Low-dose and high-dose adrenocorticotropin testing: indications and shortcomings

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Purpose of review

The 250 μg adrenocorticotropin test (high-dose test) is the most commonly used adrenal stimulation test, though the use of physiologic doses (1.0 μg or 0.5 μg/1.73 m2) (low-dose test) has recently gained wider acceptance. These variants and the use of adrenocorticotropin test in the ICU, however, remain controversial. The validity of the low-dose test and the parameters for evaluation of high- and low-dose tests in different situations need reevaluation.

Recent findings

In the last few years, numerous studies have used the low-dose test as a single test following previous findings that it is more sensitive and accurate than the high-dose test. It is used mainly in secondary adrenal insufficiency and after treatment with therapeutic glucocorticosteroids to define hypothalamo-pituitary-adrenal suppression. Unless there is a very recent onset of disease, the results are interpreted by most researchers as diagnostic. The treatment of relative adrenal insufficiency, based on delta cortisol, has not yielded proof of correlation between this diagnosis and better prognosis with glucocorticoid treatment.


For interpretation of an adrenocorticotropin test, only peak – and not delta – cortisol should be used. The use of 240–300 mg of hydrocortisone daily in ICU patients, including septic shock, should be considered as pharmacologic, rather than as a replacement dose. Using the low-dose test for this purpose will lead to further misdiagnosis.

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