Comparison of the cortisol responses to testing with two doses of ACTH in patients with suspected adrenal insufficiency

Abstract

Objectives: To compare the cortisol response of the 1 mg and the 250 mg ACTH test in a large study of patients with suspected adrenal insufficiency. Design: Retrospective cohort study. Methods:Single center study assessing patients tested for primary or secondary adrenal insufficiency between January 2004 and December 2007, who had both ACTH tests (1 mg and 250 mg; nZ207) within a time interval of 6 weeks. Test results were compared with a Bland-Altman plot and McNemar's test. Results: The mean difference between the cortisol responses in the two ACTH tests was 26 nmol/l (95% confidence interval (CI) 13, 40), showing a marginally higher response for the 250 mg test. The diagnostic performances of the two tests were similar (PZ0.49) using a cut-off value for cortisol of 550 nmol/l. A normal cortisol response to the 1 mg ACTH test could be accompanied by an abnormal response to the 250 mg ACTH test, and vice versa. Conclusion: This study shows that the 1 mg and the 250 mg ACTH tests have comparable cortisol responses in patients with suspected adrenal insufficiency. However, in individual patients, the difference in cortisol response to the two tests can be substantial, and the response in the 250 mg test is not invariably higher than the response in a 1 mg test.

An Update on Addison’s Disease

“…The advantages and disadvantages of both tests in the diagnosis of adrenal insufficiency have been extensively discussed [35,36]. Since both tests give comparable results for the serum cortisol concentration at least 30 min after stimulation and based on the fact that the "high-dose" (250 µg) corticotropin test is more comprehensively validated compared to the "low-dose" (1 µg) corticotropin test, it is suggested to perform the "low-dose" (1 µg) corticotropin test in the diagnosis of PAI only when the substance is in short supply [27,34,35,37,38].…”

Central adrenal insufficiency: open issues regarding diagnosis and glucocorticoid treatment

“…Contrasting data about SST diagnostic accuracy are reported: some authors reported a superior role of 1 μg [58,59] or 250 μg [52,54,60] SSTs, and others reported that both tests presented similar results [55,56,61].…”

“…Because the rationale for SST is the assumption that cortisol response is blunted in chronic ACTH deficiency, it is important to define when we consider the condition that probably will induce the CAI as "chronic". Few papers investigated the optimal time shift to perform SST (suggesting that it can be carried out at least 4 weeks after pituitary surgery [51,52]), but the major part of the studies proposed the stimulation test 2-3 months after surgery [53][54][55][56]. Therefore, in clinical practice, SST is scheduled 2-3 months after every HPA axis injury.…”

“…There is an ongoing debate about the optimal dose of corticotropin in SST: it is suggested that 250 μg is a supraphysiological stimulus, eliciting very high circulating ACTH levels, therefore excessive to detect mild CAI [56]. In patients with partial endogenous ACTH deficiency, the adrenal responsiveness to high doses of ACTH may be preserved, with a resultant false-negative SST.…”

Assessment of the Effect of Continuous Sedation with Mechanical Ventilation on Adrenal Insufficiency in Patients with Traumatic Brain Injury

“…Kazlauskaite et al 23 reviewed the literature from 1966 to 2006 and found that the low-dose corticotropin test was superior to the standard dose test. In a study by Dekkers et al ,24 in which low-dose and standard dose tests were directly compared, the investigators found that the tests produced comparable results. However, they noted that the tests can produce different results in individual patients.…”