Chronic Hyperinsulinemia Masquerading as Neuropsychiatric Disease: A Case of Uncinate Process Insulinoma Managed with Pancreaticoduodenectomy

Abstract

Insulinoma is the most surgically curable cause of endogenous hyperinsulinemia, yet it carries one of the longest average diagnostic delays in clinical endocrinology. The central reason is deceptively simple: its symptoms sweating, tremor, behavioral change, loss of consciousness are not intuitively hormonal. They are intuitively psychiatric, neurological,
or cardiac. Patients are investigated for epilepsy, panic disorder, and cardiac arrhythmia while their fasting insulin levels remain unmeasured. This case illustrates that pattern in its most striking form: a 33-year-old woman whose recurrent episodes of syncope and progressive weight gain were attributed to lifestyle factors for two years before a structured
biochemical evaluation revealed glucose of 26 mg/dL with a simultaneously elevated insulin and C-peptide. The clinical question this case raises is not merely how this was missed but why the correct diagnostic test was never ordered, and what structural changes in clinical practice might prevent the same delay from recurring.

Case Presentation: A 33-year-old Albanian woman presented electively to Barleti University Polyclinic, Tirana, requesting a definitive diagnostic evaluation. She described a twoyear history of episodic weakness, profuse diaphoresis, dizziness, and recurrent loss of consciousness, with symptoms reliably occurring in the fasting state or during prolonged physical exertion. She had gained 20 kilograms over the same period and reported persistent hunger as a constant companion between episodes.

Multiple emergency department visits had not yielded a diagnosis. Blood glucose had been recorded around 60 mg/dL on at least one occasion; she had been administered intravenous saline and counselled to eat sweets when symptoms arose. No hormonal investigation insulin, C-peptide, proinsulin had been ordered at any of these visits. No endocrinological referral had been made.

On the day of her elective presentation, fasting blood samples were drawn during a symptomatic period. The results were unambiguous: glucose 26 mg/dL, insulin 26.3 μU/mL, C-peptide 3.64 ng/mL. An elevated endogenous C-peptide at that degree of hypoglycemia is definitive biochemical proof of autonomous insulin secretion, precluding exogenous administration and factitious hypoglycemia. HbA1c was 4.84%, consistent with chronic recurrent hypoglycemia rather than any form of diabetes. Cortisol was 205.6 nmol/L normal excluding adrenal insufficiency. Imaging was requested after the diagnosis was biochemically secured.

Abdominal MRI identified a 20 × 16.7 mm hypervascular nodular lesion in the uncinate process of the pancreas: T2 hyperintense, T1 hypointense, with restricted diffusion on DWI and the early intense arterial enhancement followed by delayed washout that is pathognomonic for a pancreatic neuroendocrine tumor. The main pancreatic duct was of
normal caliber throughout, and no lymphadenopathy was identified.

Surgery was performed following multidisciplinary team review. Enucleation the preferred approach for small, benign-appearing insulinomas was judged technically unsafe due to the tumor’s depth within the uncinate process and its anatomical proximity to both the main pancreatic duct and the superior mesenteric vessels. A pancreaticoduodenectomy (Whipple procedure) was performed. The patient was discharged on postoperative day seven with completely normalized blood glucose and no surgical complications.

Results: Fasting biochemical studies confirmed endogenous hyperinsulinemia with glucose 26 mg/dL, insulin 26.3 μU/mL, and C-peptide 3.64 ng/mL satisfying all established diagnostic criteria for insulinoma. Multimodal MRI identified a solitary 20 × 16.7 mm hypervascular lesion in the pancreatic uncinate process. A pancreaticoduodenectomy was performed based on anatomical constraints that precluded safe enucleation. Postoperative recovery was uneventful (discharge day 7), glucose normalized to physiological range, and no complications were recorded. The case represents a textbook biochemical–radiological–surgical cure of an insulinoma that had been clinically present for two years without investigation.

Conclusions: The principal lesson of this case is not anatomical it is cognitive. Insulinoma is consistently misclassified as a neuropsychiatric or cardiac condition in its early stages because clinicians encountering hypoglycemia in a non-diabetic patient rarely extend their differential diagnosis to include a functioning endocrine tumor. The diagnostic tools required to do so are inexpensive and universally available: fasting glucose, insulin, and C-peptide. The barrier is not technical it is a knowledge gap reinforced by the rarity of the condition and the tendency to treat hypoglycemia symptomatically rather than investigatively.

For clinicians in primary care and emergency medicine, the practical takeaway is direct: any non-diabetic patient presenting with unexplained hypoglycemia particularly if recurrent, fasting-predominant, or accompanied by weight gain should have insulin and C-peptide measured at the time of the event. This single step transforms a symptom into a diagnosis.

For surgeons, the lesson is anatomical: the uncinate process is among the most technically demanding regions of the pancreas, and tumor location not tumor size determines whether enucleation is safe. When a lesion in this region lies in close proximity to the main pancreatic duct and the superior mesenteric vessels, pancreaticoduodenectomy is not
an escalation of treatment but the anatomically correct response. Framing this choice accurately prevents both under-treatment and unnecessary patient anxiety about receiving a ‘bigger operation’ than expected.

Insulinoma is a curable disease. The diagnostic and surgical tools to cure it exist and are accessible. What this case demonstrates is that multidisciplinary awareness spanning emergency medicine, endocrinology, radiology, and surgery is the non-negotiable prerequisite for translating those tools into outcomes.