Diagnosing adrenal insufficiency using ACTH stimulation test

From the authors:

We acknowledge B. Lipworth's work and significant contribution in highlighting the metabolic consequences of steroid therapy in airways disease over the past decades. In their letter he and colleagues refer to a post-synthetic adrenocorticotropic hormone (ACTH, Synacthen) cortisol level of 500 nmol·L⁻¹ as the accepted cut-off to diagnose impaired adrenal function. These diagnostic values were derived using older cortisol assays; however, the cortisol levels in our report relate specifically to the newer Roche Elecsys II Cortisol assay used at our centre that gives, on average, 25% lower serum cortisol values, with a cut-off of ≥420 nmol·L⁻¹ for the 250 µg intramuscular short Synacthen test (SST) at 30 or 60 min [1]. The median cortisol level after SST was 490 nmol·L⁻¹ (interquartile range (IQR) 453–620 nmol·L⁻¹) in patients who passed the SST; in those who failed the SST the cortisol level after SST was 262 nmol·L⁻¹ (IQR 130–310 nmol·L⁻¹).

An agreed lower reference limit for a post-SST cortisol to specifically define a normal axis or sensitively diagnose adrenal failure depends on the specific assay, timing of sampling, and on population characteristics including body size [2]. Further, values over time have tended to decrease as assay methodologies have improved, measuring cortisol more accurately.

We chose the SST, as opposed to the 1 µg Synacthen test (LD-SST), as the SST has been more widely validated against the gold standard insulin tolerance test and represents the most widely used test for diagnosing adrenal insufficiency should the morning cortisol warrant further testing [3]. The SST obviates the need to dilute the Synacthen, which comes in vials of 250 µg, reducing one potential source of error. The diagnostic levels for cortisol after LD-SST are generally lower to diagnose adrenal failure or identify normality. How important the dose is considering normal physiology is moot, that teams use a reproducible test and interpret it correctly is, we argue, more important.

B. Lipworth and colleagues point out that all of our patients were taking high-dose inhaled corticosteroids, likely resulting in systemic absorption with the potential to affect the hypothalmo-pituitary-adrenal axis; whilst the authors and others have previously shown that systemic effects are less frequently seen in severe asthma patients, compared to healthy individuals [4, 5], we attempted to reduce this possible effect further and patients were asked to withhold their inhaled steroid >12 h prior to their SST. However, we agree with B. Lipworth and colleagues on the importance of recognising that any synthetic glucocorticosteroid has the potential to lead to adrenal suppression and patients always ought to be informed of this risk, and physicians must prescribe the lowest dose required to safely manage the disease.

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