Pancreatic Neuroendocrine Tumors Presenting with Hypercalcitonemia

ABSTRACT Objective: Pancreatic neuroendocrine tumors (pNETs) can be associated with discrete clinical syndromes due to the secretion of a variety of bioactive substances that are used to confirm the diagnosis and as potential tumor markers. Calcitonin (Ct) is mainly secreted by medullary thyroid carcinoma (MTC) but is also rarely secreted by pNETs, occasionally leading to diagnostic confusion. We report the diagnosis of 4 patients with metastatic pNETs and associated Ct secretion who were initially evaluated for thyroid pathology. Methods: We describe the histories of 4 patients who were referred for evaluation of thyroid diseases and proved to have metastatic pNETs and associated Ct secretion. One of the patients had erroneously undergone thyroidectomy as hypercalcitonemia was attributed to MTC. Results: Patients presented with variable Ct levels (4-fold up to 35-fold elevations), and all had thyroid nodules that were considered the cause of hypercalcitonemia. Ultrasonography and fine-needle aspiration cytology (FNAC) were used to exclude the thyroid origin of high Ct. As a result, investigations were directed towards other causes of hypercalcitonemia and pancreatic tumors were discovered. Conclusions: As in the majority of cases, Ct secretion is not associated with an obvious clinical syndrome, and these cases may be misdiagnosed as MTC, particularly in the absence of locally compressive symptoms from pNETs. Making the wrong diagnosis has potentially deleterious effects and may lead to unnecessary interventions such as a thyroidectomy and late diagnosis of an advanced pNET. Abbreviations: CgA chromogranin A Ct calcitonin FNAC fine-needle aspiration cytology IHC immunohistochemistry LI labeling index MTC medullary thyroid carcinoma NET neuroendocrine tumor pNET pancreatic neuroendocrine tumors SSA somatostatin analogue