Insulin Tolerance Test (ITT)

The insulin tolerance test uses a deliberate fall in blood glucose as a physiological stressor. Hypoglycaemia is one of the strongest natural stimuli to the somatotropic and adrenal axes, so when glucose drops below the accepted threshold, conventionally around 2.2 mmol/L with symptoms present, an intact axis answers with a growth hormone surge and a rise in ACTH and cortisol. Samples taken over the following two hours give a peak for each. It is performed under continuous medical supervision with glucose ready for immediate reversal.

Its standing comes from testing both axes at once and from doing so through a stimulus the body actually encounters. Interpretation depends on the assay: older cut-offs from polyclonal radioimmunoassays do not transfer to current monoclonal methods, which read lower. The test is contraindicated in ischaemic heart disease, seizure disorders, and older or frail patients, and those exclusions are the main reason alternatives exist: the glucagon stimulation test, and oral macimorelin, approved by the FDA in 2017 for adult growth hormone deficiency.

The test answers a question no basal measurement can. Growth hormone is secreted in pulses and is undetectable between them, so a random low value carries no information; only a provoked peak distinguishes deficiency from a normal trough. Cortisol is different, since a clearly normal morning value can make the adrenal half of the test unnecessary.

The failure mode encountered most often is the inadequate test. If glucose never falls far enough, the stimulus was never delivered, and a low peak means nothing at all, yet such results are still reported as deficiency. Cut-offs are also quoted without the assay they belong to, and body weight shifts the threshold: obesity blunts stimulated growth hormone in a completely normal axis.