LDDST interpretation
Two-stage interpretation of a low-dose dexamethasone suppression test per the 2013 ACVIM consensus statement on canine hyperadrenocorticism: first determine if HAC is present, then within HAC cases evaluate the suppression criteria for pituitary-dependent disease.
Clinical background
The Low-Dose Dexamethasone Suppression Test (LDDST) is the most informative single screening test for hyperadrenocorticism (HAC) in dogs. Compared to the ACTH stimulation test and the urine cortisol:creatinine ratio (UCCR), the LDDST has higher overall sensitivity for HAC and, uniquely among the three, can sometimes discriminate pituitary-dependent hyperadrenocorticism (PDH) from adrenal-dependent (AT) disease in the same test. The trade-off is specificity: the LDDST has a higher false-positive rate in dogs that are stressed or sick from non-adrenal disease, so the pretest probability of HAC has to be high enough to make the test worth running.
How the test works
A baseline cortisol is drawn, dexamethasone (0.01 mg/kg IV) is administered, and cortisol is re-measured at 4 hours and 8 hours post-injection. Dexamethasone is a potent synthetic glucocorticoid; in a normal dog, it suppresses ACTH release from the pituitary by negative feedback, and serum cortisol falls below 1.0–1.4 µg/dL within several hours and stays suppressed for at least 8 hours.
In dogs with HAC, the suppression is incomplete, absent, or transient depending on the underlying cause. The pattern across the 4- and 8-hour points is what discriminates HAC from non-HAC and, in some cases, PDH from AT.
Interpreting the patterns
The InfusionFox LDDST calculator implements the standard four-pattern classification:
1. Normal suppression
4-hour cortisol < 1.4 µg/dL AND 8-hour cortisol < 1.4 µg/dL → does not support HAC. The patient suppressed cortisol normally throughout the test. Look elsewhere for the cause of the clinical signs.
2. Inverse pattern
8-hour cortisol < 1.4 µg/dL but 4-hour cortisol higher than 8-hour → ambiguous. Some normal dogs show this pattern. Some HAC dogs do too. Repeat the test in 1–3 months, or pursue ACTH stim or imaging.
3. Pattern consistent with PDH (escape)
4-hour cortisol < 1.4 µg/dL OR < 50% of baseline, but 8-hour cortisol > 1.4 µg/dL → “escape from suppression.” The pituitary briefly responded to dexamethasone but escaped from feedback by 8 hours. This pattern is diagnostic of PDH in the appropriate clinical context.
4. Dexamethasone-resistant pattern
Both 4-hour and 8-hour cortisol > 1.4 µg/dL → consistent with HAC, but the test cannot distinguish PDH from AT. Move to confirmatory imaging (adrenal ultrasound) or further testing (endogenous ACTH measurement) to make the distinction.
When NOT to run the LDDST
- Acutely sick dogs with non-adrenal disease: false-positive rate is high. Stabilize the underlying illness first.
- Recent glucocorticoid administration: even topical, ophthalmic, or otic preparations can suppress the HPA axis for weeks. Confirm a clean steroid history before testing; if uncertain, wait 4–6 weeks or use the UCCR as a less-sensitive but less-confounded screen.
- Low pretest probability: a positive LDDST in a dog with only one or two nonspecific signs is more likely a false positive than true HAC. Use the InfusionFox Cushing’s score or a comparable structured assessment to confirm clinical signs are convincing before testing.
- Stressed dogs: recent boarding, recent travel, recent procedures, or significant in-clinic anxiety all elevate the false-positive rate. Try to test on a “good day” for the patient.
Laboratory practical points
- Sample timing matters. The 4- and 8-hour samples should be drawn within ±15 minutes of the target time. Earlier than 4 hours can miss the suppression nadir; later than 8 hours can miss the escape.
- Use a single cortisol assay. Cross-reactivity and assay-specific cutoffs vary; if you’re using a different reference range than the standard 1.4 µg/dL cutoff, adjust the calculator’s interpretation accordingly.
- Ship samples cold. Cortisol is reasonably stable but degrades over time at room temperature.
Sources
- Behrend EN et al: Diagnosis of spontaneous canine hyperadrenocorticism: 2012 ACVIM Consensus Statement. J Vet Intern Med 2013;27:1292–1304.
- Feldman EC, Nelson RW, Reusch CE, Scott-Moncrieff JCR: Canine and Feline Endocrinology, 4th ed., Elsevier, 2015, Chapter 11.
- Behrend EN: Hyperadrenocorticism. In: Ettinger SJ, Feldman EC, Côté E, eds. Textbook of Veterinary Internal Medicine, 8th ed., 2017.