Workup for Hypoglycemia
The appropriate workup for hypoglycemia should include assessment of blood glucose levels, comprehensive history of hypoglycemic episodes, evaluation of risk factors, and diagnostic testing to determine the underlying cause.
Definition and Classification
Hypoglycemia is categorized into three levels according to the American Diabetes Association 1, 2:
- Level 1: Blood glucose <70 mg/dL but ≥54 mg/dL
- Level 2: Blood glucose <54 mg/dL
- Level 3: Severe event with altered mental/physical status requiring assistance
Initial Assessment
History
- Document frequency, severity, timing (fasting, postprandial, exercise-related), and precipitating factors of hypoglycemic episodes 1
- Assess symptoms experienced during episodes (neurogenic symptoms like shakiness, irritability, hunger, tachycardia; neuroglycopenic symptoms like confusion, cognitive impairment) 1
- Review medication history, focusing on insulin, sulfonylureas, and other drugs that may cause hypoglycemia 3, 4
- Evaluate alcohol consumption patterns 5
- Document treatment approaches used and their effectiveness 1
Risk Factor Assessment
- Prior hypoglycemic events (strongest predictor of recurrence) 1
- Impaired hypoglycemia awareness (using validated tools like Pedersen-Bjergaard or Gold questionnaires) 1
- Insulin deficiency 6
- Aggressive glycemic targets 1
- Advanced age (≥75 years) 2
- End-stage kidney disease 2
- Cognitive impairment 2
Laboratory Evaluation
Initial Testing
- Document hypoglycemia with a plasma glucose measurement during symptoms (ideally <54 mg/dL)
- Confirm resolution of symptoms after glucose administration (Whipple's triad) 5, 7
- Basic metabolic panel to assess renal function, electrolytes
- Liver function tests to evaluate hepatic function
- HbA1c to assess overall glycemic control in diabetic patients
Extended Workup (when cause is not obvious)
Critical samples during hypoglycemic episode:
- Insulin and C-peptide levels (to differentiate endogenous vs. exogenous insulin)
- Proinsulin (elevated in insulinoma)
- Beta-hydroxybutyrate (suppressed in hyperinsulinism)
- IGF-1 and IGF-2 (for non-islet cell tumor hypoglycemia) 5
- Cortisol and ACTH (to rule out adrenal insufficiency)
- Growth hormone
Provocative testing:
- 72-hour supervised fast (gold standard for diagnosing insulinoma)
- Mixed meal test (for reactive hypoglycemia)
Antibody testing:
- Anti-insulin antibodies (for autoimmune hypoglycemia/HIRATA syndrome)
- Anti-insulin receptor antibodies 5
Imaging Studies (when endogenous hyperinsulinism is suspected)
- CT or MRI of pancreas
- Endoscopic ultrasound
- Somatostatin receptor scintigraphy
Special Considerations
For Diabetic Patients
- Review glucose monitoring data (CGM or SMBG) 1
- Correlate symptoms with glucose readings 1
- Evaluate insulin dosing, timing, and type 6
- Assess food intake patterns and exercise regimens 6
For Non-Diabetic Patients
- Consider rare causes:
Management During Workup
For conscious patients with hypoglycemia: Administer 15-20g of fast-acting carbohydrates, recheck glucose in 15 minutes, repeat treatment if needed 1, 2
For severe hypoglycemia (unconscious or unable to swallow):
Prescribe glucagon emergency kits to all patients at risk of severe hypoglycemia and train family members/caregivers on administration 1, 2
Follow-up
- For patients with hypoglycemia unawareness, implement a 2-3 week period of scrupulous avoidance of hypoglycemia 6
- Consider relaxing glycemic targets temporarily in patients with recurrent severe hypoglycemia 1
- Reevaluate treatment regimen after any episode of severe hypoglycemia 1
The workup should be tailored based on the clinical presentation, with focus on identifying the underlying cause to prevent recurrent episodes and reduce morbidity and mortality associated with hypoglycemia.