Normal hypothalamic-pituitary-adrenal axis by high-dose cosyntropin testing in patients with abnormal response to low-dose cosyntropin stimulation: A retrospective review

Objective: To analyze the interpretation of the 1-μg low-dose adrenocorticotropic hormone (ACTH) test (LDT) for assessment of the presence of adrenal insufficiency (AI) in comparison with the 250-μg or standard high-dose ACTH test (HDT), which uses the same cutoff cortisol value of 18 μg/dL (500 nmol/L) as the lower limit of normal. Methods: We present a retrospective review of 26 patients referred to the Pituitary Clinic who underwent both the LDT and the HDT for evaluation of the function of the hypothalamic-pituitary-adrenal axis. Results: Of the 26 study patients, 23 had discordant findings - abnormal LDT and normal HDT results with use of the empiric cortisol cutoff of 18 μg/dL at 30 minutes in response to the ACTH dose. Glucocorticoid replacement therapy was stopped or not started in these patients, and no clinical symptoms of AI developed during a follow-up period ranging from 19 to 24 months. Conclusion: Our retrospective review of patients' discordant LDT and HDT results questions the reliability of the LDT as a screening test for AI, as currently interpreted. Our data suggest that abnormal results should be evaluated in the context of the clinical picture and that additional testing may be indicated to prevent unwarranted treatment with glucocorticoids. Further studies are needed to establish a safe, sensitive, and specific test for the diagnosis of AI.