Flushing can be an exaggeration of a physiological process or a manifestation of a serious condition that needs to be identified and treated. Christian Nasr, M.D., presents guidelines that will help determine when a biochemical work-up is warranted from The Cleveland Clinic Disease Management Project, published December 2004.
This link is to a PubMed abstract. The full text requires a subscription to The Journal of Nuclear Medicine Online. Alexander Becherer, M.D. ; Monica Szabo, M.D. ; Georgios Karanikas, M.D. ; Patrick Wunderbaldinger, M.D. ; Peter Angelberger, PhD; Markus Raderer, M.D. ; Amir Kurtaran, M.D. Robert Dudczak, M.D. and Kurt Kletter, M.D. , PhD J . Nucl Med 2004; 45:1161-1167
This link is to a PubMed abstract. The full text requires connection to ScienceDirect. Best Pract Res Clin Endocrinol Metab. 2005 Jun;19(2):265-76. Oberg K, Eriksson B. Department of Endocrine Oncology, University Hospital, SE-751 85 Uppsala, Sweden
This link is to a PubMed abstract. The full text requires a subscription to subscription to Annals of the New York Academy of Sciences Online. Sundin A, Eriksson B, Bergstrom M, Langstrom B, Oberg K, Orlefors H. Ann N Y Acad Sci. 2004 Apr;1014:246-57
". . . In comparative studies of patients with carcinoids and endocrine pancreatic tumors, 5-HTP-PET proved better than CT and somatostatin receptor scintigraphy for tumor visualization, and many small, previously overlooked lesions were diagnosed by 11C-5-HTP-PET. . . ."
". . .With new, more sensitive PET cameras, larger field of view and procedures for whole-body coverage, the PET examination with 5-HTP is now routinely performed as reduced whole-body PET examinations with coverage of the thorax and abdomen. With this method we have been able to visualize small neuroendocrine lesions in the pancreas and thorax (e.g., ACTH-producing bronchial carcinoids) not detectable by any other method, including octreotide scintigraphy, MRI, and CT. . . ."
NOTE: This scan is currently only available in Sweden.
Full text with permission from the authors Warner RR, O'dorisio TM. Semin Nucl Med 2002 Apr;32(2):79-83
The author briefly reviews radiopeptides currently approved for use in the United States. They present a short review of the peptide somatostatin's actions and also note the five somatostatin receptors (SSTRs) to which the peptide and its synthetic analogs octreotide, lanreotide, and vapreotide bind. The many conditions besides neuroendocrine tumors having SSTRs are listed.
This link is to a PubMed abstract.The full text is available online from the PUB MED abstract. Orlefors H, Sundin A, Garske U, Juhlin C, Öberg K, Langstrom B, Bergstrom M, Eriksson B. J Clin Endocrinol Metab. 2005 Mar 8; Conclusion: This study indicates that 11C-5-HTP-PET is a sensitive method for detection of NET´s and it exceeds both SRS and CT in tumor visualization. The contribution of patient tumor status with this technique is considerable. With the exception for poorly differentiated NET´s and possibly non functioning tumors, we believe that 11C-5-HTP can be used as a universal technique for imaging of NET´s, with the greatest benefit in imaging of small tumor lesions e.g. primary tumors. This study also reflects that many different NET´s process biogenic amines to some degree regardless of functionality and endocrine syndrome. NOTE: This scan is currently only available in Sweden
By E. Seregni, L. Ferrari, E. Bajetta, A Martinetti, E. Bombarderi Annals of Oncology 12 ( Suppl. 2: S69-S72, 2001) Conclusions: CgA was confirmed to be the best tumour marker currently available for identifying patients suffering from NETs of the GEP system, lung carcinoids and neuroblastomas. CgA is recommended in the follow-up of patients with such tumours
Elevated Plasma Chromogranin A Is the First Indication of Recurrence in Radically Operated Midgut Carcinoid Tumors
Staffan Welina Mats Stridsbergb Janet Cunninghama Dan Granberga Britt Skogseida Kjell Öberga Barbro Erikssona Eva T. Jansona Department of Medical Sciences, Unit of a Endocrine Oncology,b Clinical Chemistry, University Hospital, Uppsala , Sweden
Conclusion: P-CgA was the first marker to indicate tumor recurrence in the majorityof radically operated midgut carcinoid patients. To avoid unnecessaryand costly examinations in asymptomatic patients,we suggest that follow-up should comprise measurementsof P-CgA twice a year and annual ultrasonographyuntil P-CgA is elevated or clinical symptoms occur, at which time all efforts should be made to identify recurrent tumorlesions in order to give the patient the best possible treatment which, if possible, should be surgical removal of the recurrence. . . .Read More Here NOTE: The importance of Chromogranin A as a neuroendicrine marker has been known and documented in the medical literature for over 20 years. CgA Medical References
This link is to the PubMed abstract. From the abstract, there are direct lines to the full text article on the Science Direct website (requires subscription payment). By Lamberts SW, Hofland LJ, Nobels FR. Frontiers in Neuroendocrinology. 2001 Oct;22 (4):309-39. Review. "Markers, such as chromogranin A, neuron-specific enolase, and alpha-subunit, as well as peptide receptor visualization, are of increasing importance in the diagnosis and follow-up of neuroendocrine and non-neuroendocrine tumors."
By Laurent Taupenot, Ph.D., Kimberly L. Harper, M.D., and Daniel T. O'Connor, M.D. N Engl J Med. 2003 Mar 20;348(12):1134-49. (Full text PDF)
"The highest levels of serum chromogranin A (up to 1000 times the upper limit of the normal range) have been found in patients with metastatic carcinoid tumors. The stability of serum chromogranin A speaks favorably for its use in detecting carcinoid tumors and monitoring their progression; alternative diagnostic tests for carcinoid tumors include tests of urinary 5-hydroxyindoleacetic acid, serum serotonin (5-hydroxytryptamine), and serum neuron-specific enolase. In multiple endocrine neoplasia type I, there is a clear correlation between the tumor mass and the circulating level of chromogranin A. In patients with midgut carcinoid tumors, an elevated chromogranin A level is an independent predictor of death."
By J E S Ardill and B Eriksson1 Regional Regulatory Peptide Laboratory, Royal Hospitals Trust & Queens University Belfast, Mulhouse Building, Belfast BT12 6BJ, UK Department of Medical Sciences, Uppsala University Hospital, Sweden December 2003 Volume 10, Issue 4
Abstract: The measurement of general and specific biochemical markers in patients with neuroendocrine tumours assists with diagnosis, gives an indication of the effectiveness of treatment and may be used as prognostic indicators. There is much agreement that Chromogranin A is the most universally helpful marker which is found to be elevated in the circulation of about 90% of patients with metastatic neuroendocrine tumours and there are several excellent commercially available kits, which give reliable estimations of chromogranin A. Specific markers are useful for diagnosis also, and are helpful indicators of the effectiveness of treatment particularly where tumour bulk may not change so much as tumour activity. Sporadic pancreatic neuroendocrine tumours may secrete more that one peptide and this indicates worsening prognosis. Because of the wide variation in the progression of neuroendocrine tumours, a prognostic indicator gives a significant advantage to the clinician in order to facilitate optimum treatment at the optimum stage of disease. Both chromogranin A and neurokinin A have been used as powerful prognostic indicators for midgut carcinoid tumours.
Diagnosis and Surveillance - Immunohistochemical markers
La Rosa S, Rigoli E, Uccella S, Chiaravalli AM, Capella C. Virchows Arch. 2004 Sep;445(3):248-54. Epub 2004 Jul 29
Gastroenteropancreatic (GEP) endocrine tumors (ETs) are neoplasms showing different hormonal profiles and different clinical and prognostic features, which depend consistently on the site of origin. Histological features and general endocrine markers do not differentiate tumors in relation to their location, making it difficult to establish the site of origin of a GEP ET that has metastasized to the liver or lymph nodes. A site-specific marker would be particularly useful in the examination of small specimens where there is not sufficient material for an extensive study of the hormonal expression. CDX2 is a transcription factor that has been recently proposed as a marker of intestinal adenocarcinomas. Our aim was to evaluate the immunohistochemical expression of CDX2 in normal tissues and in 184 formalin-fixed and paraffin-embedded ETs to verify whether it could be used to identify intestinal ETs with a high degree of sensitivity and specificity. Of these cases, 154 were primary tumors (99 GEP and 55 non-GEP tumors), 101 were well-differentiated endocrine tumors, and 53 were poorly differentiated endocrine carcinomas (PDECs). Of the cases, 30 were metastases from differently located ETs. Nuclear CDX2 immunoreactivity was found in all EC-cells (serotonin-producing cells), in about 10% of G-cells (gastrin-producing cells), in about 30% of GIP-cells (gastric inhibitory peptide cells) and in a few motilin-positive cells of the normal intestinal mucosa, while other gastrointestinal endocrine cell types were CDX2 negative. All midgut EC-cell tumors, their metastases, and two of three pancreatic EC-cell ETs were diffusely and intensely CDX2 positive. The other GEP ETs, their metastases, as well as the non-GEP ETs, were all CDX2 negative, with the exception of four PDECs, five gastrinomas and one pheochromocytoma, which were only focally positive. We conclude that CDX2 may be considered a sensitive and specific marker of midgut EC-cells and EC-cell tumors, and its expression may be useful in the diagnosis of metastases from occult ETs.