A comparison of the naloxone test with the insulin stress test in patients following transsphenoidal surgery.
OBJECTIVE
To study the reliability of the naloxone test in assessing the hypothalamic-pituitary-adrenal (HPA) axis in patients following transsphenoidal pituitary surgery, by comparison with the insulin stress test (IST). Also, to establish a normal range for the response to naloxone in healthy controls.


METHODS
All patients had the IST performed, soluble insulin 0.1-0.3 U/kg (usually 0.15 U/kg) being administered intravenously, followed by venous sampling for plasma glucose and serum cortisol at 0, 15, 30, 45, 60, 75 and 90 minutes. Naloxone (125 micrograms/kg body weight) was similarly administered to all patients 6 days later, with sampling at -15, 0, 15, 30, 45, 60, 90 and 120 minutes for plasma glucose, serum cortisol and plasma ACTH. The naloxone test was also performed on control subjects using an identical protocol.


METHODS
Twenty patients (11F/9M) aged 48.8 +/- 2.8 years (mean +/- SE) 4-6 weeks following transsphenoidal pituitary surgery. Twelve normal healthy control subjects (6F/6M) aged 31.5 +/- 3.0 years.


METHODS
Serum cortisol was measured by radioimmunoassay and plasma ACTH by immunoradiometric assay.


RESULTS
Adequate hypoglycaemia (< or = 2.0 mmol/l) was achieved in all patients. Peak cortisol was > 550 nmol/l in 17 subjects (range: 572-867 nmol/l) and a subnormal response observed in 3 (peak cortisol 163-498 nmol/l). In the 17 patients with a normal cortisol response to hypoglycaemia the response to naloxone was extremely variable, with serum cortisol falling in 4 and an increment of < or = 100 nmol/l in 6 others. In the 3 patients who failed the IST, two responded to naloxone and one did not. In normal controls, 3 of the 12 had little or no response to naloxone.


CONCLUSIONS
As the naloxone test fails to produce a response in all normal subjects it is impossible to define a 'normal' response. The numerous discrepancies with the IST in patients are further evidence of the test's lack of reliability in assessing the HPA-axis and it is consequently not a viable alternative to traditional dynamic methods such as the IST.
Sir George E. Clark Metabolic Unit, Royal Victoria Hospital, Belfast, United Kingdom.
A S
AS
McAllister
D R
DR
McCance
D R
DR
Hadden
P M
PM
Bell
H
H
Leslie
B
B
Sheridan
A B
AB
Atkinson
D000324:Adrenocorticotropic Hormone / Q000097:blood; D016022:Case-Control Studies; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology*; D007328:Insulin; D008875:Middle Aged; D009270:Naloxone; D009292:Narcotic Antagonists; D010911:Pituitary Neoplasms / Q000601:surgery*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*; D011184:Postoperative Period; D015203:Reproducibility of Results
D007328:Insulin; D009292:Narcotic Antagonists; D009270:Naloxone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone