In patients with
ACTH-secreting
pituitary tumor the peri-tumoral normal corticotrophs were supposed to be suppressed by cronic hypercortisolemia since frequently they develop transient secondary
adrenal insufficiency after
pituitary tumor resection and during early postoperative days. We evaluated the
ACTH dynamics during transsphenoidal surgery in 16 patients with
ACTH-secreting
pituitary tumors (6 cured by surgery, 8 not cured
Cushing's disease patients and 1 cured by surgery and 1 not cured Nelson's syndrome patients) and tested the hypothesis that in these patients,
ACTH secretion from the peri-tumoral normal corticotrophs is inhibited and hence removal of the entire
tumor should result in subtle postoperative reduction in plasma
ACTH. Blood samples for
ACTH determination were obtained from 14
Cushing's disease patients immediately before pituitary gland manipulation and 10, 30, 60, 90, 120, 150 and 300 min after
pituitary tumor resection and on postoperative day one. In Nelson's syndrome patients the blood sample was obtained only after
tumor removal. All patients received intravenous
hydrocortisone during surgery and on the first postoperative day. Patients were considered cured by surgery if they presented
adrenal insufficiency after
hydrocortisone withdrawal. Mechanical pituitary manipulation induced increase in
ACTH level. In all 14
Cushing's disease patients (cured and not cured), mean plasma
ACTH levels were significantly greater 10 min after
pituitary tumor resection (54.4+/-12.8 pmol/l) than in the premanipulation period (
ACTH=26.3+/-5.3 pmol/l) (p=0.005). In
Cushing's disease patients, the
ACTH levels did not change significantly until 300 min after
pituitary tumor resection either in those 6 patients cured by surgery (
at 10 min after
pituitary tumor resection
ACTH was 54.4+/-12.8 pmol/l for all 14
Cushing's disease patients and at 300 min after
tumor removal
ACTH was 39.0+/-12.6 pmol/l for cured and 41.3+/-15.7 pmol/l for not cured
Cushing's disease patients). The
ACTH level also persisted high until 300 min after complete
pituitary tumor resection in one cured patient with Nelson's syndrome.
ACTH level does not change in the early recovery period after
ACTH-secreting
pituitary tumor, even in those cured patients, and probably peri-tumoral normal corticotrophs are not completely suppressed by cronic hypercortisolemia (and acute
glucocorticoid administration) when these patients are under intense stress, like transsphenoidal surgery. Mechanical pituitary manipulation may induce
ACTH release in patients with
ACTH-secreting
pituitary tumors but probably does not interfere in the maintenance of high
ACTH-levels during the early postoperative period, since
ACTH half-life is only 8-15 min. In patients with
ACTH-secreting
pituitary tumors, the behavior of the human hypothalamic-pituitary-adrenal system during transsphenoidal surgery does not conform to the specifications of a negative feedback mechanism.