Insulin Tolerance Test

What is the Insulin Tolerance Test?

The Insulin Tolerance Test (ITT) is a medical diagnostic procedure used to evaluate the body’s sensitivity to insulin and assess how well the body's endocrine system responds to changes in blood sugar levels. By inducing a state of controlled hypoglycemia (low blood sugar) through the administration of insulin, this test provides crucial insights into the function of the pituitary, adrenal glands, and overall glucose metabolism. While the ITT is not commonly performed, it is used in specialized situations, primarily to diagnose conditions like hypopituitarism, and adrenal insufficiency, and to evaluate growth hormone (GH) and cortisol responses.

Purpose of Insulin Tolerance Test

The main purpose of the Insulin Tolerance Test is to assess the body's ability to regulate blood sugar and its hormonal responses to hypoglycemia. It helps diagnose conditions related to the body's endocrine function, particularly in cases where the functionality of the pituitary gland, adrenal glands, and other hormonal systems are in question.

A. Evaluation of Growth Hormone Deficiency

One of the key uses of the ITT is to assess the secretion of growth hormone (GH) in individuals suspected of having growth hormone deficiency (GHD). GH is released from the pituitary gland in response to stress, such as hypoglycemia, which the ITT intentionally induces. If the pituitary gland is functioning normally, it should release GH in response to low blood sugar levels during the test. In people with GHD, this response may be absent or significantly reduced.

B. Diagnosis of Hypopituitarism

Hypopituitarism is a condition characterized by a decreased or absent production of one or more of the hormones produced by the pituitary gland. The ITT helps evaluate the pituitary gland's ability to secrete not only GH but also adrenocorticotropic hormone (ACTH). ACTH stimulates the adrenal glands to produce cortisol, a hormone crucial for maintaining glucose levels during stress. A lack of cortisol response during the ITT may indicate pituitary dysfunction.

C. Assessment of Adrenal Insufficiency

Adrenal insufficiency is a condition in which the adrenal glands do not produce enough cortisol. The ITT is used to test the hypothalamic-pituitary-adrenal (HPA) axis, which is responsible for regulating cortisol production in response to stress. By inducing hypoglycemia, the test stimulates the release of ACTH, which should, in turn, prompt the adrenal glands to release cortisol. A failure to produce sufficient cortisol during the test indicates adrenal insufficiency.

Steps Involved in Insulin Tolerance Test

The ITT is a complex and carefully controlled procedure that should only be conducted in a hospital or clinical setting due to the potential risks of inducing hypoglycemia. It requires the expertise of medical professionals to ensure patient safety throughout the test.

A. Preparation for the Insulin Tolerance Test

Before the test, the patient must follow certain guidelines:

1.) Fasting: The patient is usually required to fast for about 8 hours before the test to ensure baseline glucose levels are low but stable.

2.) Medication Adjustments: Patients may be asked to stop taking medications that could interfere with the test results, particularly corticosteroids or other hormone-related treatments.

3.) Monitoring and Consent: Since the test involves risks, patients must provide informed consent, and medical professionals will closely monitor vital signs and blood glucose levels throughout the procedure.

B. Procedure of the Insulin Tolerance Test

Baseline Measurements: The test begins with drawing baseline blood samples to measure glucose, GH, and cortisol levels. These baseline values are important for comparison with the post-insulin values.

Insulin Administration: A specific dose of intravenous insulin is administered to induce hypoglycemia. The dose depends on the patient's weight and overall health. The goal is to lower the patient's blood glucose to a critical level (typically less than 2.2 mmol/L or about 40 mg/dL) to stimulate a stress response from the body.

Monitoring Blood Sugar: After insulin administration, blood sugar levels are carefully monitored at regular intervals, typically every 15–30 minutes, over a period of 1-2 hours. During this time, blood samples are collected to measure glucose, GH, and cortisol levels at different points.

Assessment of Symptoms: As hypoglycemia develops, patients may experience symptoms such as sweating, shaking, confusion, dizziness, and sometimes even loss of consciousness. Medical staff are prepared to manage these symptoms, and the test is stopped if severe hypoglycemia occurs.

Recovery: Once the blood sugar reaches the target low level and sufficient data is collected, the hypoglycemia is corrected by giving the patient glucose, either orally or intravenously, to quickly raise blood sugar levels back to normal. The patient is observed until their glucose levels stabilize.

C. Post-Test Monitoring

Following the test, patients are monitored to ensure they fully recover from the hypoglycemic state. Blood sugar levels are checked periodically, and the patient is allowed to eat a normal meal once they are stable.

Interpretation of Results

The results of the ITT are evaluated by comparing the baseline levels of GH and cortisol with the levels measured during hypoglycemia. A normal response to hypoglycemia involves a significant increase in both growth hormone and cortisol levels, indicating proper function of the pituitary and adrenal glands.

A. Growth Hormone Response

Normal: A normal GH response to hypoglycemia is an increase in GH levels to above 5–10 ng/mL (depending on the lab’s reference values).

Abnormal: A failure to reach these levels indicates growth hormone deficiency, which could be due to pituitary dysfunction.

B. Cortisol Response

Normal: Cortisol levels should rise to at least 18–20 μg/dL (500–550 nmol/L) in response to hypoglycemia.

Abnormal: Low cortisol levels indicate adrenal insufficiency, suggesting either primary adrenal failure or secondary adrenal failure due to pituitary dysfunction.

The combination of GH and cortisol responses allows clinicians to assess both the hypothalamic-pituitary axis and adrenal function, leading to more accurate diagnoses of hormonal deficiencies.

Risks and Complications of Insulin Tolerance Test

Although the Insulin Tolerance Test is a valuable diagnostic tool, it carries certain risks due to the deliberate induction of hypoglycemia, which can lead to severe symptoms if not managed carefully. The most common risks include:

1.) Severe Hypoglycemia: In some cases, patients may experience extreme hypoglycemia, which can result in seizures, loss of consciousness, or coma. To mitigate this, medical staff are present to intervene and administer glucose quickly if needed.

2.) Cardiovascular Complications: Patients with pre-existing heart conditions are at higher risk of complications during hypoglycemia, as the body’s stress response can strain the cardiovascular system.

3.) Nausea and Vomiting: These are common side effects during the test due to the body’s reaction to low blood sugar levels.

Due to these risks, the ITT is contraindicated in patients with severe heart disease, epilepsy, or certain other serious health conditions.

Conclusion

The insulin tolerance test is a medical procedure used to diagnose conditions related to the body's ability to produce or use insulin, including hypoglycemia and growth hormone deficiency. It involves the administration of insulin to the patient and the measurement of glucose and other hormone levels in the blood over time. 

The insulin tolerance test can be a stressful and uncomfortable experience for some patients and is associated with risks and potential complications, including hypoglycemia. It is essential that the test is performed under close medical supervision, and the patient's blood glucose levels and symptoms are closely monitored throughout the procedure.