Veterinary Handbook - Canine Adrenal

VETERINARY HANDBOOK

CANINE ADRENAL

Canine Hyperadrenocorticism (HAC - Cushing's Disease)

Pituitary-dependent hyperadrenocorticism (PDH) occurs in about 80% of dogs with HAC. Adrenal-dependent hyperadrenocorticism (ADH) occurs in about 20% of dogs with HAC. Cortisol - Basal cortisol levels are of little value in diagnosing HAC as there is a lot of variation and overlap between healthy dogs. The Cortisol/Creatinine Ratio (CCR) is a very sensitive test to exclude HAC but must not be used to diagnose HAC as it is not specific and non-adrenal illness will give a positive result. A morning urine sample is collected and this reflects the cortisol release over several hours. Normal dogs will have a CCR less than 10 x 10-6.

Which test should be used to diagnose HAC reliably in the dog?

ACTH stimulation is the best screening test in the first instance and is the test of choice for differentiating iatrogenic Cushing's. It will reliably diagnose about 85% of PDH cases but only 50% of ADH cases. It is quick and simple to perform and is less affected by stress. The initial values are useful as a reference to monitor effectiveness of treatment. Low-dose Dexamethasone screening test is more reliable than the ACTH stimulation test in confirming HAC as all the results are diagnostic in ADH and about 95% for PDH. It is a much longer procedure and can be severely affected by stress.

ACTH Stimulation Test

1. Collect basal blood sample (between 9 am and 10 am if possible).

2. Immediately inject 0.25 mg synthetic ACTH (Synacthen, Alliance Pharmaceuticals) i/v or i/m

3. Collect a second blood sample one hour later.

4. Label samples clearly and request Cortisol analysis.

Interpretation
Normal dogs will show an increase in cortisol levels of up to 450 nmol/L post stimulation. An exaggerated response is expected in animals with PDH and cortisol concentrations rise above 600 nmol/L and often above 1000 nmol/L. Dogs with an adrenal tumour usually have basal cortisol above the 250 nmol/L with little or no change after stimulation. However the ACTH stimulation test is not as sensitive at detecting adrenal tumours and results which are not non-diagnostic should be confirmed with a low dose dexamethasone test (see over) especially in animals showing clinical signs of Cushing's Disease.

Low Dose Dexamethasone Screening Test (LDDT)

1. Collect a basal blood sample (between 9am and 10 am if possible)

2. Inject 0.01mg/kg i/v of Dexamethasone.

3. Collect two further blood samples 3 hours and 8 hours later

4. Label sample times clearly on the tubes and request cortisol.

Interpretation
Normal dogs will depress their cortisol concentrations by at least 50% at 3 hours and cortisol levels remain below about 40 nmol/L at 8 hours. Dogs with PDH will depress their cortisol levels at 3 hours but will "escape" at 8 hours and rise above 40 nmol/L. Dogs with an adrenal tumour will not depress by 50% at 3 hours and will remain above 40 nmol/L at 8 hours.

Baseline Cortisol(nmol/L)	100%	100%	100%
3 hour sample	>50%suppression	>50%suppression	<50%suppression
8 hour sample	<40 nmol/L	<40 nmol/L	>40 nmol/L
Interpretation	NORMAL	PDH	PDH or Adrenal Tumour

High Dose Dexamethasone Suppression Test (HDDT)

This test is used to distinguish between PDH and an adrenal tumour. It must only be used after a low dose dexamethasone test has confirmed Cushing's. We strongly suggest endogenous ACTH be used instead of the HDDT as it is less likely to be affected by environmental factors.

1. Collect a basal blood sample (between 9am and 10 am if possible)

2. Inject 0.1 - 1.0 mg/kg i/v of Dexamethasone.

3. Collect two further blood samples 3 hours and 8 hours later

4. Label sample times clearly on the tubes and request cortisol.

Interpretation

Baseline Cortisol(nmol/L)	100%	100%	100%	100%
3 hour sample	>50%suppression	>50%suppression	<50%suppression	<50%suppression
8 hour sample	>50%suppression	<50%suppression	>50%suppression	<50%suppression
Interpretation	PDH	PDH	PDH	Adrenal Tumour (*or PDH)

* Some PDH dogs will never suppress even with a HDDT

ACTH - Endogenous

Endogenous - ACTH may be used as a reliable assay to differentiate PDH and ADH but it should not be used as a single test in the first instance. Special sample handling procedures apply, see details below.

ACTH Sample Preparation - sample MUST be EDTA plasma

1. Take the blood sample into a cooled plastic (not glass!) EDTA tube kept on ice.

2. Mix well but gently and centrifuge as quickly as possible (ideally in a refrigerated centrifuge).

3. Transfer the plasma into a cooled plastic (not glass!) PLAIN tube kept on ice.

4 Immediately freeze (< -10°C) the plasma sample and keep frozen until dispatch in the transport pack.

5. Request a transport pack for delivery to the laboratory.

Urine Cortisol:Creatinine Ratio & Dexamethasone Suppression Test

When Cushing's disease is strongly suspected, this is a test that can be used when the dog is easily stressed as all the sampling is done at home by the owner and samples sent on to the lab together.

1. Day 1, collect a first morning urine sample.

2. Mix the urine and half fill Sample Tube 1, place in the fridge until dispatch.

3. Day 2, collect a first morning urine sample.

4. Mix the urine and half fill Sample Tube 2, place in the fridge until dispatch.

5. Immediately after urine collection, note the time and give the dog the required number of Dexamethasone tablets (dose = 0.1mg/kg).

6. 8 hours later give the dog the 2nd set of Dexamethasone tablets.

7. 16 hours later give the dog the 3rd set of Dexamethasone tablets.

8. Day 3, collect a first morning urine sample.

9. Mix the urine and half fill Sample Tube 3, place in the fridge until dispatch.

10. Send all 3 urine samples straight to the laboratory for UCCR test.

Interpretation
HAC is suspected if the UCCR is greater than 30 x 10-6 in two consecutive morning urine samples.

If the UCCR in the 3rd urine sample is depressed by 50% of the mean UCCR of the first two samples, PDH is the likely diagnosis.

If the suppression is less than 50%, an endogenous ACTH is suggested to confirm an adrenal tumour.

Normal dogs will have a UCCR less than 10 x 10-6. PDH or ADH dogs usually have a UCCR greater than 30 x 10-6.

Canine Hypoadrenocorticism - Addision's Disease

Addision's Disease - Primary hypoadrenocorticism results when more than 90% of both adrenal cortices are destroyed and this leads to a clinical deficiency of all adrenal hormones.

The ACTH stimulation test will provide confirmation of Addision's. It is also useful to measure the Sodium/Potassium ratio.

Interpretation
The basal cortisol will be low with little or no response after ACTH. A classic Addision's ACTH response test would be Pre cortisol = <20 nmol/L, Post cortisol = <20 nmol/L.

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