What is the appropriate workup for a patient presenting with hypoglycemia (low blood sugar)?

Hypoglycemia Workup

The appropriate workup for hypoglycemia must include documentation of Whipple's triad (symptoms of hypoglycemia, low plasma glucose concentration, and resolution of symptoms after glucose administration), measurement of specific laboratory values during hypoglycemic episodes, and systematic investigation of potential causes. 1

Initial Assessment and Immediate Management

Severity Classification

• Level 1 (mild): Glucose <70 mg/dL but ≥54 mg/dL
• Level 2 (moderate): Glucose <54 mg/dL
• Level 3 (severe): Any glucose level with altered mental status requiring assistance 1

Immediate Treatment

• Conscious patients: Administer 15-20g oral glucose, recheck in 15 minutes, repeat if glucose remains <70 mg/dL 1
• Unconscious patients: Administer glucagon 1 mg subcutaneously, intramuscularly, or intravenously for adults and pediatric patients >25 kg; 0.5 mg for pediatric patients <25 kg 2
• After patient responds, provide a substantial meal to restore liver glycogen and prevent recurrence 1, 2

Diagnostic Workup

Document Whipple's Triad

1. Symptoms of hypoglycemia
2. Low plasma glucose concentration (<70 mg/dL)
3. Resolution of symptoms after glucose administration 1, 3

Laboratory Tests During Hypoglycemic Episode

• Plasma glucose (confirm with laboratory test if point-of-care test shows hypoglycemia)
• Insulin level
• C-peptide level
• Proinsulin level
• β-hydroxybutyrate level
• Sulfonylurea/meglitinide screen
• Insulin antibodies 1, 3

Additional Tests Based on Clinical Suspicion

• Cortisol and ACTH (to rule out adrenal insufficiency)
• Growth hormone
• IGF-1 and IGF-2 (for non-islet cell tumors)
• Liver function tests
• Renal function tests 1, 3

Etiologic Investigation

Diabetic Patients

• Review medication regimen (insulin, sulfonylureas)
• Assess for pattern of hypoglycemia (overnight, postprandial)
• Evaluate food intake and exercise patterns
• Check for alcohol consumption or drug interactions 1, 4

Non-Diabetic Patients

1. Fasting Hypoglycemia

   • 72-hour supervised fast if symptoms occur in post-absorptive state 3
   • Monitor for:
     • Insulinoma
     • Non-islet cell tumors
     • Adrenal insufficiency
     • Hepatic failure
     • Renal failure 1, 3

2. Reactive/Postprandial Hypoglycemia

   • Mixed meal test if symptoms occur after meals 3
   • Monitor for:
     • Post-bariatric surgery hypoglycemia
     • Alimentary hypoglycemia
     • Early diabetes 3

3. Medication-Induced Hypoglycemia

   • Review all medications
   • Consider factitious hypoglycemia (self-administration of insulin or sulfonylureas) 3, 4

Special Considerations

• Insulinoma: Glucagon stimulation test can help differentiate insulinoma (glucose rises >30 mg/dL after glucagon) from other causes 5
• Critical Illness: Hypoglycemia in hospitalized patients is associated with increased mortality, particularly spontaneous (non-insulin-related) hypoglycemia 6

Management Based on Etiology

Diabetic Patients

• Simplify insulin regimen for recurrent hypoglycemia by reducing basal insulin dose by 10-20%
• Consider alternative insulin formulations with lower hypoglycemia risk
• Set less stringent A1C targets (<8.0%) for patients with moderate risk factors 1

Non-Diabetic Patients

• Treat underlying cause (tumor removal, hormone replacement, etc.)
• For patients with confirmed insulinoma or non-islet cell tumor hypoglycemia who respond to glucagon, continuous glucagon infusion may be an effective temporary measure 5

Follow-up and Prevention

Emergency Preparedness

• Prescribe glucagon for emergency use
• Train family members/caregivers on administration
• Consider medical alert identification 1, 2

Follow-up Care

• Schedule follow-up within 1-2 weeks to assess effectiveness of interventions
• Review blood glucose logs with particular attention to overnight readings
• Consider referral to a diabetes education program for comprehensive management strategies 1

Discharge vs. Admission Criteria

• Consider discharge for diabetic patients with a clear cause and good response to treatment
• Consider admission for recurrent hypoglycemia, use of long-acting insulin or sulfonylureas, inadequate home support, or underlying serious illness 1

Common Pitfalls to Avoid

• Failing to document Whipple's triad before extensive workup
• Not obtaining critical samples during hypoglycemic episodes
• Overlooking non-diabetes-related causes in patients with diabetes
• Ignoring the risk of recurrent hypoglycemia in patients with compromised counterregulatory mechanisms 1, 4
• Administering glucagon to patients with insufficient hepatic glycogen (starvation, adrenal insufficiency, chronic hypoglycemia) 2