Suppression of the Hypothalamo-Pituitary-Adrenal Axis and Growth Hormone Release with Dexamethasone

Four healthy volunteers were subjected to insulin tolerance tests (ITT) during which blood glucose, plasma 11-hydroxycorticosteroids (11-OHCS), and immunoreactive growth hormone (IRGH) were measured. One ITT served as control, and the others were performed after various ACTH suppressive treatments using 2 mg, 3 mg and 5 mg of dexamethasone. This was given as 1 mg every six hours, the last dose two hours before the ITT. In all tests adequate hypoglycemia (blood glucose less than 40 mg/100 ml) was achieved. Results showed that all four subjects had a normal rise in plasma 11-OHCS and IRGH in response to hypoglycemia during the control ITT. Dexamethasone administration (2 mg) eight hours before the ITT lowered the rise of total plasma 11-OHCS but did not affect IRGH release. Dexamethasone pretreatment (3 mg) for 14 hours almost completely abolished the plasma 11-OHCS response to hypoglycemia, whereas IRGH release was not significantly affected. After 26 hours of dexamethasone (5 mg), no rise in plasma 11-OHCS was seen and the IRGH release was significantly diminished compared to control. These findings demonstrate: 1) stress-induced activation of the hypothalamo-pituitary-adrenal axis (HPAA) is subject to feedback control by corticosteroids; 2) length of administration of corticosteroids is critical in inhibiting the activation of the HPAA; 3) dissociation of HPAA and IRGH suppressibility with dexamethasone.