Medically Reviewed by: Dr. Dipak Ladda, M.D.
Expertise: Consultant Pathologist
Last Updated: July 14, 2026
Medical Analysis
Understanding the Insulin Tolerance Test (ITT): A Comprehensive Clinical Guide
Basics of Insulin Tolerance Test (ITT)
The Insulin Tolerance Test (ITT) is recognized as the gold standard procedure for assessing Adult Growth Hormone Deficiency and for evaluating ACTH/Cortisol deficiency [5, 11]. To ensure the accuracy of this diagnostic procedure, an adequate level of hypoglycemia—defined as blood glucose levels below 40 mg/dL—must be achieved [16]. When this target is reached, the established GH cut-point for diagnosis is 3-5 μg/L [5, 6]. This clinical procedure is systematically performed to assess pituitary function, adrenal function, and systemic insulin sensitivity [11, 16]. Its primary clinical applications include the precise measurement of insulin sensitivity, evaluation of the HPA axis integrity, and overall assessment of adrenal function [8, 11].
Clinical Indications for ITT
The primary indications for performing an Insulin Tolerance Test include the assessment of cortisol and human Growth Hormone (hGH) reserves [5, 6]. It is a critical diagnostic tool for conditions such as dwarfism and acromegaly, which involve hGH deficiency [2]. Furthermore, the test is utilized to investigate cortisol/ACTH deficiency and to assist in the clinical distinction between Cushing’s syndrome and Pseudo-Cushing’s syndrome [8, 11]. It is also indicated for the evaluation of primary adrenal insufficiency [8].
Additional uses for the ITT include the evaluation of suspected GH deficiency and secondary adrenal insufficiency, as well as the assessment of insulin resistance in specialized research settings [4, 5, 11]. Additionally, it is employed for pre-surgical adrenal assessment to ensure patient stability and proper hormonal function [8].
Contraindications for ITT
The Insulin Tolerance Test is a powerful diagnostic tool, but it carries inherent risks due to the induction of hypoglycemia [4]. Consequently, it is strictly contraindicated in patients with the following conditions:
Ischemic Heart Disease
Epilepsy or a history of seizures
Untreated hypothyroidism (as this condition may significantly impair hGH and Cortisol response)
Untreated severe hypoadrenalism
Glycogen storage diseases
Preparation Before Test (ITT)
To ensure patient safety and test reliability, rigorous preparation is required. Patients must stop all estrogen therapy a minimum of 6 weeks before the scheduled test [5]. The patient should remain in a fasting state from midnight—with only water permitted—and must be instructed to arrive at the clinical facility by 8:30 am.
The standard protocol for insulin administration is 0.15 U/kg [7]. Before starting, the medical team must perform several mandatory safety steps:
Take a baseline ECG.
Record the patient’s blood pressure while both sitting and lying down.
Ensure that emergency treatment for hypoglycemia is immediately at hand.
During the test, the patient is not permitted to eat, although they may drink plain water. Blood sugar samples are collected at regular intervals throughout the procedure [7]. While minimum collection is required up to 2 hours, the process may be extended up to three hours if necessary [7]. At the conclusion of the test, the clinical team must remove the intracaths and ensure the patient does not leave the room until they have consumed food.
Test Protocol
The ITT requires strict one-to-one nursing supervision throughout the procedure. The clinical protocol involves the following steps:
Insert two intravenous intracaths on both sides: one designated for the insulin injection and the other for blood sample collection.
Administer 0.15 units/kg of short-acting insulin as an intravenous bolus dose [7]. If insulin resistance is suspected, practitioners may consider a higher starting dose of 0.3 units/kg [7].
The goal is for blood glucose to drop to less than 40 mg/dL to induce test hypoglycemia [7]. If this level is not achieved, the initial dose may be repeated after 45 minutes.
The team must assess bedside blood glucose readings every 5 minutes to monitor safety and efficacy.
Blood samples for glucose, cortisol, and GH estimation must be collected at 30, 45, 60, 90, and 120 minutes [7].
All blood samples showing hypoglycemia must be clearly labeled with the exact timing.
The team must reverse hypoglycemia changes with either oral or intravenous glucose, determined by the patient’s specific needs.
Interpretation of Test Results
Interpretation of the ITT relies on comparing hormonal peaks against the achieved hypoglycemia [5, 11].
Corresponding blood samples taken during the period of hypoglycemia should demonstrate a cortisol peak of more than 25 mcg/ml and a Human Growth Hormone peak of more than 14 ng/ml [2].
If the hGH peak is less than 3 ng/ml, it indicates severe deficiency of Growth Hormone [5, 6].
A normal rise in plasma cortisol effectively excludes ACTH and cortisol deficiency [8, 11].
The KITT value, which represents the glucose disappearance rate, correlates directly with insulin sensitivity [7].
The observed hormonal responses (GH and cortisol rise) confirm the integrity of the HPA axis [11].
A normal cortisol increase confirms adequate adrenal function [8, 11].
Clinical Utility
The ITT provides vital clinical information, including confirming GH deficiency in both children and adults and diagnosing secondary adrenal insufficiency [2, 5, 11]. Ultimately, the results of this test are used to guide critical hormone replacement therapy decisions [5, 6].
Advantages and Limitations
The primary advantage of the ITT is that it is the gold standard for assessing the HPA axis and insulin sensitivity [5, 11]. However, it requires close medical monitoring and is contraindicated in patients with epilepsy or cardiovascular disease. The risk of induced hypoglycemia remains a major limitation of this procedure [4, 7].
For Non-Medicos
What is the Insulin Tolerance Test (ITT)? Think of the Insulin Tolerance Test as a “stress test” for your hormones. Sometimes, doctors need to know if your pituitary and adrenal glands are working correctly [11]. They do this by gently lowering your blood sugar using insulin and then measuring how your body fights back by releasing essential hormones like cortisol and Growth Hormone (GH) [5, 7].
How to Prepare
Medication: If you are on estrogen therapy, you must stop at least 6 weeks before the test [5].
Fasting: Do not eat anything after midnight before your appointment. You may drink plain water.
Arrival: Arrive at the clinic by 8:30 am.
What to Expect During the Test
Safety First: You will have one-on-one nursing care the entire time.
The Process: Nurses will place two small tubes (intracaths) in your veins—one to give the insulin and one to take blood samples [7].
Monitoring: The team will watch your blood sugar closely every 5 minutes [7].
Ending the Test: Once the test is finished, you must eat a snack before you are allowed to leave the hospital.
Important Considerations
Why is it done? It helps doctors diagnose issues like Growth Hormone deficiency or problems with your adrenal glands [5, 11].
Safety Warning: Because this test purposefully lowers your blood sugar, it is not suitable for everyone, especially those with heart problems or a history of seizures [4]. Your doctor will carefully review your history before recommending this test to ensure it is safe for you.
References:
Grossman, A. B. (2010). The diagnosis and management of central hypoadrenalism. Journal of Clinical Endocrinology & Metabolism, 95(11), 4855–4863.
Joss, E. E., Zuppinger, K. A., & Zahnd, G. R. (1970). Diagnostic procedures in hypopituitary dwarfism. I. Evaluation of growth hormone deficiency: Plasma growth hormone response to insulin-induced hypoglycemia, effect of HGH on nitrogen retention, insulin-tolerance-test and growth velocity. Helvetica Paediatrica Acta, 25(4), 371–381.
Copinschi, G., L’Hermite, M., Leclerq, R., Golstein, J., Vanhaelst, L., Virasoro, E., & Robyn, C. (1975). Effects of glucocorticoids on pituitary hormonal responses to hypoglycemia. Inhibition of prolactin release. Journal of Clinical Endocrinology & Metabolism, 40(3), 442–449.
Toogood, A., Brabant, G., Maiter, D., Jonsson, B., Feldt-Rasmussen, U., Koltowska-Haggstrom, M., Rasmussen, A. K., Buchfelder, M., Saller, B., & Biller, B. M. K. (2012). Similar clinical features among patients with severe adult growth hormone deficiency diagnosed with insulin tolerance test or arginine or glucagon stimulation tests. Endocrine Practice, 18(3), 325–334.
Yuen, K. C. J. (2023). Growth Hormone Stimulation Tests in Assessing Adult Growth Hormone Deficiency. Endotext [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK395585/
Kim, J. H. (2020). Diagnosis and treatment of growth hormone deficiency. Endocrinology and Metabolism, 35(2), 272–285.
Yeoh, P., Dwyer, A. A., Anghel, E., Bouloux, P. M., Khoo, B., Chew, S., Wernig, F., Carroll, P., Aylwin, S. J. B., Baldeweg, S. E., Drake, W., Todd, J., Mangena, L., & Grossman, A. (2022). A comparison of the blood glucose, growth hormone, and cortisol responses to two doses of insulin (0.15 U/kg vs. 0.10 U/kg) in the insulin tolerance test: A single-centre audit of 174 cases. International Journal of Endocrinology, 2022, 7360282.
Charoensri, S. (2024). A contemporary approach to the diagnosis and management of adrenal insufficiency. Endocrinology and Metabolism, 39(1), 1–13.
Lewandowski, K. C. (2025). Comparison of glucagon stimulation test and insulin tolerance test for assessment of an anterior pituitary function—A cross-over study. Journal of Clinical Medicine, 14(18), 6567.
Yudina, A. E., et al. (2013). The glucagon stimulation test in comparison to the insulin tolerance test to diagnose growth hormone deficiency and central adrenal insufficiency in patients following craniospinal irradiation in young ages. Experimental and Clinical Endocrinology & Diabetes, 121(09), 555–559.
Karaca, Z., Grossman, A., & Kelestimur, F. (2021). Investigation of the hypothalamo-pituitary-adrenal (HPA) axis: A contemporary synthesis. Reviews in Endocrine and Metabolic Disorders, 22, 179–204.
Leong, K. S., Walker, A. B., Martin, I., Wile, D., Wilding, J., & MacFarlane, I. A. (2001). An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone and ACTH secretion in patients with hypothalamic-pituitary disease. Clinical Endocrinology, 54(4), 463–468.
Giritharan, S., Cox, J., Heal, C. J., Hughes, D., Gnanalingham, K., & Kearney, T. (2017). The prevalence of growth hormone deficiency in survivors of subarachnoid haemorrhage: Results from a large single centre study. Pituitary, 20, 624–634.
Giuffrida, F. M. A., Berger, K., Monte, L., Oliveira, C. H. M. C., Hoff, A. O., Maciel, R. M. B., & Vieira, J. G. H. (2009). Relationship between GH response and glycemic fluctuations in the glucagon stimulation test. Growth Hormone & IGF Research, 19(1), 77–81.
FAQ’s:
- What is the ITT used for?
It identifies adult growth hormone deficiency and evaluates adrenal or pituitary function. - Who should avoid this test?
Patients with epilepsy, heart disease, untreated hypothyroidism, or severe hypoadrenalism should avoid it. - Can I eat before testing?
No, you must remain fasting from midnight before your appointment; only water is permitted. - When should I stop estrogen?
Stop all estrogen therapy at least 6 weeks before undergoing this diagnostic test. - What is the insulin dose?
The standard dose is 0.15 units per kilogram of body weight, administered intravenously. - How long does testing take?
Samples are collected for at least 2 hours, though the procedure may last up to 3 hours. - What is the test goal?
The test aims to lower blood glucose levels to less than 40 mg/dL to stimulate hormones. - Is supervision required?
Yes, the procedure requires strict one-to-one nursing supervision throughout the entire duration of the test. - Are samples labeled by time?
Yes, all blood samples taken during the test must be clearly labeled with the exact collection time. - What happens after the test?
You must consume food before leaving the room to ensure hypoglycemia is fully reversed.
