Endocrine Abstracts

Introduction: Proinsulinoma is an infrequent subtype of pancreatic neuroendocrine tumor (pNET), characterized by the excessive secretion of proinsulin, leading to pronounced hypoglycemia. Clinical manifestations comprise neuroglycopenic and autonomic symptoms, including cognitive impairment, seizures, visual disturbances, diaphoresis, tremors, syncope or coma. Diagnostic modalities involve blood assays and imaging to detect heightened proinsulin production and determine the tumor’s location within the pancreas. Surgical intervention stands as the primary modality for curative intent and relief of symptoms in locoregional disease. In scenarios where surgical excision is unfeasible, alternative therapeutic modalities may be explored for symptomatic management.

Clinical Case: A 25-year-old male with normal body weight exhibiting a four-year history of hypoglycemia. Initially asymptomatic, the condition was identified during routine laboratory examinations and subsequently manifesting symptoms such as confusion, fatigue and incoherent speech, all of which were resolved following carbohydrates intake. Relevant medical history includes allergic rhinitis, profilin allergy, and eosinophilic esophagitis. Presently under medication involving proton pump inhibitor (IBP), nasal fluticasone and antihistamine on an as-needed basis. Admitted for elective study of hypoglycemia, underwent a 5-hour fasting test which revealed symptomatic hypoglycemia of 45 mg/dl with confusion, sweating and tachycardia, all resolved after carbohydrates intake. Analytical study during fasting test revealed elevated serum proinsulin (141.4 pmol/l), while serum C-peptide and insulin levels were inappropriately normal (2.41 ng/ml and 10.2 µU/ml, respectively). Beta-hydroxybutyrate was within reference values (0.21 nmol/l). The patient underwent imaging studies (abdomen CT and MRI) identifying an 8 mm hypervascular nodule in the pancreatic body consistent with a pNET. The ⁶⁸Ga-SSA-PET-CT was negative. The patient underwent surgical resection of tumor. The anatomopathological examination confirmed a 13 mm grade 1 neuroendocrine tumor (the immunohistochemistry study showed strong diffuse positivity for synaptophysin and chromogranin A, with Ki67 <2%, with complete resection (pT1N0), confirming the diagnosis of a proinsulin secreting pNET.

Conclusions: Given the rarity of proinsulinoma, recently recognized as a distinct entity from insulinoma, it is essential to maintain heightened awareness of its nonspecific clinical symptoms. Diagnosing proinsulinoma can be challenging due to its uncommon occurrence and its diagnostic criteria not yet fully defined on a globally agreed-upon basis. Prompt recognition of subtle signs is crucial to prevent delays in diagnosis and ensure accurate treatment.