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

Insulin

Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

 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 hypoglycemia

Hypoglycemia

Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...

. In response, Adrenocorticotropic hormone (ACTH) and Growth Hormone

Growth hormone

Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...

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

Adrenal cortex

Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively. It is also a secondary site of androgen synthesis.-Layers:Notably, the reticularis in...

 to release cortisol

Cortisol

Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...

. Normally, both cortisol and GH serve as Counterregulatory hormone

Counterregulatory hormone

A counterregulatory hormone is a hormone that opposes the action of another.The action of insulin is counterregulated by glucagon, adrenaline , noradrenaline , cortisol, and growth hormone...

s, opposing the action of insulin, i.e. acting against the hypoglycemia.

Thus ITT is considered to be a Gold standard

Gold standard (test)

In medicine and statistics, gold standard test refers to a diagnostic test or benchmark that is the best available under reasonable conditions. It does not have to be necessarily the best possible test for the condition in absolute terms...

 for assessing the integrity of the hypothalamo-pituitary-adrenal axis. Sometimes ITT is performed to assess the peak adrenal capacity, e.g. before surgery

Surgery

Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

. 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.

This test is potentially very dangerous and must be undertaken with great care. A health professional must attend it at all times.

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

ACTH stimulation test

The ACTH stimulation test is a medical test usually ordered and interpreted by endocrinologists to assess the functioning of the adrenal glands stress response by measuring the adrenal response to adrenocorticotropic hormone...

 has much less risk

Contraindications

• This test should not be performed on children outside a specialist pediatric endocrine unit
• Ischemic heart disease
• Epilepsy
  Epilepsy
  Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
  
  
• Severe panhypopituitarism, hypoadrenalism
• Hypothyroidism
  Hypothyroidism
  Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
  
  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.