Case Report: RARE CASE OF INSULINOMA

Introduction

Insulinoma is a rare, functional pancreatic neuroendocrine tumor (PNET), which originates from the insulin-secreting beta cells of the islets of Langerhans in the pancreas. Despite being the most common type of functioning PNET, the estimated incidence ranges from 1 to 4 cases/million people is reported annually.¹ During the 1980s to 1990s, Massachusetts General Hospital performed only 1 to 7 PNET surgeries per year. Following that, there was a gradual increase to a current average of more than 15 operations per year.² These tumors are typically sporadic and occur predominantly in adults between the ages of 40 and 60 years, although they can present at any age.^1,3 Up to 90% of insulinomas, smaller than 2 cm in diameter, are benign and treatable through surgical procedures.²

Clinically, insulinoma is characterised by episodes of hypoglycemia resulting from excessive level of insulin secretion.⁴ The hallmark symptoms are usually nonspecific, encompassing both neuroglycopenic and autonomic manifestations. Neuroglycopenic symptoms, due to inadequate glucose delivery to the brain, may include confusion, seizures, visual disturbances, behavioral changes, and even loss of consciousness.⁵ Autonomic symptoms may show differently, such as palpitations, tremors, diaphoresis, and hunger.⁶ These episodes are typically more common and recurring in fasting or after exertion but relieved by food intake.⁷ Therefore, it shows mixed symptoms, which ultimately lead to misdiagnosis and unsuitable treatment.

A major diagnostic challenge with insulinomas is their ability to mimic more common neurological and psychiatric conditions. Patients often undergo extensive evaluations for seizure disorders, mood disorders, or other neurologic dysfunctions before hypoglycemia is considered.⁷ In the actual world, a significant amount of insulinomas are misdiagnosed as epilepsy, anxiety, or other psychiatric diseases, causing delays in diagnosis and effective treatment.⁸ Therefore, this delay is further entangled by the intermittent nature of hypoglycemic episodes and the failure to timely document plasma glucose levels in symptomatic periods.⁹ As a result, without a definite link between symptoms and hypoglycemia, clinical suspicion of insulinoma may remain low.

The classical approach to diagnosing insulinoma involves establishing Whipple’s triad: (1) symptoms consistent with hypoglycemia, (2) documented low plasma glucose (<2.8 mmol/L or <50 mg/dL) during the symptomatic episode, and (3) relief of symptoms following glucose administration.^10,11 This criterion helps to distinguish insulinoma from other causes of hypoglycemia, such as exogenous insulin use, sulfonylurea consumption, and non-insulin-producing tumors. The 72-hour supervised fasting test remains the gold standard for biochemical confirmation of the diagnosis of insulinoma.¹² During this test, patients are observed in a controlled setting while fasting until hypoglycemia symptoms occur or 72 hours have passed.¹² Measurements of β-hydroxybutyrate, proinsulin, C-peptide, insulin, glucose, and insulin were noted at regular intervals. Insulin levels are abnormally increased in insulinoma despite hypoglycemia, with measurable C-peptide and proinsulin levels, indicating endogenous insulin synthesis. The absence of β-hydroxybutyrate suggests suppressed ketogenesis due to high insulin levels.¹³ Following the confirmation and establishing the biochemical parameters, tumour localisation is an important required step. Cross-sectional imaging modalities represent the preferred initial choice to determine pancreatic ductal adenocarcinoma location as they comprise contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI). The high sensitivity of endoscopic ultrasound (EUS) stems from its ability to provide detailed pancreatic images because it approaches the pancreas closely.⁴ The localization of pancreatic neuroendocrine tumors remains challenging for healthcare professionals because somatostatin receptor scintigraphy and positron emission tomography (PET) employing radiolabeled tracers as 68Ga-DOTATATE serve as alternative functional tests when standard imaging techniques prove to be inadequate.¹⁴

Surgical resection serves as the primary treatment approach for localized insulinomas because it provides excellent treatment results for benign tumors. Small single tumors receive treatment through enucleation whereas distal pancreatectomy or pancreaticoduodenectomy becomes necessary for tumors in challenging locations or tumors suspected of malignancy.¹⁵ Doctors usually treat hypoglycemia through medical management that uses diazoxide or somatostatin analogs when patients cannot get surgery or when tumors remain non-localizable.¹⁶ Targeted therapies together with peptide receptor radionuclide therapy (PRRT) represent advanced treatment options for uncommon cases of metastatic or advanced insulinomas.¹⁷

In this study, we present an extremely unusual case of a 32-year-old Vietnamese patients who was admitted to our hospital with the symptoms of repeated episodes of cognition and perceptual disorders. Laboratory tests and contrast-enhanced abdominal computed tomography (CT) revealed the diagnosis of insulinoma. The patient were received intensive treatment and then was treated successfully by laparoscopic distal pancreatectomy.

Case report

A Vietnamese 32-year-old female without a prior reported history of endocrine or psychiatric or neurological disorders experienced multiple prolonged sleeping bouts of 1–2 days along with somnambulism and limb movements in sleep and heavy sweating and occasional urinary incontinence since October 2021. The woman experienced these incidents 3–4 times monthly. The patient was initially diagnosed with cerebral vasomotor dysregulation and suspected narcolepsy at a private clinic but showed no improvement with treatment. From January to October 2022, during pregnancy, she was asymptomatic. However, post-cesarean delivery in October 2022, the episodes recurred with increased frequency (4–6 times/month), including loss of consciousness, seizures, yelling, and incoherent speech. She was treated with valproic acid and sertraline for five months without clinical improvement.

In November 2024, she was hospitalized in a regional hospital due to prolonged unconsciousness (>2 days). Blood tests revealed hypoglycemia and hypomagnesemia. She was diagnosed with epilepsy associated with hypoglycemia and electrolyte disturbances, but did not improve despite supportive care. She was transferred to our hospital - a tertiary hospital in January 2025 for further evaluation. The patient was admitted to our department in drowsy state and stable overall vital signs. She had a repeated episodes of seizures. The routine blood tests suggested intermittent hypoglycemia. The electroencephalogram showed normal result that ruled out epilepsy. The diagnostic reports were performed at the time of admission, which showed fasting glucose was 1.63 mmol/L, insulin was 90.3 uU/mL, and C-peptide was 6.99 ng/mL ( Table 1). Abdominal CT scan showed a well-defined 40 × 39 mm mass in the pancreatic tail, isodense with pancreatic parenchyma and without evidence of vascular invasion or metastasis ( Figure 1 (A and B)). The patient was diagnosed with insulinoma. We conducted the consultation with endocrinologist and neurologists. The aim was controlling serum glucose level and seizure by intravenous glucose 30% and sedatives. Closely blood glucose monitoring measuring glucose in capillary blood was performed every 4 hours. After 1 week of treatment, the patient underwent laparoscopic partial pancreatectomy successfully ( Figure 2). The procedure lasted 210 minutes with the blood loss was 600 ml. The patient’s postoperative progress was favorable. Then she was discharged from the hospital 5 days later without any hypoglycemic episodes. Tumour pathology indicated a poorly differentiated carcinoma of the pancreas ( Figure 3).

Figure 1. A: Axial view showing the mass in the tail of the pancreas, measuring approximately 40.17 mm x 39.02 mm. B: Coronal view showing the mass in close proximity to the splenic artery and vein.

Figure 2. Postoperative image showing the excised pancreatic tail tumor.

Figure 3. Postoperative tumour pathology findings.

C: Chromatin showing a "salt-and-pepper" pattern; D: Pancreatic tumor tissue arranged in cords and clusters; E: Tumor cells invading blood vessels (HEx4); F: Tumor cells invading blood vessels (HEx10).

Discussion

Consent

Written informed consent was obtained from patient prior to publication of this report and the use of accompanying images.