Context: Adrenal venous sampling is the “gold standard” test in the diagnosis of an aldosterone-producing adenoma (APA) among patients with primary aldosteronism (PA) but is available only in specialized medical centers. Meanwhile, an APA is reported to be generally more sensitive to ACTH than idiopathic hyperaldosteronism.
Objective: The aim was to evaluate the diagnostic accuracy of the ACTH stimulation test in the diagnosis of an APA among those with suspicion of PA.
Patients and Setting: Fifty-nine patients admitted to Kyoto University Hospital on suspicion of PA were included in the study.
Interventions: ACTH stimulation tests with 1-mg dexamethasone suppression were performed.
Main Outcome Measure: Plasma aldosterone concentrations (PAC) were examined every 30 min after ACTH stimulation. Receiver-operated characteristics curve analysis was used to evaluate the diagnostic accuracy.
Results: PAC after ACTH stimulations were significantly higher in patients with an APA than in patients with idiopathic hyperaldosteronism or non-PA. Receiver-operated characteristics curve analyses showed that the PAC after ACTH stimulation was effective for the diagnosis of an APA among patients suspected of PA. The diagnostic accuracy was highest at 90 min after ACTH injection, with the optimal cutoff value greater than 37.9 ng/dl corresponding with sensitivity and specificity of 91.3 and 80.6% for the diagnosis of an APA.
Conclusions: Our study indicates that the ACTH stimulation test is useful in the diagnosis of an APA among patients suspected of PA. This test can be used to select patients who are highly suspected of an APA and definitely require adrenal venous sampling.
Why this study?
- It's always good to review the workup of hyperaldosteronism.
- It's always difficult to make an exact diagnosis (in my opinion), because of limitations of test methods.
- It's always good to see what researchers consider to be the gold standard for diagnosing a particular condition, since their new test has to be measured against some existing standard.
To screen for PA they used aldosterone concentration (PAC) over plasma reninin activity (PRA) to get the aldosterone-renin ratio (ARR). A value of > 20 ng/dL was considered positive. All anti-hypertensive medications except calcium channel blockers and alpha blockers were stopped at least 2 weeks prior.
The captopril challenge test was used to confirm the diagnosis. An ARR of at least 20 ng/dl per ng/ml*h at 60 min after 50 mg captopril was considered positive for primary aldosteronism. Adrenal CT scanning was used for initial localization. They used adrenal venous sampling to definitively subtype the primary aldosteronism.
Subjects that met study criteria underwent ACTH stim testing as follows: 1 mg dexamethasone at 2300h. 0800 0.25 mg cosyntropin. Plasma aldosterone at baseline and every 30 min for 120 min. 20/23 patients in the APA group underwent laparoscopic adrenalectomy and all of those had pathologically confirmed adrenal adenomas.
Why ACTH stim testing? Back in 1978 apparently Kem et al. reported a difference in PAC in response to ACTH between aldosterone producing adenomas (APA) and idiopathic hyperaldosteronism (IHA). The posture stimulation test had made use of the observation that the PAC in IHA patients increased when changing from a supine to standing position based on enhanced sensitivity of the adrenal zona glomerulosa to changes in angiotensin II (AII). However, later reports showed that actually a number of APA are actually responsive to AII (AII-R), therefore making the postural stim test unhelpful in distinguishing APA and IHA. On the other hand, both AII unresponsive APA (AII-U) and AII-R APA were shown to be more responsive to ACTH stim than IHA. Therefore this study was designed to show that the difference in ACTH stim response could be used to distinguish APA from IHA. This could potentially be helpful in locations where adrenal venous sampling is done infrequently.
As seen above, the sensitivity and specificity are fairly high at distinguishing the two conditions at 90 minutes. The idea as far as I can gather is that this test could be used to rule in IHA and spare the need for adrenal venous sampling in those patients and therefore treat medically. Those who are suspected of having an APA would be referred to locations where adrenal venous sampling is done often enough to be deemed accurate.