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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.

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