Cushing's Disease vs. PLE in Dogs: How to Tell Them Apart
Last reviewed: April 2026
Same symptom. Opposite bloodwork.
Cushing's disease
Very high ALP · normal albumin · pot belly from muscle loss + fat redistribution
PLE
Low albumin + low total protein · normal ALP · pot belly from fluid accumulation
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Check My Dog's ResultsA pot-bellied dog who's losing muscle, drinking more, and has abnormal bloodwork is a familiar scenario at the vet. Two of the most common culprits — Cushing's disease and protein-losing enteropathy (PLE) — can look eerily similar from the outside. But their bloodwork, causes, and treatments are completely different.
Why These Two Get Confused
Both conditions can cause a pot-bellied appearance in dogs, and both primarily affect middle-aged to older dogs. That's often enough to put both on the differential list. The confusion deepens because some symptom overlap is real:
- • Both can cause muscle wasting and a generally unwell appearance
- • Both can cause lethargy and reduced activity
- • Both can cause some degree of weight change
- • Both can cause GI symptoms (though far more prominently in PLE)
- • Both can mildly affect albumin (Cushing's through cortisol-driven protein catabolism; PLE through intestinal leakage)
The key is that while the symptoms overlap at the surface level, the mechanisms and bloodwork patterns are opposite. Once you know what to look for, the two are usually distinguishable from routine bloodwork alone — before any specialized testing.
The Pot Belly: Two Very Different Causes
Cushing's pot belly
- • Excess cortisol breaks down abdominal muscles (body wall weakens)
- • Fat redistributes toward the abdomen
- • Liver enlarges (hepatomegaly) from steroid effect
- • Result: firm, pendulous belly — but no fluid inside
PLE pot belly
- • Low albumin can't hold fluid inside blood vessels
- • Fluid leaks into the abdominal cavity (ascites)
- • Result: distended belly that feels fluid-filled
- • A "fluid wave" can often be felt when the belly is tapped
An ultrasound immediately separates these: free abdominal fluid is visible in PLE ascites. A Cushing's belly shows no free fluid — just an enlarged liver and reduced muscle mass.
See Which Condition Your Dog's Bloodwork Points To
Upload your dog's chemistry panel and CBC to see ALP, albumin, total protein, and cholesterol in context — and know which condition fits the pattern.
Analyze My Dog's ResultsBloodwork Comparison: Cushing's vs. PLE
This is where the two conditions diverge clearly. Routine bloodwork — a standard chemistry panel and CBC — is usually enough to point strongly in one direction or the other.
| Bloodwork Value | Cushing's Disease | PLE |
|---|---|---|
| ALP | Very high (often 5–10× normal) | Normal |
| ALT | Mildly elevated (steroid hepatopathy) | Normal |
| Albumin | Normal or mildly low | Low — often below 2.0 g/dL |
| Total protein | Normal | Low (pan-hypoproteinemia) |
| Globulin | Normal or high | Low (key distinguishing clue) |
| Cholesterol | High | Low (especially in lymphangiectasia) |
| Blood glucose | High or borderline (cortisol is anti-insulin) | Normal |
| Urine specific gravity | Dilute (low — cortisol interferes with ADH) | Normal |
| Urine protein (UPC) | Variable (can be elevated) | Normal (protein lost via gut, not kidneys) |
| Stress leukogram (CBC) | Classic — high WBC, high neutrophils, low lymphocytes | Variable; may be normal |
ALP (alkaline phosphatase)
Albumin
Total protein & globulin
Cholesterol
Blood glucose & urine
Symptom Comparison
| Symptom | Cushing's Disease | PLE |
|---|---|---|
| Pot belly | Yes — muscle wasting + fat redistribution (firm) | Yes — ascites/fluid (fluid-filled, sloshy) |
| Increased thirst / urination | Very common — often the first symptom | Not typical |
| Increased appetite | Common (polyphagia) | Often decreased or absent |
| Weight change | Variable — may gain or redistribute weight | Weight loss despite eating (protein wasting) |
| Diarrhea / vomiting | Occasional, not a primary feature | Common — often chronic |
| Skin / coat changes | Hair loss, thin skin, comedones | Not typical |
| Leg / face swelling | Not typical | Can occur from edema |
| Onset speed | Gradual — develops over months to years | Variable — can be sudden or gradual |
Strongly suggests Cushing's:
- • Excessive thirst and urination
- • Ravenous appetite
- • Hair loss (body, not face or legs)
- • Thin, fragile skin
- • Firm pot belly without GI symptoms
Strongly suggests PLE:
- • Chronic diarrhea or vomiting
- • Weight loss despite eating
- • Fluid-filled pot belly (ascites)
- • Difficulty breathing (pleural effusion)
- • Swollen legs or face
The Fastest Way to Tell Them Apart on Bloodwork
If you have routine bloodwork results in hand, these three values give you the clearest signal:
1. Check ALP
ALP 5–10× normal in an older dog with a pot belly, thirst, and hair loss? Cushing's is at the top of the list. ALP is normal? Cushing's becomes much less likely — look elsewhere.
2. Check albumin and total protein
Low albumin (below 2.0 g/dL) with low total protein? PLE — or kidney protein loss — should be investigated. Normal albumin? PLE is unlikely to be the primary problem.
3. Check globulin
Both albumin AND globulin low? This pan-hypoproteinemia strongly points to intestinal protein loss (PLE) rather than kidney loss. Albumin low but globulin normal or high? Kidney disease or liver disease moves higher on the list.
What if both ALP is high and albumin is low?
This combination is uncommon and warrants careful investigation. Possible explanations include: severe liver disease (the liver fails to make albumin and also leaks ALP), concurrent Cushing's and PLE (rare), or Cushing's with cortisol-driven protein catabolism (albumin rarely drops dramatically from this alone).
A dramatically low albumin — below 1.5 g/dL — is not explained by Cushing's alone. That level of protein loss requires intestinal or kidney evaluation.
How Each Condition Is Confirmed
Routine bloodwork raises suspicion. These are the specialized tests that confirm each diagnosis:
Confirming Cushing's
- • LDDS test — most common; cortisol should suppress after dexamethasone but doesn't in Cushing's
- • ACTH stimulation test — measures cortisol response; also used to monitor treatment
- • Urine cortisol:creatinine ratio — good screening tool; high sensitivity
- • Abdominal ultrasound — checks for adrenal tumors (pituitary vs. adrenal-dependent Cushing's)
Confirming PLE
- • Urine protein:creatinine (UPC) — normal UPC rules out kidney protein loss; confirms gut origin
- • Fecal alpha-1 protease inhibitor — directly measures intestinal protein loss
- • Abdominal ultrasound — looks for intestinal wall thickening, ascites, lymph node changes
- • Endoscopy + intestinal biopsy — required to distinguish IBD from lymphangiectasia from lymphoma
Treatment: Completely Different Paths
This is why the distinction matters clinically. Treating for the wrong condition doesn't just fail to help — it can cause harm:
Cushing's treatment
- • Trilostane (Vetoryl) — blocks cortisol production; most commonly used
- • Mitotane (Lysodren) — destroys cortisol-producing adrenal cells
- • Surgery — for adrenal tumors, if the dog is a good candidate
- • Requires lifelong monitoring with ACTH stim tests
PLE treatment
- • Immunosuppressants (prednisone, budesonide) — for IBD-driven PLE
- • Ultra-low-fat diet — essential for lymphangiectasia
- • Chemotherapy — for GI lymphoma
- • B12 supplementation, diuretics for fluid management
Note: Using immunosuppressants (prednisone) in a dog with undiagnosed Cushing's can be dangerous — cortisol is already elevated, and adding steroids can precipitate a crisis. Always confirm the diagnosis before starting treatment.
Key Takeaway
A pot-bellied dog with abnormal bloodwork needs to have the right value identified before any treatment starts. High ALP points to Cushing's. Low albumin with low globulin points to PLE. These conditions have opposite bloodwork patterns, opposite mechanisms, and completely different treatments.
When in doubt: check albumin, globulin, ALP, cholesterol, and a urine sample. Those five data points will almost always tell you which way the workup should go.
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- ✓ Whether ALP, albumin, and protein point toward Cushing's or PLE
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Frequently Asked Questions
Can Cushing's disease cause a pot belly in dogs?
Yes. Cushing's causes a pot-bellied appearance through muscle wasting along the body wall, fat redistribution toward the abdomen, and liver enlargement. The belly feels firm, not fluid-filled — unlike the ascites seen in PLE.
What is the key bloodwork difference between Cushing's and PLE?
The clearest single difference: Cushing's causes very high ALP (often 5–10× normal) with normal albumin. PLE causes very low albumin and low total protein, with normal ALP. If ALP is high and albumin is normal, Cushing's is far more likely. If albumin is significantly low, PLE moves to the top.
Does Cushing's disease affect albumin levels?
Mildly, yes — excess cortisol promotes protein breakdown, which can nudge albumin slightly downward. But Cushing's alone doesn't cause dramatically low albumin (below 1.5–2.0 g/dL). A severely low albumin level requires investigation for PLE or kidney protein loss.
Can a dog have both Cushing's and PLE at the same time?
Yes, though uncommon. Soft-Coated Wheaten Terriers are predisposed to both. When both are present, bloodwork may show high ALP alongside low albumin — a combination that's unusual for either condition alone and warrants careful workup for both.
My dog has high ALP and low albumin — which is it?
Both markers being abnormal is unusual. This pattern suggests either two concurrent diseases, severe liver disease (the liver fails to make albumin and leaks ALP), or Cushing's with an unrelated cause of protein loss. Don't assume one diagnosis — your vet should investigate both with specific hormone testing and urine protein evaluation.
Which is more urgent — Cushing's or PLE?
PLE with severely low albumin (below 1.5 g/dL) can be acutely dangerous — blood clots and respiratory distress from pleural effusion are serious risks. Cushing's develops slowly and is rarely an emergency. Both require prompt veterinary attention, but severe PLE is the more time-sensitive condition.
Is the pot belly in Cushing's the same as in PLE?
No — they look similar from the outside but differ internally. Cushing's belly is firm (muscle wasting + fat + liver enlargement). PLE belly is fluid-filled (ascites from low albumin — it may feel sloshy when tapped). An ultrasound immediately distinguishes the two.
What tests tell Cushing's and PLE apart?
Routine bloodwork provides the first clues (ALP vs. albumin). Confirming Cushing's requires a hormone test: LDDS, ACTH stimulation, or urine cortisol:creatinine ratio. Confirming PLE requires ruling out kidney loss with a urine protein:creatinine ratio, then finding the gut cause with fecal testing, ultrasound, and intestinal biopsy.