The short answer
Canine Cushing's syndrome is a disorder of chronic glucocorticoid excess. About 85% of naturally occurring cases come from an ACTH-secreting pituitary tumor, and the rest come from a cortisol-secreting adrenal tumor. Diagnosis combines compatible clinical signs and routine laboratory changes with a dynamic test of the pituitary-adrenal axis, followed by a differentiating test or imaging to separate pituitary from adrenal disease. Trilostane is the most common medical treatment, and a review describes a move toward lower, twice-daily dosing [3]. Monitoring usually relies on ACTH stimulation testing, although the sources say there is no consensus on test timing or the target cortisol range.
Key takeaways
- Merck reports that roughly 85% of dogs with naturally occurring hyperadrenocorticism have pituitary-dependent disease and 15% have an adrenal tumor [1].
- The Merck chapters call the low-dose dexamethasone suppression test (LDDST) the screening test of choice, but they note that more than half of dogs with nonadrenal illness test positive [1][2].
- The 2025 ALIVE consensus calls the urine corticoid:creatinine ratio "at best, a poor screening test," and Merck describes it as highly sensitive but not highly specific [1][4].
- Merck gives a trilostane starting dosage of 1-3 mg/kg, PO, with food every 12 hours [1]. A Canadian Veterinary Journal review suggests 0.5 to 1 mg/kg BW, q12h, when twice-daily dosing is used [3].
- Across 11 trilostane studies reviewed in the Canadian Veterinary Journal, adverse effects occurred in 13% of dogs dosed q24h and 19% of dogs dosed q12h [3].
- The same review reports that hypertension, proteinuria, and hypercoagulability can persist despite trilostane therapy [3].
Doses on this pageEvery dose below is quoted from the cited source. Verify against the current label/formulary and the patient's full clinical picture.
Definition and terminology
Merck uses "Cushing syndrome" as the umbrella term for elevated adrenocortical hormones from any cause. It reserves "Cushing disease" for pituitary-dependent hyperadrenocorticism (PDH) and uses adrenal-dependent hyperadrenocorticism (ADH) for disease caused by a functional adrenal adenoma or adenocarcinoma [1][2]. The ESVE/SCE consensus project known as ALIVE (Agreeing Language in Veterinary Endocrinology) defines Cushing's syndrome as clinical syndromes "caused by a chronic excess of glucocorticoid activity." The panel discourages using "Cushing's disease or hyperadrenocorticism" for the umbrella term, and its classification names the PDH and ADH subtypes pituitary-dependent hypercortisolism and adrenal-dependent hypercortisolism [4].
Iatrogenic disease, according to Merck, comes from chronic excessive administration of exogenous steroids [1]. ALIVE defines iatrogenic Cushing's syndrome as caused by chronic administration of systemic or topical glucocorticoids. Elsewhere in the consensus, ALIVE emphasizes that topical routes include ophthalmic and otic [4].
Signalment and presentation
Merck reports that Cushing disease (PDH) occurs mostly in dogs 7 to 12 years old. Predisposed breeds include Poodles, especially the Miniature Poodle, and Staffordshire terriers. PDH occurs predominantly in smaller dogs. ADH also often affects medium and large breeds, with reported median body weights of 18 to 20 kg [1]. Some studies cited by Merck find that about 75% of affected dogs are female, and other studies find no sex association [1].
Merck lists the most common signs in dogs as polyuria/polydipsia, polyphagia, a pendulous abdomen, panting, muscle wasting, and skin changes such as alopecia, pyoderma, and thin skin. It notes that many affected dogs have systemic hypertension [2]. Calcinosis cutis is listed as a dog-only finding [1]. Merck calls increased ALP activity the most common laboratory abnormality, driven by a corticosteroid-induced isoenzyme found only in dogs. Other common findings include hyperlipidemia, mild hyperglycemia, a stress leukogram, low urine specific gravity, and proteinuria [1][2]. About 10% of affected dogs have concurrent diabetes mellitus, according to Merck [1].
Diagnostic testing
Screening tests
Merck states that no single test or combination of tests is 100% accurate. It says the diagnosis should rest on clinical signs, supporting database abnormalities, and an appropriate screening test [1]. ALIVE's criteria for diagnosing PDH likewise require clinical features plus "demonstration of an excess of cortisol through dynamic testing of pituitary-adrenal function" [4].
| Test | Protocol per sources | Reported performance |
|---|
| LDDST | Dexamethasone 0.01 mg/kg IV in dogs; cortisol measured before and at 4 and 8 hours [2][4] | Merck reports 5%-8% false negatives in PDH and more than 50% positive results in nonadrenal illness [1] |
| ACTH stimulation | Synthetic ACTH at the ALIVE preferred dose for dogs, given intravenously where possible; cortisol before and 60 minutes after [4] | Merck gives sensitivity of approximately 80%-85% with much higher specificity than the LDDST [1] |
| UCCR | First morning urine collected at home [1][4] | ALIVE reports sensitivity can fall below 70% and specificity is under 70% [4] |
The two Merck chapters weigh the ACTH stimulation test differently. One describes it as preferred for dogs with concurrent conditions such as renal disease or diabetes mellitus [1]. The other says it is not recommended as a first-line test and that nearly 50% of dogs with ADH may have a normal result [2]. ALIVE describes the ACTH stimulation test as "the only test that can document iatrogenic Cushing's syndrome" [4].
Differentiating PDH from ADH
According to Merck, an LDDST with an elevated 8-hour cortisol is consistent with PDH in any of three cases: the 4-hour value is below 50% of baseline, the 4-hour value is below the reference interval, or the 8-hour value is below 50% of baseline [2]. Merck describes endogenous ACTH measurement as the most expedient way to discriminate PDH from adrenal tumors. Dogs with adrenal tumors have low to undetectable concentrations, and dogs with PDH have normal to increased concentrations [1]. The high-dose test uses 0.1 mg/kg IV in dogs [2][4]. Merck notes that dogs with pituitary macroadenomas, which make up 15%-50% of PDH cases, do not suppress on it [1]. ALIVE states: "The lack of suppression in response to dexamethasone is not confirmation of ADH" [4]. Abdominal ultrasonography or CT can identify bilaterally symmetrical adrenals or a unilateral tumor and assists with surgical planning [2].
Testing pitfalls
- Merck recommends retesting in 3-6 months rather than treating when results are inconclusive or when lab changes appear in a dog without clinical signs [1].
- Dogs with nonadrenal illness should recover before an LDDST retest, per Merck [1].
- ALIVE advises collecting urine at home more than 2 days after a clinic visit or stressful event [4].
- ALIVE discourages in-house cortisol assays. It also notes that in clinical settings where tubes may be underfilled, the use of EDTA-plasma significantly increases measured cortisol [4].
- ALIVE stresses that basal UCCR and endogenous ACTH are not dynamic tests of pituitary-adrenal function [4].
Classification
ALIVE divides naturally occurring Cushing's syndrome into two groups, with iatrogenic Cushing's syndrome as a separate category [4]:
- ACTH-dependent forms: PDH, ectopic ACTH, and subdiagnostic disease.
- ACTH-independent forms: ADH, aberrant adrenal receptor expression, and subdiagnostic disease.
"Subdiagnostic Cushing's syndrome" replaces the older terms atypical or occult disease. It describes a dog that appears to have the syndrome while dynamic test results fall within reference intervals [4]. For the ACTH-dependent subdiagnostic form, ALIVE recommends retesting in 2-3 months if signs persist. The panel warns that treatment trials "can pose significant risks" and should be reserved for cases where euthanasia is being considered or welfare is at significant risk [4]. ALIVE also publishes a 15-point Cushing's Clinical Score covering drinking, urination, appetite, appearance, and attitude [4].
Trilostane treatment
Trilostane competitively and reversibly inhibits 3-beta-hydroxysteroid dehydrogenase, an enzyme needed for cortisol and other steroid synthesis, according to the Canadian Veterinary Journal review by Lemetayer and Blois [3]. Merck calls it the treatment of choice in dogs except for those with calcinosis cutis or atypical disease, which Merck says respond better to mitotane [1].
The review reports a manufacturer's starting dose of 2.2 to 6.6 mg/kg BW, PO, q24h [3]. Cortisol suppression after a dose often lasts less than 12 hours, so the authors summarize studies of twice-daily dosing. They recommend starting "at doses of 0.5 to 1 mg/kg BW, q12h, with a maximum initial dose of 30 mg/dog for dogs > 30 kg" [3]. Merck lists 1-3 mg/kg, PO, with food every 12 hours [1].
Three studies directly compared q24h and q12h dosing. One of them (Cho et al) included 7 dogs dosed q24h and 9 dosed q12h [3]. Separately, the review notes that the literature lacks large prospective, randomized, controlled studies comparing trilostane with mitotane [3]. The authors also advise giving trilostane with food, including on recheck test days. They say compounded capsules are rarely necessary now that licensed 5 mg and 10 mg capsules exist [3].
Monitoring during trilostane therapy
The review calls the ACTH stimulation test "the gold standard test used to monitor" treatment. It cites the following testing schedule [3]:
- 10 to 14 days after starting or changing the dose
- 1 month and 3 months
- every 3 to 6 months once the dose is stable
The early test is meant only to rule out excessive suppression, and the authors caution against raising the dose at that point [3]. The manufacturer recommends testing 4 to 6 hours post-dose. The lowest cortisol concentrations usually fall 2 to 4 hours after dosing, and the authors advise starting each patient's test at a consistent interval after the dose [3].
The authors recommend a post-ACTH cortisol target below 150 nmol/L. They accept leaving the dose unchanged if clinical control is good below 250 nmol/L. They suggest decreasing or stopping trilostane when pre- and post-ACTH values are below 40 to 55 nmol/L [3]. They note that cutoffs vary by laboratory [3].
As an alternative, Merck cites pre-trilostane and 3-hour post-trilostane cortisol concentrations of 138 nmol/L or less and 62 nmol/L or less, respectively, as associated with excellent control [1]. The study behind that approach used owner questionnaires, and 85% of its 110 tests involved once-daily dosing, which limits how well it applies to q12h protocols [3]. Periodic electrolyte checks are also recommended because hyperkalemia and hyponatremia are common during treatment [3].
Safety, other treatments, and prognosis
Reported adverse effects include anorexia, lethargy, vomiting, diarrhea, and hypoadrenal states, which may or may not involve adrenal necrosis [3]. Permanent hypoadrenocorticism has been described [1][3]. The review says trilostane use is not recommended in dogs with liver or renal insufficiency [3].
Merck describes adrenalectomy as the treatment of choice for ADH. It reports 1-month mortality of 14%-60% after unilateral adrenalectomy and a median survival of approximately 18 months [1][2]. Pituitary radiotherapy is indicated for dogs with neurological signs and a macroadenoma, and hypophysectomy is available on a limited basis [1].
Merck estimates median survival with PDH at 2 years with or without medical treatment. It also cites a study of low-dose twice-daily trilostane that reported a median survival of 998 days (range 26-1,832 days) [1]. A retrospective study cited in the review found shorter survival in 26 untreated dogs than in 17 trilostane-treated dogs. The review authors noted that many deaths in the untreated group had unknown or unrelated causes [3].
Client communication
The sources support several points for owner conversations:
- Merck says UCCR samples should be free-catch urine collected at home, because clinic transport or cystocentesis can raise the result [1].
- The review notes that improvement in signs is gradual and that skin changes can take several more months to resolve [3].
- In the context of mitotane treatment, Merck advises monitoring for anorexia, vomiting, and diarrhea as signs of hypoadrenocorticism [1].
- The review notes that hypertension and proteinuria can persist on trilostane and may require specific therapy [3].
