The Low Dose (1-μg) Adrenocorticotropin Stimulation Test in the Evaluation of Patients with Suspected Central Adrenal Insufficiency

Abstract

Currently, the most popular test for adrenal insufficiency is the conventional rapid ACTH stimulation test (250 microg ACTH). This method is quick and safe, but incorporates a dose of ACTH that is supraphysiological and capable of transiently stimulating the adrenal cortex in many patients with documented central adrenal insufficiency. In recent years, several investigators have published substantial evidence for a more sensitive ACTH stimulation test using a lower dose of ACTH (1 microg). Further analysis of these data, including the calculation of likelihood ratios, demonstrates that the 1-microg test performs significantly better than the 250-microg test compared to the gold standard, insulin tolerance test. We suggest that the 1-microg ACTH stimulation test replace the conventional 250-microg test when evaluating for central adrenal insufficiency. A cortisol level below 500 nmol/L after 30 min signifies impaired adrenocortical reserve. An insulin tolerance test should be performed if this low dose test results in a borderline value and the diagnosis is questioned. The 1-microg test should not be used if recent pituitary injury is suspected. Pharmaceutical companies should be encouraged to provide synthetic ACTH in 1-microg vials.

Adrenal function during coronary artery bypass grafting

“…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). However, the literature remains controversial about the cut-off point representing a normal adrenal response to 1 mg ACTH, and about the sensitivity of the low-dose (1 mg) ACTH test in the diagnosis of secondary hypoadrenalism (9).…”

A comparison between the effects of low dose (1 microg) and standard dose (250 microg) ACTH stimulation tests on adrenal P450c17alpha enzyme activity in women with polycystic ovary syndrome

“…However, during the last years it has been reported that the 250 mg ACTH stimulation test is a supraphysiological test and it may cause misdiagnosis in secondary and primary adrenal failure (8 -11). The sensitivity of the low dose (1 mg) test (LDT) is higher than that of the standard dose (250 mg) test (SDT) in the assessment of the hypothalamo -pituitary-adrenal (HPA) axis, particularly in pituitary disease (12,13). There are not enough data evaluating adrenal steroidogenesis, particularly P450c17a enzyme activity, with LDT in women with PCOS.…”

Adrenal function in 23 children with paracoccidioidomycosis

“…Nowadays, a lower dose of ACTH (1 µg) is being used as a sensitive test in patients with subtle adrenal dysfunction, which is considered to be the test of choice in the evaluation of adrenal function in pituitary diseases 20 . Lower doses are considered to be more physiological, avoiding a hyper-stimulus, and the results obtained are similar to hypoglycemia induced by insulin or a great physical stress 14 .…”