hyperinsulinism

Hyperinsulinism: A Condition Characterized by Excess Insulin Production

Hyperinsulinism, also known as congenital hyperinsulinism (HI), is a rare genetic disorder that affects the pancreas's ability to regulate insulin production. In individuals with this condition, the beta cells of the pancreas secrete too much insulin, leading to an excessive amount of insulin in the blood.

Key Features:

• Excess Insulin Production: The primary characteristic of hyperinsulinism is the inappropriate secretion of insulin by the pancreas.
• Hypoglycemia: This condition often leads to persistent hypoglycemia (low blood sugar), which can cause a range of symptoms, including seizures, intellectual disability, and permanent brain damage in severe cases.
• Genetic Cause: Hyperinsulinism is typically caused by genetic mutations that affect the functioning of the pancreas's beta cells.

Causes and Risk Factors:

• Genetic Predisposition: Individuals with a family history of hyperinsulinism are more likely to develop this condition.
• Infancy and Childhood: This condition most commonly affects infants and young children, although it can occur at any age.

Symptoms and Complications:

• Hypoglycemia: The primary symptom of hyperinsulinism is persistent hypoglycemia, which can lead to a range of complications, including seizures, intellectual disability, and permanent brain damage.
• Other Symptoms: Additional symptoms may include weakness, apathy, fainting, convulsions, and coma during severe hypoglycemic crises.

References:

• [3] Congenital hyperinsulinism (HI) is a genetic disorder in which the insulin cells of the pancreas, called beta cells, secrete too much insulin.
• [9] Hyperinsulinism is defined as the elevation of insulin levels in blood and is the most frequent cause of hypoglycemia in infants and children.
• [15] Hyperinsulinism (HI) due to dysregulation of pancreatic beta-cell insulin secretion is the most common and most severe cause of persistent hypoglycemia in infants and children.

Common Signs and Symptoms of Hyperinsulinism

Hyperinsulinism, also known as hyperinsulinemia, can manifest in various ways depending on the individual and the underlying cause. Here are some common signs and symptoms associated with this condition:

• Hypoglycemia: One of the primary symptoms of hyperinsulinism is hypoglycemia, or abnormally low blood sugar levels [1].
• Confusion and Altered Mental Status: In children, hyperinsulinism can cause sudden aggressiveness, confusion, or loss of consciousness [7].
• Excessive Hunger and Fatigue: People with hyperinsulinism may experience excessive hunger and fatigue due to the body's inability to regulate blood sugar levels properly [8].
• Feeding Difficulty: Infants and young children with hyperinsulinism may have difficulty feeding, leading to irritability or lethargy [9].
• Shakiness and Weakness: In severe cases, hyperinsulinism can cause shakiness, weakness, seizures, and even coma if left untreated [5].

Other Possible Symptoms

While not everyone with hyperinsulinism will experience all of these symptoms, they may also include:

• Irritability
• Lethargy
• Excessive sweating
• Altered mental status or abnormal behavior in children

It's essential to note that some people with hyperinsulinism may not exhibit any noticeable symptoms at all. If you suspect you or a loved one has this condition, consult a healthcare professional for proper diagnosis and treatment.

References:

[1] Context 2 [5] Context 5 [7] Context 7 [8] Context 8

Diagnostic Tests for Hyperinsulinism

Hyperinsulinism, also known as congenital hyperinsulinism (CHI), is a rare condition characterized by excessive insulin production in the body. Diagnosing this condition requires a combination of clinical evaluation and laboratory tests.

• Fasting Plasma Glucose Test: This test measures blood sugar levels after an overnight fast. In individuals with hyperinsulinism, fasting plasma glucose levels are typically low (< 60 mg/dL) [4].
• Insulin Blood Test: This test measures insulin levels in the blood. Elevated insulin levels (higher than 2 µU/mL) can indicate hyperinsulinism [13].
• Beta-Hydroxybutyrate and Free Fatty Acids Tests: These tests measure the levels of beta-hydroxybutyrate and free fatty acids in the blood. Suppressed levels (< 1 µmol/L for beta-hydroxybutyrate and < 1 mmol/L for free fatty acids) can indicate hyperinsulinism [13].
• Glucagon Stimulation Test: This test involves administering glucagon to stimulate insulin production. A positive response (i.e., increased insulin levels) can confirm the diagnosis of hyperinsulinism [2].

Imaging Studies

In addition to laboratory tests, imaging studies may be used to diagnose and manage hyperinsulinism.

• Ultrasound, Computerized Tomography (CT), and Magnetic Resonance Imaging (MRI): These imaging techniques can help identify focal lesions or tumors in the pancreas that may be causing hyperinsulinism [8].

Genetic Testing

Genetic testing may also be used to diagnose hyperinsulinism.

• Molecular Genetic Testing: This test can identify genetic mutations responsible for hyperinsulinism, such as those affecting the ABCC8 and KCNJ11 genes [10].

It's essential to note that a diagnosis of hyperinsulinism typically requires a combination of clinical evaluation, laboratory tests, and imaging studies. A healthcare professional should be consulted for an accurate diagnosis and treatment plan.

References:

[2] - The utility of the glucagon stimulation test at the end of a fast in establishing the diagnosis of congenital hyperinsulinism was demonstrated in a study of 14 children

Treatment Options for Hyperinsulinism

Hyperinsulinism, also known as congenital hyperinsulinism (CHI), is a rare condition characterized by excessive insulin production in the body. The primary goal of treatment is to manage blood sugar levels and prevent hypoglycemia.

Medications Used to Treat Hyperinsulinism

Several medications are used to treat hyperinsulinism, including:

• Diazoxide: This is the first-line treatment for persistent HI and the only drug approved by the FDA for long-term treatment of hyperinsulinemic hypoglycemia [1]. Diazoxide works by inhibiting insulin release from the pancreas.
• Octreotide: This medication can be used to reduce insulin production in patients who do not respond to diazoxide [2].
• Glucagon: Administering glucagon intravenously or subcutaneously can help elevate blood sugar levels quickly [3].

Other Treatment Options

In addition to medications, other treatment options for hyperinsulinism include:

• Lifestyle modifications: Making changes to diet and lifestyle can be beneficial in managing type 2 diabetes, which is often associated with hyperinsulinemia [4].
• Surgical intervention: In some cases, surgical removal of the pancreas or a portion of it may be necessary to treat hyperinsulinism [5].

Rare Conditions

Tumor hyperinsulinism (HI) is a rare condition that occurs when a tumor in the pancreas produces excess insulin. Ersodetug (RZ358) has been granted Orphan Drug designation by the FDA for the treatment of hypoglycemia due to tumor HI [6].

Important Notes

It's essential to note that glucocorticoids should not be used to treat hyperinsulinism or unspecified hypoglycemia, and forced feeds or continuous feeds can lead to feeding aversion [7].

References:

[1] Lerch C, Kummer S, et al. Long-term medical treatment in congenital hyperinsulinism: a descriptive analysis in a large cohort of patients from different ...

[2] Dec 29, 2022 — Medications used to manage hyperinsulinism include diazoxide, octreotide, nifedipine, glucagon, growth hormone, and glucocorticoids.

[3] by AP De Cosio · 2019 · Cited by 43 — Currently, the only available approved treatment for hyperinsulinism is diazoxide. Patients unresponsive to diazoxide may benefit from specialized evaluation ...

[4] by A Welters · 2015 · Cited by 108 — In summary, diazoxide is still the first line drug in the treatment of hyperinsulinism. It is easy to apply and generally well tolerated. Common ...

[5] The majority of patients with hyperinsulinemia begin treatment by addressing its underlying cause, such as insulin resistance, insulinoma, or nesidioblastosis.

[6] The FDA’s Orphan Drug Designation is intended to encourage the development of treatments for rare diseases. Orphan Drug Designation offers benefits including seven years of market exclusivity protection and may shorten the clinical development path through potential qualification for expedited pathways to approval. About Tumor Hyperinsulinism ...

[7] Do not use glucocorticoids to treat hyperinsulinism or unspecified hypoglycemia; Do not use forced feeds or continuous feeds to control blood glucose (can develop feeding aversion) ... AA., Stanley, CA. A specialized team approach to diagnosis and medical versus surgical treatment of infants with congenital hyperinsulinism. Semin Pediatr Surg ...

[8] Diazoxide is the first-line drug for treating hyperinsulinism and the only pharmacological agent approved for hyperinsulinism by the Federal Drug Administration. This systemic review and meta-analysis aimed to investigate the efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia (HH). The meta-analysis of the efficacy and safety of diazoxide in treating HH was performed ...

Differential Diagnoses of Hyperinsulinism

Hyperinsulinism, also known as congenital hyperinsulinism (CHI), is a group of disorders that cause persistent hypoglycemia due to congenital excess secretion of insulin. The differential diagnosis of hyperinsulinism includes various conditions that can lead to similar symptoms.

Causes of Hyperinsulinism

• Congenital Hyperinsulinism: A genetic disorder that causes the pancreas to produce excess insulin, leading to persistent hypoglycemia.
• Insulinoma: A rare tumor of the pancreas that produces excess insulin.
• Factitious Hypoglycemia: Intentional administration of insulin or other substances to cause hypoglycemia.

Other Conditions to Consider

• Transient Neonatal Hyperinsulinism: A condition that causes temporary excess insulin production in newborns.
• Hyperinsulinism and Hyperammonaemia (HI/HA) Syndrome: A rare condition characterized by elevated serum ammonia concentration, hyperinsulinism, and hypoglycemia.
• Focal Adenomatous Hyperplasia: A rare condition that causes focal adenomatous hyperplasia in infancy.

Diagnostic Tools

• Glucagon Stimulation Test: A test used to establish the diagnosis of congenital hyperinsulinism by measuring the response to glucagon stimulation.
• Imaging Studies: Various imaging studies, such as [18F]-DOPA PET/CT imaging, can be used to diagnose and differentiate between different forms of hyperinsulinism.

References

• [3] Congenital hyperinsulinism (CHI) is a group of disorders that cause persistent hypoglycemia due to congenital excess secretion of insulin; it does not include acquired causes.
• [4] Congenital hyperinsulinism (HI) is the leading cause of persistent hypoglycemia in infants and children.
• [5] Congenital hyperinsulinism is caused by genetic mutations that result in inappropriate and excess insulin secretion from the pancreas.

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