Περίληψη:
Insulin-induced hypoglycemia causes a sequential stimulation of all
three components of the hypothalamic-pituitary-adrenal axis. States of
acute glucocorticoid excess, such as the overnight (1 mg) dexamethasone
suppression test (DST), inhibit both the basal cortisol level and the
response to an insulin tolerance test (ITT). However, whether this
negative feedback effect is exerted primarily at the hypothalamic or the
pituitary level is not clear.
To explore this question further we have examined the cortisol response
to insulin-induced hypoglycemia in three experimental settings, in the
following order: 1) a control ITT performed at 0900 h after an overnight
hospital stay (cITT); 2) an ITT at 0900 h after oral dexamethasone, 1
mg, at 2300 h on the previous evening (DST + ITT); and 3) an ITT at 0900
h after dexamethasone, 1 mg, at 2300 h and hCRH, 1 mug/kg iv, at 90 min
intervals from 0100-0700 h (DST + hCRH + ITT). The response to ITT was
defined as the peak cortisol increment (peak minus baseline). Since the
study objective was to test whether overnight pulsatile hCRH could
prevent dexamethasone-induced suppression of the response to a morning
ITT, only subjects that demonstrated a greater than 25% decrease in the
cortisol response to DST + ITT vs. cITT received the full protocol (five
of nine normal men). Basal ACTH and cortisol secretion remained
suppressed throughout the night during both the Dex + ITT and Dex + hCRH
+ ITT studies when compared to the control study (cITT, P < 0.05).
However, the cortisol response to hypoglycemia during DST + hCRH + ITT
was significantly greater than during DST + ITT (P < 0.05) and was
similar to the cITT response. Thus, pulsatile hCRH, administered during
the 10 h between dexamethasone and the subsequent hypoglycemic stimulus,
prevented acute suppression by dexamethasone of the cortisol response to
hypoglycemia.
We conclude that the dexamethasone-induced inhibition of the cortisol
response to hypoglycemia results primarily from suppression by
dexamethasone of basal hypothalamic corticotropin-releasing factor and
the consequent impairment of corticotroph responsiveness to exogenous
and endogenous corticotropin-releasing factor.
Συγγραφείς:
AVGERINOS, PC
KIAMOURIS, CK
PETRAKOS, IP
KLEANTHOUS, IK and
ZORZOS, PA
DIMITRIADIS, TN
RAPTIS, SA
CUTLER, GB
