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

Workup for Hypoglycemia

The appropriate workup for hypoglycemia should first establish Whipple's triad (symptoms consistent with hypoglycemia, low plasma glucose, and resolution of symptoms with correction of glucose) before proceeding with diagnostic testing to determine the underlying cause. 1

Initial Assessment

Confirm Hypoglycemia

• Document blood glucose level <70 mg/dL (3.9 mmol/L)
• Classify severity according to established levels 2:
  • Level 1: <70 mg/dL but ≥54 mg/dL (mild)
  • Level 2: <54 mg/dL (moderate)
  • Level 3: Any level with altered mental/physical state requiring assistance (severe)

Immediate Management

1. For conscious patients:

   • Administer 15-20g fast-acting carbohydrates (glucose tablets preferred) 3
   • Recheck blood glucose after 15 minutes
   • Repeat treatment if hypoglycemia persists
   • Follow with a meal or snack containing complex carbohydrates and protein once blood glucose normalizes

2. For unconscious/severe hypoglycemia:

   • Administer glucagon:
     • Adults and children >25kg or ≥6 years: 1 mg subcutaneously or intramuscularly 4
     • Children <25kg or <6 years: 0.5 mg subcutaneously or intramuscularly 4
   • Call emergency services
   • Provide oral carbohydrates once patient regains consciousness

Diagnostic Workup

History

• Medication review (insulin, sulfonylureas, meglitinides)
• Timing of hypoglycemic episodes (fasting, postprandial, random)
• Relationship to meals, exercise, alcohol consumption
• Recent changes in diet or activity
• Symptoms of hypoglycemia awareness/unawareness
• Previous episodes of severe hypoglycemia
• Comorbidities (renal/hepatic disease, adrenal insufficiency)

Laboratory Evaluation

During a hypoglycemic episode (blood glucose <70 mg/dL), obtain:

1. Plasma glucose (to confirm hypoglycemia)
2. Insulin level
3. C-peptide level
4. Proinsulin level
5. Beta-hydroxybutyrate (to assess for ketosis)
6. Sulfonylurea/meglitinide screen
7. Insulin antibodies

Provocative Testing

If spontaneous hypoglycemia cannot be documented:

• For suspected fasting hypoglycemia: 72-hour supervised fast
• For suspected postprandial hypoglycemia: Mixed meal tolerance test

Differential Diagnosis Based on Clinical Context

Diabetic Patients

• Iatrogenic hypoglycemia (most common cause) 5
  • Insulin excess
  • Sulfonylurea or meglitinide use
  • Decreased carbohydrate intake
  • Increased physical activity
  • Alcohol consumption
  • Decreased insulin clearance (renal failure)

Non-Diabetic Patients

• Endogenous hyperinsulinism
  • Insulinoma
  • Post-bariatric hypoglycemia
  • Noninsulinoma pancreatogenous hypoglycemia
  • Autoimmune hypoglycemia syndrome
• Medication-induced
• Non-islet cell tumors
• Hormonal deficiencies (adrenal insufficiency, hypopituitarism)
• Critical illness
• Factitious hypoglycemia

Management of Recurrent Hypoglycemia

For Diabetic Patients

• Adjust medication regimen (reduce insulin/secretagogue doses)
• Evaluate timing of insulin administration relative to meals
• Consider medications with lower hypoglycemia risk
• Modify eating patterns (regular small meals with carbohydrates)
• Increase monitoring frequency, especially before high-risk activities
• For hypoglycemia unawareness: implement 2-3 week period of strict hypoglycemia avoidance 3, 5

For Non-Diabetic Patients

• Treatment depends on underlying cause
• Surgical intervention for insulinoma
• Dietary modifications for reactive hypoglycemia
• Hormone replacement for endocrine deficiencies

Special Considerations

• Patients with insulinoma may experience paradoxical hypoglycemia after glucagon administration 4
• Patients with decreased hepatic glycogen (starvation, adrenal insufficiency) may not respond to glucagon 4
• Hypoglycemia unawareness indicates compromised glucose counterregulation and requires adjustment of glycemic targets 2

By following this structured approach to hypoglycemia workup, clinicians can effectively diagnose the underlying cause and implement appropriate treatment strategies to prevent recurrent episodes.