Hyperadrenocorticism 2 Flashcards
What do you see with ACTH stim in hyperadrenocorticism
Excessive over response to stimulation
Is the ACTH stim test a good test?
- poorly diagnostic in a proportion of cases
- post ACTH cortisol less than upper limit of normal range
- post ACTH cortisols between 500-750nmol/l
> extremely accurate with post ACTH >1000nmol/l
> never discriminatory for PDH v ADH - so works in % of cases and is convenient
- BUT 20% HAC dogs will have negative ACTH stim tests
Outline low dose dex suppression test
- measure plasma cortisol at 0, 4 and 8 hours after administering dexamethosone
- dose 0.01mg/kg dex IV
- dexamethosone not assayable
- BOTH 4 and 8 HR cortisol should be if either are high this is ABNORMAL
Which test is more appropriate for hyperadrenocorticism dx
> general rule use SUPPRESSION tests for overactive disorders and STIMULATION tests for underactive disorders
- so dex suppression best for HAC
How can pituitary dependant and adrenal dependant hyperadrenocorticism be distinguished?
> PDH
- 70% suppressed at 4 hours post ACTH then increased at 8hrs
- 30% no suppression seen at 4 or 8 hours
ADH
- all show no suppression
- but remember 30% cases PDH also show this profile
Why may some ADH and PDH animals respond the same to low dose dex ?
- with PDH different set points of GC activity seen as normal so if one PDH animal set point x and another set point 2x then results of GC activity induced by dex suppression will differ over time
- normal dog dex injected, at all time points surplus to requirement so ACTH
What may impair the low dose dex test?
- illness -> false positives because ^ cortisol produced with ANY non-adrenal disease
So which test is most appropriate to confirm hyperA?
- LDDST
- providing not ill
- NB: dose very low and must be delivered accurately
Is SHOP test useful?
No rubbish don’t use
“ shop stimulation test”
- progesterone
How do we discriminate between ADH and PDH?
> when LDDST suppression at 4hrs with rebound at 8hrs (though not seeing this does not rule out)
adrenal ultrasound
- difference l and r
- smaller adrenal smaller than Normal with ADRENAL dependent (d/t negative feedback of ^ cortisol -> v ACTH -> atrophy)
- small min 2 basal plasma ACTH levels (plasma separated and frozen in 30mins, values not subnormal but not elevated either)
- NOT high dose dex suppression test (useless)
Tx PDH
> medically
- trilostane (lic)
- mitotane
surgical
Tx ADH
> medical
- trilostane
surgical
What is trilostane?
- inhibits 3b hydroxysteroid dehydrogenase
- inhibits synth of cortisol (and MCs and sex steroids)
- different efficacy in different species (ineffective humans, variable cats and dogs)
- potentially safer than mitotane (suppresses rather than destroys)
What protection of dogs do not respond to trilostane?
25%
What side effect may trilostane have on the adrenals?
> group of PDH Tx with trilostane (NOT very effective for ADH, also less risk of necrosis and haemorrhage in ADH d/t ACTH levels)
- develop adrenal necrosis (seen on ultrasound as hyperlucency in the adrenal cortex fluid accumulation)
-> Hypoadrenocorticism
^ ACTH -> ^ adrenal cortical blood flow -> haemorrhage -> acute v cortisol which can be clinically significant
be ready for addisonian crisis
Which form of cortisol/cortisone is active?
- cortisol active
Trilostane dilemma
- inhibits cortisol production for something not making sense (not adrenal haemorrhagic effect, potential peripheral effects)
How does 11b HSD2 leukocyte expression change in PDH treatment
- normal levels = non-adrenal illness = PDH untreated
- PDH treated individuals levels ^ (should be DOWN)
- this increase not seen in humans (and not effective in humans)
How should trilostane be used?
- with food (^ bioavailability)
Is low dose BID dosing recommended ?
In America yes but here thought not to be such a good idea
- v compliance
- don’t overdose BUT low dose ALSO bad(not sure why???)
If trilostane not effective what are the options?
^ freq dosing
- or use mitotane
> v cortisol by adrenocorticolysis d/t
- direct cytotoxic activity to zona fasiculata and reticularis (GC)
- generalised adrenocorticol destruction (enhanced adrenocorticol blood flow mediated via ^Acth)
> induction and maintainance phases
Outline induction and maintainance phases of mitotane
- 25mg/kg/12hr for 5-7d
- always with food
- check demeanour and appetite
- evaluate with ACTH stimulation (24-36hrs after last mitotane,Moore and post cortisols maintainance
- 25mg/kg/12hr once a week
- monitor as for induction
- if control lost RESTART INDUCTION don’t increase maintainance
Adverse effects of mitotane
- variably reversible GIT signs
- lack of sensitivity to mitotane
- neuropathies (esp cranial nerve palsies)
- unpredictable onset clinically significant Hypoadrenocorticism
Is mitotane still a reasonable Tx?
- YES!! (For pituitary only, ADH needs trilostane)
- remember adverse effects
- remember consistency of efficacy (sometimes not very efficacious)
> only option not requiring daily meds
What are the surgical options for hyperadrenocorticism ?
> bilateral adrenalectomy and Tx as an addisonian
- RVC only!!
- hydrocortisone sodium succinate infusion implemented at time of surgery
1mg/ml solution, 0.5mg/kg/hr for 24hrs, 0.25mg/kg/HR 24-48hrs
- transfer to oral medication
cortisone acetate 0.5mg/kg/12hr
fludrocortisone acetate 10-15ug/kg/24hrs
How can hyperadrenocorticism be diagnosed?
> haem and biochem - stress leuckogram - liver enzyme ^ - ALP>>ALT > USG - generally unhelpful > basal plasma cortisol estimation > basal urinary corticosteroid excretion > dynamic testing - ACTH stim - low dose dex suppression testing
Outline ACTH stimulation test
- measure plasma cortisol at 0 and 1 hr after administration of synth ACTH
- tetracosactrin IV/IM
- expect post ACTH cortisol to be 300-600nmol/l
Do all adrenal masses produce cortisol?
No may be a medullary mass -> catecholamines
- look for small contralateral adrenal as chronic overproduction cortisol -> v ACTH -> atrophy
Summary clinical signs and diagnosis hyperadrenocorticism
- nowadays subtle dz
- may be just a difficult to manage diabetic mellitis
- always contextualise test results to clinical picture
Summary Tx options hyperadrenocorticism
- medical (trilostane, mitotane)
- surgical (bilateral adrenalectomy and steroid supplements (fludrocortisone, cortisone small dogs
