How is the rapid adrenocorticotrophic hormone test interpreted in the workup of Addison disease?

Updated: Mar 11, 2020
  • Author: George T Griffing, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Interpreting the rapid adrenocorticotrophic hormone test [42, 43, 44, 45]

  • Two criteria are necessary for diagnosis: (1) an increase in the baseline cortisol value of 7 mcg/dL or more and (2) the value must rise to 20 mcg/dL or more in 30 or 60 minutes, establishing normal adrenal glucocorticoid function.

  • A low aldosterone value of less than 5 ng/100 mL that fails to double or increase by at least 4 ng/100 mL 30 minutes after ACTH administration denotes abnormal mineralocorticoid function of the adrenal cortex.

  • The 30-minute aldosterone value is more sensitive than the 60-minute value because aldosterone levels actually have been shown to decrease in the 60-minute sample.

  • The absolute 30- or 60-minute cortisol value carries more significance than the incremental value, especially in patients who may be in great stress and at their maximal adrenal output. These patients may not show a significant increase in cortisol output with ACTH stimulation.

  • A normal 30- or 60-minute rapid ACTH test excludes Addison disease but may not adequately exclude mild impairment of the hypothalamic pituitary adrenal axis in secondary adrenal insufficiency.

  • In patients with Addison disease, both cortisol and aldosterone show minimal or no change in response to ACTH, even with prolonged ACTH stimulation tests lasting 24-48 hours.

  • When the results of the rapid ACTH test are equivocal and do not meet the 2 criteria mentioned above, further testing might be required to distinguish Addison disease from secondary adrenocortical insufficiency. Plasma ACTH values and prolonged ACTH stimulation tests may be useful in making this distinction.

  • ACTH levels often are elevated to higher than 250 pg/mL in patients with Addison disease. However, ACTH is unstable in plasma, and specimen collection and storage may require special attention. The specimen should be collected in iced anticoagulated plastic containers and frozen immediately.

  • Importantly, note that ACTH levels also may be high in patients recovering from steroid-induced secondary adrenocortical insufficiency and in patients with ACTH-refractory syndromes.

  • ACTH-inducing tests such as metyrapone stimulation and insulin-induced hypoglycemia, which may be useful in the evaluation of some cases of secondary adrenocortical insufficiency, have no role in the diagnosis of Addison disease and may in fact be lethal to the patient with Addison disease.

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