This article is more than 5 years old. Information may no longer be current.
ACTH testing may be ‘misleading’ in identifying adrenal insufficiency
Click Here to Manage Email Alerts
Both low-dose and high-dose adrenocorticotropic hormone stimulation tests have similar diagnostic accuracy in identifying adrenal insufficiency; however, the tests have limitations and cannot necessarily rule out the condition, according to research in The Journal of Clinical Endocrinology & Metabolism.
In a systematic review and meta-analysis comparing adrenocorticotropic hormone (ACTH) stimulation tests in patients with primary or secondary adrenal insufficiency, researchers found that, although the tests are helpful in determining the conditions when positive, the tests are not as helpful in ruling out the conditions when negative.
Naykky Singh Ospina
“When considering the diagnosis, physicians should have an understanding of the pretest possibility of the disease,” Naykky Singh Ospina, MD, of the Evidence-Based Practice Research Program at the Mayo Clinic in Rochester, Minnesota, and colleagues wrote. “This is important since the presented likelihood ratios of both the high- and low-dose ACTH stimulation test suggest that, although helpful, these tests are not perfect and can be misleading in some cases.”
Ospina and colleagues analyzed data from 35 observational or randomized studies that assessed the diagnostic accuracy of high- and low-dose ACTH stimulation tests for the diagnosis of primary adrenal insufficiency (n = 5) or secondary adrenal insufficiency (n = 30). Researchers used the Quality Assessment of Diagnostic Accuracy Studies instrument to assess risk of bias. Researchers broke down secondary adrenal insufficiency tests by high-dose and low-dose tests for adults and for children.
Researchers found that both low- and high-dose tests had low sensitivity and high specificity. High-dose tests for children had the highest OR for accuracy (OR = 67; 95% CI, 1-4,152), followed by low-dose tests for adults (OR = 30; 95% CI, 18-50), high-dose tests for adults (OR = 23; 95% CI, 13-42) and low-dose tests for children (OR = 23; 95% CI, 2-313). Researchers found no statistically significant difference between accuracy of high- and low-dose tests when comparing diagnostic ORs.
Due to insufficient data, researchers only estimated sensitivity for the five primary adrenal insufficiency studies, which was 92% (95% CI, 81-97).
“Our study highlights the importance of evaluating tests results in the setting of clinical suspicion,” Ospina told Endocrine Today. “In the case of secondary adrenal insufficiency, the ACTH stimulation tests appear to be the more helpful when trying to rule in secondary adrenal insufficiency. Their performance as a rule-out test is suboptimal and needs to be interpreted with caution in the setting of the clinical suspicion.” – by Regina Schaffer
Disclosure: The researchers report no relevant financial disclosures.
Perspective
Back to TopAlexandra Ahmet, MD, FRCPC
The ACTH stimulation test is frequently used in the assessment of adrenal insufficiency because it is safe and relatively easy to perform; controversy exists as to whether a low-dose or high-dose test is better. This systematic review and meta-analysis suggests that both the low- and high-dose ACTH stimulation tests are good tests to rule in — but poor tests to rule out — secondary adrenal insufficiency. The exclusion of studies of healthy controls contrasts with previous meta-analyses and likely explains the surprisingly poor sensitivity of both tests in comparison with previous reports.
Although the accuracy of the two tests are reported to be comparable, relatively higher sensitivity with the low-dose test and relatively higher specificity with the high-dose test may be a consideration when selecting a test for a specific patient. The overall findings contribute to the challenge of diagnosing adrenal insufficiency and highlight the importance of considering clinical suspicion and ensuring adequate follow-up when a negative result is found. The findings also need to be considered in the context of the challenges of evaluating ACTH-stimulation testing, including differences in patient populations, cortisol assays and cut-off values; technical issues with the tests; and clinical significance of mild biochemical abnormalities.
Click Here to Manage Email Alerts