Equine Endocrinopathies Flashcards
What is PPID Also known as?
- equine Cushings disease ( don’t use this term, nothing wrong with adrenal)
What is the pituitary? Outline the anatomy and what is produced here
> gland base of brain, produces hormones in response to signals from hypothalamus
anatomy: 2 lobes
- anterior adenohypophysis
~ divided into pars intermedia, pars distalis, pars tuberalis
- posterior neurohypophysis
~ pars nervosa produces ADH and oxytocin
What section of the pituitary is affected in “equine Cushings” and in other animals?
- horses pars intermedia
- other animals pars distalis
What cells is the pars intermedia comprised of?
Melanotropes
- process POMC -> b endorphin, aMSH, CLIP &
How is production of ACTH regulated?
- unaffected by GC
- regulated by dopamine (-ve) and 5-HT (+ve) from hypothalamus
Outline Pathophysiology of PPID
- cause unknown
- loss of dolaminergic inhibition of pars intermedia d/t oxidative damage (slowly progressive)
- marked overproduction of pars intermedia derived hormones (b-endorphin, aMSH, CLIP
- modest increase in ACTH
> GC effects are d/t modest increase in ACTH AND INCREASED ACTIVITY of ACTH plus NO NEGATIVE FEEDBACK - not simply excess ACTH like in dogs or humans
- less important compression of surrounding pituitary and brain -> reduction in hormones (ADH, OT) and seizures and blindness
Epidemiology PPID
- old horses average 19yo, rarely horses
Clinical signs of PPID
> hypertrichosis
-common, pathognomonic
- delayed shedding/thick curly coat
- affects 55-80% cases
- poss d/t excess melatonin or corticoid/androgen effect or pressure on hypothalamic thermoreg centre
laminitis
- recurrent or chronic
- probs d/t excess cortisol and/or insulin
- often cause of eventual euthanasia
weight loss
- 90%cases
- metabolic effects of cortisol
- ^ susceptibility to infection (parasitism)
- poor management of old horses (dental care, feeding, v excercise d/t retirement or OA)
hyperhydrosis
- long hair causing overheating
- b adrenergic sweat glands affected by ^ catecholamines
PUPD
- can concentrate if water deprived
- d/t cortisol antagonising action ADH, causing hyperglyceamia with concurrent osmotic diuresis, destruction of other areas pituitary v ADH production or combo of these
bulging supra orbital fat
susceptibility to infections (sinusitis, parasitism, skin)
- v neutrophil function d/t excess hormones
lethargy
- endorphin/cortisol effect?
- may not notice until Tx
Diagnosis PPID
> Hx, signalment, clinical signs
hormone assays
- basal ACTH conc (results vary in PPID and normal horses - peak in Autumn, affected by feeding, may not detect early cases, variation in relevance in individual animals so if conc 19-40pg/ml consider further testing)
dynamic testing
- new test so seasonally adjusted range not yet decided
-TRH stim test (not logical but TRH physiologic release factor for pituitary - measure ACTH not cortisol - at 0 & 10m or 30mins
- ACTH >100pg/ml @10mins or >36pg/ml @ 30mins =PPID
- seasonal effect greatest July-Nov cf Februrary
insulin dysregulation
- feature in some but not all case
- may be d/t cortisol antagonising insulin -> ^ release, CLIP stimulating insulin or low grade inflam and oxidative stress from EMS -> PPID
- tests as for EMS. ASSOCIATED WITH LAMINITIS AND WORSE PROG
histology
- hard to dx, even histopath cannot agree
Will all owners opt to Tx PPID?
No depends on clinical signs and severity
- normally laminitis most limiting
- manage clinical signs only
Tx PPID
> DA agonists
- replace lost inhibition of pituitary gland
- PERGOLIDE (prascend) lic so must be 1* line choice of Tx
- 65-80% effective
- 1mg/500kg/day
5-HT antagonists
- replace lost inhibition of pituitary gland
- CYPRIHEPTIDINE (indirect ^ DA)
- less effective cf. DA ags
cortisol antagonists (OUT OF FASHION, USED IN SMALLIES)
- TRILOSTANE - inhibits at level of adrenal: 3b-HSD inhibitor so only prevents effects d/t cortisol
Side effects of prascend?
- D+
- depression
- anorexia
- colic
> stop and restart at lower dose
What happens to all pituitary hormones in the horse throughout the year?
^ in Autumn.
- PPID horses do a greater ^ in Autumn
How can PPID horses be monitored?
- monitor clinical response (min 2 months initially, can take up to a year)
- adjust dose monthly
- +- repeat testing
- repeat initial test after 30d (if neg keep on same dose, recheck q6mo)
- if positive, but clinical response, can keep dose same or increase
- if positive and NO clinical response, increase dose by 1-2mg/kg/d, recheck after 30d
> probably better to base on clinical signs but some people think you need to normalise lab numbers
Prognosis for PPID?
- lifelong Tx and management
- some can continue for several years comfortably
- doesn’t usually -> death, if it does likely d/t laminitis
What is EMS?
- cluster of clinical/metabolic abnormalities associated with ^ risk of laminitis
- stems from human form of dz
> characterised by - obesity
- insulin
- dysregulation
- hypertension
- abnormal plasma lipid profile
- pro-inflammatory state
- altered adipokines
- develops in genetically susceptible individuals with excessive dietary intake and inactivity over time
> risk factor for CV dz and type 2 diabetes, and laminitis
What was previously EMS classified as?
- generalised/regional adiposity + IR + recurrent laminitis
- features that define EMS still Up for debate as obesity/IR/plasma lipid vary between studies and individuals
Most common features of EMS thought now?
- insulin dysfunction
- ^ fasting TG
- altered adipokines
- not necessarily obese but may exacerbate components of phenotype and marker of underlying metabolic factors
- EMS horses get laminitis WHEN GRAZING PASTURE esp with ^ WSC [water soluble carbs]content
- promotes pronounced insulinaemic response -> induces laminitis (poss via endothelial dysfunction) may also -> hind hut carb overload -> inflammatory injury to lamellae
- high planes of nutrition or changes in pasture do not induce laminitis in all animals, only individuals pdf genetically
How is EMS diagnosed
- Hx, signalment, clinical signs
- detection insulin dysfunction
- assessment of contributing factors for obesity
- signalment
What are the 2 main players for ^ EMS risk?
Genetics and environment NEED BOTH
What are the clinical signs of EMS
- altered adipokines
- insulin dysregulation
- hypertriglyceridaemia
- ^ risk lamnitnies (recurrent with no apparent cause)
+- obesity
+- hypertension
+- pro-inflammatory state
> studies do not agree on all signs
How can insulin dysregulation be identified?
- resting insulin and glucose concentrations - hyperinsulinaemia (rarely hyperglycaemia) after 6hrs overnight fasting
- combined glucose insulin test (infusion glucose and insulin after 6hr fast, IR if blood glucose is above baseline and insulin >100uIU/ml @ 45mins)
- oral glucose test (feed 1g/kg glucose after 6 hr fast, ID if blood glucose >85uIU/ml @ 120mins)
- oral sugar test (0.15ml/kh PO Karo light syrup, ID if blood glucose >60uIU/ml @ 60-75mins)
Tx EMS
- wt loss to reduce omental fat if obese only
- limit sioluble carbs (ideally feed hay only 1.5% body weight - can add beet pulp substitute 11lb beet pulp for 1.5lb hay)
- can add vit and mineral supplement esp if soaking, avoid fat supplement as worsens IR
- excerce promotes glucose uptake and use by skeletal muscle by an insulin -independent route and ^ insulin sensitivity. v inflammaotion and feed intake
- diet and exercise should be sufficient but is hard work!!*
> pharmacological interventions - reserve for short term 3-6mo while management changes take effect
- METFORMIN (now out of fashion) used human type 2 diabetes. Improves insulin sensitivity and vascular endothelial function. Low bioavailbility in horses. MAY work by v intestinal glucose absorption)
- THYROXINE (0.1mg/kg SID PO can ^ 0.15 @ 3mo) ^ metabolic rate
- BUT UK have to use dog tablets -> prohibitively expensive
- side effects: hyperphagia, wean off when wt lost
> supplements and neutraceuticals - no evidence
Egs of supplements and neutracueticals suggested for use with EMS
- chromium
- magnesium
- cinnamon
- chasteberry
> NO EVIDENCE - supposedly insulin sensitising
- but if it helps owner do mamagement changes may be useul
