title: Hypoglycemic Syndrome without Hyperinsulinemia. A Diagnostic Challenge.
abstract: The most common cause of organic fasting hypoglycemia in adults is the presence of an insulin-producing pancreatic adenoma, but when high insulin levels are not found, the differential diagnosis is challenging. Misdiagnosis can lead to an unnecessary pancreatectomy. Insulin concentrations may be low in some cases despite a clinical history suggestive of insulinoma. In these cases, a proinsulinoma should be suspected, although the rarity of this condition requires an extensive workup before reaching a final diagnosis. We describe an unusual case of a 38-year-old man with a severe hypoglycemic syndrome due to a proinsulin-secreting pancreatic adenoma. Insulin was measured by the specific assay and suppressed under the lower detection limit during fasting hypoglycemia. Serum proinsulin and C-peptide levels were abnormally elevated, and further tests revealed an islet cell tumor. The tumor was surgically removed, relieving the fasting hypoglycemia. Histopathological study showed a conventional well-differentiated neuroendocrine tumor with high immunoreactivity against proinsulin and with lesser intensity against insulin. Interestingly, GS-9A8 antibody clone used for immunostaining proinsulin did not cross-react with human insulin or C-peptide, providing an unbiased picture of proinsulin secretion. The resolution of symptoms, the fall of proinsulin concentrations after tumor removal and the histopathology study confirmed the diagnosis of proinsulinoma.
authors.affiliation: Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Spain. bppevida@unav.es.
authors.forename: Belén
authors.initials: B
authors.lastname: Pérez-Pevida
authors.affiliation: Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Idoate
authors.affiliation: Department of Biochemistry, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Fernández-Landázuri
authors.affiliation: Department of Biochemistry, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Varo
authors.affiliation: Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Escalada
mesh_terms: D007516:Adenoma, Islet Cell / Q000097:blood* / Q000473:pathology / Q000601:surgery; D000328:Adult; D002096:C-Peptide / Q000032:analysis / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism; D007003:Hypoglycemia / Q000209:etiology*; D007328:Insulin / Q000097:blood*; D008297:Male; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D011384:Proinsulin / Q000097:blood*; D013577:Syndrome
chemical_list: D002096:C-Peptide; D007328:Insulin; D011384:Proinsulin
keywords: Hypoglycemic syndrome; Monoclonal antibody GS-9A8 against proinsulin; Neuroendocrine tumors; Proinsulin-producing pancreatic adenoma; Proinsulinoma