Endocrine disorders - The Adrenal Gland: Hyperadrenocorticism 'Cushings'

HPA axis

• Hypothalamic-Pituitary-Adrenal

• Cortisol goes around the body

Cushing’s Disease (HAC) (common in dogs > cats)

Can be:

• Pituitary dependant hyperadrenocorticism (PDH)

• Adrenal dependant hyperadrenocorticism (ADH)

• Iatrogenic hyperadrenocorticism

Pituitary dependant hyperadrenocorticism (PDH) is often due to a tumour ..

This tumour releases ATCH → leads to increased cortisol

Adrenal dependant hyperadrenocorticism (ADH)

Patient has too much cortisol

Iatrogenic hyperadrenocorticism

Something we’re given to the patient, for example, steroids

Predisposing factors for HAC - Pituitary

• Smaller breeds

• Middle aged-older animals

• more common (80-85%)

Predisposing factors for HAC - Adrenal

• Larger breeds

• Older animals

• Females > males

Clinical signs of HAC

• PU/PD/PP

• Pot-bellied appearance

• Muscle wasting and weakness

• Lethargy & panting

• Dermatological changes (calcinosis cutis)

• Alopecia - bilaterally symmetrical, normally on the trunk

Diagnosis of HAC - Haematology

• Stress leucogram (SMILED)

• Segmented neutrophils and Monocytes → Increased

• Lymphocytes and Eosinophils → Decreased

Diagnosis of HAC - Biochemistry

Raised ALP/ALKP +/- cholesterol and glucose

Diagnosis of HAC - Urinalysis

• SG <10.10 (low SG due to drinking lots)

• Elevated urine cortisol:creatinine ratio (UCCR) - screening test

Diagnosis of HAC - Imaging

• Ultrasonography - hepatomegaly, enlarged adrenal glands, neoplasia

• CT - smaller neoplastic lesions

Urine cortisol:creatinine ratio

• Penitents with cushings will have cortisol in their bloodstream and this is excreted in their urine

• A negative (or low) UCCR rules out cushings

• A positive (or high) results means the diagnosis remains a possibility

• Stress should be minimised during sampling (free catch at home in the morning is best)

ACTH stimulation test - HAC

This test has high specificity but variable sensitivity. This means a low likelihood of false positives but potential for false negatives - especially ADH.

1. Fasted blood sample for baseline cortisol

2. Inject synthetic ACTH IV

3. Repeat cortisol blood sample 1hr later

Low dose dexamethasone suppression test process

1. Blood sample for baseline cortisol

2. Inject 0.0mg/kg dex IV

3. Repeat cortisol blood sample 4hr and 8hr later

Low dose dexamethasone suppression test

• High sensitivity (means false negatives are rare), but lower specificity (means false positives are common)

• Given steroid will inhibit ADH and ACTH

• Lost negative feedback loop (adrenal) or in pituitary (have a negative feedback loop) can be used to determine which one it is so a tumour could be removed

Diagnostic tests - screening tests

• UCCR urine test

• ACTH stimulation test

• Low dose dexamethasone suppression test

Diagnostic tests - differentiating tests

• Low dose dexamethasone suppression test

• High dose dexamethasone suppression tests (rarely used)

High dose dexamethasone suppression test

• High-dose dexamethasone suppression (HDDS) is indicated for use in dogs already diagnosed as having hyperadrenocorticism where no suppression is seen on the LDDS at 4 and 8 hours.

• Suppression during an HDDS test, in dogs already diagnosed as having hyperadrenocorticism, is consistent with pituitary-dependent hyperadrenocorticism.

• Failure to suppress could occur with both pituitary-dependent or adrenal-dependent hyperadrenocorticism and further diagnostics would be necessary to differentiate (e.g. abdominal ultrasound).

High dose dexamethasone suppression test - protocol

• Collect a baseline blood sample (1-2 ml in a plain/gel tube). o Inject 0.1 mg/kg of dexamethasone intravenously, via IV catheter.

• Collect the second blood sample (1-2 ml in a plain/gel tube) 4 hrs post-injection.

• Collect the third blood sample (1-2 ml in a plain/gel tube) 8 hrs post-injection.

• Ensure the samples have clotted and centrifuge the samples 30-120 minutes after collection.

• For samples collected in plain tubes, please separate the serum into another plain tube (this step is not necessary for samples collected in gel tubes).

• Please label all tubes with the patient’s name and the time of sampling.

• Please include the patient history, including drug history, on the request form.

• Submit the separated serum samples and the request form to the reference laboratory (Test code DEXH).

• Cortisol will be measured in all three samples.

Medical treatment of HAC

• Tristan (vetoryl)

• Regular ACTH stimulation/biochemistry/lytes at 10d/4w/12w

• Can use pre-vetoryl cortisol

• Can do a blood sample pre-administration to gain baseline

Surgical treatment of HAC

• Adrenalectomy

• Hypophysectomy

Triolstane

• Antagonist of the enzymes involved in cortisol production - blocks the production

• This lowers cortisol levels which resolves clinical signs in the patient - polyphagia, polyuria/polydipsia will be relatively quickly, coat changes will take months

Trolstane - pharmacology

• Pharmacokinetics variable so dose needs to be tailored to the individual - based on weight

• Administered orally and presence of food enhances bioavailability - should be given with food

• Risk of iatrogenic hypoadrenocorticism if overdosed - can be more prevalent in smaller patients due to tablet sizes - cannot get smaller sizes or be split in half

Nursing care of the cushingoid patient

• Minimise stress during procedures (increase cortisol)

• Ensure water availability (PD) - can become dehydrated quicker than a normal patient would

• Regular toileting opportunities (PU)

• Care with venepuncture

• Owner support and education