Submitted to: Pancreas
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/20/2006
Publication Date: 10/1/2006
Citation: Woltering, E.A., Hilton, R.S., Thomson, J.L., Zietz, S., Liang, V.W., Vinik, A.I., Vinik, E., O'Dorisio, T.M. 2007. Validation of serum versus plasma measurements of chromogranin A levels in patients with carcinoid tumors. Pancreas. 33:250-254. Interpretive Summary: Neuroendocrine cells produce and secrete hormones. When these cells become cancerous, often resulting in carcinoid tumors, they grow and overproduce their hormone secretions. Chromogranin A (CGA) is one compound secreted by cancerous neuroendocrine cells that can be used to confirm the diagnosis of carcinoid tumor, as well as monitor the growth of the tumor. Common symptoms of carcinoid tumor include flushing (sudden appearance of warmth and redness in the face and neck that can last from minutes to hours), diarrhea, and wheezing. Octreotide in its long-acting repeatable (LAR) form is one drug used to treat the symptoms of carcinoid tumor. Blood levels of CGA and octreotide, as well as the number of episodes of flushing and diarrhea, were measured in 40 patients with carcinoid tumors treated with octreotide LAR. Neither higher blood levels of octreotide nor higher doses of octreotide were associated with lower blood levels of CGA, as would be expected if octreotide controlled tumor growth. Similarly, patients with less flushing episodes had significantly higher CGA levels which is contrary to control of symptoms. However, patients with less diarrhea episodes had slightly lower CGA levels, as would be expected for octreotide symptom control. Because a single measurement of CGA blood levels cannot be used to accurately predict carcinoid tumor symptom control, patients should be monitored for CGA blood levels at multiple times during their treatment with octreotide LAR.
Technical Abstract: Chromogranin A (CGA) levels are used to confirm the diagnosis, and monitor the course of patients with neuroendocrine tumors. Chromogranin A levels are significantly reduced when patients are acutely treated with octreotide; however, limited data is available that correlates octreotide long-acting reapeatable (LAR) dose or steady state octreotide blood levels to the absolute value of serum or plasma CGA. Plasma, serum, and clinical information on carcinoid syndrome symptoms were collected anonymously from 40 patients treated with long-term octreotide LAR therapy for carcinoid syndrome. We found a strong positive linear relationship existed between serum and plasma CGA levels (r = 0.9858, P < 0.0001). No correlation existed between plasma octreotide levels or LAR dose and the static, absolute plasma/serum CGA levels. Although higher mean CGA values were seen in the group whose diarrhea was “not under optimal control” than for the group “under optimal control,” these results did not reach statistical significance (P = 0.24). Contrary to our hypotheses, a statistically significant inverse relationship was found between the frequency of flushing and the CGA levels (P = 0.0372). Higher mean CGA values were observed in the “under optimal control” group with flushing symptoms. Either serum or plasma can be used to measure CGA levels. Absolute (static) CGA levels do not positively correlate with symptom intensity during LAR therapy. Dynamic (serial) measurements of CGA are necessary to monitor the effectiveness of medical or surgical therapy.