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. (AACE Clinical Case Rep. 2015;1:e269-e272) 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.

Hypercalcitoninemia and Insulinoma – a rare association

“…There are some reports in the literature of both operational and non-functioning calcitonin-secreting PanNETs. [7][8][9][10][11][17][18][19][20][21][22][23][24][25][26] The exact incidence of calcitonin expression in these tumours is unknown. Uccela S et al 26 performed a review of the literature and found a predominance of calcitonin-immunoreactive VIPpomas among FPanNETs, contrary to what the authors found in their own study, in which insulinomas predominated.…”

“…In some of the reported cases of functioning and non-functioning calcitonin-secreting PanNET, calcitonin was requested in the context of nodular thyroid disease. 7,[21][22][23][24][25] In others no thyroid disease was identified, leading to unnecessary total thyroidectomies due to the suspicion of a small MTC. In some case reports, calcitonin-secreting PanNET were diagnosed due to systemic or gastrointestinal symptoms (diarrhoea, abdominal pain, etc.)…”

“…and the presence of a suspected image on CT scan or abdominal ultrasound. 11,[22][23][24]28 It appears that serum values of unstimulated calcitonin greater than 100 pg/mL are more suggestive of a MTC. 16,27 However, some case reports calcitonin-secreting insulinomas had serum calcitonin levels above 100 pg/mL.…”