Insulin Tolerance Test
Assessment of ACTH and cortisol reserve.
Assessment of growth hormone reserve in children with definite growth retardation and a subnormal growth hormone stimulation test (see exercise test).
Differentiation of Cushing's syndrome from depression.
GH response in adults.
Ischaemic heart disease
Untreated hypothyroidism (impairs the GH and cortisol response).
The patient should fast overnight (water permitted) and be recumbent during the test.
ECG must be normal and the patient's weight known.
In peri-pubertal children (bone age > 10 years) priming is needed
M: 100 mg testosterone i.m. 3 days before testing
F: 100 mcg ethinyloestradiol p.o. each for three days before the test.
Calculate Actrapid Insulin dose:
Normal pituitary function 0.15 U/kg
Hypopituitary 0.10 U/kg
Acromegaly, diabetes, Cushing's 0.2-0.3 U/kg
If the patient is hypoadrenal for any reason (or on hydrocortisone), the case must be discussed with senior medical staff before administration of insulin.
50mls 50% dextrose available for immediate administration
Indwelling cannula gauge 19.
6 fluoride oxalate tubes (grey top Vacutainers)
6 serum (clotted) tubes (red top Vacutainers)
Sweating, palpitations, loss of consciousness and rarely convulsions.
- Site indwelling cannula.
- At 0 minutes, take baseline bloods and then inject insulin i.v.
- Take samples for GH, cortisol and glucose at 30, 60, 90, and 120 mins, flushing the cannula with saline between samples.
- At 30 minutes check whole blood glucose with Glucometer and repeat the insulin dose if not hypoglycaemic (this will mean prolonging sampling by 30 min).
- Adequate hypoglycaemia (£2.2mmol/l) should be symptomatic. Record symptoms in the notes.
- There must be at least 2 specimens following adequate hypoglycaemia.
- At all times a doctor or nurse must be in attendance.
- Reverse hypoglycaemia by giving i.v. 50% dextrose, or 1 mg i.m. glucagon (1 amp) if symptoms very severe or patient unrousable, and continue sampling.
- Obtain specimen for glucose before reversal of symptoms.
- Check whole blood glucose on glucometer every time a specimen is taken.
- If a patient has a hypoadrenal crisis they should receive i.v. 0.9% saline and i.v. hydrocortisone 100 mg.
- Once test completed, give supervised meal.
- Patient should not drive for 2 hours after the test.
- The test cannot be interpreted unless hypoglycaemia (<2.2mmol/l) is achieved.
- Adequate cortisol response is defined as a rise of greater than 170 nmol/l to above 500 nmol/l. Patients with slightly impaired cortisol responses may only need steroid cover for major illnesses or stresses. They will need instruction about this and should carry a steroid card.
- In Cushing's syndrome there will be a rise of less than 170 nmol/l above the fluctuations of basal levels of cortisol.
- Adequate GH response is a rise to >20 mU/l. In adults this may be a sensitive indicator of hypopituitarism but its principal role is in children who may require GH treatment. In children a rise to greater than 39 mU/l (15ng/ml) is considered normal (2.59 mU/l = 1ng/ml). Appropriate priming is very important if they are peri-pubertal. Before treatment with growth hormone children should have two stimulatory tests.
SENSITIVITY AND SPECIFICITY
If there is adequate hypoglycaemia and the patient is not hypothyroid then cortisol response is a good test of ACTH/adrenal reserve. 5-15% of normals will show a suboptimal response as defined by these two criteria.
20% of patients with Cushing's syndrome will show a rise greater than 170nmol/l but a rise of less than this is rare in depression or alcoholic pseudo-Cushing's.
GH responses are reduced in 20% of normal children and some small children whose peak GH is 10-20mU/l may benefit from GH replacement.
Plumpton et al., Br. J. Surg. 56, 21 (1969).
Greenwood et al., J. Clin. Invest. 45, 429 (1965).