Insulin tolerance test

An insulin tolerance test (ITT) is a medical diagnostic procedure during which insulin is injected into a patient's vein to assess pituitary function, adrenal function, and sometimes for other purposes. An ITT is usually ordered and interpreted by endocrinologists.

Insulin injections are intended to induce extreme hypoglycemia below 2.2 mmol/l (40 mg/dl). 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. Normally, both cortisol and GH serve as counterregulatory hormones, opposing the action of insulin, i.e. acting against the hypoglycemia.^[1]

Thus ITT is considered to be the gold standard for assessing the integrity of the hypothalamic–pituitary–adrenal axis. Sometimes ITT is performed to assess the peak adrenal capacity, e.g. before surgery. 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.^[2]

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

Contraindications

• This test should not be performed on children outside a specialist pediatric endocrine unit.
• Ischemic heart disease
• Epilepsy
• 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.

See also

• ACTH stimulation test
• Hypopituitarism
• Triple bolus test

References