Neuroendocrine Tumour Markers

The neuroendocrine cells of the gastroenteropancreatic (GEP) axis belong to the APUD-system, because they are capable of amine precursor uptake and decarboxylation, leading to the production of amines and small peptides. Currently, over 50 peptides have been identified, secreted by more than IS different types of neuroendocrine cells scattered throughout the gut. Tumours of these cells are generally characterized by an excessive production of one or several of these peptides. The presence of peptides in tumour tissue can usually be easily identified with immunohistochemical methods, or by demonstrating their mRNA with in situ hybridization techniques . The peptides are also frequently released into the circulation, where they can exert their endocrine effects on various targets, often inducing a typical clinical syndrome of hormonal overproduction. These tumours can be called clinically jilllctioning neuroendocrine tumours. The circulating peptides can usually be measured with radioimmunologic methods, allowing them to be used as tumour markers. One tumour generally releases several amilles or peptides in the circulation. Therefore the choice of possible tumour markers is much wider than in the case of non-endocrine tumours. The situation is much more difficult in so-called clinically nonjilllctioning neuroendocrine tumours, not inducing symptoms or signs relating to hormonal hypersecretion. Sometimes, these tumours remain hormonally active, producing peptides without clinical effect, which still can be used as tumour markers. When the tumour has lost all abilities to produce hormonally active substances one has to resort to the use of non-endocrine secretion markers, such as certain enzymes or other contents of secretory granules. In the choice of an adequate tumour marker, the following criteria should be taken into account: the marker must be useful (l) to screen populations for the presence of a tumour, (2) to differentiate between the different types of neuroendocrine tumours, (3) to distinguish between benign, intermediate or malignant tumour types, (4) to provide an estimate of the tumour load, (5) to follow the course of a particular tumour over time, in order to be able to evaluate the response to therapeutic interventions, and to rapidly detect an eventual relapse, and (6) to assess the prognosis. Unfortunately none of the current tumour markers can fulfill all these goals. Therefore, the search for better markers still goes on, and is at present one of the main activities of neuroendocrine research. In addition to the use of the circulating peptides themselves, the receptors for some peptides have recently been shown to be velY valuable markers. Their presence on tumour tissue can be demonstrated in vivo by radioisotopic techniques, using radionuclide labeled peptide, which specifically binds to a specific receptor

Long-term treatment with the dopamine agonist quinagolide of patients with clinically non-functioning pituitary adenoma

OBJECTIVE: This study was performed to evaluate the effect of prolonged treatment with the dopamine agonist quinagolide on serum gonadotropin and alpha-subunit concentrations and tumor volume in patients with clinically non-functioning pituitary adenomas (CNPA). DESIGN: Ten patients with CNPA were treated with quinagolide (0.3 mg daily). The median duration of treatment was 57 months (range 36-93 months). Blood samples for measurement of serum gonadotropin and alpha-subunit concentrations were drawn before treatment, after 5 days, and at each outpatient visit. Computerized tomography or magnetic resonance imaging of the pituitary region and Goldmann perimetry were done before and at regular intervals during treatment. RESULTS: A significant decrease of serum FSH, LH or alpha-subunit concentrations was found in nine patients. The levels remained low during the entire treatment period. In two out of three patients with pre-existing visual field defects a slight improvement was shown during the first months of treatment, but eventually deterioration occurred in all three patients. A fourth patient developed unilateral ophthalmoplegia dur

Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones

Chromogranin A (CgA) is gaining acceptance as a serum marker of neuroendocrine tumors. Its specificity in differentiating between neuroendocrine and nonneuroendocrine tumors, its sensitivity to detect small tumors, and its clinical value, compared with other neuroendocrine markers, have not clearly been defined, however. The objectives of this study were to evaluate the clinical usefulness of CgA as neuroendocrine serum marker. Serum levels of CgA, neuron-specific enolase (NSE), and the alpha-subunit of glycoprotein hormones (alpha-SU) were determined in 211 patients with neuroendocrine tumors and 180 control subjects with nonendocrine tumors. The concentrations of CgA, NSE, and alpha-SU were elevated in 50%, 43%, and 24% of patients with neuroendocrine tumors, respectively. Serum CgA was most frequently increased in subjects with gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%), nonfunctioning tumors of the endocrine pancreas (69%), and medullary thyroid carcinomas (50%). The highest levels were observed in subjects with carcinoid tumors. NSE was most frequently elevated in patients with small cell lung carcinoma (74%), and alpha-SU was most frequently elevated in patients with carcinoid tumors (39%). Most subjects with elevated alpha-SU levels also had elevated CgA concentrations. A significant positive relationship was demonstrated between the tumor load and serum CgA levels (P < 0.01, by chi 2 test). Elevated concentrations of CgA, NSE, and alpha-SU were present in, respectively, 7%, 35%, and 15% of control subjects. Markedly elevated serum levels of CgA, exceeding 300 micrograms/L, were observed in only 2% of control patients (n = 3) compared to 40% of patients with neuroendocrine tumors (n = 76). We conclude that CgA is the best general neuroendocrine serum marker available. It has the highest specificity for the detection of neuroendocrine tumors compared to the other neuroendocrine markers, NSE and alpha-SU. Elevated levels are strongly correlated with tumor volume; therefore, small tumors may go undetected. Although its specificity cannot compete with that of the specific hormonal secretion products of most neuroendocrine tumors, it can have useful clinical applications in subjects with neuroendocrine tumors for whom either no marker is available or the marker is inconvenient for routine clinical use

Somatostatin receptor scintigraphy: Its value in tumor localization in patients with Cushing's syndrome caused by ectopic corticotropin or corticotropin-releasing hormone secretion

purpose: To assess the feasibility of somatostatin receptor scintigraphy for patients with Cushing's syndrome caused by tumors secreting ectopic corticotropin or corticotropin-releasing hormone (CRH). patients and methods: Ten patients with Cushing's syndrome, nine with ectopic corticotropin-secreting tumors and one with a CRH-secreting tumor, were consecutively studied. For comparison purposes, eight patients with corticotropin-secreting pituitary tumors and one patient with an autonomous adrenal adenoma were investigated. In vivo tumor localization was performed for all patients using a radionuclide-coupled somatostatin analog. The results obtained with this technique were compared with those obtained with conventional imaging techniques. For some patients, the clinical effects of octreotide therapy were evaluated. results: Somatostatin analog scintigraphy successfully identified the primary ectopic corticotropin-secreting and CRH-secreting tumors or their metastases, or both, in 8 of 10 patients; in 2 patients with corticotropin-secreting bronchial carcinoids, the tumors could not be visualized. Normal scans were obtained for the 8 patients with corticotropin-secreting pituitary tumors and the one patient with an adrenal adenoma. conclusion: Somatostatin analog scintigraphy can be included as a diagnostic step in the workup of Cushing's syndrome patients with a suspected ectopic corticotropin-secreting tumor or a CRH-secreting tumor