54. Hyperinsulinism - classification, etiology, pathogenesis, clinical manifestations.

Hyperinsulinism

Definition

Hyperinsulinism refers to a condition with excessive insulin levels in the blood, leading to hypoglycemia.

Classification

Etiology

1. 1 Endogenous hyperinsulinism

• Insulinoma (pancreatic β-cell tumor ) —most common endogenous cause.
• β-cell hyperplasia (nesidioblastosis), especially in infants and neonates.
• Genetic mutations (e.g., activating mutations of glucokinase gene or defects in KATP channel genes).
• Islet cell hyperplasia after gastric surgery (e.g., post-gastric bypass, known as "dumping syndrome").

1. 2 Exogenous hyperinsulinism

• Excessive insulin administration (accidental or intentional, common in diabetes patients).
• Sulfonylurea overdose (stimulate endogenous insulin release).

Pathogenesis

1. High insulin levels → increased glucose uptake by muscle and fat.
2. Suppression of hepatic gluconeogenesis and glycogenolysis.
3. Reduced blood glucose levels → hypoglycemia.
4. Counter-regulatory hormones (glucagon, catecholamines) try to correct, but if insulin is too high → fail to restore glucose.

Clinical manifestations

Symptoms of hypoglycemia

Autonomic (adrenergic) symptoms

• Sweating.
• Tremors.
• Palpitations.
• Hunger.
• Anxiety.

Neuroglycopenic symptoms

• Weakness.
• Confusion.
• Visual disturbances.
• Seizures.
• Loss of consciousness, coma.

Specific features

Insulinoma patients often present with fasting hypoglycemia, relieved by eating ("Whipple's triad"):

1. Hypoglycemic symptoms.
2. Low plasma glucose measured during symptoms.
3. Symptom relief after glucose intake.

Complications

• Recurrent severe hypoglycemia → brain damage.
• Accidents or trauma during episodes (e.g., falls).

Summary Table