Proinsulinoma causing severe hypoglycemia in a patient with type 1 diabetes mellitus

Abstract

Case presentation: A 49 year male a 35 year history of Type 1 Diabetes Mellitus (T1DM) was evaluated for recurrent episodes of hypoglycemia. After being weaned off of all exogenous insulin, the patient continued to have frequent and severe episodes of hypoglycemia often associated with seizures. Results:During an observed hypoglycemic reaction in our office he was found to have a serum glucose level of 64 mg/dl, a serum insulin level of 64 μIU/ml (reference range is <17 μIU/ml) and a C-peptide level of 0.6 ng/ml (reference range is 0.8 ng/ml -3.1 ng/ml). Serum and urine sulfonylurea levels were negative. During a formal diagnostic 72 hour fast, he developed severe hypoglycemia within four hours of beginning the fast and seized. No diagnostic laboratory studies were obtained during the hypoglycemic event! He underwent surgical exploration, where a 0.8 cm well-differentiated, islet cell tumor was resected. Following resection of the tumor, the spontaneous hypoglycemia resolved, and maintenance exogenous insulin was reinstituted. Histoimmunochemical staining was positive for chromogranin, synaptophysin, amylin, and proinsulin but negative for insulin. Immunostaining of the tumor was also positive for Toll-like receptors-3 (TLR3) and Wnt5a.Conclusion: This is the first case report of a patient with a long history of T1DM who developed a recurrent hypoglycemia due to a proinsulin-secreting islet cell tumor which resolved following its resection.

The Transformation of a Nonfunctioning Islet Cell Tumor of the Pancreas into a Proinsulinoma under Conditions of Lung Metastasis

“…However, the proinsulin continuously produced by a proinsulinoma is thought to play a role similar to the insulin produced by an insulinoma. Tumors that secrete proinsulin alone, such as that observed in our patient, are very rare (6)(7)(8)(9)(10). In the present case, the immunohistochemical examination did not confirm the production of insulin by the tumors, including the original tumor as well as the liver and lung metastases.…”

Morphologically ‘invisible’ proinsulin – secreting adenoma detected by Ga‐68 Exendin‐4 (GLP‐1 Receptor) positron emission tomography/CT

“…As this condition is far more rare, only a few case reports are available, almost all emphasizing the importance of routine assessment of proinsulin, as commonly used ultra-specific insulin assays cannot detect this precursor. [8][9][10][11][12][13] In our institution, a proinsulin test is always done at the end of all fasting tests carried out.…”