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. 2001 Mar;84(6):808–812. doi: 10.1054/bjoc.2000.1677

Chromogranin A and the α -subunit of glycoprotein hormones in medullary thyroid carcinoma and phaeochromocytoma

L Guignat 1, J M Bidart 2, M Nocera 1, E Comoy 2, M Schlumberger 1, E Baudin 1
PMCID: PMC2363821  PMID: 11259096

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 http://www.bjcancer.com

Keywords: chromogranin A, α-subunit of glycoprotein hormones, medullary thyroid carcinoma, phaeochromocytoma, neuroendocrine tumours

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Selected References

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  1. Averbuch S. D., Steakley C. S., Young R. C., Gelmann E. P., Goldstein D. S., Stull R., Keiser H. R. Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine. Ann Intern Med. 1988 Aug 15;109(4):267–273. doi: 10.7326/0003-4819-109-4-267. [DOI] [PubMed] [Google Scholar]
  2. Baudin E., Bidart J. M., Rougier P., Lazar V., Ruffié P., Ropers J., Ducreux M., Troalen F., Sabourin J. C., Comoy E. Screening for multiple endocrine neoplasia type 1 and hormonal production in apparently sporadic neuroendocrine tumors. J Clin Endocrinol Metab. 1999 Jan;84(1):69–75. doi: 10.1210/jcem.84.1.5445. [DOI] [PubMed] [Google Scholar]
  3. Baudin E., Gigliotti A., Ducreux M., Ropers J., Comoy E., Sabourin J. C., Bidart J. M., Cailleux A. F., Bonacci R., Ruffié P. Neuron-specific enolase and chromogranin A as markers of neuroendocrine tumours. Br J Cancer. 1998 Oct;78(8):1102–1107. doi: 10.1038/bjc.1998.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blind E., Schmidt-Gayk H., Sinn H. P., O'Connor D. T., Raue F. Chromogranin A as tumor marker in medullary thyroid carcinoma. Thyroid. 1992 Spring;2(1):5–10. doi: 10.1089/thy.1992.2.5. [DOI] [PubMed] [Google Scholar]
  5. Boomsma F., Bhaggoe U. M., Man in 't Veld A. J., Schalekamp M. A. Sensitivity and specificity of a new ELISA method for determination of chromogranin A in the diagnosis of pheochromocytoma and neuroblastoma. Clin Chim Acta. 1995 Jul 31;239(1):57–63. doi: 10.1016/0009-8981(95)06100-r. [DOI] [PubMed] [Google Scholar]
  6. Ciofu A., Baudin E., Chanson P., Cailleux A. F., Comoy E., Sabourin J. C., Ducreux M., Schaison G., Schlumberger M. Catecholamine production in patients with gastroenteropancreatic neuroendocrine tumors. Eur J Endocrinol. 1999 May;140(5):434–437. doi: 10.1530/eje.0.1400434. [DOI] [PubMed] [Google Scholar]
  7. Cryer P. E., Wortsman J., Shah S. D., Nowak R. M., Deftos L. J. Plasma chromogranin A as a marker of sympathochromaffin activity in humans. Am J Physiol. 1991 Feb;260(2 Pt 1):E243–E246. doi: 10.1152/ajpendo.1991.260.2.E243. [DOI] [PubMed] [Google Scholar]
  8. Deftos L. J. Chromogranin A: its role in endocrine function and as an endocrine and neuroendocrine tumor marker. Endocr Rev. 1991 May;12(2):181–187. doi: 10.1210/edrv-12-2-181. [DOI] [PubMed] [Google Scholar]
  9. Degorce F., Goumon Y., Jacquemart L., Vidaud C., Bellanger L., Pons-Anicet D., Seguin P., Metz-Boutigue M. H., Aunis D. A new human chromogranin A (CgA) immunoradiometric assay involving monoclonal antibodies raised against the unprocessed central domain (145-245). Br J Cancer. 1999 Jan;79(1):65–71. doi: 10.1038/sj.bjc.6690013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eisenhofer G., Lenders J. W., Linehan W. M., Walther M. M., Goldstein D. S., Keiser H. R. Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von Hippel-Lindau disease and multiple endocrine neoplasia type 2. N Engl J Med. 1999 Jun 17;340(24):1872–1879. doi: 10.1056/NEJM199906173402404. [DOI] [PubMed] [Google Scholar]
  11. Ferrari L., Seregni E., Martinetti A., Van Graafeiland B., Nerini-Molteni S., Botti C., Artale S., Cresta S., Bombardieri E. Chromogranin A measurement in neuroendocrine tumors. Int J Biol Markers. 1998 Jan-Mar;13(1):3–9. doi: 10.1177/172460089801300102. [DOI] [PubMed] [Google Scholar]
  12. Ghillani P. P., Motté P., Troalen F., Jullienne A., Gardet P., Le Chevalier T., Rougier P., Schlumberger M., Bohuon C., Bellet D. Identification and measurement of calcitonin precursors in serum of patients with malignant diseases. Cancer Res. 1989 Dec 1;49(23):6845–6851. [PubMed] [Google Scholar]
  13. Hsiao R. J., Parmer R. J., Takiyyuddin M. A., O'Connor D. T. Chromogranin A storage and secretion: sensitivity and specificity for the diagnosis of pheochromocytoma. Medicine (Baltimore) 1991 Jan;70(1):33–45. [PubMed] [Google Scholar]
  14. Héron E., Chatellier G., Billaud E., Foos E., Plouin P. F. The urinary metanephrine-to-creatinine ratio for the diagnosis of pheochromocytoma. Ann Intern Med. 1996 Aug 15;125(4):300–303. doi: 10.7326/0003-4819-125-4-199608150-00008. [DOI] [PubMed] [Google Scholar]
  15. Kimura N., Miura W., Noshiro T., Mizunashi K., Hanew K., Shimizu K., Watanabe T., Shibukawa S., Sohn H. E., Abe K. Plasma chromogranin A in pheochromocytoma, primary hyperparathyroidism and pituitary adenoma in comparison with catecholamine, parathyroid hormone and pituitary hormones. Endocr J. 1997 Apr;44(2):319–327. doi: 10.1507/endocrj.44.319. [DOI] [PubMed] [Google Scholar]
  16. Leboulleux S., Baudin E., Young J., Caillou B., Lazar V., Pellegriti G., Ducreux M., Schaison G., Schlumberger M. Gastroenteropancreatic neuroendocrine tumor metastases to the thyroid gland: differential diagnosis with medullary thyroid carcinoma. Eur J Endocrinol. 1999 Mar;140(3):187–191. doi: 10.1530/eje.0.1400187. [DOI] [PubMed] [Google Scholar]
  17. Marcillac I., Troalen F., Bidart J. M., Ghillani P., Ribrag V., Escudier B., Malassagne B., Droz J. P., Lhommé C., Rougier P. Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms. Cancer Res. 1992 Jul 15;52(14):3901–3907. [PubMed] [Google Scholar]
  18. Nobels F. R., Kwekkeboom D. J., Coopmans W., Schoenmakers C. H., Lindemans J., De Herder W. W., Krenning E. P., Bouillon R., Lamberts S. W. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones. J Clin Endocrinol Metab. 1997 Aug;82(8):2622–2628. doi: 10.1210/jcem.82.8.4145. [DOI] [PubMed] [Google Scholar]
  19. Norheim I., Oberg K., Theodorsson-Norheim E., Lindgren P. G., Lundqvist G., Magnusson A., Wide L., Wilander E. Malignant carcinoid tumors. An analysis of 103 patients with regard to tumor localization, hormone production, and survival. Ann Surg. 1987 Aug;206(2):115–125. doi: 10.1097/00000658-198708000-00001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. O'Connor D. T., Deftos L. J. Secretion of chromogranin A by peptide-producing endocrine neoplasms. N Engl J Med. 1986 May 1;314(18):1145–1151. doi: 10.1056/NEJM198605013141803. [DOI] [PubMed] [Google Scholar]
  21. O'Connor D. T., Pandlan M. R., Carlton E., Cervenka J. H., Hslao R. J. 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. 1989 Aug;35(8):1631–1637. [PubMed] [Google Scholar]
  22. Oberg K. The ultimate biochemical diagnosis of gastro-enteropancreatic tumours. Digestion. 1996;57 (Suppl 1):45–47. doi: 10.1159/000201394. [DOI] [PubMed] [Google Scholar]
  23. Ozturk M., Bellet D., Manil L., Hennen G., Frydman R., Wands J. Physiological studies of human chorionic gonadotropin (hCG), alpha hCG, and beta hCG as measured by specific monoclonal immunoradiometric assays. Endocrinology. 1987 Feb;120(2):549–558. doi: 10.1210/endo-120-2-549. [DOI] [PubMed] [Google Scholar]
  24. Sanduleanu S., Stridsberg M., Jonkers D., Hameeteman W., Biemond I., Lundqvist G., Lamers C., Stockbrügger R. W. Serum gastrin and chromogranin A during medium- and long-term acid suppressive therapy: a case-control study. Aliment Pharmacol Ther. 1999 Feb;13(2):145–153. doi: 10.1046/j.1365-2036.1999.00466.x. [DOI] [PubMed] [Google Scholar]
  25. Schlumberger M., Abdelmoumene N., Delisle M. J., Couette J. E. Treatment of advanced medullary thyroid cancer with an alternating combination of 5 FU-streptozocin and 5 FU-dacarbazine. The Groupe d'Etude des Tumeurs a Calcitonine (GETC). Br J Cancer. 1995 Feb;71(2):363–365. doi: 10.1038/bjc.1995.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stridsberg M., Husebye E. S. Chromogranin A and chromogranin B are sensitive circulating markers for phaeochromocytoma. Eur J Endocrinol. 1997 Jan;136(1):67–73. doi: 10.1530/eje.0.1360067. [DOI] [PubMed] [Google Scholar]
  27. Takiyyuddin M. A., Baron A. D., Cervenka J. H., Barbosa J. A., Neumann H. P., Parmer R. J., Sullivan P. A., O'Connor D. T. Suppression of chromogranin-A release from neuroendocrine sources in man: pharmacological studies. J Clin Endocrinol Metab. 1991 Mar;72(3):616–622. doi: 10.1210/jcem-72-3-616. [DOI] [PubMed] [Google Scholar]
  28. Takiyyuddin M. A., Cervenka J. H., Pandian M. R., Stuenkel C. A., Neumann H. P., O'Connor D. T. Neuroendocrine sources of chromogranin-A in normal man: clues from selective stimulation of endocrine glands. J Clin Endocrinol Metab. 1990 Aug;71(2):360–369. doi: 10.1210/jcem-71-2-360. [DOI] [PubMed] [Google Scholar]
  29. Wiedenmann B., Huttner W. B. Synaptophysin and chromogranins/secretogranins--widespread constituents of distinct types of neuroendocrine vesicles and new tools in tumor diagnosis. Virchows Arch B Cell Pathol Incl Mol Pathol. 1989;58(2):95–121. doi: 10.1007/BF02890062. [DOI] [PubMed] [Google Scholar]
  30. Yanaihara H., Hata M., Nishikawa Y., Hoshino M., Yanaihara N., Murai M. Application of region-specific immunoassay for human chromogranin A: substantial clue for detection and measurement of chromogranin A in human plasma. Regul Pept. 1999 Mar 17;80(1-2):83–90. doi: 10.1016/s0167-0115(99)00015-4. [DOI] [PubMed] [Google Scholar]

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