What are the signs and symptoms of hyperinsulinism?

Signs of Hyperinsulinism

Hyperinsulinism presents primarily with recurrent hypoglycemia and its associated symptoms, including tremors, sweating, confusion, seizures, and in severe cases, permanent neurological damage—particularly dangerous in infants and children where prompt recognition is critical to prevent brain injury. 1, 2

Acute Hypoglycemic Manifestations

The hallmark of hyperinsulinism is dysregulated insulin secretion causing persistent hypoglycemia, which manifests differently across age groups:

In Infants and Children

• Seizures and altered consciousness from severe hypoglycemia 1, 2
• Early symptom onset (80% present in early infancy) 3
• Developmental delay and permanent brain damage if untreated 1, 2
• Recurrent hypoglycemic episodes requiring aggressive treatment 1
• Risk of neurological sequelae in 28% of cases (abnormal neurodevelopment in 22%, epilepsy in 13%) 3

In Older Children and Adults

• Tremors and sweating 4
• Light-headedness and confusion 4
• Irritability and drowsiness 4
• In younger children: inattention, falling asleep at inappropriate times, unexplained behavior changes, and temper tantrums 4

Chronic Metabolic Syndrome Features (Adult Hyperinsulinemia)

In adults with chronic hyperinsulinemia and insulin resistance, a distinct constellation of findings emerges:

• Obesity, particularly central/abdominal fat distribution (elevated waist:hip ratio) 5, 6
• Hypertension 5, 6
• Dyslipidemia: elevated triglycerides, elevated total cholesterol, and low HDL-cholesterol 5, 6
• Impaired glucose tolerance or type 2 diabetes 5, 6
• Acanthosis nigricans (in cases with insulin receptor mutations) 4
• Virilization and enlarged cystic ovaries in women (polycystic ovary syndrome association) 4

Critical Diagnostic Context

A key pitfall is that insulin levels may appear "normal or elevated" in the context of hypoglycemia—the critical abnormality is that insulin is inappropriately high for the low glucose level. 2 This distinguishes hyperinsulinism from appropriate physiologic responses.

Laboratory Findings During Hypoglycemic Episodes

• Inappropriately elevated plasma insulin relative to low blood glucose 2
• Suppressed plasma beta-hydroxybutyrate (ketones should be elevated during hypoglycemia but are suppressed by insulin) 2
• Suppressed plasma fatty acids 2
• Elevated plasma ammonia (in hyperinsulinism-hyperammonemia syndrome) 1, 2

Genetic and Morphologic Variants

• Congenital forms associated with mutations in SUR-1, Kir6.2, glucokinase, glutamate dehydrogenase, and other genes 2
• Transient neonatal forms associated with perinatal asphyxia, maternal diabetes, prematurity, or intrauterine growth retardation 1, 2

When to Suspect Hyperinsulinism

Suspect hyperinsulinism in any infant or child with recurrent hypoglycemia, particularly if blood glucose drops below 70 mg/dL (3.9 mmol/L) and requires frequent feeding or medical intervention. 2 In adults, suspect chronic hyperinsulinemia when multiple metabolic syndrome features cluster together—isolated presentation of obesity, hypertension, or dyslipidemia is rare (prevalence 1-2%), while combined presentations are common (64% of affected individuals) 6.

Emergency Recognition

Severe hypoglycemia from hyperinsulinism can progress to unconsciousness and convulsions, requiring immediate treatment with glucagon. 4 The goal is maintaining plasma glucose above 70 mg/dL to prevent permanent brain damage 2.