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Clinical Subject Page

Insulinoma

An insulinoma is a rare insulin-secreting tumor of the pancreatic beta cells. It is the most common cause of endogenous hyperinsulinism and is benign in about 90% of cases.

ICD-10

D13.7

Specialty

Gastroenterology

Onset

Chronic

Reviewed

July 2026

On This Page

Overview

  • Arises from the beta cells of the pancreas.
  • Causes excess insulin production, leading to recurrent hypoglycemia (low blood glucose), especially during fasting.
  • Most cases occur sporadically, but some are associated with Multiple Endocrine Neoplasia type 1 (MEN1).

Etiology & Risk Factors

-Etiology

  • Insulinoma is a neuroendocrine tumor that arises from the beta cells of the pancreas.
  • Most cases occur sporadically.
  • About 90% are benign.
  • Around 5% are associated with Multiple Endocrine Neoplasia type 1 (MEN1).

Risk Factors

  • Multiple Endocrine Neoplasia type 1 (MEN1) (major inherited risk factor).
  • Age: Most commonly 30–60 years.
  • Sex: More common in females than males.

Pathophysiology

Pancreatic β-cell tumor (insulinoma) → Autonomous (unregulated) insulin secretion → ↑ Insulin levels despite low blood glucose → ↑ Glucose uptake by muscle and fat + ↓ Hepatic glucose production → Hypoglycemia → Neuroglycopenic symptoms (confusion, blurred vision, seizures, loss of consciousness) + Autonomic symptoms (sweating, tremor, palpitations, hunger) → Symptoms improve after glucose intake (Whipple triad)

Clinical Presentation

Presentation

  • Recurrent hypoglycemia, especially several hours after meals, during fasting, or after exercise/alcohol.

Neuroglycopenic symptoms:

  • Confusion
  • Lethargy
  • Double/blurred vision
  • Weakness
  • Syncope
  • Seizures

Autonomic (sympathetic) symptoms:

  • Sweating
  • Tremor
  • Palpitations
  • Anxiety
  • Headache
  • Hunger
  • Symptoms are relieved by glucose administration (Whipple triad).
  • Weight gain may occur due to the anabolic effects of excess insulin.
  • In patients with MEN1, symptoms of other endocrine tumors may also be present.

 

History Taking

-Ask about : 

  • When do the symptoms occur? (Fasting, several hours after meals, after exercise, or after alcohol?)
  • What symptoms do you experience during the episodes? (Sweating, tremor, palpitations, hunger, confusion, blurred vision, weakness, seizures, fainting)
  • Do the symptoms improve after eating or taking glucose?
  • How often do the episodes occur, and how long do they last?
  • Have you ever measured a low blood sugar during an episode?
  • Do you have diabetes or use insulin or glucose-lowering medications (e.g., sulfonylureas)?
  • Do you have any severe illness that could explain hypoglycemia?
  • Is there a family history of Multiple Endocrine Neoplasia type 1 (MEN1) or endocrine tumors?
  • Have you had symptoms of other endocrine tumors? (Suggestive of MEN1)
  •  

Physical Examination

  • Physical examination is often normal between hypoglycemic episodes.
  • During a hypoglycemic episode, look for:
  • Sweating (diaphoresis)
  • Tremor
  • Tachycardia/palpitations
  • Confusion or altered mental status
  • Visual disturbances (e.g., diplopia)
  • Weakness
  • Seizures (severe hypoglycemia)
  • Loss of consciousness/syncope
  • Weight gain may be present.

-Examine for features of MEN1, including:

  • Signs of other endocrine tumors
  • Skin examination for neurocutaneous syndromes

Investigations

1. Laboratory Tests

  • Blood glucose ↓ (< 55 mg/dL during symptoms)
  • Serum insulin ↑
  • C-peptide ↑
  • Proinsulin ↑
  • β-hydroxybutyrate ↓
  • Sulfonylurea screen (negative)
  • Insulin antibodies (negative)

2. Confirmatory Test

  • 72-hour supervised fasting test (gold standard if spontaneous hypoglycemia is not documented)

3. Tumor Localization

  • CT scan (pancreas)
  • MRI (pancreas)
  • Endoscopic ultrasound (EUS) (especially if CT/MRI are negative)

4. Assess for Associated Syndrome

  • Evaluate for MEN1 (history, examination, and appropriate endocrine assessment)

Diagnosis

Diagnosis is based on :

  • Whipple triad
    • Symptoms of hypoglycemia
    • Low blood glucose during symptoms
    • Symptoms improve after glucose administration
  • Laboratory confirmation of endogenous hyperinsulinism
    • ↓ Blood glucose (< 55 mg/dL)
    • Insulin
    • ↑ C-peptide
    • ↑ Proinsulin
    • Negative sulfonylurea screen
  • 72-hour supervised fasting test (gold standard if spontaneous hypoglycemia is not documented)
  • Imaging to localize the tumor
    • CT or MRI pancreas
    • Endoscopic ultrasound (EUS) if needed

Management

1. Acute Management (Treat Hypoglycemia)

  • Oral glucose if the patient is conscious.
  • IV dextrose if severe hypoglycemia or unable to take orally.
  • IM glucagon if IV access is not available.

2. Definitive Treatment (First-line)

  • Surgical resection after localizing the tumor.
    • Enucleation (preferred for most localized tumors).
    • Partial pancreatectomy if the tumor is close to the pancreatic duct.

3. Medical Treatment

Used when surgery is delayed, not possible, or for recurrent/inoperable disease:

  • Diazoxide – inhibits insulin secretion.
  • Somatostatin analogs (e.g., octreotide) – reduce insulin secretion.

4. Follow-up

  • Monitor for resolution of hypoglycemia.
  • Monitor for tumor recurrence after surgery (risk is low after complete resection).
  • Evaluate and manage MEN1 if present.

 

Surgery is the treatment of choice and is usually curative for localized insulinoma.

Complications

  • Recurrent severe hypoglycemia
  • Seizures
  • Loss of consciousness (coma)
  • Permanent neurological deficits (if hypoglycemia is prolonged or recurrent)
  • Cardiac arrhythmias
  • Death (rare, due to severe untreated hypoglycemia)
  • Tumor recurrence (uncommon after complete surgical resection)
  • Malignant disease/metastasis (rare; most insulinomas are benign)

Prognosis

  • Excellent prognosis in most patients.
  • About 90% of insulinomas are benign.
  • Surgical resection (especially enucleation) is usually curative for localized tumors.
  • Low risk of recurrence after complete tumor removal.
  • Prognosis is less favorable in patients with malignant or inoperable insulinomas, who may require long-term medical therapy.

Key Points / Clinical Pearls

  • Rare pancreatic β-cell tumor that secretes excess insulin.
  • Causes recurrent fasting hypoglycemia.
  • Whipple triad is the classic presentation.
  • Diagnosis: ↑ Insulin + ↑ C-peptide during hypoglycemia (± 72-hour fasting test).
  • CT/MRI or EUS to localize the tumor.
  • Surgery is the treatment of choice and is usually curative.
  • Most insulinomas are benign and have an excellent prognosis.
  • National Center for Biotechnology Information (NIH). Insulinoma, StatPearls.
  • de Herder WW, Zandee WT, Hofland J. Approach to the Patient: Insulinoma. J Clin Endocrinol Metab. 2024.
  • Placzkowski KA, Vella A, Thompson GB, et al. Secular Trends in the Presentation and Management of Insulinoma. J Clin Endocrinol Metab. 2009;94:1069-1073. PMC3574879.
  • A Five-Year Journey to Diagnosis: Resolving Persistent Hypoglycemia Through Successful Insulinoma Resection - A Case Report. PMC11928290.
  • MedlinePlus, National Library of Medicine (NIH). Insulinoma: Medical Encyclopedia.