Insulin tolerance test
This test is potentially very dangerous and must be undertaken with great care. A DOCTOR OR NURSE MUST BE IN ATTENDANCE AT ALL TIMES.
Assessment of GH and ACTH/cortisol reserve.
Differentiation of Cushing's syndrome from pseudo-Cushing's syndromes eg depression, alcohol excess.
- Age > 60 years
- This test should not be performed on children outside a specialist paediatric endocrine unit
- Ischaemic heart disease
- Severe panhypopituitarism, hypoadrenalism (0900 cortisol < 100 nmol/L)
- 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.
Principle of test
ACTH and growth hormone are both released as a part of the stress mechanism triggered by hypoglycaemia.
Sweating, palpitations, loss of consciousness and rarely convulsions due to severe hypoglycaemia. Once hypoglycaemia has occurred, pituitary stimulation will have occurred and iv glucose should be given if extreme symptoms are present. An Addisonian crisis may be precipitated in subjects with no adrenal reserve.
The patient should fast overnight (water permitted) and be recumbent during the test.
ECG must be normal and the patient's weight known.
The side effects of the test should be clearly explained to the patient.
- 50 mL 50% dextrose available for immediate administration for hypoglycaemia
- Glucose test strips and lancets
- Indwelling cannula gauge 19
- 6 fluoride and 6 plain tubes
- see protocol for emergency treatment of hypoglycaemia during ITT
- Actrapid insulin dose:
- 0.15 U/kg for subjects with normal pituitary function
- 0.10 U/kg for hypopituitary subjects
- 0.2-0.3U/kg for subjects with acromegaly, diabetes or Cushing's
Site an indwelling cannula in the antecubital fossa with good access for administration of glucose, if required
take 3 mL blood in plain tubes for GH, cortisol and 1 mL in fluoride tube for glucose and inject insulin iv.
take 3 mL blood in plain tubes for GH, cortisol and 1 mL in fluoride tube for glucose.
If there have been no clinical signs of hypoglycaemia by 45 min, the dose of insulin should be repeated and the test continued with blood samples timed again from 0 min.
- Adequate hypoglycaemia (< 2.2mmol/l) should be symptomatic. Record symptoms in the notes
- There must be at least 2 specimens following adequate hypoglycaemia
- Hypoglycaemia should be reversed if there are severe symptoms ie loss of consciousness, cardiac symptoms, extreme anxiety or fits. If necessary, iv. 50% dextrose 0.4 mL/kg (ie 28 mL for a 70 kg adult) should be administered and blood sampling continued.
- If clear symptoms of hypoglycaemia develop, the patient can eat and drink after 1 hour whilst continuing the test (since adequate stimulation of the hypothalamus-pituitary has occurred).
- Once test is completed, the subject should be given a supervised meal.
- Subject should not drive for 2 hours after the test.
The test cannot be interpreted unless hypoglycaemia (< 2.2 mmol/L) is achieved.
Hypopituitarism: An adequate cortisol response is defined as a rise to greater than 550 nmol/L. Patients with impaired cortisol responses ie < 550 but > 400 nmol/L may only need steroid cover for major illnesses or stresses. An adequate GH response occurs with an absolute response > 20 mU/L (7µg/L).
Cushing's syndrome: There will be a rise of less than 170 nmol/L above the fluctuations of basal levels of cortisol.
Sensitivity and Specificity
If there is adequate hypoglycaemia and the patient is not hypothyroid then the cortisol response is a good test of ACTH/adrenal reserve. However, 5-15% of normal subjects will show a suboptimal response as defined by cortisol < 550nmol/L.
20% of patients with Cushing's syndrome will show a rise greater than 170 nmol/L but a rise of less than this is rare in depression or alcoholic pseudo-Cushing's syndromes.
- Greenwood FC, Landon J, Stamp TCB. The plasma sugar, free fatty acid, cortisol and growth hormone response to insulin. 1. in control subjects. J Clin Invest 1965;45:429-
- Plumpton FS, Besser GM. The adrenocortical response to surgery and insulin-induced hypoglycaemia in corticosteroid-treated and normal subjects. Br J Surg 1969;56:216-219.