Study sharpens cortisol testing strategy for suspected Addison’s
Bottom line
A new Journal of Veterinary Internal Medicine study evaluated basal cortisol and ACTH stimulation test results in 982 dogs being investigated for hypoadrenocorticism, examining how different cortisol cutoffs, prior glucocorticoid exposure, and added hormone measurements affect diagnostic performance. The study reinforces the long-standing role of the ACTH stimulation test as the diagnostic standard, but adds nuance around how basal cortisol is used in real-world cases, especially when recent steroid treatment may complicate interpretation. Existing guidance already supports basal cortisol values above 2 µg/dL as useful for ruling out hypoadrenocorticism, while values at or below that threshold still require confirmatory ACTH stimulation testing. (academic.oup.com)
Why it matters: For veterinary professionals, the practical issue is triage: when a low basal cortisol should trigger full endocrine workup, and when a normal result can safely move Addison’s lower on the list. Prior research has shown that lowering the basal cortisol cutoff can improve specificity, but at the cost of sensitivity, and current expert guidance cautions that basal cortisol alone shouldn’t be used to confirm the diagnosis. The new paper also appears to highlight how recent glucocorticoid administration can produce misleading low cortisol responses, creating a risk of false-positive interpretation unless clinicians consider drug history and, in selected cases, aldosterone or endogenous ACTH testing. (pubmed.ncbi.nlm.nih.gov)
What to watch: Watch for whether this study shifts how internists and diagnostic labs recommend cutoff selection, steroid washout considerations, and use of adjunctive aldosterone or endogenous ACTH testing in equivocal cases. (academic.oup.com)
Key facts
- Study
- Journal of Veterinary Internal Medicine study
- Sample size
- 982 dogs
- Condition
- Hypoadrenocorticism
- Tests evaluated
- Basal cortisol and ACTH stimulation test
- Main focus
- Effect of cortisol cutoffs, prior glucocorticoid exposure, and added hormone measurements on diagnostic performance
- Diagnostic standard
- ACTH stimulation test
- Screening guidance
- Basal cortisol above 2 µg/dL helps rule out hypoadrenocorticism
- Interpretation caution
- Low basal cortisol still requires confirmatory ACTH stimulation testing
- Clinical issue
- Recent glucocorticoid treatment can complicate cortisol interpretation
A newly published study in the Journal of Veterinary Internal Medicine takes a fresh look at one of small animal internal medicine’s most familiar endocrine dilemmas: how to interpret basal cortisol and ACTH stimulation testing in dogs being worked up for hypoadrenocorticism. Drawing on 982 dogs, the paper examines not just screening performance, but also how prior glucocorticoid exposure and additional hormone data can change the meaning of a low cortisol result in practice. (academic.oup.com)
That question matters because the field has long relied on a two-step framework. Basal cortisol is widely used as a screening tool, largely because a value above 2 µg/dL makes hypoadrenocorticism unlikely in most untreated dogs. But the tradeoff has always been specificity: many dogs with low basal cortisol do not have Addison’s, which is why AAHA guidance and diagnostic laboratory recommendations still say that low resting cortisol should be followed by an ACTH stimulation test rather than treated as diagnostic on its own. (meridian.allenpress.com)
Earlier studies helped define those tradeoffs. A 2007 JAVMA study found that basal cortisol concentrations of 2 µg/dL or less were highly sensitive, but much less specific, whereas a lower 1 µg/dL threshold improved specificity substantially. A larger 2016 JVIM analysis likewise found that 2 µg/dL was useful for ruling disease out, while a lower cutoff around 0.8 µg/dL improved the balance between sensitivity and specificity, though at the cost of missing some affected dogs. (pubmed.ncbi.nlm.nih.gov)
The new 982-dog paper builds on that literature with a larger contemporary dataset and a more clinically messy population, including dogs with recent glucocorticoid exposure. According to the article record, the investigators also examined dogs without hypoadrenocorticism that nevertheless had “flat-line” ACTH stimulation test results, and used aldosterone and endogenous ACTH data in at least some cases to sort out whether those results reflected true adrenal disease or suppression related to prior steroid treatment. That’s an important distinction, because exogenous glucocorticoids can suppress the hypothalamic-pituitary-adrenal axis and produce low pre- and post-ACTH cortisol values that mimic hypoadrenocorticism. (academic.oup.com)
Expert guidance has been pointing in that direction for some time. Michigan State University’s Veterinary Diagnostic Laboratory notes that recent glucocorticoid treatment can make ACTH stimulation results difficult to interpret, and that aldosterone testing may help when cortisol findings are confounded. A recent review on diagnosis of canine spontaneous hypoadrenocorticism similarly notes that basal cortisol is best used as a screening test, not a confirmatory one, and that endogenous ACTH and aldosterone testing can help distinguish primary disease, central disease, and isolated glucocorticoid deficiency in selected cases. (cvm.msu.edu)
Why it matters: For general practitioners, emergency clinicians, and internists, this is less about replacing the ACTH stimulation test than about using each test more intelligently. A dog with compatible signs and a basal cortisol above 2 µg/dL can often be moved away from an Addison’s diagnosis, saving time and cost for the pet parent. But a low basal cortisol still opens a broad differential, not a conclusion. The study’s focus on prior steroid exposure is especially relevant in referral and emergency settings, where dexamethasone, prednisone, topical steroids, or ear medications may already be in the picture before endocrine testing is pursued. (meridian.allenpress.com)
The deeper clinical takeaway may be about avoiding overdiagnosis as much as catching true disease. If more dogs without hypoadrenocorticism can show very low cortisol responses after glucocorticoid exposure, then medication history, sample timing, and selective use of aldosterone or endogenous ACTH become more important parts of the diagnostic algorithm. That could be particularly useful in dogs with normal sodium and potassium concentrations, where “atypical” or glucocorticoid-deficient presentations already complicate interpretation. (academic.oup.com)
What to watch: The next question is whether this paper changes frontline recommendations from specialty groups, reference labs, or teaching hospitals, especially around cortisol cutoffs and workup of dogs tested after recent glucocorticoid exposure. It may also spur more interest in adjunctive testing, including aldosterone and endogenous ACTH, for equivocal cases where a standard ACTH stimulation result doesn’t cleanly answer the question. (academic.oup.com)