VIPoma with expression of both VIP and VPAC1 receptors in a patient with WDHA syndrome.

We report a case of VIPoma in a 72-year-old female patient who presented with excessive diarrhea, severe hypokalemia, and acidemia. She had been referred to our hospital three times because of severe diarrhea. No primary tumor site was found by conventional techniques, including contrast-enhanced CT and MRI, angiography, endoscopy, and positron emission tomography (PET), but a tumor was subsequently found in the head of the pancreas by octreotide scanning. Her diarrhea diminished dramatically after octreotide treatment, while her diarrhea has ceased without the therapy of octreotide at the first admission in the course of 2 years of her disease. Immunohistochemial analysis of the excised tumor tissue revealed the expression of both vasoactive intestinal peptide (VIP) and VIP and pituitary adenylate cyclase-activating peptide 1 (VPAC1) receptors. This is the first case report of a VIPoma that immunostains for VIP and VPAC1 receptors and indicates that abundant VIP produced by VIPoma might inhibit its growth and reduce VIP secretion via the VPAC1 receptor in vivo.

Massive amyloid deposition in pancreatic vipoma: a case report.

We present a case of a pancreatic islet cell tumor, demonstrating typical clinical and immunohistochemical characteristics of a VIPoma, but with the novel feature of massive stromal amyloid deposition. Amyloid deposition has been reported in association with insulinomas of the pancreas, but as far as the available literature suggests, it has not been reported in VIPomas. Islet associated polypeptide (IAPP) and calcitonin are both candidates for the amyloidogenic peptide in this case, based on observations in other tumors.

Identification of a new chromogranin B fragment (314-365) in endocrine tumors.

A rabbit antiserum was raised against the fragment (350-365) of human chromogranin B corresponding to the C-terminal end of a putative proteolytic fragment generated by the cleavage of a dibasic doublet located in position 366-367 of the precursor. A radioimmunoassay was developed. Chromatographic analysis of 10 endocrine tumor extracts (one liver metastasis of a gastrinoma, one liver metastasis of a medullary carcinoma of the thyroid, one VIPoma, one insulinoma, one nonsecreting pancreatic endocrine tumor, one local recurrence of a gut carcinoid, two pituitary gonadotropinoma, and two non-secreting pituitary adenomas) revealed the presence of two forms of immunoreactive material. The most abundant form had an apparent molecular weight of 4500 and was purified to homogeneity by successive reverse-phase HPLC chromatographies and partially sequenced. The N-terminal sequence of the peptide, established by automated Edman degradation, was A-S-E-E-E-P-E-Y-G-E-E-I-K-G-Y-P-V-Q and corresponded to the 314-332 sequence of human chromogranin B. Taking into account the specificity of the antiserum used for peptide identification, we deduced that the purified peptide was chromogranin B(314-365) and represented a new form generated by limited proteolysis of chromogranin B.

PreproVIP-derived peptides in tissue and plasma from patients with VIP-producing tumours.

To elucidate the biosynthetic processing of the precursor for vasoactive intestinal peptide (prepro-VIP) in tumours producing VIP we have used newly developed radioimmunoassays directed against the five functional domains of the VIP precursor molecule: preproVIP 22-79, peptide histidine methionine (PHM), preproVIP 111-122, VIP and preproVIP 156-170 in combination with HPLC to identify and quantify the peptides in tumour specimen and plasma from patients with the watery diarrhoea syndrome. Elevated quantities of all the five peptides were found in the 13 tumours (nine neurogenic tumours, one pheochromocytoma, three pancreatic carcinomas) examined. The preproVIP derived peptides were expressed in non-equimolar amounts and the relative proportion of the various peptides differed markedly from tumour to tumour. The pheochromocytoma was the only tumour type which contained large amounts of preproVIP 156-170 in comparison with the other peptides. A proportion of the VIP precursor which varied from 7% to 73% followed a pathway in which the dibasic conversion site after PHM was uncleaved as evidenced by the presence of PHV, a C-terminally extended form of PHM. It was also found that unlike normal tissue a fraction of the C-terminal VIP precursor peptide, preproVIP 156-170, was having its C-terminal lysine residue removed during processing. The findings indicate that various post-translational processing pathways of preproVIP exist. All the peptide sequences produced in the tumour tissue were secreted as evidenced by their presence in plasma in elevated concentrations. The plasma levels of preproVIP 22-79, preproVIP 111-122 and PHV exceeded those of the remaining preproVIP-derived peptides suggesting that determination of these peptides in patients with VIP-secreting tumours may be better markers than VIP.