How to assess response to Adrenocorticotropic hormone (ACTH) stimulation test for Congenital Adrenal Hyperplasia (CAH) in an adult woman?

From the Guidelines

To assess response to an ACTH stimulation test for Congenital Adrenal Hyperplasia (CAH) in an adult woman, measure baseline serum 17-hydroxyprogesterone (17-OHP) levels, then administer 250 mcg of synthetic ACTH (cosyntropin) intravenously or intramuscularly and collect blood samples at 30 and 60 minutes post-injection. In classic CAH, baseline 17-OHP is typically elevated (>200 ng/dL), with exaggerated responses after ACTH stimulation (often >1000 ng/dL) 1. For non-classic CAH, baseline levels may be normal or mildly elevated, but stimulated values typically exceed 1000 ng/dL. Additional hormones to measure include androstenedione, testosterone, DHEA-S, and cortisol. Testing should ideally be performed in the morning (7-9 AM) during the follicular phase of the menstrual cycle to minimize interference from normal hormonal fluctuations. Patients should discontinue oral contraceptives or glucocorticoids (if possible) for at least 6 weeks before testing, as these can suppress adrenal hormone production. This test is valuable because CAH involves enzymatic defects in cortisol synthesis, most commonly 21-hydroxylase deficiency, leading to accumulation of precursor hormones like 17-OHP and increased androgen production, which the ACTH stimulation test can effectively reveal 1.

Key Considerations

• The high-dose (250-μg) ACTH stimulation test is the most popular diagnostic test for adrenal insufficiency and is easy to perform and safe 1.
• The low-dose ACTH test requires some preparation at the bedside and has similar diagnostic accuracy to the high-dose test for secondary adrenal insufficiency 1.
• Measurement of serum free cortisol levels is not recommended over plasma total cortisol level in patients with suspected CIRCI due to cumbersome techniques and inconsistent findings 1.

Hormone Measurements

• Baseline serum 17-hydroxyprogesterone (17-OHP) levels
• Androstenedione
• Testosterone
• DHEA-S
• Cortisol
• These hormones should be measured at baseline and after ACTH stimulation to assess the response to the test.

Timing and Preparation

• Testing should be performed in the morning (7-9 AM) during the follicular phase of the menstrual cycle.
• Patients should discontinue oral contraceptives or glucocorticoids (if possible) for at least 6 weeks before testing.
• The ACTH stimulation test should be performed after an overnight fast to minimize interference from food intake.

Interpretation of Results

• Classic CAH: baseline 17-OHP >200 ng/dL, stimulated 17-OHP >1000 ng/dL.
• Non-classic CAH: baseline 17-OHP normal or mildly elevated, stimulated 17-OHP >1000 ng/dL.
• The results of the ACTH stimulation test should be interpreted in the context of the patient's clinical presentation and medical history.

From the FDA Drug Label

Stop estrogen containing drugs 4 to 6 weeks before cosyntropin for injection testing to allow cortisol binding globulin levels to return to levels within the reference range. Alternatively, concomitant measurement of cortisol binding globulin at the time of testing can be done; if cortisol binding globulin levels are elevated, plasma total cortisol levels are considered inaccurate.

To assess response to ACTH stim test for CAH in an adult woman, estrogen-containing drugs should be stopped 4 to 6 weeks before the test. Alternatively, cortisol binding globulin levels can be measured at the time of testing. If cortisol binding globulin levels are elevated, plasma total cortisol levels may not be accurate 2.

• Key considerations:
  • Stop estrogen-containing drugs before testing
  • Measure cortisol binding globulin levels if necessary
  • Interpret plasma total cortisol levels with caution if cortisol binding globulin is elevated

From the Research

Assessing Response to ACTH Stim Test for CAH in Adult Women

To assess the response to the Adrenocorticotropic hormone (ACTH) stimulation test for Congenital Adrenal Hyperplasia (CAH) in an adult woman, several factors and test results must be considered:

• The ACTH stimulation test is used to evaluate adrenal gland function, particularly in diagnosing and managing CAH 3.
• The test involves measuring cortisol and 17-hydroxyprogesterone (17-OHP) levels before and after administering synthetic ACTH (cosyntropin) 4, 5.
• In adults with suspected CAH, the diagnosis can be confirmed by an ACTH-stimulated 17-OHP level > 30 nmol/L, though this threshold may vary depending on the assay used 3.
• However, diagnosing non-classic CAH based solely on serum 17-OHP measurements (basal or post-stimulated) can lead to false-positive diagnoses, emphasizing the need for confirmation via 24-hour urinary steroid profile analysis and/or genetic testing 6.
• The timing of cortisol measurement after ACTH stimulation is crucial; some studies suggest that measuring cortisol at both 30 and 60 minutes may be necessary to avoid overdiagnosing adrenal insufficiency 7.
• Assay-specific cutoffs for cortisol levels are essential for accurate interpretation of the ACTH stimulation test, with proposed thresholds varying by immunoassay method 5.

Key Considerations

• The choice of assay for measuring cortisol and 17-OHP can affect the interpretation of test results, with different assays having different cutoff values for diagnosing adrenal insufficiency or CAH 5.
• Patient characteristics, such as weight status, may influence the timing of peak cortisol levels after ACTH stimulation, with overweight and obese individuals potentially peaking earlier than normal or underweight individuals 7.
• Clinical presentation, such as hirsutism, and symptoms suggestive of hyperandrogenism, should guide the decision to perform an ACTH stimulation test and interpret its results in the context of CAH or other conditions like polycystic ovary syndrome (PCOS) 3, 6.