An insulin tolerance test (ITT) is a medical diagnostic procedure during which

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

is injected into a patient's vein, after which blood glucose is measured at regular intervals. This procedure is performed to assess pituitary function, adrenal function, insulin sensitivity, and sometimes for other purposes. An ITT is usually ordered and interpreted by an endocrinologist. 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 The hypothalamic–pituitary–adrenal axis (HPA axis or HTPA axis) is a complex set of direct influences and feedback interactions among three components: the hypothalamus (a part of the brain located below the thalamus), the pituitary gland ( ...

(HPA), insulin injections are continued to the point of inducing extreme

hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...

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 growth hormone (GH) are released as a part of the stress mechanism. ACTH elevation causes the adrenal cortex to release

cortisol Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...

. 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

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for assessing the integrity of the HPA. Sometimes ITT is performed to assess the adrenal function, e.g. before

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. It is assumed that the ability to respond to 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 diabetic coma. A health professional must attend it at all times. Other provocation tests which cause much less release of growth hormone include the use of glucagon,

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and clonidine.

Side effects

Side effects include sweating, palpitations, loss of consciousness and rarely convulsions due to severe hypoglycemia which may cause coma. If extreme symptoms are present, glucose should be given

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

ly. In subjects with no adrenal reserve an Addisonian crisis may occur. For cortisol stimulation, the ACTH stimulation test has much less risk.

Contraindications

Insulin tolerance test contraindications are: * This test should not be performed on children outside a specialist pediatric endocrine unit. * Ischemic heart disease *

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* Severe panhypopituitarism, hypoadrenalism * Hypothyroidism impairs the GH and cortisol response. Patients should have corticosteroid replacement commenced prior to thyroxine as the latter has been reported to precipitate an Addisonian crisis with dual deficiency. If adrenal insufficiency is confirmed, the need for a repeat ITT may need to be reconsidered after 3 months thyroxine therapy.

Interpretation

The test cannot be interpreted unless hypoglycaemia (< 2.2 mmol/L (or) < 40 mg/dL) is achieved.

Hypopituitarism

An adequate cortisol response is defined as a rise to greater than 550 nmol/L. Patients with impaired cortisol responses (less than 550 but greater than 400 nmol/L) may only need steroid cover for major illnesses or stresses. An adequate GH response occurs with an absolute response exceeding 20 mU/L.

Cushing's syndrome

There will be a rise of less than 170 nmol/L above the fluctuations of basal levels of cortisol.

References