One microgram is the lowest ACTH dose to cause a maximal cortisol response. There is no diurnal variation of cortisol response to submaximal ACTH stimulation

Abstract

There are many suggestions in the literature that the adrenal gland is more sensitive to ACTH in the evening than in the morning. However, all these studies in humans were conducted when the basal cortisol level was not suppressed, and were based on the observation that, after stimulation, the increases in cortisol differed, though the peak values were the same. To examine this, we established the lowest ACTH dose that caused a maximal cortisol stimulation even when the basal cortisol was suppressed, and used a smaller dose of ACTH for morning and evening stimulation. The lowest ACTH dose to achieve maximal stimulation was found to be 1.0 mg, with which dose cortisol concentration increased to 607.2 Ϯ 182 nmol/l, compared with 612.7 Ϯ 140.8 nmol/l with the 250 mg test (P > 0.3). The use of smaller doses of ACTH (0.8 and 0.6 mg) achieved significantly lower cortisol responses ( 312 Ϯ 179.4 and 323 Ϯ 157.3 nmol/l respectively; both P < 0.01 compared with the 1 mg test). When a submaximal ACTH dose (0.6 mg) was used to stimulate the adrenal at 0800 and 1600 h, after pretreatment with dexamethasone, no difference in response was noted at either 15 min (372.6 Ϯ 116 compared with 394.7 Ϯ 129.7 nmol/l) or 30 min (397.4 Ϯ 176.6 compared with 403 Ϯ 226.3 nmol/l; P > 0.3 for both times). These results show that 1.0 mg ACTH, used latterly as a low-dose test, is very potent in stimulating the adrenal, even when baseline cortisol is suppressed; smaller doses cause reduction of this potency. Our data show that there is probably no diurnal variation in the response of the adrenal to ACTH, if one eliminates the influence of the basal cortisol level and uses physiologic rather than superphysiologic stimuli.

The one microgram adrenocorticotropin test in the assessment of hypothalamic-pituitary-adrenal function

“…In agreement with previous authors who defined the cut-off value for peak cortisol after 1 mg ACTH as 497-500 nmol/l (11,15,18,25), all our normal controls showed a peak greater than 500 nmol/l and this limit was considered as the 'pass' criterion for the test.…”

The effect of thyrotoxicosis on adrenocortical reserve

“…In this context, sensitive tests for assessing adrenal reserve become of significant importance. In recent years, stimulation with low-dose ACTH has been used as a sensitive test to detect subtle changes in adrenal function, which would be missed if the standard ACTH test is used (10)(11)(12). The low-dose ACTH test, following dexamethasone suppression of endogenous ACTH, would therefore be a sensitive method to assess adrenocortical reserve in vivo.…”

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

“…Exact timing of blood sampling is, therefore, very important with this test, and dilution errors of the 250 mg corticotropin 1-24 ampoule can also occur. I assume that in the three patients in the paper of Ambrosi et al (10) in whom the IHT was normal but the response to 1 mg corticotropin was subnormal, blood sampling time or dilution of the ampoule was not quite exact, because a test that stimulates the adrenal maximally (19) theoretically cannot result in a smaller cortisol response than the IHT that stimulates plasma ACTH to between 100 and 300 pg/ml in normal subjects.…”

“…Dickstein et al (16) maintained that with the low-dose test, the cortisol response at 30 min after i.v. injection of corticotropin 1-24 is indistinguishable from that after 250 mg, since 1 mg was said to be 'the lowest ACTH dose to cause a maximal cortisol response' (19). Tordjman et al (18), however, found 1 mg stimulated cortisol less than 250 mg corticotropin 1-24.…”