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Insulin Tolerance Test – Procedure, Results & Risks

The Insulin Tolerance Test (ITT) is a diagnostic procedure used to assess pituitary and adrenal gland function as well as growth hormone secretion.

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Things worth knowing about "Insulin Tolerance Test"

The Insulin Tolerance Test (ITT) is a diagnostic procedure used to assess pituitary and adrenal gland function as well as growth hormone secretion.

What is the Insulin Tolerance Test?

The Insulin Tolerance Test (abbreviated: ITT) is a specialised diagnostic test used in endocrinology. A defined dose of insulin is administered intravenously to the patient, inducing a controlled drop in blood sugar (hypoglycaemia). The body´s response to this drop provides important information about the function of the pituitary gland, the adrenal cortex, and the secretion of growth hormone (GH) and ACTH/cortisol.

When is the Insulin Tolerance Test Used?

The ITT is considered the gold standard for diagnosing certain hormonal disorders. It is primarily used in the following situations:

Suspected growth hormone deficiency (GH deficiency) in children and adults
Suspected central adrenal insufficiency (secondary adrenal insufficiency)
Investigation of pituitary insufficiency (hypopituitarism)
Assessment of the hypothalamic-pituitary-adrenal axis (HPA axis)
Postoperative follow-up after pituitary surgery

How Does the Test Work?

The test is performed exclusively under inpatient or closely monitored outpatient conditions due to the risk of potentially dangerous hypoglycaemia. The procedure involves the following steps:

The patient arrives fasting (at least 8 hours without food).
An intravenous line is placed and baseline values for blood glucose, cortisol, growth hormone, and ACTH are measured.
Regular insulin (short-acting human insulin) is then injected intravenously at a typical dose of 0.1–0.15 IU/kg body weight.
Blood glucose is measured at regular intervals (e.g., every 15–30 minutes) over a period of 90–120 minutes.
Blood samples for cortisol, ACTH, and growth hormone are collected simultaneously.
The test is considered valid when blood glucose falls below 2.2 mmol/l (40 mg/dl) and the patient shows symptoms of hypoglycaemia.

Interpretation of Results

The hormonal response to hypoglycaemia is evaluated as follows:

Growth Hormone (GH)

A rise in growth hormone above 3–5 ng/ml (depending on the laboratory and guideline used) is considered a normal response. An absent or blunted rise indicates growth hormone deficiency.

Cortisol

A cortisol rise above 500–550 nmol/l is considered an adequate stress response. Lower values suggest secondary adrenal insufficiency.

Risks and Contraindications

The Insulin Tolerance Test is an invasive procedure with potential risks. It must only be performed under direct medical supervision with immediately available glucose (e.g., 50% glucose solution) for emergency use.

The following contraindications apply:

Epilepsy or known seizure disorder
Coronary artery disease or severe cardiac conditions
Known hypoglycaemia unawareness
Severe adrenal insufficiency without prior cortisol replacement
Young children, below age thresholds defined by individual centres

Symptoms that may occur during the test include sweating, trembling, palpitations, confusion, and in rare cases seizures. Medical staff are trained to manage these complications immediately.

Alternatives to the Insulin Tolerance Test

Due to the risks associated with the ITT, alternative tests are used in certain clinical situations:

GHRH-Arginine Test: Used to assess growth hormone secretion with a lower risk profile
Glucagon Stimulation Test: An alternative for evaluating cortisol and GH reserve
Metyrapone Test: Used to assess the ACTH reserve capacity
Short ACTH Stimulation Test (Synacthen Test): Primarily for primary adrenal insufficiency

References

Grossman A et al. - Society for Endocrinology Endocrine Emergency Guidance: Emergency management of hypopituitarism. Endocrine Connections, 2021.
Molitch ME et al. - Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism, 2011.
Fleseriu M et al. - Hormonal replacement in hypopituitarism in adults: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism, 2016.

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