Low-dose adrenocorticotropin test reveals impaired adrenal function in patients taking inhaled corticosteroids.

Abstract

The aim of the present study was to examine the use of low-dose ACTH-(1-24) stimulation for assessment of adrenal function and the detection of mild adrenal insufficiency. The criteria for normal response to ACTH-(1-24) are a peak cortisol level of more than 500 nmol/L (18.1 micrograms/dL) and an increment of the cortisol level above the basal one of more than 200 nmol/L (7.2 micrograms/dL). These criteria were satisfied by 32 of 33 healthy children and adults subjected to an ACTH-(1-24) dose 500 times lower (0.5 micrograms/1.73 m2) than the dose of 250 micrograms in the standard test. At 20 min, the peak cortisol level was the same in the low-dose test [(621 +/- 28 nmol/L) (22.5 +/- 1.0 microgram/dL)] as in the standard ACTH test [(654 +/- 31 nmol/L) (23.7 +/- 1.1 microgram/dL)]. Of 46 asthmatic patients who had been treated with inhaled beclomethasone dipropionate (482 +/- 42 micrograms/m2 daily; n = 32) or budesonide (507 +/- 62 micrograms/m2 daily; n = 14) for over 6 months, 16 (35%) failed to reach a cortisol peak of more than 500 nmol/L (18.1 micrograms/dL) following stimulation with 0.5 micrograms ACTH-(1-24)/1.73 m2. Of these, 11 (24%) showed a cortisol increment of less than 200 nmol/L (7.2 micrograms/dL). These 16 patients, showing insufficient response to low-dose ACTH-(1-24), also had a significantly lower (P < 0.01) mean 24-h urinary free cortisol excretion [(71 +/- 10 nmol/m2.24 h) (25.7 +/- 3.6 micrograms/m2.24 h)] than patients who responded normally [(118 +/- 11 nmol/m2.24 h) (42.8 +/- 4.0 micrograms/m2.24 h). Nonetheless, all but one of the poor responders to a 0.5 microgram ACTH showed normal stimulation with the standard 250 micrograms ACTH test. Therefore, it appears that a low-dose ACTH test is capable of revealing mild adrenal insufficiency, which is not detected by the standard high-dose ACTH test.

Profile, mean residence time of ACTH and cortisol responses after low and standard ACTH tests in healthy volunteers

“…In the case of patients with mild adrenal insufficiency, a higher stimulus could increase the risk of falsenegatives (good responders). Thus, our data seem coherent with the statement of several authors 6,15,23,24,27 about the higher sensitivity of LDT in detecting cases of secondary adrenal insufficiency.…”

“…4 Likewise, some authors have recently demonstrated that serum cortisol response to 1 µ g is similar to that obtained with 250 µ g in normal subjects and pointed out that the LDT has a greater diagnostic sensitivity than the HDT in secondary adrenal insufficiency. [5][6][7][8][9] However, considerable debate exists in the literature about the reliability of both tests and whether LDT is better than HDT in the evaluation of secondary adrenal insufficiency. 10 Little is known with regard to the profiles of ACTH(1-24) and ACTH(1-39) after HDT and LDT in healthy volunteers, and even less about the elimination rate of ACTH in humans after these tests.…”

The low dose ACTH test in chronic fatigue syndrome and in health

“…The application of different response criteria (Broide et al, 1995;Hurel et al, 1991) to the cortisol responses in our healthy group and CFS cohort revealed marked inconsistencies in 'pass-fail' patterns of response. This may be explained by testing time differences-Hurel performed his study at 0900 h when basal cortisol values can be expected to be higher than the early afternoon samples of this study.…”

“…An incremental cortisol response of 250 nmol/l cortisol was found to distinguish best between the two groups. Results were also analysed on the basis of response criteria forwarded by Broide et al (1995) and Hurel et al (1996) of a peak response of > 500 nmol/l and > 600 nmol/l respectively.…”

Inhaled Corticosteroids in Childhood Asthma

“…Moreover, final growth impairthat of patients who had never been treated with corticosteroids. [45][46][47][48] The systemic activity of ICS is determined by several factors, including corticosteroid receptor potency, receptor binding affini- Finally, from this metaing, the circadian rhythm of cortisol, and free urine cortisol excreanalysis it emerged that there is no correlation between dose and tion.…”