From the Guidelines
Insulin levels should be ordered when evaluating patients with suspected insulinoma, particularly those with persistent or recurrent hypoglycemia, or when other localization tests are equivocal or negative. When investigating insulinoma, serum insulin, proinsulin, and C peptide should be tested 1. If the diagnosis of insulinoma is uncertain, a 48- to 72-hour observed or inpatient observed fast may also be helpful, with insulin levels greater than 3 mcIU/mL, C peptide concentrations of at least 0.6 ng/mL, and proinsulin levels of greater than or equal to 5 pmol/L when fasting blood glucose is less than 55 mg/dL indicating the presence of these tumors 1. Key indications for ordering insulin levels include:
- Unexplained hypoglycemia (blood glucose <55 mg/dL)
- Suspected insulinoma
- Persistent or recurrent hypoglycemia
- Equivocal or negative localization tests Insulin levels must be interpreted in context, as high levels with normal glucose suggest insulin resistance, while high insulin with low glucose points to inappropriate insulin secretion (as in insulinoma) 1. Proper timing of insulin level measurement is crucial, with fasting samples being most interpretable, and insulin levels should be measured simultaneously with glucose 1. This testing helps distinguish between endogenous insulin production and exogenous insulin administration, which guides treatment decisions for various metabolic disorders, including insulinoma 1.
From the Research
Ordering Insulin Levels
To determine when to order insulin levels, several factors should be considered, including symptoms of hypoglycemia, glucose handling, and diagnostic features.
- Symptoms of hypoglycemia, such as neuroglycopenia and catecholamine response, should be evaluated, and blood glucose levels should be measured during these episodes 2.
- Insulin levels should be ordered when blood glucose levels are less than 40 mg/dl (less than 2.2 mmol/l), and concomitant insulin levels should be > or =6 IU/ml (> or =43 pmol/l) and concomitant C-peptide levels > or =0.2 pmol/l 2.
- A 72-hour fasting test is the current standard for the diagnosis of insulinoma, but a 5-hour oral glucose tolerance test (OGTT) can also be used to evaluate the ratios of serum concentrations of insulin and C-peptide to glucose 3.
- The diagnosis of insulinoma can be challenging, and factitious hypoglycemia should be considered in the differential diagnosis, especially when laboratory findings are inconsistent or confusing 4, 5.
- Current guidelines have lowered the diagnostic insulin threshold to 3 μU/ml in the presence of hypoglycemia (<55 mg/dl), and post-prandial hypoglycemia can be the only presenting symptom 6.
- Insulin levels should be ordered in patients with symptoms of hypoglycemia, especially if they have a history of impaired glucose handling or previous diagnosis of diabetes mellitus 6.
Diagnostic Criteria
Diagnostic criteria for insulinoma include:
- Blood glucose levels less than 40 mg/dl (less than 2.2 mmol/l) during symptoms of hypoglycemia
- Concomitant insulin levels > or =6 IU/ml (> or =43 pmol/l) and concomitant C-peptide levels > or =0.2 pmol/l
- A 72-hour fasting test or a 5-hour OGTT can be used to evaluate the ratios of serum concentrations of insulin and C-peptide to glucose
- Current guidelines have lowered the diagnostic insulin threshold to 3 μU/ml in the presence of hypoglycemia (<55 mg/dl) 2, 6.
Special Considerations
Special considerations should be taken into account when ordering insulin levels, including:
- Factitious hypoglycemia should be considered in the differential diagnosis, especially when laboratory findings are inconsistent or confusing 4, 5
- Post-prandial hypoglycemia can be the only presenting symptom 6
- Previous diagnosis of diabetes mellitus or impaired glucose handling should not rule out the diagnosis of insulinoma 6.