PATHOLOGY - Hyperadrenocorticism Flashcards
What are the two classifications of hyperadrenocoticism?
Iatrogenic hyperadrenocorticism
Spontaneous hyperadrenocorticism
What are the two classifications of spontaneous hyperadrenocorticism?
Pituitary dependent hyperadrenocorticism
Adrenal dependent hyperadrenocorticism
Which classification of spontaenous hyperadrenocorticism is most common?
Pituitary dependent hyperadrenocorticism
What causes pituitary dependent hyperadrenocorticism?
Pituitary tumour
What is the pathophysiology of pituitary dependent hyperadrenocortocism?
Anterior pituitary gland tumours lead to excessive adrenocorticotropic hormone (ACTH) production which will stimulate excessive cortisol production in the adrenal glands, causing hyperadrenocorticism. Usually, there is a negative feedback mechanism where ACTH production will decrease in response to increased cortisol, however, the pituitary tumour will override this normal negative feedback and continue to produce ACTH which will continue to stimulate cortisol production
What causes adrenal dependent hyperadrenocorticism?
Adrenal tumour
What is the pathophysiology of adrenal dependent hyperadrenocortocism?
Adrenal tumours lead to excessive cortisol production, causing hyperadrenocorticism. For healthy adrenal glands, when blood cortisol levels are high, the anterior pituitary gland will release less adrenocorticotropic hormone (ACTH) which will reduce stimulation of the adrenal glands and thus decrease cortisol production. However, in adrenal cortical hyperfunction, the affected adrenal gland with functional neoplasia will override normal negative feedback mechanisms and continue producing cortisol
What are the effects of excessive cortisol production?
Excessive cortisol causes inhibition of antidiuretic hormone (ADH) (only in dogs), inhibition of insulin, alopecia, immune supression which makes the animal more susceptible to secondary infection, increases protein catabolsim causing muscle wasting, increased appetite and increased glycogen metabolism in the liver causing vacuolar hepatopathy
Which dog breeds are particularly prone to hyperadrenocorticism?
Bichon Frise
Poodle
Yorkshire Terrier
Why do older dogs more commonly present with hyperadrenocorticism?
Older dogs more commonly present with hyperadrenocorticism as older dogs are more prone to neoplasia
What is a very important history question to ask if you suspect a patient has hyperadrenocorticism?
Ask the owner if the animal is being treating with steroids to determine if this is an iatrogenic hyperadrenocorticism or spontaneous hyperadrenocorticism
What are the clinical signs of hyperadrenocorticism?
PUPD
Dermatological changes
Abdominal distension
Polyphagia
Lethargy
Respiratory signs
Muscle weakness
Obesity
Poor wound healing
Reproductive abnormalities
Neurological signs
Myotonia
Diabetes (almost ALWAYS in cats, not so common in dogs)
How does hyperadrenocorticism cause PUPD?
Hyperadrenocorticism inhibits antidiuretic hormone (ADH), thus preventing the urine from concentrating at the level of the collecting duct, resulting in hyposthenuria. This results in excessive loss of water into the urine
Which dermatological changes can be seen with hyperadrenocorticism?
Symmetric, non-pruritic alopecia
Skin thinning
Comedones
Calcinosis cutis
Recurrent pyoderma
Loss of skin elasticity
How does skin thinning due to hyperadrenocorticism present in cats?
In cats with hyperadrenocorticism, their skin becomes so thin and fragile that it can spontaneously tear
What is calcinosis cutis?
Calcinosis cutis is a condition in which calcium salts are deposited in the skin and subcutaneous tissue
What causes the abdominal distension seen in hyperadrenocorticism?
Fat redistribution
Muscle weakness due to protein catabolsim
Vacuolar hepatopathy
What are some of the reproductive abnormalities that can be seen in animals with hyperadrenocorticism?
Anoestrus
Small, soft testicles
Pendulous prepuce
Penis will be smaller
What is myotonia?
Myotonia is a condition in which the muscles cannot relax after they contract
What are the typical findings on biochemistry in a patient with hyperadrenocorticism?
Increased alkaline phosphatase (ALP)
Hypercholesterolaemia
Hypertriglyceridemia
Hyperglycaemia (not usually at the renal threshold unless concurrent diabetes)
Increased ALT, AST and GGT
Increased bile salts
Decreased urea
Decreased creatinine
Why do patients with hyperadrenocorticism have increased ALT, AST and GGT?
Hyperadrenocorticism will cause a steroid-induced vacuolar hepatopathy which will cause an increase in ALT, AST and GGT
What are the typical findings on haematology in a patient with hyperadrenocorticism?
Stress leukogram
What are the features of a stress leukogram?
Erythrocytosis
Mature neutrophilia
Lymphopenia
Eosinopenia
Monocytosis
What are the typical findings on urinalysis in a patient with hyperadrenocorticism?
Low urine specific gravity (USG)
Proteinuria
Evidence of UTI
Glucosuria (if has concurrent diabetes mellitus)
Why do hyperadrenocorticism patients often have proteuria?
Hyperadrenocorticism can cause hypertension which will increase the hydrostatic pressure in the glomeruli resulting in increased leakage of proteins into the ultrafiltrate and into the urine
Why are hyperadrenocorticism patients at an increased risk of urinary tract infections (UTIs)?
Hyperadrenocorticism causes immunosuppression as well as muscle weakness - including the detrusor muscle - which can result in incomplete emptying of the bladder, which allows bacteria to remain in the urinary tract for longer periods of time
How can hyperadrenocorticism appear on radiography?
Pot-belly appearance
Excess fat
Hepatomegaly
Bladder may be half full (not able to fully empty the bladder due to muscle weakness)
Which diagnostic tests can be done to confirm a diagnosis of hyperadrenocorticism?
ACTH stimulation test
Low dose dexamethasone suppression test
How do you carry out an ACTH stimulation test?
- Take a blood sample of basal cortisol levels
- Administer 0.2mg of ACTH IV or IM
- Take a second blood sample for cortisol levels 0.5 - 2 hours later
How do you interpret an ACTH stimulation test?
An increase in serum cortisol following ACTH adminstration is expected (usually up to 400nmol/L), however an excessive increase in serum cortisol *(usually over 600nmol/L) is indicative of enlargement of the adrenal glands in response to excessive ACTH stimulation and thus spontaneous hyperadrenocorticism. If the serum cortisol levels do not increase in response to ACTH, this indicates iatrogenic hyperadrenocorticism as steroids are being provided iatrogenically which causes the adrenal glands to atrophy due to loss of function and thus they will not respond adequately to ACTH stimulation
Rewatch lecture if confused
How do you carry out a low dose dexamethasone suppression test?
- Take a blood sample of basal cortisol levels
- Administer 0.015 mg/kg of dexamethasone IV
- Take another blood sample to measure cortisol levels 3 and 8 hours later
How do you interpret a low dose dexamethasone suppression test?
Administration of dexamethasone should usually suppress ACTH secretion and thus cortisol secretion for up to 8 hours. If cortisol secretion is suppressed at 3 hours but begins to increase at 8 hours, this indicates pituitary mediated hyperadrenocorticism. If cortisol is not suppressed at all this can be indicative of pituitary or adrenal mediated hyperadrenocorticism
(T/F) The ACTH stimulation test is more sensitive for hyperadrenocorticism than the low dose dexamethasone suppression test
FALSE. The ACTH stimulation test is not as sensitive as the low dose dexamethasone suppression test, so there will be less false positives with the ACTH stimulation test
Which diagnostic tests can be done if a patient tests negative for both the ACTH stimulation test and the low dose dexamethasone suppression test but still appears to have hyperadrenocorticism?
17 hydroxyprogesterone test
Urine corticoid : creatinine ratio
Which diagnostic tests can you do to differentiate between pituitary and adrenal mediated hyperadrenocorticism?
ACTH assay
Diagnostic imaging
How does an ACTH assay differentiate between pituitary and adrenal mediated hyperadrenocorticism?
High ACTH levels on an ACTH levels is indicative of pituitary mediated hyperadrenocorticism, however, low ACTH levels is indicative of adrenal mediated hyperadrenocorticism
How can diagnostic imaging be used to differentiate pituitary and adrenal mediated hyperadrenocorticism?
Radiography and ultrasound can be used to identify adrenal tumours and CT and MRI can be used to identify pituitary tumours
What is the main treatment option for pituitary dependent hyperadrenocorticism?
Trilostane
What are some of the other treatment options for pituitary dependent hyperadrenocorticism?
Mitocane
Ketocanozole
Hypophysectomy
What is a hypophysectomy?
A hypophysectomy is a surgical procedure used to remove a tumour of the pituitary gland
Specialist neurological surgery
What are the main treatment options for adrenal dependent hyperadrenocorticism?
Trilostane
Unilateral adrenalectomy
What is the mechanism of action of trilostane?
Trilostane is a steroid enzyme inhibitor which inhibits the enzyme 3-β-hydroxysteroid dehydrogenase within the adrenal cortex to reduce the synthesis of cortisol in the adrenal glands
What is the starting dose for trilostane?
2mg/kg oral trilostane every 24 hours
How should you alter trilostane adminstration if the clinical signs are not improving?
If there is no improvement in your patient within one month you should increase the dose of trilostane and/or consider twice daily dosing
What are the potential side effects of trilostane?
Electrolyte abnormalities
Diarrhoea
Lethargy
Anorexia
Vomiting
Hypoadrenocorticism
Which factors should you have owners monitor and report back to you when treating a patient with trilostane?
Get owners to monitor for improvements in clinical signs in response to the trilostane (clinical signs should improve within a month)
What can you use to monitor patients on trilostane to ensure they are not developing hypoadrenocorticism?
ACTH stimulation test
Pre-vetoryl cortisol test
How often should you do an ACTH stimulation test to monitor patients on trilostane?
10 - 14 days after starting treatment, then at 1 month, then every 3 - 4 months. Do the ACTH stimulation test 2-4 hours after the trilostane has been administered
How do you carry out a pre-Vetoryn cortisol test?
- Book an appointment just before the patient’s next trilostane is due
- Take a history and do a clinical examination of the patient. Make sure the owner has not given the patient it’s trilostane and nothing stressful has happened
- Take a blood sample immediately after clinical examination into a serum or heparin tube
- Send the sample to an external laboratory to evaluate the cortisol levels
