ESA-SRB-AOTA 2019

A case of a calcitonin secreting malignant insulinoma  (#618)

Mina Mohammad Ebrahim 1 , Rosemary Wong 1 , Christopher Gilfillan 1
  1. Department of Diabetes and Endocrinology, Eastern Health, Box Hill, VIC , Australia

Background: Neuroendocrine tumors (NETs) are a heterogeneous tumors that express general biomarkers and specific peptide hormones.1 Insulinomas are rare NETs causing hyperinsulinemic hypoglycaemia and can be malignant in 10% of cases.1,2,3

Case: A woman aged 34 lives in supported accommodation, found incidentally to have deranged liver function tests and multiple liver lesions on CT scanning. She had history of Fragile X syndrome and severe intellectual impairment.

Further liver biopsy showed neoplastic cells strongly positive for synaptophysin, chromogranin and calcitonin, weakly positive for somatostatin and insulin and negative for glucagon, CK7, CK20, TTF-1 and PAX-8; Ki-67 10% (Fig 1).5cf8f3a31e2e8-figure1.JPG

Histology was highly suggestive of metastatic medullary thyroid carcinoma (MTC). Serum calcitonin was elevated with peak of 400 pmol/L. CT staging showed multiple liver and skeletal metastases (Fig 2). 5cf8f3a31e2e8-figure2.JPG

She was treated with vandetanib which was stopped three months later due to worsening of liver metastases and development of symptomatic hypoglycaemia. The C-peptide and insulin levels were elevated (Table 1).5cf8f3a31e2e8-Table1.JPG

The PET GaTATE scan confirmed a metastatic neuroendocrine tumour (Fig 3). 5cf8fbced9613-figure3.JPG

A palliative treatment was chosen with the main challenge being severe hypoglycaemia. She was treated with continuous dextrose infusions, prednisolone, diazoxide and cornstarch. Due to limited success, octreotide and everolimus were added with good effect. 

Discussion: Calcitonin is a marker of medullary thyroid carcinoma (MTC) but can be rarely secreted by other NETs as in our patient.4,5 The treatment objectives are tumoral and hormonal control. As with our case, at metastatic stage the treatment aim is palliative with hypoglycaemia remaining the main challenge. 3 In addition to conventional treatment like diazoxide, dietary changes and debulking strategies, somatostatin analogs and mTOR inhibitors can successfully control severe hypoglycemia.3 Octerotide, lanreotide , everolimus and sunitinib, a multitargeted tyrosine kinase inhibitor, have all also been shown to improve progression-free survival in pancreatic NETs.6,7,8,9 

  1. Schott M, Klöppel G, et al. Neuroendocrine neoplasms of the gastrointestinal tract. Dtsch Arztebl Int 2011;108: 305–12.
  2. Yu R, Nissen N, et al. A clinicopathological study of malignant insulinoma in a contemporary series. Pancreas 2017;46: 48-56.
  3. Baudin E, Caron P, et al. Malignant insulinoma: recommendations for characterisation and treatment. Annales d’Endocrinologie 2013;74: 523-533.
  4. Toledo SPA, Lourenço Jr DM, et al. Hypercalcitoninemia is not pathognomonic of medullary thyroid carcinoma. Clinics 2009;64: 699-706.
  5. Ansari UA, Ramirez CL, et al. Calcitonin-secreting pancreatic neuroendocrine tumor in a patient with multiple endocrine neoplasia type 1. AACE Clinical Case Rep 2017;3:317-321.
  6. Rinke A, Muller H, et al. Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients With Metastatic Neuroendocrine Midgut Tumors: A Report From the PROMID Study Group. J Clin Oncol 2009;27:4656-4663.
  7. Caplin ME, Pavel M, et al. Lanreotide in Metastatic Enteropancreatic Neuroendocrine Tumors. N Engl J Med 2014;371:224-33.
  8. Yao JC, Shah MH, et al. Everolimus for Advanced Pancreatic Neuroendocrine Tumors. N Engl J Med 2011;364:514-23.
  9. Raymond E, Dahan L, et al. Sunitinib Malate for the Treatment of Pancreatic Neuroendocrine Tumors. N Engl J Med 2011;364:501-13.