Insulin is administered, 0.1 U/kg body weight IV. A smaller dose should be used if hypopituitarism is suspected. IV glucose should be kept available to prevent severe reaction. Blood is obtained for serum glucose and cortisol assays (and for growth hormone [GH], if indicated) immediately before insulin is injected and 30 and 45 minutes thereafter. All patients, in whom adequate hypoglycemia is achieved, defined as 35 mg/dL or less should have some symptoms of hypoglycemia, either of sympathetic discharge or of CNS glucose deprivation, such as simply falling asleep.
Use
Assessing syndromes of extreme insulin resistance
Crude classification of insulin sensitivity
Assessing GH deficiency
Interpretation
Blood glucose normally falls to 50% of fasting level within 20 " “30 minutes and returns to fasting level within 90 " “120 minutes.
Blood glucose that falls <25% and returns rapidly to fasting level represents an increased tolerance to insulin.
Increased In
Hypothyroidism
Acromegaly
Cushing syndrome (peak cortisol response <18 " “20 ˇ ¼g/dL and change over baseline <7 ˇ ¼g/dL indicate glucocorticoid deficiency)
DM (some patients; especially older, obese ones)
Decreased In
Increased sensitivity to insulin (excessive fall of blood glucose)
Hypoglycemic nonresponsiveness (lack of response by glycogenolysis)
Pancreatic islet cell tumor
Adrenocortical insufficiency
Adrenocortical insufficiency secondary to hypopituitarism
Hypothyroidism
von Gierke disease (some patients)
Starvation (depletion of liver glycogen)
Limitations
In premenopausal women, the test can be performed at any phase of the menstrual cycle, because there are no cycle effects on the hypothalamic " “pituitary " “adrenal axis response to insulin-induced hypoglycemia.
Almost all patients have some degree of perspiration. If the patient does not perspire, the adequacy of the stress stimulus must remain suspect irrespective of the serum glucose concentration.
Most patients also have a hyperactive precordium (but not tachycardia or hypotension, because they are supine) and feelings of hunger, drowsiness, detachment, or anxiety. The last is common and sometimes severe, and many patients find this an unpleasant experience.
Patients with primary or secondary adrenal insufficiency or long-standing DM have an impaired compensatory response to hypoglycemia.
The criteria for a normal serum cortisol response ranged from 18 to about 22 ˇ ¼g/dL in multiple studies. Ideally, reference ranges would be determined locally, but this is rarely done in practice. If serum cortisol reaches this level, it is unimportant whether hypoglycemia was adequate. On the other hand, failure to reach this level is indicative of an inadequate response only if the serum glucose fell to 35 mg/dL or less. If this was not achieved, the stimulus was inadequate and the test must be repeated. It is the serum cortisol concentration that is achieved rather than the increment that is important.