Why Cushing’s Pre-Test Probability Matters
Hyperadrenocorticism (Cushing’s disease, HAC) is one of the most common canine endocrinopathies in older dogs — and also one of the most over- and under-diagnosed. The problem cuts both ways:
- Under-diagnosis: classic signs (PU/PD, pot belly, hair loss, muscle weakness) are often dismissed as “old age” for months or years
- Over-diagnosis: testing dogs with low pre-test probability produces false positives, leading to unnecessary lifelong treatment
A structured pre-test probability assessment before testing helps. This calculator integrates clinical signs, suspicious bloodwork, age and breed predisposition into a tiered probability that guides whether confirmatory testing is warranted, and which test makes most sense.
The Disease In Brief
Cushing’s disease in dogs is an excess of cortisol, usually from one of two sources:
- Pituitary-dependent hyperadrenocorticism (PDH) — 85% of cases. A pituitary tumour secretes excess ACTH, driving bilateral adrenal hyperplasia.
- Adrenal-dependent hyperadrenocorticism (ADH) — 15% of cases. A unilateral adrenal tumour (often a carcinoma, sometimes an adenoma) directly produces excess cortisol.
Both produce the same clinical syndrome, but prognosis and treatment options differ.
Classic Clinical Signs
The published frequency of signs in confirmed HAC cases:
| Sign | Frequency | Score weight |
|---|---|---|
| PU/PD (drinking and urinating excessively) | ~90% | High |
| Polyphagia (increased appetite) | ~70% | Moderate |
| Pot-bellied appearance | ~70% | Moderate |
| Bilateral symmetric truncal alopecia | ~70% | Moderate |
| Muscle weakness | ~50% | Moderate |
| Thin skin / comedones / easy bruising | ~50% | Moderate |
| Persistent panting at rest | ~30% | Mild |
| Recurrent UTI (often subclinical) | ~40% | Moderate |
| Calcinosis cutis | ~10% | Strong (pathognomonic-ish) |
A dog with PU/PD + polyphagia + pot belly + alopecia has a very high pre-test probability of Cushing’s. Each sign in isolation has many other causes.
Suspicious Bloodwork
Routine bloodwork in HAC typically shows:
- Markedly elevated ALP — often >1000 U/L due to the steroid-induced isoenzyme. The single most consistent lab finding.
- Mildly elevated ALT — common but non-specific
- Stress leukogram — neutrophilia, lymphopenia, eosinopenia, monocytosis (the “stress pattern”)
- Mild hyperglycaemia
- Hypercholesterolaemia and hyperlipidaemia
- Low urine specific gravity (<1.020) due to PU/PD
- Insulin-resistant diabetes mellitus in some cases
Isolated elevated ALP alone has many other causes — breed-specific high ALP (Scottish Terrier, Siberian Husky), liver disease, corticosteroid administration (including topical creams), anti-convulsants (phenobarbital). Don’t test for HAC on elevated ALP alone without clinical signs.
Diagnostic Tests – The Three Options
ACTH Stimulation Test
- Inject synthetic ACTH (Cosyntropin / Synacthen) intramuscularly or intravenously
- Measure cortisol before and 1 hour after injection
- Elevated post-ACTH cortisol indicates HAC
- Specificity higher than LDDS (fewer false positives)
- Sensitivity slightly lower (more false negatives)
- The standard test in many practices
Low-Dose Dexamethasone Suppression (LDDS)
- Measure baseline cortisol, then inject 0.01 mg/kg dexamethasone IV
- Measure cortisol at 4 hours and 8 hours
- Failure to suppress at 8h indicates HAC
- Sensitivity higher than ACTH stim
- Pattern can help distinguish PDH from ADH (suppression at 4h with re-elevation at 8h suggests PDH)
- Takes a full clinic day
Urine Cortisol:Creatinine Ratio (UCCR)
- Single urine sample, ideally collected at home in low-stress environment
- High negative predictive value — a negative UCCR makes HAC unlikely
- Poor specificity — many non-Cushingoid dogs have elevated UCCR
- Used as a screening test to rule OUT, not to rule IN
The standard approach:
- Low pre-test probability: UCCR to rule out
- Moderate or higher: ACTH stim or LDDS as initial confirmatory test
- Equivocal results: repeat in 1-3 months or proceed to imaging
Differentiating PDH vs ADH
Matters because prognosis and treatment differ:
- LDDS pattern — suppression at 4h with re-elevation at 8h suggests PDH
- Abdominal ultrasound — bilateral adrenal hyperplasia in PDH; unilateral mass with contralateral atrophy in ADH
- Endogenous ACTH — elevated in PDH, low in ADH; the gold standard differentiation test
Breed Predispositions
The breeds most over-represented in published canine HAC populations:
- Miniature Schnauzer
- Poodle (especially Miniature and Toy)
- Beagle
- Boxer
- Yorkshire Terrier
- Dachshund
- Boston Terrier
- Jack Russell Terrier
- West Highland White Terrier
- Staffordshire Bull Terrier
Age of onset typically 7-12 years. Female-to-male predominance roughly 60:40.
Treatment – The Quick Overview
Trilostane (Vetoryl)
First-line for both PDH and ADH since approval in the early 2000s. Reversibly inhibits cortisol synthesis. Daily oral dosing, monitored by ACTH stimulation test at 30 days, 90 days, and every 3 months thereafter. Side effects mostly mild but Addisonian crisis (over-suppression) is possible. See PuppaDogs’ Vetoryl Dosage Calculator for starting doses.
Mitotane (Lysodren)
Older agent, selectively destroys adrenocortical cells. Less used since trilostane became available but still appropriate for some PDH cases. More complex monitoring.
Adrenalectomy
Surgical removal of the affected adrenal — curative for ADH when the tumour is small, non-invasive, and the dog is a surgical candidate. Specialist surgery; significant peri-operative risk.
Hypophysectomy
Pituitary surgery — performed at a small number of specialist centres for selected PDH cases. Potentially curative but requires lifelong cortisol replacement.
Iatrogenic Cushing’s
Chronic corticosteroid administration can produce classic Cushing’s signs. Sources include:
- Oral prednisolone, dexamethasone
- Long-term topical steroid eye/ear/skin creams (often forgotten by owners)
- Depot injectable steroids
Always review medication history before testing. Withdrawal of steroids usually resolves iatrogenic Cushing’s, but recovery of normal adrenal function can take months.
Atypical Cushing’s
Some dogs have clinical signs and elevated cortisol precursors (17-hydroxyprogesterone, sex hormones) without elevated cortisol on standard testing. Specialist endocrine investigation is required — uncommon but recognised.
The Common Misdiagnosis Pattern
A dog presents with:
- PU/PD
- Mildly elevated ALP
- Mildly increased appetite
Many of these dogs do not have Cushing’s — they have:
- Diabetes mellitus
- Chronic kidney disease
- Liver disease
- Hypothyroidism mimicking some features
- Psychogenic polydipsia
- Medications (especially steroids, phenobarbital)
A structured workup (urinalysis with USG, bloods, urine culture, +/- abdominal ultrasound) before testing for Cushing’s is appropriate. This calculator’s pre-test probability score helps decide when the Cushing’s workup is the right next step versus other differentials.
Honest Caveats
- Pre-test probability is not diagnosis. Even very high probability requires confirmatory testing.
- False positives on ACTH stim and LDDS are real, especially in stressed dogs and dogs with non-adrenal illness (chronic disease often raises baseline cortisol). Repeat testing in 1-3 months is appropriate for borderline results.
- The scoring weights in this calculator are pragmatic — they don’t precisely reflect published statistical models, but they approximate clinical judgment.
- No single test is perfect. ACVIM consensus is to combine clinical picture, multiple tests, and (often) imaging.
- Treatment should not be started without a definitive diagnosis. Lifelong trilostane has cost, side-effect and emotional implications.
Conclusion
Canine Cushing’s disease is common in older dogs and frequently both over- and under-diagnosed. A structured pre-test probability assessment using clinical signs, bloodwork, age and breed predisposition helps decide when confirmatory testing is warranted and which test makes most sense. The combination of pre-test probability scoring + appropriate confirmatory testing (ACTH stim, LDDS, UCCR screening) + abdominal ultrasound + clinical judgment is how canine HAC should be diagnosed — and once confirmed, modern trilostane-based treatment offers most dogs excellent quality of life for years.
Frequently Asked Questions
What are the signs of Cushing’s disease in dogs?
Classic signs include PU/PD (increased drinking and urination, present in ~90% of cases), polyphagia (increased appetite), pot-bellied appearance, bilateral symmetric truncal hair loss, thin skin / easy bruising, muscle weakness, persistent panting at rest, recurrent urinary tract infections, and (less commonly) calcinosis cutis (palpable mineralised plaques in skin). Onset is typically 7-12 years. A combination of several signs raises pre-test probability significantly more than any single sign in isolation.
How is dog Cushing’s disease diagnosed?
Three main tests: (1) ACTH stimulation – inject synthetic ACTH, measure cortisol before and 1h after; elevated post-ACTH cortisol indicates HAC. Higher specificity. (2) Low-dose dexamethasone suppression (LDDS) – measure cortisol at 0, 4 and 8 hours after dex injection; failure to suppress at 8h indicates HAC. Higher sensitivity. (3) Urine cortisol:creatinine ratio (UCCR) – screening test with high negative predictive value; rules OUT, not in. Plus abdominal ultrasound to assess adrenal anatomy. ACVIM consensus is to combine clinical picture with appropriate confirmatory tests.
Which dog breeds get Cushing’s disease?
Most over-represented in published canine HAC populations: Miniature Schnauzer, Poodle (especially Miniature and Toy), Beagle, Boxer, Yorkshire Terrier, Dachshund, Boston Terrier, Jack Russell Terrier, West Highland White Terrier, Staffordshire Bull Terrier. Age of onset is typically 7-12 years with slight female predominance (60:40). Pituitary-dependent HAC is 85% of cases; adrenal-dependent 15%.
How is Cushing’s disease treated in dogs?
Trilostane (Vetoryl) is first-line for both PDH and ADH – reversibly inhibits cortisol synthesis, daily oral dosing, monitored by ACTH stimulation test at 30 days, 90 days, and every 3 months. Mitotane (Lysodren) is older but still used for some PDH cases. Adrenalectomy is curative for ADH where the tumour is small and non-invasive. Hypophysectomy (pituitary surgery) is performed at a small number of specialist centres for selected PDH cases. Most dogs do well on trilostane for years with appropriate monitoring.
Can elevated ALP alone diagnose Cushing’s in dogs?
No – isolated elevated ALP has many other causes: liver disease, breed-specific high ALP (Scottish Terrier, Siberian Husky have constitutionally elevated ALP), corticosteroid administration (including topical creams, often forgotten), anti-convulsants (phenobarbital), diabetes, bone disease in young dogs. Cushing’s disease should not be tested on elevated ALP alone without clinical signs. The classic Cushing’s pattern is markedly elevated ALP (>1000 U/L) with classic clinical signs in a middle-aged to older dog.
What is iatrogenic Cushing’s syndrome?
Iatrogenic Cushing’s is the syndrome caused by chronic corticosteroid administration – classic Cushing’s clinical signs without the underlying pituitary or adrenal disease. Sources include oral prednisolone or dexamethasone, long-term topical steroid eye/ear/skin creams (often forgotten by owners), and depot injectable steroids. Always review medication history before testing for HAC. Withdrawal of steroids usually resolves iatrogenic Cushing’s, but recovery of normal adrenal function can take months and requires careful tapering.
Related PuppaDogs Calculators
Continue building your dog’s personalised care plan with these related PuppaDogs calculators:
- Dog Pregnancy / Whelping Due-Date Calculator
- Puppy Weight Predictor (Adult Weight Calculator)
- Heatstroke Risk Calculator for Dogs
- Bloat (GDV) Risk Calculator for Dogs
- Dog Life Expectancy Calculator (Breed, Body Condition, Lifestyle)
- Spay/Neuter Timing Calculator for Dogs (Breed-Specific)
References & Further Reading
The dosing ranges and safety information on this page are drawn from the following veterinary references. Always defer to your own veterinarian and the manufacturer’s label for your specific product.
- Behrend EN, Kooistra HS, Nelson R, Reusch CE, Scott-Moncrieff JC. Diagnosis of spontaneous canine hyperadrenocorticism: 2012 ACVIM Consensus Statement (small animal). Journal of Veterinary Internal Medicine.
- Feldman EC, Nelson RW. Canine and Feline Endocrinology, 4th ed. Saunders Elsevier – canine hyperadrenocorticism chapter.
- Reusch CE. Hyperadrenocorticism. In Ettinger SJ, Feldman EC, Cote E (eds). Textbook of Veterinary Internal Medicine, 8th ed. Elsevier, 2017.
- Galac S, Reusch CE, Kooistra HS, Rijnberk A. Adrenals. In Rijnberk A, Kooistra HS (eds). Clinical Endocrinology of Dogs and Cats, 2nd ed.
- Ramsey IK. Trilostane in dogs. Veterinary Clinics of North America: Small Animal Practice, 2010.
- Plumb’s Veterinary Drug Handbook – trilostane and mitotane.
- PuppaDogs. Vetoryl Dosage Calculator and Water Intake & Polydipsia Calculator. puppadogs.com.
