What is the diagnostic approach for insulinoma?

From the Guidelines

The diagnostic approach for insulinoma should begin with a 72-hour supervised fast, which is the gold standard test, measuring serum glucose, insulin, C-peptide, and proinsulin levels while fasting, as this approach has been consistently supported by recent guidelines and studies 1. The initial step in diagnosing insulinoma involves establishing the presence of Whipple's triad: hypoglycemia symptoms, documented low blood glucose levels (<50 mg/dL), and symptom resolution after glucose administration.

Key Diagnostic Criteria

• Hypoglycemia with inappropriately elevated insulin (≥3 μU/mL)
• Elevated C-peptide (≥0.6 ng/mL)
• Elevated proinsulin (≥5 pmol/L) Sulfonylurea screening should be performed to exclude factitious hypoglycemia, as recommended by recent studies 1.

Localization Studies

Once biochemical diagnosis is confirmed, localization studies are essential, starting with non-invasive imaging such as:

• Multiphasic CT of the abdomen
• MRI of the abdomen If these are inconclusive, endoscopic ultrasound has high sensitivity for pancreatic lesions, with a reported sensitivity of approximately 82% 1. For difficult cases, more invasive procedures like:
• Selective arterial calcium stimulation testing
• Intra-operative ultrasound may be necessary, as these tests have been shown to achieve up to 90% success rate in localizing insulinomas when combined with imaging modalities 1. These tests are crucial because insulinomas are typically small (less than 2 cm) and can be challenging to locate, yet precise localization is vital for successful surgical management, which remains the definitive treatment for most patients, with 90% of insulinomas pursuing an indolent course and can be cured surgically 1.

From the Research

Diagnostic Approach for Insulinoma

The diagnostic approach for insulinoma involves several steps, including:

• Clinical presentation: Patients with insulinoma typically present with symptoms of hypoglycemia, such as confusion, shakiness, and loss of consciousness 2.
• Laboratory tests: Blood glucose levels, insulin levels, and C-peptide levels are measured to confirm hypoglycemia and hyperinsulinemia 3.
• Imaging studies: Computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, and endoscopic ultrasound (EUS) are used to localize the tumor 2.
• Functional tests: The 72-hour fast test is the current standard for diagnosing insulinoma, but it is costly and stressful for patients 4. Alternative tests, such as the 5-hour oral glucose tolerance test (OGTT), have been proposed as a more convenient and economical option 4.

Diagnostic Criteria

The diagnostic criteria for insulinoma include:

• Symptoms of hypoglycemia
• Low plasma glucose levels (< 40 mg/dl or < 2.2 mmol/l) during symptoms
• Elevated insulin levels (> 6 IU/ml or > 43 pmol/l) during symptoms
• Elevated C-peptide levels (> 0.2 pmol/l) during symptoms
• Relief of symptoms with glucose administration 3.

Localization Techniques

Localization techniques for insulinoma include:

• CT scans
• MRI scans
• EUS
• Glucagon-like peptide 1 receptor positron emission tomography/computed tomography (GLP-1R PET/CT) or positron emission tomography/magnetic resonance imaging (PET/MRI) 2.

Diagnostic Challenges

The diagnosis of insulinoma can be challenging due to the rarity of the disease and the nonspecific symptoms of hypoglycemia. A high index of suspicion and a thorough diagnostic workup are necessary to establish the diagnosis 2, 5.