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Insulin Tolerance Test 2

▪ The tolerance test or ITT is a laboratory diagnostic test in which the individual receives insulin through an IV to check to see if the and the adrenal glands are functioning properly. ▪ An ITT is usually ordered and interpreted ITT by endocrinologists. ▪ The insulin tolerance test is believed to be one of the best ways of telling whether the hypothalamic-pituitary- adrenal axis is normal or not. It can be done prior to to make sure the adrenal glands can cope with the stress of having a major surgery or being acutely ill. 3

▪ When used to assess insulin sensitivity, a standard dose of insulin is administered, and blood glucose is monitored with frequent sampling; the plasma glucose disappearance rate (KITT) indicates the degree of whole-body insulin sensitivity, and correlates well with the gold-standard glucose clamp technique. ▪ When used for assessing the integrity of the hypothalamic–pituitary–adrenal axis (HPA), insulin Method injections are continued to the point of inducing extreme below 2.2 mmol/l (40 mg/dl). Patient must have symptomatic neuroglycopenia to trigger counter-regulatory cascade. Glucose levels below 2.2 mmol/L are insufficient absent symptoms. The brain must register low glucose levels. In response, adrenocorticotropic hormone (ACTH) and (GH) are released as a part of the stress mechanism. 4 ▪ ACTH elevation causes the to release . Normally, both cortisol and GH serve as counterregulatory hormones, opposing the action of insulin, i.e. acting against the hypoglycemia. ▪ ITT to the point of extreme hypoglycemia is considered to be the gold standard for assessing the integrity of the HPA. Sometimes ITT is performed to assess the peak adrenal capacity, e.g. before surgery. It is assumed that the ability to respond to Method insulin induced hypoglycemia translates into appropriate cortisol rise in the stressful event of acute illness or major surgery. ▪ The extreme hypoglycemic version of the ITT is potentially very dangerous and must be undertaken with great care, because it can iatrogenically induce the equivalent of a . A health professional must attend it at all times. ▪ Other provocation tests which cause much less release of growth hormone include the use of , arginine and . 5

The patient must be in a setting where low blood sugar levels can be easily treated. This may mean that the test should be done in a hospital setting. When the test is being performed, the following things are required: ▪ Tubes to collect the blood levels of cortisol and growth hormone ▪ An IV catheter that is at least 19-gauge What is ▪ Test strips and lancets to monitor the necessary for ▪ A glucometer to measure the blood sugar level ▪ 50 milliliters of 50 percent dextrose solution in case the blood the test? sugar needs to be treated quickly ▪ Insulin at a rate of 0.15 U/kg for injection in patients who have normal pituitary glands ▪ Insulin at a rate of 0.1 U/kg for injections in patients who have decreased pituitary gland function ▪ Insulin at a rate of 0.2-0.3 U/kg in patients who have Cushing’s disease, , or acromegaly 6

▪ The patient should first have a large bore (greater than 19-gauge IV catheter in place with good access to give both the insulin and glucose, if that is necessary. Blood should be taken before the insulin is given that will measure the growth hormone and cortisol levels at baseline. Insulin is then injected. Blood is then drawn at 30 minutes, 45 minutes, 60 minutes, 90 minutes, and 120 minutes after the insulin has been injected. The blood will be checked for cortisol and growth hormone levels. ▪ If the patient does not show signs of hypoglycemia after 45 Procedure minutes, a second dose of insulin should be given and the clock should start at zero again. If the blood sugar is truly less than 40 Directions mg/dL, the patient will likely have identifiable symptoms. ▪ After hypoglycemia has been achieved, there should be at least two blood samples taken to measure the cortisol and growth hormone levels. ▪ If the symptoms of hypoglycemia are severe, the 50 percent dextrose solution should be given to rescue the patient. Sampling of the blood should continue even if the dextrose solution has been given. The patient should be allowed to eat a meal following the test in order to bring up the blood sugar levels. 7

▪ The patient should be told that they will be given insulin to check the function of their pituitary gland and adrenal glands. Blood samples will be taken before and after giving insulin. The patient cannot eat or drink anything except water after midnight before the test. Sometimes, medications will be withheld until after the test. ▪ The patient should come to the test prepared to have an IV started prior to the test. The IV site is not only the site of injection but blood can be drawn from the IV site to avoid having to poke the Instructions for person so many times after insulin has been given. ▪ Insulin will be given through the catheter to lower the blood patient sugar. The patient may experience signs of low blood sugar after that. The low blood sugar should trigger the pituitary gland to release growth hormone and the should release cortisol. If this does not happen and the blood sugar does not rise, the patient will be given glucose in order to bring the blood sugar back up. The test will last for up to three hours after which the patient can eat. 8

▪ When a person gets the insulin tolerance test, there can be side effects. Typical side effects of the insulin tolerance test include loss of consciousness, palpitations, and sweating. In severe cases, seizures can Side effects occur because the blood sugar has gotten too low. If this happens, the doctor should be available to inject glucose into the vein to quickly bring the blood glucose levels back to normal. 9

The test cannot be performed on anybody. Under certain conditions, the test should not be performed ▪ In cases of , as this blocks the responsiveness of cortisol and growth hormone. If the person is hypothyroid and needs the test, cortisol should be given before taking thyroid medications so that the person doesn’t develop an Addisonian crisis. ▪ In cases of panhypopituitarism, in which the pituitary gland is Contra- known to be dysfunctional. ▪ In cases where the adrenal glands are known to be dysfunctional. indications ▪ In cases of epilepsy, because low blood sugar can trigger seizures in susceptible people. ▪ In cases of ischemic heart disease because low blood sugar can trigger a heart attack. ▪ In people who are older than 60 years of age. ▪ In children, unless it is done in a hospital that can care for sick children. 10

▪ The test is considered invalid if the blood sugar doesn’t get any lower than 40 mg/dL or 2.2 mmol/liter. If the amount of cortisol rise after giving insulin is greater than 550 nmol/liter, the test is considered to be normal. Interpretation ▪ People who have cortisol levels of between 400 and of results 550 nmol/liter can still have surgery but they will need to have cortisol given prior to the surgery. A normal growth hormone response occurs when the level is higher than 20 mU/liter. 11

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