Pheochromocytomas are rare
catecholamine-secreting
tumors that arise from chromaffin tissue within the adrenal medulla and extra-adrenal sites. Typical clinical manifestations are sustained or paroxysmal
hypertension, severe
headaches, palpitations and sweating resulting from
hormone excess. However, their presentation is highly variable and can mimic many other diseases. The diagnosis of
pheochromocytomas depends mainly upon the demonstration of
catecholamine excess by 24-h urinary
catecholamines and metanephrines or plasma metanephrines. Occurrence of malignant
pheochromocytomas can only be asserted by imaging of metastatic lesions, which are associated with a poor survival rate. The characterization of tissue, circulating or
genetic markers is therefore crucial for the management of these
tumors.
Proteins of the
granin family and their derived
peptides are present in dense-core secretory vesicles and secreted into the bloodstream, making them useful markers for the identification of neuroendocrine cells and
neoplasms. In this context, we will focus here on reviewing the distribution and characterization of
granins and their processing products in normal and tumoral chromaffin cells, and their clinical usefulness for the diagnosis and prognosis of
pheochromocytomas. It appears that, except SgIII, all members of the
granin family i.e. CgA, CgB, SgII, SgIV-SgVII and proSAAS, and most of their derived
peptides are present in adrenomedullary chromaffin cells and in pheochromocytes. Moreover, besides the routinely used CgA test assays, other assays have been developed to measure concentrations of tissue and/or circulating
granins or their derived
peptides in order to detect the occurrence of
pheochromocytomas. In most cases, elevated levels of these entities were found, in correlation with
tumor occurrence, while rarely discriminating between benign and
malignant neoplasms. Nevertheless, measurement of the levels of
granins and derived
peptides improves the diagnostic sensitivity and may therefore provide a complementary tool for the management of
pheochromocytomas. However, the existing data need to be substantiated in larger groups of patients, particularly in the case of malignant disease.