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.

Figure 1

Imaging studies and intraoperative appearance. (a) A contrast-enhanced computed tomography slice of the upper abdomen, showing a mildly hyperintense nodule, about 1 cm in diameter, located between the body and the tail of the pancreas (red arrow). (b) A gadolinium-enhanced magnetic resonance slice of the upper abdomen, showing a mildly hyperintense nodule, about 1 cm in diameter between the body and the tail of the pancreas (red arrow), in the same location as identified by CT. (c) A digital subtraction angiography with the catheter positioned in the proximal splenic artery, showing nodular vascularization from the arteria pancreatica magna (red arrow). (d) Isolation and enucleation of the adenoma using the CUGA Excel system. (e) Macroscopic appearance of the adenoma soon after resection (scale bar in cm).

Figure 2

Histopathological analysis of the surgical specimen. (a) Hematoxylin and eosin staining (low magnification) showing gross appearance of the tissue and presence of a pseudocapsule with variable thickness. (b) Hematoxylin and eosin staining (200x) showing monomorphic cells with abundant granular cytoplasm and central nuclei, in contact with capillary basement membranes, stained with Period-Acid Schiff (PAS) reaction (c, 200x). (d) Capillaries are stained with anti-CD34 (200x). The strong chromogranin (e) and Synaptophysin (f) immunoreactivity indicates a neuroendocrine origin, while the few areas staining for cytokeratin-7 (g) are residual exocrine tissue (100x). A visual comparison between insulin (h) and proinsulin (i) staining (200x) suggests a stronger proinsulin immunoreactivity.