Overview
The Insulin Tolerance Test (ITT) is a dynamic endocrine test used to assess the integrity of the hypothalamic–pituitary–adrenal (HPA) axis and growth hormone (GH) reserve. It is considered the gold standard test for the diagnosis of adult growth hormone deficiency and for evaluating ACTH–cortisol deficiency.
The test involves administration of intravenous insulin to induce controlled hypoglycemia. Hypoglycemia acts as a strong physiological stimulus for the release of growth hormone and cortisol. An adequate hormonal response confirms normal pituitary and adrenal function, while an impaired response indicates hormonal deficiency. The ITT is also used to assess insulin sensitivity and HPA axis integrity. Insulin Tolerance Test (ITT)
Principle of the Test
The principle of the insulin tolerance test is based on the body’s counter-regulatory hormonal response to hypoglycemia. When blood glucose levels fall below a critical threshold, the hypothalamus stimulates the pituitary gland to release growth hormone and ACTH.
ACTH subsequently stimulates cortisol secretion from the adrenal cortex. Measurement of GH and cortisol levels following induced hypoglycemia allows evaluation of pituitary reserve and adrenal responsiveness. Adequate hypoglycemia is defined as blood glucose levels below 40 mg/dL.
Indications
The primary indication for ITT is assessment of growth hormone and cortisol reserves. It is used in the evaluation of suspected growth hormone deficiency in adults and children, including conditions such as dwarfism and acromegaly.
The test is also indicated in the diagnosis of ACTH and cortisol deficiency and helps distinguish true Cushing’s syndrome from pseudo-Cushing’s states. It is useful in assessing primary and secondary adrenal insufficiency. Additional applications include evaluation of insulin resistance in research settings and pre-surgical assessment of adrenal function.
Contraindications
The insulin tolerance test is contraindicated in several conditions due to the risk associated with induced hypoglycemia. These include ischemic heart disease, epilepsy, or a history of seizures.
Untreated hypothyroidism is a contraindication because it may impair growth hormone and cortisol responses. The test should not be performed in patients with untreated severe hypoadrenalism or in those with glycogen storage diseases.
Patient Preparation
Proper preparation is essential to ensure safety and accurate results. Estrogen therapy should be discontinued at least six weeks before the test.
The patient must remain fasting from midnight before the test, with only water permitted. The test is usually performed in the morning, and patients are instructed to report at around 8:30 am. Baseline electrocardiography is performed, and blood pressure is recorded in both sitting and lying positions. Emergency treatment for hypoglycemia must be readily available before starting the test.
Test Protocol
The test requires strict one-to-one nursing supervision throughout the procedure. Two intravenous cannulas are inserted, one for insulin administration and the other for blood sample collection.
A short-acting insulin dose of 0.15 units per kilogram body weight is administered as an intravenous bolus. In patients with suspected insulin resistance, a higher starting dose of up to 0.3 units per kilogram may be used. Blood glucose levels are monitored every five minutes to ensure adequate hypoglycemia.
If blood glucose does not fall below 40 mg/dL, the insulin dose may be repeated after 45 minutes. Once adequate hypoglycemia is achieved, blood samples are collected at regular intervals.
Sample Collection
Blood samples are collected for glucose, cortisol, and growth hormone estimation at 30, 45, 60, 90, and 120 minutes. Each sample showing hypoglycemia must be clearly labeled with the corresponding time.
The test may be extended up to three hours in selected cases. At the end of the test, hypoglycemia is reversed using oral or intravenous glucose based on the patient’s condition. Patients are advised not to leave the test area until they have eaten and symptoms have resolved.
Interpretation of Results
During hypoglycemia, cortisol levels should rise to more than 25 µg/mL, and growth hormone levels should peak above 14 ng/mL. These responses indicate normal pituitary and adrenal function.
A growth hormone level below 3 ng/mL indicates severe growth hormone deficiency. A normal rise in plasma cortisol excludes ACTH and cortisol deficiency. The glucose disappearance rate, known as the KITT value, correlates with insulin sensitivity.
An appropriate rise in both GH and cortisol confirms intact HPA axis function and adequate adrenal reserve.
Clinical Utility
The insulin tolerance test is widely used to confirm growth hormone deficiency in both children and adults. It is a key diagnostic tool for secondary adrenal insufficiency.
The test also guides hormone replacement therapy decisions and helps clinicians determine the need for long-term GH or corticosteroid treatment.
Advantages and Limitations
The major advantage of ITT is that it remains the gold standard for assessing growth hormone reserve, adrenal function, and insulin sensitivity.
However, the test requires close medical supervision and carries a significant risk of hypoglycemia. It is contraindicated in patients with epilepsy or cardiovascular disease. Because of these risks, ITT should only be performed in specialized centers with experienced staff.
