Episode 20 - Endocrinopathies II - Hyperadrenocorticism, 'the stuff you never really understood about Cushing’s'

1.The GP hook

A GP-friendly walk-through of canine Cushing’s that joins the dots from cortisol physiology to everyday decisions in consults. Expect practical testing tips, monitoring that actually helps, and a few “ah, that’s why!” moments.

A GP-friendly walk-through of canine Cushing’s that joins the dots from cortisol physiology to everyday decisions in consults. Expect practical testing tips, monitoring that actually helps, and a few “ah — that’s why!” moments.

You know the consult: a cheerful, pot‑bellied oldie waddles in, the owner shrugs “she’s fine, just thirsty,” and you quietly suspect hyperadrenocorticism. This article ties the physiology to the signs you see, which tests to pick (and when), practical monitoring approaches if you start medical therapy, and the owner conversations that win consent.

2.Cortisol’s prime directive — and why Cushing’s looks like it does

Think of cortisol as a survival hormone with one main job: make sure the brain has glucose in a crisis (stress, trauma, starvation, bleeding). Once you view the clinical picture through that lens, many Cushingoid features fall into place.

Quick check (stress leukogram)

Not Much Eats Leopards — Neutrophils & Monocytes up; Eosinophils & Lymphocytes down.

Absence of a stress leukogram in a systemically unwell dog should make you consider hypoadrenocorticism.

• Polyphagia — an immediate way to get glucose into the body.
• Muscle wasting and pot‑belly — cortisol promotes proteolysis (muscle → gluconeogenesis). It also promotes lipolysis so peripheral tissues can burn fatty acids and spare glucose for the brain. When there’s no real starvation, that circulating energy gets re‑stored as fat, producing the classic redistribution and abdominal enlargement.
• Hepatomegaly with high ALP but often normal ALT — glycogen‑filled hepatocytes (vacuolar change) plus a species‑specific steroid effect on ALP.
• Insulin resistance and diabetes — muscle insulin resistance preserves glucose for the brain; this explains why diabetic control can be very difficult until the Cushing’s is managed.
• Hypertension and proteinuria — cortisol increases vascular sensitivity to catecholamines; systemic and glomerular hypertension can follow and drive protein loss.
• Skin, hair and immunity changes — hair follicle activity and epidermal turnover are deprioritised in a “survival” state, giving truncal alopecia, thin skin and susceptibility to low‑grade infections (pyoderma, demodicosis, bacteriuria).
• Hypercoagulability — increased clotting factors plus loss of natural anticoagulants (e.g. with protein‑losing nephropathy) raises thrombotic risk.

3.The five “P”s (plus a pant)

Common trap: don’t test for Cushing’s in a dog without true PUPD. Ask about night‑time toilet trips and unexpected water bowl refills — owners often under‑report.

• Polyphagia — central appetite drive to feed the brain.
• Pot‑belly — muscle catabolism + fat redistribution + hepatomegaly from glycogen.
• Panting — increased metabolic heat and insulation from fat (also seen after high‑dose steroids).
• Polyuria/Polydipsia (PUPD) — cortisol antagonises ADH/vasopressin, producing dilute urine and thirst.
• (Bonus) Panting — commonly reported and can be striking.

4.First‑line tests GPs use (what they tell you)

What to send routinely

Rule‑out and rule‑in tests

Monday‑morning move: if you’re on the fence, use UCCR first in a well dog — it’s non‑invasive and can save cost if normal.

• Haematology: often a mild stress leukogram (see mnemonic).
• Biochemistry: high ALP is common (sometimes very high), hypercholesterolaemia and hypertriglyceridaemia; lipaemic samples can interfere with analysers.
• Urinalysis: dilute urine is typical; check sediment and UPC.
• Urine cortisol:creatinine ratio (UCCR)
• Great as a rule‑out in a well dog: a normal UCCR makes Cushing’s unlikely.
• A raised UCCR is nonspecific (many conditions and stressed dogs can raise it). Use a raised result to justify definitive testing rather than as a diagnosis on its own.
• Low‑dose dexamethasone suppression test (LDDST)
• Useful for diagnosis. Dexamethasone should suppress pituitary drive in normal dogs; failure to suppress or “escape” suggests endogenous Cushing’s. The suppression pattern can give clues toward pituitary vs adrenal disease.
• ACTH stimulation test
• Useful to assess if the adrenal cortex can respond (also used in hypoadrenocorticism assessment). An exaggerated post‑ACTH cortisol supports Cushing’s in many cases but it’s not 100% sensitive.
• Endogenous ACTH measurement
• In theory useful to differentiate pituitary (high ACTH) vs adrenal tumour (low ACTH), but pre‑analytic handling and frequent intermediate (“grey zone”) results limit utility for many practices.

5.Pituitary vs adrenal — imaging and decision points

Practice move: discuss the “fork in the road” early — is the owner prepared for imaging and the possibility of surgery, or would they prefer a trial of medical control with realistic expectations?

• LDDST patterns and clinical context help, but they’re not definitive.
• Complete failure to suppress at 4 and 8 hours may be adrenal or pituitary — look at dog size/breed and the overall picture. Large breeds with full non‑suppression should raise adrenal tumour suspicion earlier.
• Imaging: abdominal ultrasound can detect adrenal lesions but glands are often tricky (right gland especially). CT gives clearer detail and helps staging for referral/surgery.

6.Treatment and monitoring that work in practice

Medical mainstay

Monitoring — gold standard vs pragmatism

Home metrics that help

Bacteriuria and antibiotics

Proteinuria and clot risk

Owner safety net: Addisonian red flags on trilostane

Practical owner conversation

“Quality of life sells treatment. House‑soiling, loud panting, restless nights and limited walks add up. Framing treatment as a win for both dog and household helps owners commit to testing and monitoring.”

• Trilostane is the commonly used medical option. Check your chosen product’s data sheet for licensed indications, dosing guidance and monitoring recommendations. (Do not rely on a remembered dose — always check the current UK datasheet.)
• Data sheets typically recommend baseline labs and scheduled biochemical and ACTH stimulation checks after starting treatment and after dose changes. In real clinics cost, access to ACTH and owner factors mean you may need to adapt the schedule — be transparent with owners about what is ideal versus what is feasible.
• Where ACTH stimulation is difficult or costly, many clinicians use pragmatic alternatives: pre‑dose (trough) cortisol measurements or careful clinical monitoring coupled with owner‑recorded metrics.
• Important parameters to follow: clinical signs (especially PUPD and activity), blood pressure, UPC (proteinuria), and biochemistry (including electrolytes if concerned).
• 24‑hour water intake trendlines are simple and motivating for owners. For single‑dog households this is an easy, actionable monitoring tool and often shows improvement before lab results do.
• Asymptomatic bacteriuria is common in Cushingoid dogs. If there are no lower urinary tract signs and the sediment shows no active inflammation, consider watchful waiting and re‑checking rather than reflexive antibiotics. If glucose is present (concurrent diabetes) or the dog develops signs, treat appropriately.
• Significant proteinuria (protein‑losing nephropathy) increases thrombotic risk (loss of antithrombin III, plus hypercoagulable state from cortisol effects). Consider antithrombotic therapy (e.g. clopidogrel) on a case‑by‑case basis — discuss risks/benefits with owners and re‑evaluate as proteinuria resolves. Avoid antithrombotics if there is thrombocytopenia or clear bleeding risk.
• If any of the following occur — inappetence, vomiting, diarrhoea or marked lethargy — advise owners to stop trilostane and seek veterinary assessment promptly. These can be signs of over‑suppression (hypoadrenocorticism) and need urgent evaluation.
• If you’re highly concerned while awaiting tests, some clinicians will give a short course of physiological‑dose glucocorticoid pending confirmation — document and communicate this clearly.

7.A practical pathway you can use this week

Clinical pearl

Demodex loves quiet follicles — think demodicosis in Cushingoid dogs presenting with podal or periocular lesions.

Common trap

Positive urine culture, no signs — asymptomatic bacteriuria is frequent. Without dysuria, haematuria, or an active sediment, consider delaying antibiotics and re‑assessing.

• Suspect Cushing’s when the 5 Ps cluster and the dog is otherwise reasonably well.
• Baseline: CBC, biochemistry, urinalysis (sediment and UPC). Expect stress leukogram, high ALP (often), lipaemia.
• If unsure: UCCR as a low‑cost rule‑out.
• If UCCR or clinical suspicion points toward Cushing’s: choose LDDST or ACTH stimulation based on local logistics and the clinical question; use one test and interpret it alongside history and routine labs.
• If adrenal tumour suspected: discuss imaging options, surgical referral and realistic expectations about medical control versus surgery.
• If starting trilostane: follow the product data sheet for licensed monitoring; where needed, use pragmatic monitoring (clinical signs, water log, blood pressure, UPC, and pre‑dose cortisol) and maintain a clear safety net for Addisonian signs.

8.Take‑home points

Cushing’s stops being a fuzzy “pot belly and panting” diagnosis when you remember what cortisol is trying to do. Once that clicks, your test choices tighten up, your monitoring becomes meaningful and your owner conversations get a lot easier.

• Most Cushingoid signs make sense when you remember cortisol’s role: secure brain glucose and maintain perfusion.
• Genuine PUPD matters. Don’t chase Cushing’s in dogs without real PUPD.
• UCCR is a useful non‑invasive rule‑out; a raised result needs confirmatory testing.
• LDDST and ACTH stimulation both have roles — choose based on the clinical question and practice context.
• Trilostane is the main medical option — always follow current data sheets and adapt monitoring pragmatically with owner agreement.
• Monitor blood pressure, UPC and clinical signs; treat bacteriuria based on signs and sediment, not culture alone.
• Owner education on Addisonian red flags (stop therapy and seek help) is essential.