Causes of Hypoglycemia in Pediatric Patients
Hypoglycemia in children results from defects in glucose homeostasis involving metabolic systems for fasting adaptation, hormonal control mechanisms, or both, with the most common causes being diabetes mellitus and idiopathic ketotic hypoglycemia, though endocrine disorders and inborn errors of metabolism must be systematically excluded. 1
Age-Dependent Etiologic Framework
Neonatal Period (First 28 Days)
Most neonates with hypoglycemia have transient disorders that resolve spontaneously, but persistent hypoglycemia requires investigation for: 2
- Hyperinsulinism (congenital hyperinsulinism requiring specific pancreatic surgery in some cases) 1
- Hypopituitarism (requiring cortisol replacement therapy) 1
- Hereditary hepatic enzyme deficiencies (glycogen storage diseases) 2
Beyond Neonatal Period Through Childhood
Idiopathic ketotic hypoglycemia (IKH) is the most common cause of hypoglycemia in childhood outside the neonatal period. 2 This diagnosis is made after excluding other pathologic causes and is managed by limiting fasting duration and maintaining high glucose intake during illnesses. 1
Systematic Etiologic Categories
Diabetes-Related Causes
In children with established diabetes, hypoglycemia occurs from: 3
- Excessive insulin administration relative to carbohydrate intake 3
- Missed or delayed meals 4
- Increased physical activity beyond usual levels 4
- Intercurrent illness with vomiting or diarrhea altering insulin requirements 4
Endocrine Disorders Requiring Specific Treatment
- Adrenal insufficiency (requires cortisol replacement) 1
- Congenital hyperinsulinism (may require pancreatic surgery) 1
- Growth hormone deficiency 2
- Hypopituitarism 2
Metabolic Disorders (Inborn Errors of Metabolism)
These represent 1.49% of hypoglycemic presentations but are nonnegligible causes requiring specific diagnosis: 5
- Glycogen storage diseases (particularly Type III, which causes hypoglycemia during prolonged fasting and intercurrent illness) 3
- Fatty acid oxidation defects 1
- Disorders of gluconeogenesis 6
Infection-Associated Hypoglycemia
86.32% of pediatric emergency department hypoglycemia cases are associated with: 5
- Gastroenteritis causing protracted fasting 5
- Other infectious diseases preventing adequate oral intake 5
- Influenza and other illnesses (immunizations preventing these illnesses reduce hypoglycemia risk) 3
Medication-Induced Hypoglycemia
High-Risk Medications
The most important agents causing hypoglycemia are: 3
- Insulin and insulin secretagogues (sulfonylureas) 3
- Beta-blockers (mask hypoglycemia symptoms and should be used with great caution) 3
- Salicylates (aspirin) 4
- Sulfa antibiotics 4
- Certain antidepressants 4
- Alcohol (predisposes to hypoglycemia) 3
Clinical Severity Indicators for Differential Diagnosis
Features Suggesting Metabolic/Endocrine Etiology Rather Than Simple Fasting
Children with hypoglycemia due to different etiology (HDE) versus infection-related fasting show: 5
- Impaired level of consciousness (adjusted OR 2.50, P=0.025) 5
- Clinical onset within 12 hours (adjusted OR 3.98, P<0.001) 5
- More severe triage codes (P<0.001) 5
- Neuroglycopenic symptoms (confusion, seizures, altered consciousness) 5
Critical Diagnostic Approach
Essential "Critical Sample" During Hypoglycemic Episode
The value of obtaining diagnostic tests at presentation of spontaneous hypoglycemia cannot be overemphasized, including: 2
This critical sample allows assessment of the integrity of fasting adaptation systems and distinguishes between hyperinsulinemic states (suppressed ketones) versus counter-regulatory hormone deficiency versus metabolic defects. 6
Between-Episode Evaluation
For recurrent hypoglycemia, additional workup includes: 1
- Biochemical tests between episodes 1
- Dynamic endocrine testing 1
- Molecular genetic testing for suspected inborn errors of metabolism 1
Common Clinical Pitfalls
Beta-blockers mask hypoglycemia symptoms through suppression of adrenergic warning signs (sweating, palpitations, tremor), making recognition more difficult and potentially delaying treatment. 3 Alternative medications should be considered before using beta-blockers in at-risk children. 3
Hypoglycemia unawareness develops after repeated hypoglycemic episodes, with failure of adrenergic responses (defective glucose counterregulation), requiring more frequent blood glucose monitoring to prevent severe episodes. 3
Age-dependent symptom recognition is critical—infants and toddlers have limited ability to detect and communicate hypoglycemia symptoms, necessitating higher blood glucose targets and more frequent monitoring in this age group. 7