What causes hypoglycemia (low blood glucose) in a 16-month-old male?

Hypoglycemia in a 16-Month-Old Male: Causes

In a 16-month-old child, hyperinsulinism is the most common cause of persistent hypoglycemia and must be ruled out first, as it carries the highest risk of permanent brain damage and neurocognitive impairment. 1, 2, 3

Primary Diagnostic Consideration: Hyperinsulinism

• Congenital hyperinsulinism is the most frequent cause of both transient and permanent hypoglycemia in infants and young children, characterized by dysregulated insulin secretion that results in persistent mild to severe hypoglycemia 1, 2, 4
• This condition carries a high risk of irreversible brain damage, seizures, developmental delay, and lifelong neurodisability if not promptly recognized and treated 1, 2, 4
• Approximately 60% of identifiable cases involve inactivating mutations in genes encoding the ATP-sensitive potassium channel (KATP hyperinsulinism), particularly ABCC8 and KCNJ11 5
• Other genetic causes include mutations in glucokinase, glutamate dehydrogenase, short-chain 3-hydroxyacyl-CoA dehydrogenase, and SLC16A1 2

Secondary Causes to Consider

Perinatal Stress-Related Hyperinsulinism

• Hyperinsulinism can be associated with perinatal stress including birth asphyxia, maternal toxemia, prematurity, or intrauterine growth retardation, resulting in prolonged neonatal hypoglycemia that may persist into early childhood 2

Syndromic Associations

• Beckwith-Wiedemann syndrome is commonly associated with hyperinsulinism and should be evaluated based on clinical features 2, 5
• Other syndromes include Kabuki syndrome, Turner syndrome, and congenital disorders of glycosylation 5

Endocrine Disorders

• Neonatal panhypopituitarism (growth hormone and cortisol deficiency) can present with persistent hypoglycemia in this age group 2
• Adrenal insufficiency with cortisol deficiency impairs counterregulatory responses 6, 7

Metabolic Disorders

• Hereditary hepatic enzyme deficiencies must be considered in persistent hypoglycemia outside the neonatal period 3

Critical Diagnostic Workup at Time of Hypoglycemia

The value of obtaining specific diagnostic tests during spontaneous hypoglycemia cannot be overemphasized 3:

• Blood glucose level (confirm true hypoglycemia <70 mg/dL) 6
• Plasma insulin level (elevated insulin during hypoglycemia confirms hyperinsulinism) 2, 3
• Plasma beta-hydroxybutyrate (suppressed in hyperinsulinism) 2
• Plasma fatty acids (suppressed in hyperinsulinism) 2
• Urine ketone bodies (absent or low in hyperinsulinism) 2, 3
• Plasma cortisol and growth hormone (to rule out hypopituitarism) 3
• Plasma ammonia (elevated in glutamate dehydrogenase mutations) 2
• Plasma acylcarnitine profile and urine organic acids (to identify metabolic disorders) 2

Important Clinical Pitfalls

Pseudohypoglycemia

• High triglycerides, uric acid, or bilirubin can cause falsely low glucose readings on point-of-care meters, which could lead to misdiagnosis 8
• Verify glucose measurements with laboratory hexokinase method if readings seem inconsistent with clinical presentation 8

Medication-Induced Hypoglycemia

• Drug-induced hypoglycemia should be excluded, though less common in this age group 2

Ketotic Hypoglycemia

• While ketotic hypoglycemia is the most common cause of hypoglycemia in childhood, it typically presents after age 18 months and is characterized by presence of ketones, making it less likely in a 16-month-old with persistent hypoglycemia 3

Treatment Urgency

• Maintaining plasma glucose levels above 70 mg/dL is critical to prevent brain damage from hypoglycemia 2
• Immediate supportive treatment with intravenous glucose should be initiated while diagnostic evaluation proceeds 3
• Early and appropriate recognition and treatment is vital to minimize neurocognitive impairment, as approximately half of all children with congenital hyperinsulinism experience negative cognitive impact from early-life hypoglycemia 4, 5