Human pheochromocytoma: different patterns of catecholamines and chromogranins in the intact tumour, urine and serum in clinically unsuspected cases

Abstract

Clinically unsuspected pheochromocytoma is usually discovered either at autopsy or during surgical intervention for unrelated conditions, despite often enormous neoplastic masses producing and storing catecholamine (CA). In order to assess whether these tumours share some common features we have compiled data for six patients admitted to hospital without previous diagnosis of their pheochromocytoma. The clinical variables and the morphological and immunohistochemical characteristics of the tumours revealed that these cases represented quite different expressions of adrenomedullary neoplasms. They differed not only with respect to nuclear ploidity and overall cytoplasmic morphology but also in catecholamine storage and expression of immunoreactive chromogranin A sequences in the intact tissue. In two of the patients hypertension had been overlooked as a diagnostic indicator of their CA-producing tumours. There was no clear relationship between the mean arterial pressure, the tumour content of CA and the serum levels of CA. Processed chromogranin A dominated in the serum of the two hypertensive cases. The 24-h urine values of CA and its main metabolite (vanillin mandelic acid) were, together with the serum values of chromogranin A and B, proportional to tumour mass and provided the most reliable diagnostic indicators for the non-hypertensive as well as the hypertensive cases.

Characterisation of N-terminal chromogranin A and chromogranin B in mammals by region-specific radioimmunoassays and chromatographic separation methods

“…This was in apparent contrast to the sheep, goat, horse and pig circulation, with serum levels of free vasostatin in the 2 nM range. In porcine serum, the concentration of vasostatin was of the same order as that detected in the preoperative serum sample of a patient suffering from a metastatic pheochromocytoma (patient number 5 in Aardal et al 1996).…”

“…**CgA levels are not given due to limited interspecies cross-reactivity in the bCgA radioimmunoassay. In human serum vasostatin immunoreactivity was 2·8 nM in the preoperative serum sample of a patient with metastatic pheochromocytoma (patient 5, Aardal et al 1996), while <0·1 nM in the post-operative sample was consistent with serum concentrations of <0·1 nM for healthy volunteers (n=6).…”

“…The concentration of vasostatin in cattle was comparable to the level measured in one human patient after a successful operation for pheochromocytoma, where the serum level is likely to be 'normal' (Aardal et al 1996). Hence, these data can be interpreted in two ways, either that the serum concentrations of CgA, or the degree of N-terminal processing to yield free vasostatin, differ among these mammals.…”

“…Normal human adrenal glands and pheochromocytoma tumour tissue were obtained with institutional approval as discarded tissue from patients undergoing radical nephrectomy at the University Hospital in Bergen (Aardal et al 1996).…”

Activation of the Inositol 1,4,5-Trisphosphate Receptor by the Calcium Storage Protein Chromogranin A

“…In healthy individuals, CGA and its peptide fragments are present in the circulatory system in low nanomolar quantities. However, in patients suffering from pheochromocytoma and other neuroendocrine tumors, concentrations are significantly higher (14). Elevated plasma levels of CGA are associated with a number of pathological conditions making the protein an ideal marker not only for neuroendocrine tumors but also for chronic heart failure and brain disorders such as Parkinson's and Alzheimer's diseases (15).…”