Hypoglycemic Syndrome in a Patient with Proinsulin-Only Secreting Pancreatic Adenoma (Proinsulinoma)

Abstract

We describe an unusual case of hypoglycemic syndrome in a 69-year old woman with a proinsulin-only secreting pancreatic endocrine adenoma. The clinical history was highly suggestive of an organic hypoglycemia, with normal or relatively low insulin concentrations and elevated proinsulin levels. Magnetic resonance and computed tomography of the abdomen showed a 1 cm pancreatic nodule and multiple accessory spleens. The diagnosis was confirmed by selective angiography, showing location and vascularization of the nodule, despite no response to intra-arterial calcium. After resection, the hypoglycemic syndrome resolved. The surgical specimen was comprised of a neuroendocrine adenomatous tissue with high proinsulin immunoreactivity. Study of this unusual case of proinsulinoma underlines (i) the need to assay proinsulin in patients with hypoglycemia and normal immunoreactive insulin, (ii) the differential diagnosis in the presence of accessory spleens, (iii) the unresponsiveness to intra-arterial calcium stimulation, and (iv) the extensive evaluation needed to reach a final diagnosis.

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.…”

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

“…Even more unusual is the finding that the tumor demonstrated immunostaining for proinsulin but not insulin in spite of us trying three different commercial preparations. There have been two previous cases of insulinomas occurring in patients preexisting T1DM [5,7] with multiple cases of insulinomas arising individuals with type 2 diabetes mellitus reported [19] . There have also been several cases of spontaneous hypoglycemia caused by proinsulinomas [5,7,20] ; however this is the first case report of a proinsulinoma developing in a patient with pre-existing T1DM.…”

“…Insulinomas are rare islet cell tumors derived primarily from beta cells which autonomously synthesize and secrete inappropriate and excessive amounts of proinsulin and/or insulin resulting in the development of spontaneous hypoglycemia [3,4] . The incidence of insulinoma is approximately 3-10 cases per million persons per year in the United States [4,6] and proinsulin-only secreting islet cell tumors causing hypoglycemia are even rarer [5][6][7][8] . The diagnosis of an insulinoma or proinsulinomas is confirmed biochemically with a simultaneous low blood sugar and inappropriately elevated serum insulin, pro-insulin and/or c-peptide levels [4,9,10] .…”

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.…”