HPA Axis Disorders- LA Flashcards
describe the equine HPA axis in health and how PPID relates
hypothalamus:
-in response to stressors, releases CRH that acts on the pars distalis, which releases ACTH to the adrenal cortex, which releases cortisol that gives negative feedback to the hypothalamus
-hypothalamus also has dopamine-producing neurons; dopamine also acts as negative feedback for the hypothalamic hormones that act on the pars intermedia, which releases ACTH, a-MSH, and CLIP, which have various cellular effects
-in PPID those dopamine producing neurons die so pars intermedia is no longer inhibited, makes ACTH, and more, making bunches of cortisol
(however: cortisol is not always high when measured in PPID horses, so we suspect something else is happening with the other hormones produced by the pars intermedia working on other pathways that also mimic what cortisol does to horses)
describe PPID pathophysiolgy
-mechanism of death of hypothalamic dopamine-producing neurons is unknown!
-may be a genetic predisposition, may be part of a normal aging change, could be due to chronic inflammation (perhaps due to obesity or insulin dysregulation)
describe PPID clinical presentation
- older horses (>15yrs)
- hypertrichosis/hirsuitism:
-abnormal shedding patterns
-shedding at the wrong time of year, not shedding fully, end stage is long curly hair coat - sweating disturbance:
-hyperhidrosis or anhidrosis (more common, so could present for resp distress in the summer because cannot cool themselves) - weight loss/loss of muscle mass
-may be masked by round abdomen fat distribution though! - tendon/ligament injuries
-LAMINITIS - chronic/recurrent laminitis
-often pasture-associated - +/- PU/PD
-reported as less common but could be underestimating if on pasture - increased susceptibility to infection:
-skin infections, indolent corneal ulcers
all look like cortisol responses but when measure cortisol in animal, is not always high!
describe common clinicopathologic abnormalities of PPID
- stress leukogram
- mild hyperglycemia
-hyperinsulinemia - increased liver enzymes
-in some - not really glucosuria or UTI
all look like cortisol responses but when measure cortisol in animal, is not always high!
describe PPID clinical diagnosis
- CLINICAL JUDGEMENT
-hypertrichosis/shedding changes = most sensitive and specific test so no further testing needed!!
—unless just came from a neglect malnourished situation then feed - strongly suspicious clinical signs:
-older horse with abnormal shedding, weight loss, or laminitis
-consider further testing OR treatment trial - questionable clinical signs:
-middle-aged horse, good body condition, laminitis
-further testing necessary
describe PPID laboratory diagnosis static testing
resting hormone concentrations:
1. basal cortisol = USELESS, do NOT do for PPID diagnosis in horses!
- basal ACTH: pretty good screening test of choice (much more common than SA)
-but stress effects, sample handling issues (difficult to obtain in field), the lab matters, seasonal reference ranges, geographical factors
describe seasonality of basal ACTH
pretty low and stable until autumn equinox, will see increase, then goes back down to stable in normal horses
horses with PPID higher to begin with throughout the year, then a GIANT spike in the fall
so have 3 ranges:
-PPID unlikely
-interpretive zone: most horses fall here :(
-PPID likely
-MUST consider ACTH concentration in context of clinical signs and signalment!!!
describe dynamic testing for PPID laboratory diagnosis
- maybe low dose dexamethasone suppression test
(no need to use HDDST and canNOT use ACTH stim test)
- TRH stimulation test
- testing for insulin resistance:
-not diagnostic for PPID but still important for management and prognosis (more later)
describe low dose dexamethasone suppression test for PPID diagnosis
- premise:
-dexamethasone suppresses endogenous ACTH and cortisol
-loss of suppression in PPID - equine protocol:
-4-6pm, take basal cortisol (serum)
-give 0.04mg/kg dex IM
-at noon, if cortisol is at or below 1ug/dl = normal but is >1ug/dL = PPID - HOWEVER:
-is sensitive (when horse looks PPID) but not specific so false negatives are possible!!
-false positives in the fall!
-laminitis risk increased!!
so we NEVER do this test anymore!! because only works well in horses that look PPID anyways plus risks with immune suppression
describe the TRH stimulation test for PPID diagnosis
- premise: TRH causes increase ACTH release from pituitary, and should see an exaggerated response in PPID
-crosstalk between thyroid and HPA axes in horses because if one fails = dead - protocol:
-take basal ACTH
-give 1mg TRH IV (supraphysiologic dose, give half if tiny horse <200kg)
-if ACTH >100-200pg/ml at 10 minutes after TRH = PPID - HOWEVER:
-more sensitive and specific, esp in early stage PPID
-but in the FALL interpret with CAUTION (normal 10 min ACTH 300-500pg/ml in the fall!!)
-also hard to obtain medical grade TRH, so have to use chemical grade or compounded
-once again, MUST interpret TRH stim results in context of clinical signs and signalment!!
describe the reality of PPID diagnosis
- this is a progressive disease of aging with seasonal, geographical, age, color, and breed effects on a continuum with a lot of diagnostic grey areas
- so if borderline results:
-and clinical signs: treatment trial or re-test in 3-6 months
-no clinical signs: re-test in 6-12 months
-or consult a LAIM specialist - pituitary imaging not available
- no current test for a-MSH or CLIP to see if those other hormones are playing a role
describe PPID management
- ideal WOULD be removal of affected pituitary tissue but this is NOT an option in horses
- medical: decrease secretion of POMC-peptides
-pergolide: dopamine agonist to replace the missing dopamine but loss of efficacy over time because you are not stopping neuron death so will have to increase the dose, if anorexia, stop temporarily and with lower dose
-cyproheptadine: serotonin agonist, less effective alone, useful with pergolide in refractory cases (FDA approved so HAVE to prescribe for PPID though)
- monitoring:
-clinical signs
-evidence of insulin dysregulation: hyperinsulinemia
- +/- repeat diagnostic testing
–ACTH in SAME SEASON EACH YEAR
–TRH stim testing
describe equine hypoadrenocorticism
- not very common in any form
- primary or atypical like in dogs is not described in horses
- transient HPA axis insufficiency is described
-in premature foals: very late maturation of adrenal versus other species
-in septic neonatal foals
-in horses with colic/systemic inflammation (SIRS)
-in horses undergoing intense exercise/training
-CIRCI: critical illness-related corticosteroid insufficiency
describe CIRCI
- previously called relative adrenal insufficiency
- inadequate cortisol production activity for existing degree of illness
- key points:
-transient
-cortisol still elevated from unstress healthy levels. just not high enough for current sickness - 3 major pathophysiologic events:
-suppression of part(s) of the HPA axis by infection: microbes and/or host cytokines
-altered cortisol metabolism
-tissue resistance to glucocorticoids - diagnostic approaches:
-measurement of resting hormone concentrations is hard to interpret due to variable levels of stress
-DYNAMIC TESTING: ACTH STIM TEST!!!!
-clinical status of patient!
describe CIRCI in equine critical illness
- see in 40% of septic foals
-increased incidence with disease severity
-results in decreased survival - in horses with GI disease and SIRS
-20-80% incidence, similar association with disease severity and survival as foals - low-dose hydrocortisone replacement
-attenuates inflammation in foals
-but unknown effect on sepsis outcome due to lack of studies
