromocytoma patients. We conclude that chromogranin A measurement is not recommended for the diagnosis of medullary thyroid carcinoma patients. It may be useful in patients with functioning and non-functioning phaeochromocytomas as a follow-up marker. In neuroendocrine tumour patients with elevated calcitonin secretion, the serum α-subunit of glycoprotein hormone measurement may help differentiate medullary thyroid carcinoma or phaeochromocytoma patients from other endodermal-derived neuroendocrine tumour patients in whom it is frequently elevated. © 2001 Cancer Research Campaign
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Averbuch SD, Steakley CS, Young RC, Gelmann EP, Goldstein DS, Stull R and Keiser HR (1988) Malignant phaeochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine and dacarbazine. Ann Intern Med 109: 267–273
Baudin E, Gigliotti A, Ducreux M, Ropers J, Comoy E, Sabourin JC, Bidart JM, Cailleux AF, Bonacci R, Ruffie P and Schlumberger M (1998) Neuron-specific enolase and chromogranin A as markers of neuroendocrine tumours. Br J Cancer 78: 1102–1107
Baudin E, Bidart JM, Rougier P, Lazar V, Ruffie P, Ropers J, Ducreux M, Troalen F, Sabourin JC, Comoy E, Lasser P, DeBaere T and Schlumberger M (1999) Screening for multiple endocrine neoplasia type 1 and hormonal production in apparently sporadic neuroendocrine tumors. J Clin Endocrinol Metab 84: 69–75
Blind E, Schmidt-Gayk H, Sinn HP, O’Connor DT and Raue F (1992) Chromogranin A as tumor marker in medullary thyroid carcinoma. Thyroid 2: 5–10
Boosma F, Bhaggoe UM, Man in ‘t Veld AJ and Schalekamp MADH (1995) Sensitivity and specificity of new ELISA method for determination of chromogranin A in the diagnosis of phaeochromocytoma and neuroblastoma. Clin Chim Acta 239: 57–63
Ciofu A, Baudin E, Chanson P, Cailleux AF, Comoy E, Sabourin JC, Ducreux M, Schaison G and Schlumberger M (1999) Catecholamine production in patients with gastroenteropancreatic neuroendocrine tumors. Eur J Endocrinol 140: 434–437
Cryer PE, Wortsman J, Shad SD, Nowak RM and Deftos LJ (1991) Plasma chromogranin A as a marker of sympathochromaffin activity in humans. Am J Physiol 260: E243–246
Deftos LJ (1991) Chromogranin A: its role in endocrine function and as an endocrine and neuroendocrine tumor marker. Endocr Rev 12: 181–187
Degorce F, Goumon Y, Jacquemart L, Vidaud C, Bellanger L, Pons-Anicet D, Seguin P, Metz-Boutigue MH and Aunis D (1999) A new human chromogranin A (CgA) immunoradiometric assay involving monoclonal antibodies raised against the unprocessed central domain (145–245). Br J Cancer 79: 65–71
Eisenhoffer G, Lenders JWM, Linehan M, Walther MM, Goldstein DS and Keiser HR (1999) Plasma normetanephrine and metanephrine for detecting pheochromocytoma in Von Hippel-Lindau disease and multiple endocrine neoplasia type 2. N Engl J Med 340: 1872–1879
Ferrari L, Seregni E, Martinetti A, Van Graafeiland B, Nerini-Molteni S, Botti C, Artale S, Cresta S and Bombardieri E (1998) Chromogranin A measurement in neuroendocrine tumors. Int J Biol Markers 13: 3–9
Ghillani PP, Motte P, Troalen F, Jullienne A, Gardet P, Le Chevallier T, Rougier P, Schlumberger M, Bohuon C and Bellet D (1989) Identification and measurement of calcitonin precursors in serum of patients with malignant diseases. Cancer Res 49: 6845–6851
Héron E, Chatellier G, Billaud E, Foos E and Plouin PF (1996) The urinary metanephrine-to-creatinine ratio for the diagnosis of phaeochromocytoma. Ann Intern Med 125: 300–303
Hsiao RJ, Parmer RJ, Takiyyuddin MA and O’Connor DT (1991) Chromogranin A storage and secretion: sensitivity and specificity for the diagnosis of phaeochromocytoma. Medicine 70: 33–45
Kimura N, Miura W, Noshiro T, Mizunashi K, Hanew K, Shimizu K, Watanabe T, Shibukawa S, Sohn HE, Abe K, Miura Y and Nagura H (1997) Plasma chromogranin A in phaeochromocytoma, primary hyperparathyroidism and pituitary adenoma in comparison with catecholamine, parathyroid hormone and pituitary hormones. Endocr J 44: 319–327
Leboulleux S, Baudin E, Young J, Caillou B, Lazar V, Pellegriti G, Ducreux M, Schaison G and Schlumberger M (1999) Gastroenteropancreatic neuroendocrine tumor metastases to the thyroid gland: differential diagnosis with medullary thyroid carcinoma. Eur J Endocrinol 140: 187–191
Marcillac I, Troalen F, Bidart JM, Ghillani P, Ribrag V, Escudier B, Malassagne B, Droz JP, Lhomme C, Rougier P, Duvillard P, Prade M, Luguagne PM, Richard F, Poynard T, Bohuon C, Wands J and Bellet D (1992) Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms. Cancer Res 52: 3901–3907
Nobels FRE, Kwekkeboom DJ, Coopmans W, Schoenmakers HH, Lindemans J, De Herder WW, Krenning EP, Bouillon R and Lamberts SWJ (1997) Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the α-subunit of glycoprotein hormones. J Clin Endocrinol Metabt 82: 2622–2628
Norheim I, Oberg K, Theodorsson-Norheim E, Lindgren PG, Lundqvist G, Magnusson A, Wide L and Wilander E (1987) Malignant carcinoid tumors. An analysis of 103 patients with regard to tumor localization, hormone production, and survival. Ann Surg 206: 115–125
Öberg K (1996) The ultimate biochemical diagnosis of gastro-enteropancreatic tumours. Digestion 57: 45–47
O’Connor DT and Deftos LJ (1986) Secretion of chromogranin A by peptide-producing endocrine neoplasms. N Engl J Med 314: 1145–1151
O’Connor DT, Pandian MR, Carlton E, Cervenka JH and Hsiao RJ (1989) Rapid radioimmunoassay of circulating chromogranin A: in vitro stability, exploration of the neuroendocrine character of neoplasia, and assessment of the effects of organ failure. Clin Chem 35: 1631–1637
Ozturk M, Bellet D, Manil L, Hennen G, Frydman R and Wands J (1987) Physiological studies of human chorionic gonadotropin (hCG), hCGα, and hCGβ as measured by specific monoclonal immunoradiometric assays. Endocrinology 120: 549–558
Sanduleanu S, Stridsberg M, Jonkers D, Hameeteman W, Biemond I, Lundqvist G, Lamers C and Stockbrugger RW (1999) Serum gastrin and chromogranin A during medium- and long-term acid suppressive therapy: a case-control study. Aliment Pharmacol Ther 13: 145–153
Schlumberger M, Abdelmoumene N, Delisle MJ, Couette JE and the Groupe d’Etude des tumeurs a Calcitonine (GETC) (1995) Treatment of advanced medullary thyroid cancer with an alternating combination of 5 FU-streptozocin and 5 FU-dacarbazine. Br J Cancer 71: 363–365
Stidsberg M and Husebye ES (1997) Chromogranin A and chromogranin B are sensitive circulating markers for phaeochromocytoma. Eur J Endocrinol 136: 67–73
Takiyyuddin MA, Cervenka JH, Pandian MR, Stuenkel CA, Neumann HP and O’Connor DT (1990) Neuroendocrine sources of chromogranin A in normal man: clues from selective stimulation of endocrine glands. J Clin Endocrinol Metab 71: 360–369
Takiyyuddin MA, Baron AD, Cervenka JH, Barbosa JA, Neumann HP, Parmer RJ, Sullivan PA and O’Connor DT (1991) Suppression of chromogranin A release from neuroendocrine sources in man: pharmacological studies. J Clin Endocrinol Metab 72: 616–622
Wiedenmann B and Huttner WB (1989) Synaptophysin and chromogranins / secretogranins – widespread constituents of distinct types of neuroendocrine vesicles and new tools in tumor diagnosis?. Virchows Archiv B Cell Pathol 58: 95–121
Yanaihara H, Hata M, Nishikawa Y, Hoshino M, Yanaihara N and Murai M (1999) Application of region-specific immunoassay for human chromogranin A: substantial clue for detection and measurement of chromogranin A in human plasma. Regul Pept 80: 83–90
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Guignat, L., Bidart, J., Nocera, M. et al. Chromogranin A and the α-subunit of glycoprotein hormones in medullary thyroid carcinoma and phaeochromocytoma. Br J Cancer 84, 808–812 (2001). https://doi.org/10.1054/bjoc.2000.1677
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1054/bjoc.2000.1677
Keywords
This article is cited by
-
New therapeutic approaches to treat medullary thyroid carcinoma
Nature Clinical Practice Endocrinology & Metabolism (2008)