Hyperadrenocorticism Flashcards
Define hyperadrenocorticism
- clinical problem brought about by sub-acute overexposure to GCs
- natural (ADH or PDH) or iatrogenic (chronic underdosage of steroids)
Differentiate ADH and DH frequency
- ADH 10-15%
- PDH 85-90%
Clinical picture - hyperadrenocorticism
- subtle changes early in dz
- insidious onset means presentation occurs at variable stages
- secondary problems frequently result in death
Hx - hyperadrenocorticism
- PD and PU 85-90%
- excellent appetite 80%
- exercise intolerance 60%
- abdominal distension 50%
- coat changes 50%
- alopecia and hyperpigmentation 35%
anoestrous 90% (of intact females)
CS - hyperadrenocorticism
- panting
- mm weakness and atrophy
- hepatomegaly and abdominal distension
- increased abdominal fat deposition
- testicular atrophy, increased vulval size
- dermal changes
- altered mentation (underwhelmed)
- appear ‘old for age’ (epaxial mm wasting)
Dermal changes - hyperadrenocorticism
- non-primary skin changes
- symmetrical alopecia (trunk –> extremities)
- non-pruritic
- hyperpigmentation
- hyperkeratosis and ‘flaking skin’
- comedones
- clacinosis cutis
- infections or infestations (recurring)
Cause of PD and PU in hyperadrenocorticism
= PRIMARY PD
- also cortisol interferes with ADH action in CD but this effect is relatively minimal compared with the primary PD
Clinical picture - cat with hyperadrenocorticism
- cat with DM that is difficult to manage
- varying degrees of IR
- resent for varying periods of time
- usually no other CS
- uncommon problem
Clinical pathology
- eosinopaenia, lymphoctyopaenia (STRESS LEUKOGRAM)
- increased ALP (dog - much increased, disproportionate cf ALT), increased ALT
- hypercholesterolaemia
- increased thrombocyte count
- ‘low’ USG
Why can’t you remove water from a PUPD dog with hyperadrenocorticism?
because they are prone to infections (UTI) –> PUPD that is necessary so would be dangerous to remove water bowl in these instances without testing for and tx the infection.
Dx - hyperadrenocorticism
- haematology and biochemistry (stress leukogram, liver enzyme elevations, USG usually unhelpful) helps raise index of suspicion
- basal plasma cortisol estimations
- basal urinary corticoid excretion
- latter two are poor discriminators hence –> dynamic tests (ACTH stimulation test or low dose dexamethasone suppression test)
Describe ACTH stimulation test
- measure plasma cortisol at 0 hr and 1 hr after administration of synthetic ACTH
- 5 microg/kg of tetracosactrin IV ORRRRR:
- 250microg/kg/dog IV or IM
- except post-ACTH cortisol to be b/w 300-600nmol/L
- evaluate success of tx
Efficacy - ACTH stimulation test
- poorly diagnostic in a % cases (post ACTH cortisols less than upper limit of normal range, post ACTH cortisols b/w 500 to 700nmol)
- extremely accutate when post ACTH cortisols are > 1000nmol/L
- virtually NEVER discriminatory for PDH vs ADH
Outline LDDST
= low dose dexamethasone suppression test
- more appropriate for what we are trying to investigate
- samples taken over 8 hour period (plasma cortisol measured at 0, 4, 8 hours)
- 0.01mg/kg dexamethasone IV
- dexamethasone is NOT assayable
- expect 4 and 8 hr cortisols to be
Why is LDDST more appropriate (than ACTH stim) for d HAC?
- demonstrates impaired capacity to reduce cortisol production
- lack of suppression for a given level of GC activity
How do you differentiate PDH and ADH?
= LDDST results:
- PDH 4hr post will have low cortisol levels with rebound at 8hr post (i.e cortisol), this is true in 70% PDH cases
- ADH: cortisol high at 4 hr and 8hr post dexamethasone (100% ADH and 30% PDH cases)
= adrenal ultrasonography: adrenomegaly with PDH, adrenal mass with ADH (especially if unilateral, difference in size with other adrenal and the other is smaller i.e. 2-5mm)
= at least two basal plasma ACTH levels (plasma separated and frozen within 30 minutes, values aren’t subnormal but not necessarily elevated)
= NOT WITH high dose dexamethasone suppression test
How to confirm HAC
- ACTH STIM TEST: convenient (within 1 hr, concern of false negatives)
- LDDST (least convenient, concern of false positives - minimise this risk by not performing on sick patients)
What is the ‘SHOP’ stimulation test?
- designed to dx HAC
- not worth effort (inadequate precision)
- 17-OH progesterone levels pre and post ACTH
Outline tx - PDH
- ** MEDICALLY: trolostane (L) or mitotane (NL)
- SURGICALLY
Outline tx - ADH
- ** SURGICALLY
- MEDICALLY: (trilostane)
How does trilostane work?
- inhibits 3 beta-hydroxysteroid dehydrogenase
- inhibits cortisol synthesis
- different efficacy vs PDH in different spp (effective in dogs, variably in cats)
- may be safer than mitotane as ‘simply’ suppresses cortisol production
- but inhibits cortisol production for
Why can trilostane be dangerous?
inhibits cortisol synthesis and increases ACTH production –> much increased ACTH –> much increased adrenocortical BF –> adrenocortical blood supply very fragile (rate, dogs, cats) –> adrenocortical haemorrhage and damage –> acute reduction in cortisol production which can be clinically significant
* this risk is much greater in PDH than ADH
Why is risk of adrenocortical haemorrhage much worse in PDH than ADH?
- ‘efficacy’ reduce in ADH compared to PSH as;
- in trilostane-tx DH, the rises in ACTH directly damage the adrenal galnds
- hypOadrenocorticism is still a concern
What is another concern with trilostane?
- inhibits cortisol production for
