Dog Cushing’s Disease: Symptoms, Diagnosis, and Treatment Guide
This article is reviewed for clinical accuracy. Always consult your veterinarian for diagnosis and treatment.
Key Takeaways
- Cushing’s disease (hyperadrenocorticism) is caused by chronically elevated cortisol levels and is one of the most common endocrine disorders in middle-aged to older dogs; it develops slowly over months to years, so owners often attribute the early signs (increased thirst and urination, panting, pot-bellied appearance) to normal aging rather than disease.
- Approximately 80 to 85 percent of cases are pituitary-dependent hyperadrenocorticism (PDH): a microadenoma or macroadenoma in the pituitary gland secretes excess ACTH (adrenocorticotropic hormone), which drives both adrenal glands to overproduce cortisol; the remaining 15 to 20 percent are adrenal-dependent hyperadrenocorticism (ADH): a unilateral tumor (adenoma or carcinoma) in one adrenal gland autonomously produces cortisol independently of ACTH.
- Diagnosis requires a screening test (low-dose dexamethasone suppression test or urine cortisol:creatinine ratio) followed by a differentiating test (high-dose dexamethasone suppression test or ACTH stimulation test with endogenous ACTH measurement or abdominal ultrasound) to distinguish PDH from ADH; no single test is 100 percent accurate, and clinical judgment is required.
- Trilostane (Vetoryl) is the current first-line treatment in the United States and most of the world; it inhibits the adrenal enzyme 11-beta-hydroxysteroid dehydrogenase, reducing cortisol synthesis; it requires careful monitoring with ACTH stimulation tests at 10 to 14 days, 30 days, and 90 days after starting or changing the dose, then every 3 to 6 months; under-treatment and over-treatment (adrenal crisis) are both risks.
- Mitotane (Lysodren, o,p’-DDD) is an older adrenocorticolytic drug that selectively destroys adrenocortical cells; it remains an effective alternative and may be preferred when trilostane is not available or cost-prohibitive; it has a narrower therapeutic index than trilostane and requires a strict induction protocol with daily monitoring of water intake during the loading phase.
- Untreated or poorly controlled Cushing’s disease significantly increases the risk of hypertension, pulmonary thromboembolism, diabetes mellitus, recurrent urinary tract infections, skin infections, and neurological signs from a growing pituitary macroadenoma; treatment meaningfully extends life expectancy and quality of life in most affected dogs.
The owner had noticed the changes so gradually that she blamed herself for not seeing them sooner. Over two years, the 10-year-old Miniature Poodle had gone from lean and active to pot-bellied and slow. His water bowl needed refilling twice a day. His coat had thinned symmetrically on his flanks. He panted constantly, even in air conditioning. She had attributed all of it to getting old. The bloodwork told a different story: elevated alkaline phosphatase (ALP) at over 1,800 U/L (reference range 23 to 212 U/L), borderline elevated cholesterol, and a urinalysis showing very dilute urine (specific gravity 1.008) with a urinary tract infection. A low-dose dexamethasone suppression test (LDDST) was non-suppressed, confirming hyperadrenocorticism. Abdominal ultrasound showed bilateral adrenomegaly with a normal symmetrical appearance, consistent with pituitary-dependent disease. Within two months of starting trilostane, the water intake had normalized, the panting resolved, and he had regained some muscle tone. Cushing’s disease is not old age. It is a treatable endocrine condition that dogs can live well with when it is correctly diagnosed and managed.
The Hypothalamic-Pituitary-Adrenal (HPA) Axis
Understanding Cushing’s disease requires a working knowledge of the HPA axis, the feedback system that regulates cortisol production. Under normal conditions: the hypothalamus releases corticotropin-releasing hormone (CRH); CRH stimulates the pituitary gland (specifically the pars distalis and pars intermedia of the anterior pituitary) to release ACTH (adrenocorticotropic hormone); ACTH travels through the bloodstream to the adrenal cortex and stimulates the zona fasciculata and zona reticularis to produce and release cortisol (hydrocortisone); rising cortisol levels feed back to both the hypothalamus and pituitary to suppress further CRH and ACTH release (negative feedback). In pituitary-dependent Cushing’s disease, a pituitary adenoma produces ACTH autonomously, largely ignoring the cortisol negative feedback signal. The chronically elevated ACTH drives both adrenal glands to enlarge (bilateral adrenomegaly) and produce supraphysiological amounts of cortisol continuously. In adrenal-dependent Cushing’s disease, a unilateral adrenal tumor produces cortisol autonomously; the high cortisol suppresses ACTH from the normal pituitary, causing the contralateral normal adrenal gland to atrophy from disuse.
Types of Cushing’s Disease in Dogs
Pituitary-Dependent (PDH): 80 to 85%
- Cause: ACTH-secreting microadenoma (less than 1 cm, most common) or macroadenoma (1 cm or larger, can cause neurological signs) in the pituitary pars distalis or pars intermedia
- Adrenal glands: Both glands enlarged (bilateral adrenomegaly); each gland typically 0.7 to 1.0 cm in thickness on ultrasound (normal less than 0.7 cm); may appear nodular
- ACTH level: Normal to elevated
- HDDST suppression: Suppression usually occurs in classic PDH (cortisol drops to less than 50% of baseline) but not in all cases
- Breed predisposition: Poodles, Dachshunds, Boxers, Boston Terriers, Beagles, Yorkshire Terriers, Staffordshire Bull Terriers
- Treatment: Trilostane or mitotane (medical management); pituitary irradiation for macroadenomas
Adrenal-Dependent (ADH): 15 to 20%
- Cause: Unilateral adrenocortical tumor; approximately 50 percent adenoma (benign, smaller, well-encapsulated) and 50 percent adrenocarcinoma (malignant, larger, may invade vena cava or regional lymph nodes)
- Adrenal glands: One gland enlarged or with a discrete mass; contralateral gland atrophied (less than 0.3 cm); asymmetry is the key ultrasound finding
- ACTH level: Suppressed (low) due to cortisol negative feedback on normal pituitary
- HDDST suppression: No suppression (autonomous cortisol production independent of ACTH)
- Breed predisposition: Larger breeds more commonly affected than in PDH; no strong breed predisposition but Poodles and Dachshunds still over-represented
- Treatment: Adrenalectomy (surgery of choice if no metastasis); trilostane for palliation if surgery not possible
Clinical Signs of Cushing’s Disease
The clinical signs of Cushing’s disease result from the systemic effects of chronically elevated cortisol. Cortisol is a glucocorticoid with widespread metabolic, anti-inflammatory, and immunosuppressive actions; in excess, it disrupts virtually every organ system.
| Clinical Sign | Mechanism | Frequency |
|---|---|---|
| Polyuria and polydipsia (PU/PD) | Cortisol antagonizes antidiuretic hormone (ADH/vasopressin) at renal collecting ducts, reducing water reabsorption; increased urinary output drives compensatory drinking | Greater than 85% |
| Polyphagia (increased appetite) | Cortisol stimulates appetite centers in the hypothalamus; dogs may become food-obsessed or steal food | Greater than 80% |
| Pot-bellied appearance (abdominal distension) | Redistribution of fat to the abdomen (visceral adiposity); hepatomegaly from glycogen accumulation in hepatocytes (steroid hepatopathy); muscle wasting of epaxial and abdominal wall muscles reducing support | 70 to 85% |
| Bilateral symmetric alopecia | Cortisol arrests hair follicles in the telogen (resting) phase; alopecia typically spares the head and legs; the remaining coat may be thin, dry, and lacking luster | 50 to 90% |
| Muscle weakness and exercise intolerance | Protein catabolism in muscle tissue (gluconeogenesis substrate); myopathy from cortisol excess | Greater than 60% |
| Panting | Pulmonary fat deposition, reduced respiratory muscle function, hypertension; may be worsened by concurrent hypothyroidism | Greater than 60% |
| Thin, fragile skin (skin atrophy) | Cortisol suppresses collagen synthesis and skin cell proliferation; skin may tear easily, heal poorly, and show comedones (blackheads) | 40 to 60% |
| Calcinosis cutis | Calcium deposits in the skin (most commonly dorsal midline, neck, and groin); firm, white-yellow plaques that may ulcerate; associated with severe hypercortisolism | 20 to 40% |
| Recurrent infections (skin, urinary tract) | Cortisol-mediated immune suppression; increased urine glucose predisposes to UTIs; skin barrier dysfunction allows bacterial and Malassezia overgrowth | Greater than 30% |
| Neurological signs (circling, blindness, behavior change) | Pituitary macroadenoma (greater than 1 cm) compressing the hypothalamus, thalamus, or optic chiasm; indicates large pituitary tumor requiring specialist evaluation | Less than 15% (macroadenoma cases) |
| Hypertension | Cortisol increases vascular reactivity and sodium retention; systolic blood pressure often above 160 mmHg; increases risk of ocular and renal damage | 50 to 80% |
| Pulmonary thromboembolism (PTE) | Cortisol promotes hypercoagulability (increased clotting factors, reduced antithrombin III); PTE can cause sudden respiratory distress, collapse, or sudden death | 5 to 25% in some series |
Diagnosing Cushing’s Disease
Routine Laboratory Abnormalities (Supporting Evidence)
- Elevated alkaline phosphatase (ALP): The most consistent biochemistry abnormality; cortisol induces a liver-specific isoenzyme of ALP (glucocorticoid-induced ALP); values often 3 to 10 times the upper reference limit; highly sensitive but not specific for Cushing’s
- Elevated ALT: Mild to moderate elevation from steroid hepatopathy; less consistent than ALP
- Elevated cholesterol and triglycerides: Cortisol stimulates lipolysis and hepatic VLDL synthesis
- Mild stress leukogram: Mature neutrophilia, monocytosis, eosinopenia, lymphopenia from cortisol’s effects on white blood cell trafficking
- Low urine specific gravity (isosthenuria 1.007 to 1.015 or hyposthenuria below 1.007): Reflects ADH antagonism
- Urinary tract infection: Often subclinical (no clinical signs despite positive culture); a positive urine culture in a dog with PU/PD and other Cushing’s signs is strongly supportive
Specific Diagnostic Tests
| Test | Protocol | Interpretation | Use |
|---|---|---|---|
| Low-Dose Dexamethasone Suppression Test (LDDST) | Baseline cortisol sample; inject 0.01 mg/kg dexamethasone IV or IM; cortisol at 4 hours and 8 hours | Normal: 8-hour cortisol below 1.0 mcg/dL (below 28 nmol/L); Cushing’s: fails to suppress below this threshold. If 4-hour value suppresses but 8-hour does not: consistent with PDH (pituitary escapes suppression) | Best initial screening test; sensitivity approximately 85 to 95% for both PDH and ADH; low specificity (non-adrenal illness causes false positives) |
| ACTH Stimulation Test | Baseline cortisol; inject synthetic ACTH (cosyntropin 5 mcg/kg IV or IM, or 250 mcg/dog); post-ACTH cortisol at 1 hour | Normal: post-ACTH cortisol less than 18 to 20 mcg/dL; Cushing’s: exaggerated response above 20 mcg/dL. Adrenal crisis on trilostane: post-ACTH below 2 mcg/dL (dangerously low) | Preferred monitoring test for trilostane and mitotane treatment; sensitivity for Cushing’s screening only approximately 60 to 85%; less sensitive than LDDST for screening; essential for monitoring treatment |
| High-Dose Dexamethasone Suppression Test (HDDST) | Baseline cortisol; inject 0.1 mg/kg dexamethasone IV; cortisol at 4 and 8 hours | Suppression (below 50% of baseline) indicates PDH (pituitary adenoma retains some glucocorticoid sensitivity); no suppression consistent with ADH or some PDH cases | Differentiating PDH from ADH; approximately 75 to 80% sensitive for PDH; not used for initial screening |
| Urine Cortisol:Creatinine Ratio (UCCR) | Single morning urine sample collected at home (avoids stress-related cortisol elevation in the clinic); ratio calculated as urine cortisol (nmol/L) divided by urine creatinine (mmol/L) x 1,000 | Normal: less than 10 to 13 x 10^-6; elevated: suggestive of Cushing’s. High sensitivity (approximately 95%) but low specificity (many stressed or ill dogs have elevated UCCR); best for ruling OUT Cushing’s rather than ruling it in | Excellent screening tool; if UCCR is normal, Cushing’s is very unlikely; positive result requires confirmatory LDDST |
| Endogenous ACTH (eACTH) | Special handling required (chilled EDTA tube, centrifuge and freeze within 30 minutes, ship on dry ice); reference lab only | PDH: normal or elevated ACTH; ADH: suppressed ACTH (below 10 pg/mL) | Gold standard differentiating test; distinguishes PDH from ADH; requires strict pre-analytical handling or results are unreliable; not available at all practices |
| Abdominal ultrasound | Adrenal gland measurement; both adrenals measured (craniocaudal length, thickness); evaluate for masses, mineralization, vascular invasion | PDH: bilateral adrenomegaly (both glands enlarged, symmetric or nodular); ADH: one enlarged adrenal mass with contralateral atrophy | Critical differentiating and staging tool; required before adrenalectomy; identifies large tumors, vascular invasion, and regional metastasis; operator-dependent |
Treatment of Cushing’s Disease in Dogs
Trilostane (Vetoryl): Current First-Line Medical Treatment
Trilostane is a competitive inhibitor of the adrenal enzyme 3-beta-hydroxysteroid dehydrogenase, which is required early in the cortisol synthesis pathway (converting pregnenolone to progesterone). By blocking this enzyme, trilostane reduces synthesis of cortisol and, to a lesser extent, aldosterone and sex steroids from the adrenal cortex. Trilostane does not destroy adrenal tissue; it is reversible, so if a dog develops signs of hypoadrenocorticism (Addison-like crisis) on trilostane, stopping the drug allows cortisol synthesis to recover within hours to days. This reversibility is a key safety advantage over mitotane. Trilostane is licensed as Vetoryl in the United States, the EU, and most markets. Starting dose: 1 to 3 mg/kg orally once daily with food (food improves absorption and reduces gastrointestinal upset; the capsules should not be opened); some protocols use twice-daily dosing to avoid end-of-dose rebound effects.
Trilostane Monitoring Protocol
Monitoring with ACTH stimulation tests is mandatory for safe trilostane use. The goal is a post-ACTH cortisol between 2 and 5 mcg/dL (55 to 138 nmol/L) measured at the peak of drug effect (4 to 6 hours after the morning dose, given with food):
- Day 10 to 14: First ACTH stim test after starting; assess for over-suppression; adjust dose if post-ACTH cortisol is below 2 mcg/dL (increase interval or reduce dose) or clinical signs persist (post-ACTH above 5 mcg/dL may warrant dose increase, but clinical response also matters)
- Day 30: Repeat ACTH stim; reassess clinical signs (PU/PD, appetite, energy)
- Day 90: Repeat ACTH stim; if stable, continue current dose
- Every 3 to 6 months: Ongoing monitoring; a dog that was stable may experience reduced efficacy over time as adrenal glands compensate; periodic CBC, chemistry, blood pressure measurement
Mitotane (Lysodren, o,p’-DDD): Effective Alternative
Mitotane is a derivative of the insecticide DDT that selectively destroys the zona fasciculata and zona reticularis of the adrenal cortex (the cortisol-producing zones) while sparing the zona glomerulosa (aldosterone-producing) in most dogs at standard doses. Unlike trilostane, mitotane is adrenocorticolytic (it destroys adrenal tissue permanently at the treated cells), so its effects are not fully reversible. Treatment involves two phases. The induction phase uses 40 to 50 mg/kg/day (total daily dose) orally with food for 7 to 10 days or until the dog shows signs of cortisol deficiency (the treatment endpoint): the owner monitors water intake daily (a water intake below 60 mL/kg/day suggests adequate cortisol suppression) and watches for vomiting, diarrhea, depression, or anorexia (signs of over-suppression). An ACTH stimulation test is performed when these clinical endpoints are reached or after 10 days if endpoints have not been reached. Once induction is complete, maintenance dosing (approximately 50 mg/kg/week given in two or three divided doses) is started along with a physiological replacement dose of prednisone (0.2 mg/kg/day) to prevent hypoadrenocorticism. Mitotane monitoring follows a similar schedule to trilostane (repeat ACTH stim at 30 days, 90 days, then every 3 to 6 months).
Surgery (Adrenalectomy) for Adrenal-Dependent Cushing’s
Unilateral adrenalectomy is the treatment of choice for adrenal-dependent hyperadrenocorticism when the tumor is resectable (no evidence of vascular invasion of the caudal vena cava or aorta, no distant metastasis). Perioperative and postoperative management is complex: the contralateral atrophied adrenal gland cannot respond immediately to the cortisol deficit after the tumor is removed, so all dogs require perioperative and postoperative glucocorticoid and mineralocorticoid supplementation for weeks to months until the remaining adrenal gland recovers function. In experienced referral surgical centers, median survival times after successful adrenalectomy for adrenal adenoma are reported at greater than 2 years; adrenocarcinoma prognosis depends on tumor size and invasion. Medical management with trilostane is an alternative for dogs that are not surgical candidates.
Iatrogenic Cushing’s Disease
Iatrogenic (drug-induced) hyperadrenocorticism is caused by prolonged administration of exogenous glucocorticoids (prednisone, prednisolone, dexamethasone, methylprednisolone, or topical/ear preparations absorbed systemically). The clinical signs are identical to spontaneous Cushing’s disease. The ACTH stimulation test shows a flat or subnormal response (because the exogenous glucocorticoids suppress endogenous ACTH, causing both adrenal glands to atrophy). The LDDST will show suppression even at the low dose, distinguishing iatrogenic from spontaneous Cushing’s. Treatment is gradual tapering of the glucocorticoid under veterinary supervision; abrupt withdrawal can cause an Addisonian crisis because the atrophied adrenals cannot immediately resume normal cortisol production. Owners should always disclose all topical, ear, eye, and oral steroid medications to their veterinarian when Cushing’s is being investigated.
Cushing’s Disease and Concurrent Conditions
- Diabetes mellitus: Cortisol induces insulin resistance; approximately 10 percent of Cushing’s dogs develop concurrent diabetes mellitus. Treating the Cushing’s can dramatically improve or sometimes resolve the diabetes once cortisol levels normalize.
- Hypothyroidism: Cortisol suppresses thyroid hormone levels; do not diagnose hypothyroidism in a dog with active Cushing’s disease based on low total T4 alone, as this represents the “euthyroid sick syndrome” (non-thyroidal illness effect on thyroid hormones). Retest thyroid function after Cushing’s is well-controlled for several months.
- Hypertension: Present in 50 to 80 percent of Cushing’s dogs; measure blood pressure at each visit; treat with amlodipine (0.1 to 0.2 mg/kg orally once daily) when systolic pressure exceeds 160 mmHg persistently; often improves with Cushing’s treatment alone.
- Urinary tract infections: Very common; often subclinical; culture urine at baseline and periodically during treatment; treat with appropriate antibiotics based on culture and sensitivity results.
- Pulmonary thromboembolism (PTE): Cortisol excess promotes a hypercoagulable state; PTE presents as acute respiratory distress, tachypnea, or cyanosis and requires emergency intervention; some internal medicine specialists recommend low-dose aspirin (0.5 to 1 mg/kg every 24 hours) or clopidogrel as anticoagulant prophylaxis in high-risk cases, though evidence is limited.
Prognosis and Life Expectancy
With appropriate diagnosis and treatment, most dogs with pituitary-dependent Cushing’s disease can be managed well for 2 to 4 years or longer from diagnosis. Quality of life improves significantly once cortisol is controlled: PU/PD typically resolves within 4 to 8 weeks, panting reduces, energy returns, and coat may begin to regrow over 3 to 6 months. Median survival times reported in studies vary widely (approximately 30 months for PDH treated medically) but individual dogs often exceed these medians when owners are engaged and monitoring is consistent. The primary life-limiting factors in PDH are pituitary tumor growth (macroadenomas), concurrent diseases, complications such as PTE, and the natural age-related decline of an older dog. Adrenal adenoma treated with successful adrenalectomy carries an excellent prognosis; adrenocarcinoma prognosis is guarded and depends on whether metastasis has occurred at the time of surgery.
Age-Specific Considerations
Young Adults (Under 5 Years)
- Spontaneous Cushing’s disease under 5 years of age is uncommon; if present, consider adrenal-dependent disease or a large pituitary macroadenoma with aggressive behavior
- Iatrogenic Cushing’s from chronic steroid use for allergic or immune-mediated disease can occur at any age; always review steroid history before pursuing endocrine testing
- Young dogs with Cushing’s may have more years to live and are good candidates for aggressive workup and, if adrenal-dependent, surgical referral
- Breed predispositions in predisposed small breeds (Miniature Poodles, Yorkshire Terriers, Dachshunds) may begin showing subtle signs at 5 to 7 years; early recognition improves long-term outcomes
Middle-Aged Dogs (5 to 10 Years)
- This is the most common age group for PDH diagnosis; classic breed predispositions (Poodles, Dachshunds, Boxers, Beagles) in the 7 to 10 year range
- Gradual onset of PU/PD, polyphagia, pot belly, and bilateral alopecia in a middle-aged dog of a predisposed breed should prompt Cushing’s workup even if signs are mild, because early diagnosis and treatment prevents complications
- Concurrent hypothyroidism evaluation is common at this age; defer thyroid testing until Cushing’s is confirmed and under control to avoid the euthyroid sick syndrome misclassification
- Hypertension measurement at every exam is important; retinal damage (tortuous vessels, hemorrhage, retinal detachment) and renal damage are risks of poorly controlled or undiagnosed Cushing’s in this age group
Senior Dogs (Over 10 Years)
- Cushing’s disease in dogs over 10 years is very common; the slow progression may mean signs have been present for years before diagnosis; owners commonly present senior dogs with PU/PD as the chief complaint
- Treatment goals in senior dogs should emphasize quality of life and avoiding adverse effects; starting trilostane at the lower end of the dose range (1 mg/kg once daily) with conservative dose escalation reduces the risk of adrenal crisis
- Concurrent renal disease is common in senior dogs; cortisol elevation can mask mild azotemia (cortisol increases GFR); after Cushing’s treatment begins, some dogs show worsening BUN and creatinine as the GFR normalizes; monitor renal values closely in the first 4 to 8 weeks of treatment
- Pituitary macroadenoma with neurological signs (circling, head pressing, blindness, behavior change) in a senior dog requires referral to a veterinary neurologist or internist; radiation therapy (stereotactic radiosurgery) can extend survival in selected cases
US Cost Overview for Cushing’s Disease
| Item | Typical US Cost |
|---|---|
| Initial workup (exam, CBC, chemistry, urinalysis, urine culture) | $300 to $600 |
| LDDST or ACTH stimulation test | $200 to $400 |
| High-dose dexamethasone suppression test | $200 to $400 |
| Abdominal ultrasound | $300 to $600 |
| Endogenous ACTH (referral lab, special handling) | $100 to $200 |
| Trilostane (Vetoryl) per month (small dog, 10 mg capsules) | $80 to $150/month |
| Trilostane (Vetoryl) per month (large dog, 60 mg capsules) | $150 to $300/month |
| Mitotane (Lysodren) per month | $30 to $80/month |
| Monitoring ACTH stim test (every 3 to 6 months) | $150 to $300 each |
| Adrenalectomy (referral surgery, ADH) | $4,000 to $8,000+ |
| Blood pressure monitoring per visit | $20 to $60 |
Myths and Facts About Dog Cushing’s Disease
Cushing’s disease is a death sentence and there is nothing you can do about it.
Cushing’s disease is very manageable with appropriate medical treatment. Most dogs with pituitary-dependent disease treated with trilostane experience significant quality-of-life improvement and live an additional 2 to 4 or more years from diagnosis. The PU/PD resolves, panting decreases, energy returns, and many dogs resume normal activity levels. The disease is not curable with medical management but it is controllable, and many owners describe their dog’s transformation after treatment as remarkable. Early diagnosis before major complications (diabetes mellitus, PTE, significant muscle wasting) improves the prognosis further.
The pot-bellied look and increased drinking in my older dog are just normal parts of aging.
Neither a pot-bellied abdomen nor polyuria/polydipsia is a normal part of aging in dogs. Both are clinical signs that warrant investigation. A dog drinking significantly more than usual or needing to go outside at night to urinate (nocturia) has a medical problem: the differential diagnosis includes Cushing’s disease, diabetes mellitus, chronic kidney disease, diabetes insipidus, pyometra (intact females), liver disease, hypercalcemia, and primary polydipsia. A routine blood panel, urinalysis, and urine specific gravity measurement will help narrow the differential significantly. “Old dog” is not a diagnosis.
Once a dog starts Cushing’s medication, they will need it for life and the dose will never change.
The dose of trilostane or mitotane frequently needs adjustment over a dog’s course of treatment. The adrenal glands can compensate over time (particularly in PDH), requiring dose increases. Some dogs on once-daily trilostane develop end-of-dose rebound cortisol elevation (symptoms return in the late afternoon or evening) and benefit from switching to twice-daily dosing at a lower total daily amount. Conversely, dose reduction or treatment holiday may be needed if over-suppression occurs. Regular ACTH stimulation testing (every 3 to 6 months once stable) is the only reliable way to know whether the current dose is appropriate; clinical signs alone are insufficient to assess cortisol control.
Red Flags: Signs That Mean See a Vet Soon
- Any dog on trilostane or mitotane that shows sudden weakness, collapse, vomiting, or extreme lethargy: possible adrenal crisis (hypoadrenocorticism); stop the medication and seek emergency veterinary care immediately
- Sudden acute respiratory distress (labored breathing, tachypnea, cyanosis) in a dog with Cushing’s disease: possible pulmonary thromboembolism; emergency evaluation required
- Neurological signs in a dog with diagnosed or suspected Cushing’s disease: circling, head pressing, sudden blindness, behavior change, or seizures may indicate pituitary macroadenoma expansion; referral to a veterinary neurologist is urgent
- Middle-aged to older dog of a predisposed breed (Poodle, Dachshund, Boxer, Beagle) with pot-bellied abdomen, bilateral symmetric hair loss, increased thirst and urination, and constant panting: strongly suspect Cushing’s disease; schedule diagnostics without delay
- Dog on long-term steroids (prednisone, dexamethasone, topical ear or skin steroids) showing classic Cushing’s signs: iatrogenic hyperadrenocorticism; gradual steroid taper must be managed carefully to avoid Addisonian crisis
- Sudden vision change or eye abnormality (dilated non-responsive pupils, retinal hemorrhage visible) in a hypertensive Cushing’s dog: hypertensive retinopathy; immediate blood pressure measurement and antihypertensive treatment warranted
- Elevated blood glucose with PU/PD in a Cushing’s dog: concurrent diabetes mellitus developing; requires coordinated management of both conditions
Frequently Asked Questions About Dog Cushing’s Disease
How long can a dog live with Cushing’s disease?
With appropriate diagnosis and medical management, most dogs with pituitary-dependent Cushing’s disease live 2 to 4 years or more from the time of diagnosis. Published median survival times range from approximately 30 months (some studies) to longer in dogs with well-controlled disease and engaged owners. Individual dogs frequently exceed published medians. The key factors affecting longevity are: pituitary tumor size (macroadenomas carry worse prognosis), how early the disease is diagnosed before complications develop, how consistently monitoring and dose adjustments are performed, and whether serious complications like pulmonary thromboembolism or diabetes mellitus occur. Adrenal adenoma treated surgically carries an excellent prognosis of 2 or more years post-adrenalectomy.
What is the difference between Cushing’s disease and Addison’s disease in dogs?
Cushing’s disease (hyperadrenocorticism) involves excess cortisol, while Addison’s disease (hypoadrenocorticism) involves deficiency of cortisol and usually aldosterone. They are essentially opposite disorders of the adrenal cortex. Cushing’s presents gradually with PU/PD, polyphagia, pot belly, and skin changes; Addison’s typically presents as episodic or acute weakness, vomiting, and collapse (the “Addisonian crisis”). Ironically, the biggest overlap clinically is that both diseases can cause lethargy and gastrointestinal signs, and over-treatment of Cushing’s disease with trilostane or mitotane can cause iatrogenic Addison’s disease. Electrolytes (low sodium, high potassium in typical Addison’s) and hormonal testing (ACTH stim showing very low cortisol in Addison’s versus very high in Cushing’s) distinguish the two.
Can Cushing’s disease be cured without surgery?
Pituitary-dependent Cushing’s disease cannot be cured with medical management alone; trilostane and mitotane control cortisol levels but do not remove or destroy the pituitary adenoma. The pituitary tumor continues to grow (though slowly in most microadenoma cases), and medical treatment must continue for life. Pituitary-dependent Cushing’s in humans is treated surgically (transsphenoidal hypophysectomy), and this procedure is available at a small number of specialized veterinary neurology centers in the United States and Europe; it is potentially curative but technically demanding with significant perioperative risks and requires lifelong hormone replacement. Radiation therapy (stereotactic radiosurgery) can slow pituitary tumor growth and sometimes improve medical management outcomes. Adrenal-dependent Cushing’s caused by an adrenal adenoma is potentially cured by adrenalectomy.
Why does my Cushing’s dog drink so much water?
Excess cortisol directly antagonizes the action of antidiuretic hormone (ADH, also called vasopressin) at the renal collecting ducts. ADH normally signals the kidneys to reabsorb water from the forming urine back into the bloodstream, concentrating the urine. When cortisol blocks this signal, the kidneys fail to reabsorb water normally, resulting in large volumes of very dilute urine (polyuria). The dog then drinks more water to replace the lost fluid volume (compensatory polydipsia). This is why dogs with Cushing’s can produce enormous amounts of urine and need to go outside to urinate much more frequently, sometimes urgently at night. Once Cushing’s treatment normalizes cortisol levels, ADH function is restored, urine concentration returns to normal, and water intake decreases markedly within 4 to 8 weeks.
Is Cushing’s disease painful for dogs?
Cushing’s disease is generally not painful in the way that a broken bone or severe infection is painful, but it significantly degrades quality of life through muscle weakness, exercise intolerance, constant panting (which can be distressing), and fatigue. Calcinosis cutis (calcium deposits in the skin) can be painful and prone to secondary infection. Hypertension can cause ocular discomfort and headache-equivalent neurological pressure if severe. Dogs with pituitary macroadenomas may experience discomfort from tumor expansion. Uncontrolled Cushing’s causes progressive deterioration; treated dogs typically show clear improvement in energy, panting, and engagement with owners, which is a reliable indicator of subjective wellbeing.
Can I give my dog prednisone if it has Cushing’s disease?
Systemic corticosteroids (prednisone, dexamethasone, methylprednisolone) should be avoided in dogs with spontaneous Cushing’s disease because they add exogenous cortisol to an already cortisol-excess state, worsening every clinical sign and increasing the risk of complications including diabetes mellitus, opportunistic infections, pulmonary thromboembolism, and gastrointestinal ulceration. If a dog with Cushing’s requires treatment for a concurrent inflammatory condition (allergic skin disease, immune-mediated disease), non-steroidal alternatives should be used where possible (oclacitinib/Apoquel for pruritus, cyclosporine for immune-mediated disease in selected cases, lokivetmab/Cytopoint for allergic itch). If corticosteroids are truly necessary, use the lowest effective dose for the shortest possible time and monitor closely.
Does my dog need to fast before an ACTH stimulation test?
Fasting is not required for an ACTH stimulation test, though most veterinarians prefer a light meal rather than a full meal beforehand to reduce any lipemia that could affect hormone assay accuracy. More importantly, for monitoring trilostane treatment, the ACTH stimulation test should be performed 4 to 6 hours after the morning trilostane dose (given with food), because this timing represents the peak drug effect and gives the most clinically meaningful picture of cortisol suppression. If the test is performed at the wrong time relative to the dose, the result may not accurately reflect whether the dose is appropriate. Always give the trilostane as usual on the morning of a monitoring test and tell the veterinarian exactly what time the dose was given.
For more guides on keeping your dog healthy, browse all our Dog Health articles.
Explore Dog Health Articles