THE PITUITARY CORTICOTROPH IS NOT THE RATE-LIMITING STEP IN THE POSTOPERATIVE RECOVERY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN PATIENTS WITH CUSHING SYNDROME

Patients cured from endogenous Cushing syndrome usually develop postop erative adrenal suppression in the year ensuing surgery. To define whe ther the pituitary corticotroph is the rate limiting step in the posto perative recovery of this secondary/tertiary form of adrenal insuffici ency, we examined surgically cured patients with Cushing syndrome 10 d ays, 3 months, and 6-12 months after surgery, by administering ovine C RH (oCRH) iv at the dose of 1 mug/kg.h over 24 h. The pituitary cortic otroph of these patients responded vigorously to oCRH, with ACTH conce ntrations reaching above the normal range at all three times of testin g. Parallel measurements of cortisol in nonadrenalectomized patients d emonstrated subnormal adrenal responsiveness at 10 days and 3 months a nd normalization at 6-12 months after surgery. The circadian rhythm of ACTH was maintained postoperatively at 10 days and 6-12 months, and t he circadian rhythm of cortisol was also present at 6-12 months after surgery, in spite of the constant infusions of pharmacological doses o f oCRH, suggesting that factors other than CRH secretion regulate this rhythm. We conclude that the corticotroph is not the rate limiting st ep in the recovery of the hypothalamic-pituitary-adrenal axis from glu cocorticoid-induced adrenal suppression, and that the locus of the def ect resides in the hypothalamic CRH neuron and/or its higher regulator y inputs.