Repetitive graded ACTH stimulation test for adrenal insufficiency

Area of Science:

• Endocrinology
• Clinical Diagnostics
• Hormone Assays

Background:

• The hypothalamo-pituitary-adrenal axis assessment is crucial for diagnosing adrenal insufficiency.
• Current ACTH stimulation protocols lack standardized dosing and interpretation, leading to diagnostic challenges.

Purpose of the Study:

• To evaluate a novel repetitive graded adrenocorticotropic hormone (ACTH) stimulation protocol for assessing adrenal insufficiency.
• To determine the optimal ACTH dose and cortisol response threshold for differentiating primary adrenal insufficiency, secondary adrenal insufficiency, and healthy controls.

Main Methods:

• Thirty-two patients with diagnosed adrenal insufficiency and eight healthy controls participated.
• A new protocol involved intravenous injection of 1 mcg ACTH, followed by 5 mcg, 50 mcg, and 100 mcg at hourly intervals.
• Cortisol levels were measured at 30, 60, 120, 180, and 240 minutes post-injection.

Main Results:

• Secondary adrenal insufficiency patients showed intermediate cortisol responses between controls and primary adrenal insufficiency patients.
• A 1 mcg ACTH dose with a 30-minute cortisol response cutoff of 20 mcg/dL minimized overlap between secondary adrenal insufficiency and controls.
• Primary adrenal insufficiency patients exhibited maximal cortisol increments below 4 mcg/dL, with minimal overlap with secondary adrenal insufficiency cases.

Conclusions:

• The repetitive graded ACTH stimulation test offers a sensitive and reliable method for diagnosing adrenal insufficiency.
• This protocol combines the sensitivity of low-dose ACTH testing with the stress-mimicking nature of ACTH infusion tests.
• The proposed protocol enhances the diagnostic accuracy for various forms of adrenal insufficiency, including mild cases.