Adrenocorticotropin Stimulation Test: Effects of Basal Cortisol Level, Time of Day, and Suggested New Sensitive Low Dose Test*

Abstract

Adrenal response to iv administration of 1-24 ACTH (250 micrograms) was examined in normal volunteers under various conditions. The effect of basal cortisol levels was examined by performing the tests at 0800 h with and without pretreatment with dexamethasone. The effect of time of day was evaluated by performing the tests at 0800 h and at 1600 h, eliminating possible basal cortisol influence by pretreatment with dexamethasone. In the first set of tests, despite significantly different baseline levels, 30-min cortisol levels were not different (618 +/- 50 vs. 590 +/- 52 nmol/L). Afternoon cortisol levels in response to ACTH were found to be significantly higher than morning levels at 5 min (254 +/- 50 vs. 144 +/- 36 nmol/L, p less than 0.01) and at 15 min (541 +/- 61 vs. 433 +/- 52 nmol/L, p less than 0.02). This difference in response was no longer notable at 30 min (629 +/- 52 and 591 +/- 52 nmol/L). We tried also to determine the lowest ACTH dose which will elicit a maximal cortisol response. No difference was found in cortisol levels at 30 and 60 min in response to 250 and 5 micrograms 1-24 ACTH. Using 1 micrograms ACTH, the 30-min response did not differ from that to 250 micrograms (704 +/- 72 vs. 718 +/- 55 nmol/L, respectively). However, the 60-min response to 1 microgram was significantly lower (549 +/- 61 vs. 842 +/- 110 nmol/L, p less than 0.01). Using this low dose ACTH test (1 microgram, measuring 30-min cortisol level), we were able to develop a much more sensitive ACTH test, which enabled us to differentiate a subgroup of patients on long-term steroid treatment who responded normally to the regular 250 micrograms test, but had a reduced response to 1 microgram. The stability of 1-24 ACTH in saline solution, kept at 4 C, was checked. ACTH was found to be fully stable after 2 hs in a concentration of 5 micrograms/ml in glass tube and 0.5 micrograms/ml in plastic tube. It was also found to be fully stable, both immunologically and biologically, for 4 months, under these conditions. We conclude that the 30-min cortisol response to ACTH is constant, unrelated to basal cortisol level or time of day. It is therefore the best criterion for measuring adrenal response in the short ACTH test. The higher afternoon responses at 5 and 15 min suggest greater adrenal sensitivity in the afternoon, but further studies are needed to clarify this issue.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal function during coronary artery bypass grafting

“…injection of 1 mg (1 -24)-corticotropin (tetracosactrin, Synacthen, Novartis Pharma, Berne, Switzerland) was given. One vial of 250 mg tetracosactrin was diluted in sterile saline solution to a concentration of 1 mg/ml, filtered in plastic syringes, and stored at 4 8C as described elsewhere (5). The tests were carried out on the day before the operation (day 2 1), immediately after the operation on the intensive care unit (ICU) (day 0), on the next 2 days in the ICU (day 1 and day 2), and before discharge from the hospital.…”

“…However, this test is labor intensive and contraindicated in some patients. The low-dose (1 mg) ACTH test has recently been introduced and proved to be sensitive in revealing partial adrenal insufficiency by providing physiological adrenocortical stimulation (5,6). The results of the low-dose (1 mg) ACTH test correlate closely with those of the reference test for the function of the HPA axis (7), and are superior to the standard (250 mg) ACTH test (8).…”

Peri‐operative steroid supplementation

“…The 250 mg dose is grossly supraphysiological and may induce false positive cortisol responses in some patients. The use of 1 mg ACTH and measurement of the 30-min cortisol value is a more sensitive test of adrenal function and identified a small subgroup of patients on long-term steroids, who responded normally to the regular 250-mg test, but had a reduced response to 1 mg [65]. It has been suggested that the 1-mg ACTH test follows the ITT more closely and may be more sensitive than the standard SST in detecting subtle deficiencies in the hypothalamic-pituitary-adrenal axis [66].…”

The role of high- and low-dose corticotropin tests in the diagnosis of secondary adrenal insufficiency

“…injection of 250 mg corticotropin 1-24, the peak plasma corticotropin level is about 60 000 pg/ ml!! Dickstein et al (16), Broide et al (17) and Tordjman et al (18) recently published data on low-dose SCT tests (1 mg in adults or 0.5 mg/1.73 m 2 in children) that seemed to show that these low-dose SCTs are as sensitive as the IHT in detecting mild SAI in asthmatics who use topically applied corticosteroids or in patients with pituitary disease, although even a low-dose test can only measure adrenal reactivity but not endogenous ACTH reserve. Dickstein et al (16) maintained that with the low-dose test, the cortisol response at 30 min after i.v.…”