What is the protocol for an Adrenocorticotropic Hormone (ACTH) stimulation test for diagnosing Congenital Adrenal Hyperplasia (CAH) in adults?

From the Guidelines

The ACTH stimulation test for diagnosing Congenital Adrenal Hyperplasia (CAH) in adults should be performed using a high-dose (250-μg) synthetic ACTH stimulation test, as it is the most popular and widely used diagnostic test for adrenal insufficiency, with a protocol involving baseline blood samples, followed by ACTH administration, and additional blood samples at 30 and 60 minutes post-injection to measure cortisol and 17-OHP responses 1.

Key Considerations for the Test

• The test should be performed in the morning, preferably between 7-9 AM, after an overnight fast.
• Baseline blood samples should be collected before administering 250 mcg of synthetic ACTH (cosyntropin/Synacthen) intravenously or intramuscularly.
• Additional blood samples should be collected at 30 and 60 minutes post-injection to measure cortisol and 17-OHP responses.
• The test should be performed when the patient is not acutely ill and preferably not during the follicular phase in menstruating women to avoid interference with results.
• Patients should discontinue glucocorticoid medications (if possible) for at least 24 hours before testing, as these can suppress adrenal function and affect test interpretation.

Rationale for the High-Dose Test

• A recent meta-analysis found that the high-dose ACTH test had similar diagnostic accuracy to the low-dose test for secondary adrenal insufficiency, with a likelihood ratio of a positive test of 9.1 for adults 1.
• The high-dose ACTH test is easy to perform and safe, making it a practical choice for diagnosing CAH in adults.

Importance of the Test

• The ACTH stimulation test is valuable for diagnosing CAH because it reveals the enzymatic defects characteristic of the disorder, demonstrating impaired cortisol production and accumulation of precursor hormones like 17-OHP.
• The test helps clinicians distinguish CAH from other adrenal disorders, allowing for accurate diagnosis and treatment.

From the FDA Drug Label

Advise patients and/or caregivers to stop taking glucocorticoids and spironolactone on the day of cosyntropin for injection testing. However, for patients taking long-acting glucocorticoids, advise them to stop for longer periods before cosyntropin for injection testing Advise patients to stop taking estrogen-containing drugs four to six weeks before cosyntropin for injection testing Cosyntropin for injection is intended as a single-dose injection and contains no antimicrobial preservative. Any unused portion should be discarded The protocol for an ACTH stimulation test for diagnosing Congenital Adrenal Hyperplasia (CAH) in adults involves administering 0.25 mg of cosyntropin via IV or IM.

• Pre-test instructions: Patients should stop taking glucocorticoids and spironolactone on the day of testing, while those on long-acting glucocorticoids should stop for a longer period.
• Estrogen-containing drugs should be stopped four to six weeks before testing.
• Administration: Cosyntropin should be reconstituted and administered as a single dose.
• Post-test: Any unused portion of cosyntropin should be discarded 2

From the Research

Protocol for ACTH Stimulation Test

The Adrenocorticotropic Hormone (ACTH) stimulation test is a crucial diagnostic tool for Congenital Adrenal Hyperplasia (CAH) in adults. The protocol for this test involves:

• Administering a synthetic form of ACTH, known as cosyntropin, to stimulate the adrenal glands to produce cortisol and 17-hydroxyprogesterone (17-OHP) 3.
• Measuring the levels of cortisol and 17-OHP in the blood before and after the administration of cosyntropin 4.
• Using a cutoff value of 17-OHP > 30 nmol/L to diagnose non-classic CAH due to 21-hydroxylase deficiency 3, 5.

Dosage and Timing

The dosage of cosyntropin used in the ACTH stimulation test can vary, with studies using both standard (250 microg) and low dose (1 microg) tests 4.

• The test is typically performed in the morning, with blood samples taken at baseline, 30 minutes, and 60 minutes after cosyntropin administration 4, 5.

Interpretation of Results

The results of the ACTH stimulation test are interpreted based on the levels of cortisol and 17-OHP in the blood:

• A peak cortisol response at 60 minutes is expected in normal individuals, while patients with CAH may have a lower cortisol response 4.
• Elevated levels of 17-OHP (> 30 nmol/L) are diagnostic of non-classic CAH due to 21-hydroxylase deficiency 3, 5.

Special Considerations

In adults, the ACTH stimulation test may be used to diagnose non-classic CAH, which can present with symptoms such as hirsutism, irregular menses, and infertility 6, 3.

• The test should be performed in the follicular phase of the menstrual cycle, and the results should be interpreted in the context of the patient's clinical presentation and medical history 5.