Equine endocrinopathies Flashcards
1
Q
Pathophysiology - PPID
A
- loss of DA inhibitbition of pars intermedia of pituitary gland d/t oxidative damage, cause unknown
- result is marked over-production of some pars intermedia derived hormones (beta-endorphin, alpha MSH, CLIP and a modest increase in others i.e. ACTH)
- GC effects relate to mild ACTH increases
- less importantly: compression of other areas of pituitary with reduction in production of hormones they produce (ADH) and compression of adjacent brain resulting in blindness seizures
2
Q
What cells comprise the pars intermedia?
A
melanotropes
3
Q
What hormones are produced in pars intermedia?
A
Process POMC into: - beta endorphin (mainly) - alpha MSH - CLIP -
4
Q
How is production of pars intermedia hormones regulated?
A
- regulated by DA and 5-HT
- unaffected by GCs
5
Q
Epidemiology - PPID
A
- av age 19, rarely horses
6
Q
CS - PPID
A
- hypertrichosis
- laminitis
- weight loss
- hyperhidrosis
- PUPD
- bulging supraorbital fat
- susceptibility to infections increased
- other: lethargy (endorphin effect?)
7
Q
Describe hypertrichosis of PPID
A
- common
- specific
- varies from delayed shedding to thick curly coat
- 55-80% cases
- possibly d/t excess melatonin or corticoid/androgen effect or d/t pressure on hypothalamic thermoregulatory centre
8
Q
Describe laminitis of PPID
A
- frequently recurrent or chronic
- usually d/t excess cortisol and/or insulin
9
Q
Describe weight loss of PPID
A
- 88% cases
- d/t metabolic effects of cortisol, possibly related to increased susceptibility to infection (parasitism, poorer management of older horses including dental care and feeding and reduction in exercise d/t retirement or OA)
10
Q
How does hyperhidrosis occur with PPID?
A
- may be d/t long hair coat
- beta adrenergic controlled sweat glands (elevated catecholamines)
11
Q
Describe PUPD of PPID
A
- can concentrate urine if water deprived
- d/t cortisol antagonising ADH on CDs, cortisol causing hyperglycaemia and osmotic diuresis, destruction of other areas of pituitary gland with reduced ADH production or combination of thse
12
Q
Describe infection susceptibility with PPID
A
- sinusitis
- parasitism and skin infections
- reduced neutrophil function d/t excess hormones
13
Q
Dx - PPID
A
- based on hx, signalment, CS and then hormone assays and dynamic tests:
1. HORMONE ASSAY
2. DYNAMIC TESTS
3. INSULIN DYSREGULATION
4. HISTOLOGY
14
Q
Describe hormone assays for PPID
A
= basal ACTH concentration: one off blood sample
- results vary in normal and PPID animals with season (autumn peak)
- affected by feeding
- may not detect early cases
- variations of clinical relevance occur in individual animals
- in conc b/w 19-40pg/ml then consider further testing
15
Q
Describe dynamic tests in PPID dx
A
= TRH stimulation test
- TRH is physiological release factor for pituitary
- inject 1mg TRH IV and then measure ACTH (not cortisol) at 0 and 10 or 30 mins.
- ACTH >100pg/ml at 10 mins or >36pg/ml at 30 mins = PPID
- seasonal effect (greater July-November) compared to February
16
Q
Describe insulin dysregulation in PPID dx
A
- feature of PPID in some cases
- may be d/t cortisol antagonising insulin
- may be d/t CLIP stimulating insulin
- may be d/t low grade inflammation and oxidate stress from EMS –> PPID
- tests: see EMS
- associated with laminitis and worse px
17
Q
Describe histology in dx of PPID
A
- histologists cannot agree
18
Q
Tx/ management - PPID
A
- not all owners elect to tx (depends on CS and severity - normall laminitis the most limiting)
- can manage CS only
- DOPAMINE AGONISTS
- SEROTONIN ANTAGONISTS
- CORTISOL ANTAGONISTS
19
Q
Describe dopamine agonists in PPID tx
A
- 1st line tx
- replace lost inhibition of pituitary gland
= pergolide - side effects: diarrhoea, depression, anorexia, colic
- 65-80% effective
- licensed!!
- 2microg/kg/day (=1mg/500kg)
20
Q
Describe serotonin antagonists in PPID tx
A
- replace lost inhibition of the pituitary galnd
= Cyproheptidine - probably acts by indirectly increasing dopamine
- less effective than the dopamine agonists
- works in 28-60%
21
Q
Describe cortisol antagonists in PPID tx
A
- inhibiti production of excess cortisol by adrenal gland = TRILOSTANE - it is a 3 beta-HSD inhibitor - 75% efficacy - only alteres CS d/t cortisol
22
Q
Monitoring - PPID
A
- monitor response to tx (give at least 2 months initally, adjust dose monthly)
- monitor clinical response + repeat testing: repeat initial test after 30 days, if now negative keep on same dose and recheck q 6months. If test still positive and no clinical response, increase dose by 1-2mg/kg/day and recheck after 30 days.
23
Q
Px - PPID
A
- life long tx and management
- some can continue in comfort for many years (50% still alive after 4.5 years)
- laminitis usually reason for euthanasia
24
Q
What is EMS?
A
= Equine Metabolic Syndrome
- cluster of clinical/metabolic abnormalities associated with increased risk of laminitis
- stems from HMS (Human Metabolic Syndrome)
25
Features - EMS
- PREVIOUSLY: generalised/ regional obesity + IR + recurrent laminitis
- NOW: not all components present in all individuals, obesity/IR/plasma [lipid] vary b/w studies
- CURRENT THOUGHTS: insulin dysfunction, increased fasting triglyceride concentrations, altered adipokines. Obesity not a requisite feature of EMS, may exacerbate components of phenotype (e.g. IR) and it is a marker of an underlying metabolic dysfunction whose expression is influenced by environmental factors
26
Why do EMS horses develop laminitis?
- when grazing pasture
- especially under conditions which favour increased WSC contnet
- this promotes pronounced insulinaemic responce --> i fprolonged can induce laminitis in healthy horses and ponies (possibly through inducing endothelial dysfunction). May also trigger inflammatory injury to lamellae
- BUT high planes of nutirtion/pasture changes don't cause laminitis in all animals
- individual variability may be d/t underlying genetic predisposition involving genetic alleles that result in alterations in insulin, glucose and/oor lipid metabolism which can increase or decrease dz risk and work with environmental influences to determine overall dz risk
27
Dx - EMS
- based on hx, signalment, CS and detection of insulin dysfunction
- hx: assess contributing factors for obesity
- signalment:
28
CS - EMS
- ? generalised obesity
- ? regional adiposity - crest, tail head and shoulders, prepuce or mammary region
- lean EMS phenotype possible
- recurrent laminitis with no obvious cause
29
How to detect insulin dysfunction for EMS dx?
* Resting glucose and insulin cocnentrations
- hyperinsulinaemia (rarely hyperglycaemia) after 6 hours overnight fast
* combined glucose insulin test:
* oral glucose test
* oral sugar test
30
Describe combined glucose - insulin test
Infusion of glucose and insulin after 6 hour fast. IR if blood glucose is above baseline value and insulin > 100microIU/ml at 45 minutes
31
Describe oral glucose test
Feed 1g/kg glucose after 6 hour fast. ID if blood glucose >85 microIU/ml @ 120mins
32
describe oral sugar test
0.15ml/kg po Karo light syrup. ID if blood glucose > 60 microIU/ml @ 60-75 minutes
33
Tx - EMS
- WEIGHT LOSS: to reduce omental fat via diet if obese
- DIET: limit soluble carbohydrate intake, ideally feed only hay, 1.5% bodyweight, can add beet pulp, substitute 1 lb of beet pulp for 1.lb hay, can add vitamin and mineral supplement, avoid fat supplementation as worsens IR
- EXERCISE: promotes glucose uptake and use by skeletal mm by insulin-dependent route, imrpoves insulin sensitivity, reduces inflammation and decreases feed intake
- PHARMACOLOGIC INTERVENTION (metformin vs thyroxine)
34
Describe pharmacologic intervention
- METFORMIN (for human DMtype2): improves insulin sensitivity and vascular endothelial function, low bioavailability in horses (7%), only 2 studies (one no effect, one some beneficial effect), may work by decreasing GT glucose absorption
- THYROXINE: ++++++++++++++++++++
35
What supplements and neutraceuticals can be used for EMS
- insufficient scientific evidence to support use
| - chromium, magnesium, cinnamon and chasteberry commonly recommended as supposedly insulin sensitising
36
Define PPID
Pituitary Pars Intermedia Dysfunction
37
Describe thyroxine in pharmacological tx of EMS
- ACTION: increases metabolic rate --> weight loss
| - SIDE EFFECTS: hyperphagia so must restrict calories
