Hyperadrenocorticism Flashcards
What is the definition of HAC?
clinical problem brought about by sub-acute over exposure to glucocorticoids
What proportion of naturally occurring HAC is a) pituitary dependant b) adrenal dependant
a) PDH = 85-90% b) ADH = 10-15%
What is the main cause of iatrogenic HAC?
Chronically administered UNDER dosing of glucocorticoids
What proportion have PUPD?
85-90%
What proportion have excellent appetite?
80% If not polyphagic probably has something else going on as well
What proportion have exercise intolerance?
About 60%
What proportion have abdominal distension?
About 50% due to hepatomegaly and abdominal weakness
What proportion have coat changes?
About 50%
What proportion have alpecia and hyperpigmentation?
About 35%
What proportion of intact females have anoestrus?
90%
What are the most common clinical signs associated with hyperadrenocorticism?
Panting, muscle weakness and atrophy, hepatomegaly & abdo distension, increased abdominal fat deposition, testicular atrophy, vulval enlargement, dermal changes, altered mentation
What are the dermal changes which can be present with HAC?
Hyperpigmentation Symmetrical alopecia Hyperkeratosis Non-pruritic Comedones Possibly calcinosis cutis
Where are the two most common sites for infection in HAC dogs?
UTI and skin
Is PUPD in HAC patients normally primary PU or primary PD?
Primary PD - psychogenic
What are the five reasons that you can have PUPD? (generally, not just in HAC)
Primary PD Structural renal disease (loss of nephrons) Something stopping nephrons working (eg countercurrent) Osmotic diuresis Something interfering with ADH
Where does the alopecia tend to occur?
Mostly over the trunk
What’s this?
Calcinosis cutis
Calcium phosphate deposition in the skin
Why do HAC dogs tend to pant?
Muscle weakness and increased abdominal volume means that to maintain minute volume need to increase rate and decrease tidal volume
Why are HAC dogs more prone to throwing blood clots?
Prolonged GC exposure = hypercoagulability
(thrombocytosis)
What clinpath findings might you expect?
Eosinopenis, lymhocytopenia
Increased ALP, increased ALT (ALP more increased than ALT in dogs)
Hypercholesterolaemia
Increased thrombocyte count
Low USG possibly
Why do cats with HAC normally present?
difficult to manage Diabetes
What size of dog normally gets HAC?
<20kg
Primary PD can be water deprived as doesn’t need to drink, what should you rule out in HAC patients before taking away their water?
UTI
Endotoxins interfere with urine concentration
What are the two dynamic tests that you can do to test for HAC?
Low dose Dexamethasone suppression test
ACTH stimulation test
When might you have an abnormal Dex suppresiion test in a non HAC animal?
General illness-Need increased cortisol so adrenal acting above normal
How do you perform an ACTH stim test?
Measure plasma cortisol at 0 hrs and 1hr
Give 5ugm/kg of tetraosactrin IV or 250UMG/dog
What would be the normal plasma cortisol level post ACTH stim?
300-600 nmol/L
Beyond 1000nmol/L we can say that..
Animal almost definitely has HAC, below this si a grey area and some animals may even have within normal range but have HAC
Can you use an ACTH stim test to decide whether it is PDH or ADH?
No
How do you perform a LDDST?
Measure plasma cortisol at 0,4 and 8h
Dose of 0.01mg/kg dexamethasone given IV
Expect supppression at 4h AND 8h
What level of cortisols should be expected if the result of the LDDST is normal?
<20nmol/L
Can you use a LDDST to decide whether PDH or ADH?
Yes to a degree, initial suppression then increased at 8h is PDH. 70-80% of PDH cases have this pattern
Supressed at 4h and 8h could be ADH or the remaining 20-30% of PDH cases
What is the SHOP stimulation test?
17-OH progesterone levels taken before and after ACTH
Inadequate precision to be worth your time
What might you expect to see on adrenal ultrasonography if it is ADH?
You’d expect to possibly see one adrenal enlarged but more importantly, the other adrenal should be SMALLER than normal (<5mm) as no stimulation because ACTH not released due to negative feedback by high levels of circulating cortisol
What would you expect from basal plasma ACTH levels in ADH/PDH?
Important to take at least 2 ACTH assays as is a finicky tets
ADH-Should be almost no ACTH in the system
PDH-Normal or increased
Which adrenal gland is this? Is it normal or abnormal?
Left-bean shape
Which adrenal gland is this?
What is this?
An adrenal mass
What are the two available medical treatments available for PDH?
Trilostane
Mitotane
Can you do surgical treatment for PDH and ADH?
Yes. probably more likely to do surgery on ADH than PDH
What does trilostane inhibit?
Inhibits 3-B hydroxysteroid dehydrogenase
therefore inhibits steroid production
Which species is Trilostane more effective in, dogs or cats?
Dogs
Why do some dogs get adrenal necrosis?
Trilostane inhibits cortisol synthesis and therefore increases ACTH as lack of negative feedback
ACTH increases adrenocortical blood flow which is a fragile network
Adrenocortical haemorrhage
Necrosis and acute reduction in cortisol production
If treating with Trilostanem, do you get a greater degree of adrenal haemorrhage with PDH or ADH?
PDH
In ADH pre treatment levels of circulating ACTH are very low so an increase unlikely to be as bad as in PDH when they are normal or increased before treatment
Which condition is Trilostane more ‘efficacious’ PDH or ADH?
PDH for reason on last slide, more likely to create adrenal necrosis
NB this may be desirable or undesirable
Why is it a concern that Trilostane may cause adrenal necrosis?
Patient may develop acute hypoadrenocorticism
could have iatrogenic addisonian crisis
Why can’t you use urinary cortisol concentrations to assess treatment success in dogs being treated with trilostane?
Levels remain elevated because when you treat animals with trilostane, you get an increase in 11-hydroxysteroid dehydrogenase 2, which turns cortisome in to cortisol.
You DO have decreased circulating active cortiSOL which is why clinical signs look better but still have cortisONE in the circulation which is measured in the urine/blood as cortisol
What is the minimum dose for trilostane?
2-4mg/kg/24h with food
ACTH test 2-4 hrs post dose
don’t underdose
What should you do with the proportion of animals (about 25%) who don’t respond satisfactorally in the first instance?
Review dose, consider twice daily dosing but NB price and compliance issues
Consider mitotane?
How does mitotane work?
Reduces cortisol production through direct cytotoxicity to the zona fasciculata and reticularis & generalised adrenocortical destruction via increased ACTH
What instructions would you give an owner for the induction dose of mitotane?
25mg/kg/12h for 5-7 days
ALWAYS with food
Keep an eye on demeanour and appetite
How should you monitor your mitotane treatment at the end of the induction phase?
Do an ACTH stimulation 24-36h after the last mitotane
pre and post cortisols should be less than 30nmol/L
What is the general dose for maintenance with mitotane?
25mg/kg/12h on one day per week
ALWAYS with food
How should you check your treatment with mitotane once on maintenance dose?
Evaluate with an ACTH stim in the same way as before, 24-36h after the last mitotane
Pre and post cortisols of less than 30nmol/L
What should you do if you are maintaining an animal on mitotane and control is lost?
restart induction
DON’T use an increased maintenance dose
What are the possible side effects of mitotane?
Variably reversible GIT signs
Neuropathies - particularly cranial nerve palsies
Unpredictable onset of clinically significant hypoadrenocorticism
What is the other option if you cannot achieve control with mitotane OR trilostane?
Bilateral adrenalectomy
What do you need to do to supplement animals that have had a bilateral adrenalectomy?
Hydrocortisone infusion (implement at time of surgery)
Post surgical hydrocortisone infusion with transfer to oral medication
Which drug do you have to use first (in the UK) to medically manage HAC?
Trilostane-Licensed
What oral medication do you give dogs that have had bilateral adrenalectomy?
Cortisone acetate or prednisolone
and
Fludrocortisone acetate
