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Equine Final Year > PPID > Flashcards

PPID Flashcards

1
Q

At what age, type and breed is equine cushings prevelant in?

A

Prevalence: 15-30% in horses >15y.o.

Age: >7y.o. BUT avg 19-21 years of age

Typically a condition of older horses

Diagnosis in <15y.o. interpreted cautiously

Gender: no gender predilection

Breed: Ponies appear predisposed

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2
Q

What are the clinical signs of PPID (out in bold the most common)?

A
  • Weight loss/Muscle wastage (up to 88%)
  • PU/PD (up to 76%) not always obvious if animals pasture fed.
  • Hirsutism (long, curly haircoat) (55-80%)
  • Quieter demeanour/lethargy/increased docility
  • Poor performance (The owner what do they mean by poor performance)
  • Regional adiposity (supraorbital)
  • Potbellied appearance
  • Chronic laminitis
  • Recurring infections (skin, respiratory, dental)
  • Hyperglycaemia
  • Hyperhidrosis/anhydrosis (less common)
  • Neurologic: blindness/seizures/narcolepsy (if adenoma presses on parts of brain, blindness= pressing on optic nerve)
  • Absent reproductive cycle/infertility
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3
Q

What does this image show?

A

PPID

  • Hirsutism (picture taken in california pony still with winter coat though)
  • Potbellied appearance
  • Abnormal fat depots
  • Muscle loss
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4
Q

Describe the generic appearance of a cushings horse?

A
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5
Q

Label the pituitary gland?

A
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6
Q

What is the pathogenesis of PPID?

A

Pituitary Gland

Pars Distalis produces normally most of ACTH in response to stress:

  • Pain, illness
  • Excitement, travelling, exercise
  • Veterinary procedures
  • etc

Pars Intermedia produces normally very small amounts of ACTH

Pars Intermedia becomes hyperplastic/neoplastic, biologically active cells

Lack of dopaminergic inhibition of pituitary PI

ACTH mediated adrenal gland stimulation pituitary hyperadrenocorticism.

Other POMC hormones synthesised:

  • α-MSH
  • β-endorphins
  • Lipotrophins
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7
Q

What is the normal physiology of the Pars intermedia in the absence of PPID?

A
  • Pars Intermedia is in a state of tonic inhibition
  • Inhibited by dopamine released from dopaminergic neurons that extend down from the hypothalamus
  • Dopamine interacts with D2 receptors on melanotrophs and inhibits their activity
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8
Q

Illustrate the pathogenesis of PPID?

A
  • Of the 3 hypothalamic tracts involved in Dopamine production, the periventricular tract is the main one implicated the activity of the pars intermedia
  • Dopamine acts on D2-receptors on melanotropes in the Pars intermedia and this results in reduction of POMC mRNA expression and POMC-derived hormone release
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9
Q

What are POMCs cleaved to?

A
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10
Q

Why is EMS a risk factor for PPID?

A
  • Obesity and insulin resistance associated with low-grade inflammation and pro-oxidative state
  • Increased oxidative degeneration of dopaminergic neurons
  • PPID developing at an earlier age in horses with EMS
  • Key point: Insulin dysregulation exacerbated by the development of PPID
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11
Q

What causes the weightloss that is seen in PPID?

A
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12
Q

What causes the PU/PD seen in the PPID?

A
  • Neurogenic diabetes insipidus (decreased ADH production) is likely the result of compression of the pars nervosa by the adenomas in the pars intermedia which results in decrease production and secretion of ADH
  • Glucocorticoids increase GFR
  • Hyperglycaemia -> osmotic diuresis -
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13
Q
A
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14
Q

What causes the hirsutism seen in PPID?

A
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15
Q

What leads to the lethargy associated with PPID?

A

Make animal more relaxed and quiet

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16
Q

What leads to the increased risk of laminits associated with PPID?

A
17
Q

What causes the increased susceptibility of disease associated with PPID?

A

More foot abscesses than normal.

Treat the cushings to get on top of the infections.

Dermatophilus: rainscald

18
Q

What causes the poor fertility associated with PPID?

A
19
Q

What causes the hyperhidrosis associated with PPID?

A
20
Q

How can PPID be confirmed?

A

Clinical

  • History
  • Clinical Signs

Laboratory tests

  • Haematology/biochemistry
  • Resting ACTH concentration (best test at present)
  • TRH Stimulation Test
21
Q

What would be seen on haemotology/biochemistry for a equid with PPID?

A

Haematology/biochemisty

  • Anaemia
  • Neutrophilia/lymphopaenia (stress leukogram because of the cortisol production)
  • High insulin
  • Hyperglycaemia
  • Hyperlipaemia
  • High liver enzymes
  • Glucosuria

RESTING PLASMA CORTISOL NOT DIAGNOSTIC FOR PPID IN HORSES

22
Q

What is a resting ACTH test?

A

Submit EDTA plasma sample (purple top)

  • Ideally separate quickly and refrigerate within 3h of collection
  • Degenerates at room temperature (10-20% daily at room temp)
  • Submit chilled

Affected horses have high concentrations

Normally see a seasonal increase in ACTH in Aug, Sept, and Oct (autumn) season specific range that the lab will give you

Positive if > 29 pg/mL

> 47 pg/mL in Aug, Sept, Oct

Gray area 19-40pg/ml in Non-autumn months – repeat testing later

Assay dependent values in

Cost: Approximately £30-40

If sample not refrigerated potential for false negative results

Freezing full blood could give false positive result

Low sensitivity in early PPID

Stress can cause false positive results due to cortisol response to pain.

23
Q
A
24
Q

What is the TRH stimulation test?

A

TRH stimulates ACTH release from the Pars-Intermedia

More sensitive to pick-up early PPID cases – use to detect suspected cases with borderline resting ACTH

  • Inject 1.0 mg thyrotropin-releasing hormone (TRH) intravenously at time = 0
  • Collect blood at 0 + 10mins ±30mins
  • Positive if ACTH >35pg/mL at time 0 or >110pg/mL at 10 minutes

Avoid testing August to October

Sensitivity: 77%

Specificity: 82%

(DST less sensitive but more specific)

No correlation between TRH-st, resting ACTH and DST

25
Q

What is the Dexamethasone suppression test (DST)?

A

Dexamethasone suppression test (DST) Last thing you want to do is give dex to a horse with laminitis as it turns into cortisol!

*Rarely used now – historical value*

  • Inject 0.04 mg/kg dexamethasone IV or IM (20 mg for a 500-kg horse)
  • Measure cortisol at 19 or 24h (£33.50)
  • Normal response:
  • Suppresses below 27 nmol/L (=10 ng/mL; 1.0 μg/dL)
  • PPID if fails to suppress (>27nmol/L)
  • Sensitivity: 65% (or less) Specificity:76-100%

Somewhat insensitive as seems to identify only cases with obvious clinical signs – resting ACTH more suitable in these cases

High false positive rate from July to October!!

26
Q

What is the combined DST/TRH stimulation test?

A

TRH stimulates ACTH release from the Pars-Intermedia

More sensitive to pick-up early PPID cases

  • Dexamethasone: 40µg/kg, IV @8-10am
  • TRH: 1.0mg IV 3.5h after Dexamethasone
  • Collect blood at 0, 3h (before TRH), 3.5h, 24h
  • Cortisol concentration

PPID: Greater than 27nmol/L @24h OR greater than 66% increase between 3h and 3.5h (so after TRH)

NORMAL:<27nmol/L @24h AND <66% increase at 3 vs 3.5h

Sensitivity:88%

Specificity:76%

More samples required more time consuming, more expensive

27
Q

what are the targets for dopamine treatment?

A

Dopamine and Serotonin

Loss of dopaminergic neurons with aging

Lower dopamine levels allow growth of neoplastic cells and increased activity

Dopamine is an INHIBITORY neurotransmitter

Interacts with dopamine (D2) receptors on the melanotrophs of the pars intermedia. In contrast, serotonin acts as an excitatory neurotransmitter

Dopamine agonists

  • Pergolide
  • Bromocriptine

Serotonine antagonists

  • Cyproheptadine
28
Q

How should pergolide (prascend) be used?

A
  • Starting dose of 2 µg/kg SID (1x1mg tab for 500kg horse)
  • Recheck ACTH after 4 weeks
  • Lifelong treatment
  • Severe cases might not return to range but ACTH concentration should decrease considerably or clinical signs should improve
  • Clinical improvement within 4-6 weeks
  • If no improvement increase dose gradually:
    • 1µg/kg increases every 3-4weeks
    • Up to 10µg/kg (5mg/day)
  • Periodic assessment and increase dosage if:
    • ACTH increases
    • Lack of clinical improvement/deterioration
  • Some become anorexic
    • Reduce dose by 1µg/kg
    • Split dose to BID
    • Generally a transient phenomenon
  • Rarely also lethargy, colic and diarrhea
29
Q

How should Cyproheptadine (periactin) be used?

A
  • Start at 0.25mg/kg PO SID for 4-8 weeks
  • Increase to 0.25mg/kg PO BID for 4 weeks if no clinical improvement
  • But Pergolide should be used first to comply with cascade
  • Rare side effects: sedation, dry mucous membranes, tachycardia
30
Q

How is Vitex agnus-castus (herbal product) thought to work?

A
  • Supposed to stimulate dopamine receptor activity
  • Blinded study found no positive effect
31
Q

What is Trilostane (used in dogs not recommended for equids)?

A

Some subjective clinical improvement

Older studies found no improvement of DST

Currently not reccommended

32
Q

Outline general management of clinical signs?

A

Diet: adequate caloric intake vs restrictionConsider Insulin sensitivity status

Free choice hay (2%BWT)

Oil to supplement calories (1-2 cups daily)

Laminitis: NSAIDs + Farriery

Antimicrobials

±Vit E supplementations (preventing oxidative damage)

Frequent dental examinations

If PU/PD: plenty of access to water

Monitor FWEC (faecel worm egg count)

33
Q

Name the particulars of pergolide (prascend)?

A
  • Treatment of equine Cushing’s disease
  • Initial dose: 1mg total q24h by mouth
  • Maximum: 5mg total/day (Source: N: Frank)
  • 1mg tablets; pack of 60 for £70; pack of 160 for £140
  • Dopamine receptor agonist; replaces dopamine inhibition of melantrophs
  • Can see anorexia when treatment initiated, so gradually introduce
  • First expect to see improvement in attitude (brighter), then improved PU/PD, and then increased muscle mass and better haircoat shedding
  • Monitor use with plasma ACTH concentration or TRH stimulation test results
  • Approximate cost to client per month for a 500-kg horse: £1 per day; £30 to 45/mo
34
Q
A
35
Q

Name the particulars of Cyproheptadine?

A
  • Periactin
  • Treatment of Equine Cushing’s disease
  • 0.25mg/kg q24h by mouth for 2 weeks
  • Increase to q12h
  • 125mg for 500kg horse
  • Source 1: Periactin: 4mg x 30 = £1.23 wholesale
  • Source 2: Periactin: 4mg: 4p/tablet wholesale; 7p/tablet retail
  • Cyproheptadine frequently is combined with pergolide to treat PPID.
  • Cyproheptadine blocks serotonin, a brain chemical that stimulates POMC production. Often works for a while then loses its effectiveness
  • Serotonin (excitatory neurotransmitter) antagonist
  • Can cause Drowsiness and ataxia
  • “First expect to see improvement in attitude (brighter), then improved PU/PD, and then increased muscle mass and better haircoat shedding”
  • Monitor with Plasma ACTH concentration or TRH stimulation test results

Equine Final Year (102 decks)

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