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Equine Medicine Final > PPID > Flashcards

PPID Flashcards

1
Q

How many lobes of the pituitary are there?

A

3: pars intermedia, anterior pituitary, and posterior pituitary

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2
Q

Where does dopamine usually come from?

A
  • Hypothalamus
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3
Q

Normal pituitary function

A
  • see slide
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4
Q

Normal HPA axis with ACTH and cortisol

A
  • SEE the slide
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5
Q

What stimulates pars intermedia hormone release generally?

A
  • Stimulated by thyrotropin releasing hormone (TRH)
  • Robust seasonal rhythm with increase output as day length shortens
  • Other factors may be involved and just haven’t been revealed
  • Dopamine inhibits pars intermedia hormone release
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6
Q

What is the primary dysfunction in horses with PPID?

A
  • Do not have enough dopamine

- Not regulated by negative feedback of cortisol

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7
Q

Pars intermedia melanotrope production

A
  • Proopiomelanocortin

- Cleaved by prohormone convertase 1 to ACTH

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8
Q

Products of ACTH

A
  • alpha-MSH
  • Beta endorphins
  • CLIP
  • Prohormone convertase 2
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9
Q

Alpha-MSH

A
  • Product of POMC
  • Extra biologic effects via interaction with G protein coupled melanocortin receptors
  • Role in metabolism and obesity
  • Potent anti-inflammatory hormone
  • Powerful anti-pyretic
  • 25,000x more potent than acetaminophen in reducing fever
  • decreases inflammatory cytokines and chemokines (can’t find infections as well)
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10
Q

Corticotropin-like Intermediate Lobe Peptide (CLIP)

A
  • Beta endorphin opioid agonist

- Functions in analgesia and reduction of pain associated inflammation

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11
Q

When are ACTH and alpha-MSH highest normally?

A
  • Autumn (July-November)

- Helps prepare for metabolic and nutritional pressures of winter

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12
Q

When is ACTH and alpha-MSH lowest (nadir)?

A
  • June

- Summer solstice

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13
Q

Epidemiology of PPID

A
  • Common endocrinopathy of aged horses and ponies
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14
Q

Disease prevalence of PPID

A
  • 15-30% in aged horses
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15
Q

How common are hair coat abnormalities in aged horses with PPID?

A
  • 14-30%
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16
Q

What’s the most important risk factor for PPID?

A
  • Age
  • Most clinical signs between 18-20 years
  • Questions in any horse over 14 years old, but tends to be older
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17
Q

Sex predilection of horses with PPID

A
  • None
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18
Q

Breed predilection of horses with PPID

A
  • Conflicting results
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19
Q

Geographic location of horses with PPID

A
  • Not studied…yay
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20
Q

Changes often seen in pars intermedia

A
  • Hyperplasia
  • Single adenoma or multiple adenomas
  • neurodegenerative disease
  • Loss of dopaminergic inhibitory input to melanotropes
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21
Q

Timing of PPID

A
  • Slowly progressive disease
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22
Q

Oxidative stress in horses with PPID

A
  • Oxidative stress (histology shows 16x increase in levels of oxidative stress marker 3-nitrotyrosine compared to healthy adult horses)
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23
Q

Early changes in horses with PPID

A
  • Decreased athletic performance
  • change in attitude/lethargy
  • Delayed hair coat shedding
  • Change in body conformation
  • Regional adiposity
  • Laminitis
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24
Q

Late changes in horses with PPID

A
  • Lethargy
  • Generalized hypertrichosis
  • Loss of seasonal shedding
  • Skeletal muscle atrophy
  • Abnormal sweating
  • PU/PD
  • Regional adiposity
  • Recurrent infections
  • Repro issues
  • Laminitis
  • Hyperglycemia
  • Neuro deficits
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25
Q

Hirsutism/Hypertrichosis

A
  • development of abnormal hair coat
  • Lightening of coat color
  • 5x more likely to have positive PPID test than aged horses with normal coats
  • Unknown mechanism
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26
Q

Laminitis in PPID

A
  • Endocrine disease is the most common cause of laminitis
  • Both PPID and EMS are associated with increased risk
  • Hyperinsulinemia has been implicated
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27
Q

PU/PD in PPID

A
  • 30% of horses
  • Loss of ADH due to compression of pars nervosa
  • Increased thirst due to actions of hypercortisolemia
  • Osmotic diuresis because of hyperglycemia and glucosuria
  • Some horses have marked hyperglycemia without incrase in water intake
  • Osmotic diuresis less likely at least in some cases of PPID
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28
Q

Abnormal fat distribution in PPID

A
  • 15-30% of horses
  • Fat pads usually located above the eyes in the supraorbital fossa
  • Along the crest of the neck
  • Over the tail head
  • In sheath and mammary region
  • Unclear if it results from PPID or is a predisposing factor for PPID
29
Q

Insulin resistance in PPID

A
  • 60% of horses with PPID have insulin resistance
  • Increased fasting insulin levels
  • Adiposity and insulin resistance cause chronic inflammation and mitochondrial impairment resulting in chronic stress
  • May have a role in development of PPID
  • Need some other studies to determine this
30
Q

Which infections are common in PPID?

A
  • Dermatophilus (gram positive bacteria)
  • Primary sinus infection
  • Pneumonia
  • Hoof abscesses
  • All of the above
31
Q

How common are secondary infections in horses with PPID?

A
  • Very - 35% of horses approximately
32
Q

Why are secondary infections so common in horses with PPID?

A
  • More likely to have occult infections likely lack of inflammatory response to pathogens
  • Necropsy results show pathologic evidence of chronic pneumonia without history of clinical disease
33
Q

Fecal strongyle egg counts in horses with PPID

A

Higher fecal strongyle egg counts

34
Q

Which immunosuppressive hormones are increased in PPID?

A
  • Higher serum cortisol concentration
  • Also alpha-MSH, Beta-endorphin, and ACTH
  • Alter immune response and create a pathogen permissive environment
35
Q

Aging and immunosuppression in general

A
  • Aging without disease associated with changes in immune function
  • Loss in the ability to respond appropriately to challenges
  • Baseline inflammatory state
  • PPID horses have a leukocyte pro-inflammatory cytokine profile typical of adult horses, not aged horses
36
Q

Behavioral abnormalities seen with PPID

A
  • Becoming lethargic or docile
37
Q

Why could animals with PPID be lethargic?

A
  • Insulin resistance
  • Concurrent disease
  • High plasma Beta-endorphin concentrations
38
Q

What should be on the dfdx list of aged mares that fail to conceive or have abnormal estrous cycles?

A
  • PPID
39
Q

What can contribute to infertility of mares with PPID?

A
  • Decreased dopaminergic regulation of hormonal output and chronic uterine infections may contribute to infertility in mares with PPID
40
Q

Pergolide and fertility

A
  • Pergolide may restore reproductive function and normal cycling
41
Q

Safety of pergolide in pregnant mares

A
  • Appears to be safe

- Must stop before parturition if you want them to produce milk

42
Q

When should you discontinue pergolide in the pregnancy to avoid agalactia?

A
  • A month before foaling
43
Q

Neurologic disease in horses with PPID

A
  • Ataxia, blindness, seizures, and narcolepsy in 6% to 50% of PPID
  • In a herd of 37 aged horses, neurologic dysfunction was noted in horses with PPID (27%) than in normal aged horses
44
Q

Routine blood work in PPID results

A
  • Not diagnostic
  • May provide information regarding general health and PPID associated secondary infections
  • Hyperglycemia, hyperlipidemia, Hypertriglyceridemia
  • Relative neutrophilia and lymphopenia
  • Many are clinically normal
  • May include increased liver enzymes (indicating steroid induced hepatopathy)
45
Q

Hepatophy in horses with PPID

A
  • Seen in 73% of horses with PPID
  • May include increased liver enzymes
  • Histopathology shows swollen vacuolated hepatocytes
46
Q

Dexamethasone suppression test for diagnosis of PPID

A
  • NO LONGER RECOMMENDED
47
Q

Recommended tests for early PPID

A
  • TRH stimulation test using ACTH (NOT CORTISOL)

- Resting endogenous ACTH concentrations

48
Q

Recommended tests for obvious clinical signs with moderate to advanced PPID

A
  • Resting endogenous ACTH concentrations
49
Q

Normal resting Endogenous ACTH and positive for PPID

A
  • Negative: <30
  • Equivocal: 30-50 (do a TRH)
  • Positive: >50
50
Q

Normal resting Endogenous ACTH and positive for PPID in Fall months (MId-July to Mid November)

A
  • Negative: <50
  • Equivocal: 50-100
  • Positive: >100
51
Q

TRH stim Test time period

A
  • December to June
52
Q

TRH stim test protocol

A
  • Administer 1 mg thyrotropin releasing hormone
  • Blood samples collected in EDTA tubes at 0 (preTRH) and exactly 10 minutes after TRH administration
  • Submit plasma for measurement of ACTH concentrations
53
Q

TRH Stim Test Interpretation for December to June reference intervals

0 minutes

A
  • Negative: <35
  • Equivocal: 30-50
  • Positive: >50
54
Q

TRH Stim Test Interpretation for December to June reference intervals

10 minutes post

A
  • <110
  • 100-200
  • > 200
55
Q

Moderately recommended tests

A
  • Overnight Dexamethasone suppression test

- MRI imaging of pituitary (only macroadenomas

56
Q

Not recommended tests for PPID diagnosis

A
  • ACTH stim
  • Resting cortisol
  • Diurnal cortisol
  • TRH stim test with cortisol
  • Urinary cortisol
  • Salivary cortisol
  • Oral domperidone challnege
  • etc.
57
Q

Fasting Insulin Concentration

A
  • Glucose measure as well
  • Easily performed
  • can be combined with endogenous ACTH measurement
58
Q

Limitation of Fasting INsulin Concentration

A
  • Lower sensitivity when compared to oral sugar test
59
Q

Results of fasting insulin concentrations for PPID

A
  • Hyperinsulinemia if fasting >50
  • Persistent hyperglycemia would indicate diabetes mellitus (insulin normal or increased)
  • High insulin is significant, but a normal insulin is not diagnostically meaningful
  • Can be found in normal horses and in PPID horses
60
Q

Treatment for PPID

A
  • FDA approve Pergolide

- Once a day oral medication

61
Q

Monitoring before and after starting Pergolide

A
  • Perform a baseline test prior to starting and recheck in a month
62
Q

Improvement in the first 30 days with PPID

A
  • improved attitude
  • Improvement of PU/PD
  • Increased activity
  • Control of hyperglycemia
63
Q

Improvement in the first 10-12 months with PPID

A
  • Improvement of hair coat abnormalities
  • Less pronounced round abdomen
  • Decrease infections
  • Increased skeletal mass
  • Fewer/milder laminitis episode
64
Q

How should you assess PPID response to treatment and when should you assess it?

A
  • Test used to diagnose PPID should be rechecked at 30 days

- Period of two months rquired before conclusions drawn about change in clinical signs

65
Q

If adequate lab response…

A
  • Dose of Prascend held constant
  • 6 month recheck schedule with one appointment between August and October
  • Allows assessment of patient during seasonal increase in ACTH
  • Ensures treatment adequate during this time
66
Q

If inadequate lab response with good clinical response

A
  • Positive test results at 30 days
  • Patient doing well
  • Dosage could be held or increased
  • Veterinary preference
67
Q

Inadequate lab response with poor clinical response

A
  • Positive at 30 days and not responding well clinically
  • Increase dosage
  • Recheck again in 30 days
68
Q

Other treatment strategies for horses not responding to treatment

A
  • Increase dosage

- Add cyproheptadine

69
Q

What is the best test for diagnosis of early disease for PPID?

A
  • TRH

Equine Medicine Final (10 decks)

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