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Hyperinsulinism – Causes, Symptoms and Treatment

Hyperinsulinism is a condition in which the pancreas produces excessive amounts of insulin, leading to dangerously low blood sugar levels. Causes range from genetic disorders to insulin-producing tumors.

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Things worth knowing about "Hyperinsulinism"

Hyperinsulinism is a condition in which the pancreas produces excessive amounts of insulin, leading to dangerously low blood sugar levels. Causes range from genetic disorders to insulin-producing tumors.

What is Hyperinsulinism?

Hyperinsulinism is a metabolic disorder characterized by abnormally high levels of insulin in the blood, which leads to persistently low blood glucose levels -- a condition known as hypoglycemia. It can affect newborns, children, and adults, and ranges from mild to life-threatening in severity.

Causes

Hyperinsulinism can be classified into congenital (inherited) and acquired forms:

Congenital Hyperinsulinism

Genetic mutations affecting the regulation of insulin secretion in pancreatic beta cells (e.g., mutations in the KATP channel genes ABCC8 and KCNJ11)
Focal or diffuse overactivity of insulin-producing pancreatic tissue

Acquired Hyperinsulinism

Insulinoma: A usually benign, insulin-secreting tumor of the pancreas
Nesidioblastosis: Diffuse proliferation of insulin-producing cells
Post-bariatric hyperinsulinism: Non-insulinoma hypoglycemia occurring after gastric bypass surgery
Certain medications, such as sulfonylureas
Insulin autoimmune syndrome (antibodies targeting endogenous insulin)

Symptoms

Symptoms of hyperinsulinism result directly from low blood sugar (hypoglycemia) and can vary in severity:

Trembling, sweating, and palpitations
Intense hunger and nausea
Difficulty concentrating, confusion, and dizziness
Headaches
In severe cases: seizures, loss of consciousness, and coma

In newborns and infants, the condition may present as poor feeding, lethargy, trembling, and seizures. The developing brain is especially vulnerable to glucose deprivation, making early diagnosis critical.

Diagnosis

Diagnosing hyperinsulinism involves several steps:

Laboratory tests: Measurement of blood glucose, insulin, C-peptide, and proinsulin during a hypoglycemic episode (e.g., supervised fasting test or 72-hour fast)
Imaging studies: CT scan, MRI, or selective arterial calcium stimulation to localize an insulinoma
PET-CT with ¹⁸F-DOPA to differentiate focal from diffuse forms in congenital hyperinsulinism
Genetic testing when a congenital form is suspected

Treatment

Treatment depends on the underlying cause of hyperinsulinism:

Medical Treatment

Diazoxide: Inhibits insulin release from beta cells and is the first-line treatment for congenital hyperinsulinism
Somatostatin analogues (e.g., octreotide): Suppress insulin secretion
Glucagon: Used for acute management of severe hypoglycemia
mTOR inhibitors (e.g., everolimus): For cases refractory to conventional medical therapy

Surgical Treatment

For insulinoma, surgical removal of the tumor (enucleation or pancreatic resection) is the treatment of choice and offers excellent cure rates
Focal congenital hyperinsulinism can often be cured by partial pancreatectomy
Diffuse congenital hyperinsulinism may require near-total pancreatectomy in severe cases

Dietary Management

Frequent carbohydrate-rich meals to prevent hypoglycemic episodes
In severe infant cases: continuous glucose infusion via nasogastric tube

References

Arnoux J-B et al. - Congenital hyperinsulinism: current trends in diagnosis and therapy. Orphanet Journal of Rare Diseases, 2011.
Cryer PE et al. - Hypoglycemia in Diabetes. Diabetes Care, American Diabetes Association, 2023.
Stanley CA - Perspective on the Genetics and Diagnosis of Congenital Hyperinsulinism Disorders. Journal of Clinical Endocrinology and Metabolism, 2016.

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