PPID Flashcards
How many lobes of the pituitary are there?
3: pars intermedia, anterior pituitary, and posterior pituitary
Where does dopamine usually come from?
- Hypothalamus
Normal pituitary function
- see slide
Normal HPA axis with ACTH and cortisol
- SEE the slide
What stimulates pars intermedia hormone release generally?
- 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
What is the primary dysfunction in horses with PPID?
- Do not have enough dopamine
- Not regulated by negative feedback of cortisol
Pars intermedia melanotrope production
- Proopiomelanocortin
- Cleaved by prohormone convertase 1 to ACTH
Products of ACTH
- alpha-MSH
- Beta endorphins
- CLIP
- Prohormone convertase 2
Alpha-MSH
- 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)
Corticotropin-like Intermediate Lobe Peptide (CLIP)
- Beta endorphin opioid agonist
- Functions in analgesia and reduction of pain associated inflammation
When are ACTH and alpha-MSH highest normally?
- Autumn (July-November)
- Helps prepare for metabolic and nutritional pressures of winter
When is ACTH and alpha-MSH lowest (nadir)?
- June
- Summer solstice
Epidemiology of PPID
- Common endocrinopathy of aged horses and ponies
Disease prevalence of PPID
- 15-30% in aged horses
How common are hair coat abnormalities in aged horses with PPID?
- 14-30%
What’s the most important risk factor for PPID?
- Age
- Most clinical signs between 18-20 years
- Questions in any horse over 14 years old, but tends to be older
Sex predilection of horses with PPID
- None
Breed predilection of horses with PPID
- Conflicting results
Geographic location of horses with PPID
- Not studied…yay
Changes often seen in pars intermedia
- Hyperplasia
- Single adenoma or multiple adenomas
- neurodegenerative disease
- Loss of dopaminergic inhibitory input to melanotropes
Timing of PPID
- Slowly progressive disease
Oxidative stress in horses with PPID
- Oxidative stress (histology shows 16x increase in levels of oxidative stress marker 3-nitrotyrosine compared to healthy adult horses)
Early changes in horses with PPID
- Decreased athletic performance
- change in attitude/lethargy
- Delayed hair coat shedding
- Change in body conformation
- Regional adiposity
- Laminitis
Late changes in horses with PPID
- Lethargy
- Generalized hypertrichosis
- Loss of seasonal shedding
- Skeletal muscle atrophy
- Abnormal sweating
- PU/PD
- Regional adiposity
- Recurrent infections
- Repro issues
- Laminitis
- Hyperglycemia
- Neuro deficits
Hirsutism/Hypertrichosis
- 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
Laminitis in PPID
- Endocrine disease is the most common cause of laminitis
- Both PPID and EMS are associated with increased risk
- Hyperinsulinemia has been implicated
PU/PD in PPID
- 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
Abnormal fat distribution in PPID
- 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
Insulin resistance in PPID
- 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
Which infections are common in PPID?
- Dermatophilus (gram positive bacteria)
- Primary sinus infection
- Pneumonia
- Hoof abscesses
- All of the above
How common are secondary infections in horses with PPID?
- Very - 35% of horses approximately
Why are secondary infections so common in horses with PPID?
- 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
Fecal strongyle egg counts in horses with PPID
Higher fecal strongyle egg counts
Which immunosuppressive hormones are increased in PPID?
- Higher serum cortisol concentration
- Also alpha-MSH, Beta-endorphin, and ACTH
- Alter immune response and create a pathogen permissive environment
Aging and immunosuppression in general
- 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
Behavioral abnormalities seen with PPID
- Becoming lethargic or docile
Why could animals with PPID be lethargic?
- Insulin resistance
- Concurrent disease
- High plasma Beta-endorphin concentrations
What should be on the dfdx list of aged mares that fail to conceive or have abnormal estrous cycles?
- PPID
What can contribute to infertility of mares with PPID?
- Decreased dopaminergic regulation of hormonal output and chronic uterine infections may contribute to infertility in mares with PPID
Pergolide and fertility
- Pergolide may restore reproductive function and normal cycling
Safety of pergolide in pregnant mares
- Appears to be safe
- Must stop before parturition if you want them to produce milk
When should you discontinue pergolide in the pregnancy to avoid agalactia?
- A month before foaling
Neurologic disease in horses with PPID
- 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
Routine blood work in PPID results
- 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)
Hepatophy in horses with PPID
- Seen in 73% of horses with PPID
- May include increased liver enzymes
- Histopathology shows swollen vacuolated hepatocytes
Dexamethasone suppression test for diagnosis of PPID
- NO LONGER RECOMMENDED
Recommended tests for early PPID
- TRH stimulation test using ACTH (NOT CORTISOL)
- Resting endogenous ACTH concentrations
Recommended tests for obvious clinical signs with moderate to advanced PPID
- Resting endogenous ACTH concentrations
Normal resting Endogenous ACTH and positive for PPID
- Negative: <30
- Equivocal: 30-50 (do a TRH)
- Positive: >50
Normal resting Endogenous ACTH and positive for PPID in Fall months (MId-July to Mid November)
- Negative: <50
- Equivocal: 50-100
- Positive: >100
TRH stim Test time period
- December to June
TRH stim test protocol
- 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
TRH Stim Test Interpretation for December to June reference intervals
0 minutes
- Negative: <35
- Equivocal: 30-50
- Positive: >50
TRH Stim Test Interpretation for December to June reference intervals
10 minutes post
- <110
- 100-200
- > 200
Moderately recommended tests
- Overnight Dexamethasone suppression test
- MRI imaging of pituitary (only macroadenomas
Not recommended tests for PPID diagnosis
- ACTH stim
- Resting cortisol
- Diurnal cortisol
- TRH stim test with cortisol
- Urinary cortisol
- Salivary cortisol
- Oral domperidone challnege
- etc.
Fasting Insulin Concentration
- Glucose measure as well
- Easily performed
- can be combined with endogenous ACTH measurement
Limitation of Fasting INsulin Concentration
- Lower sensitivity when compared to oral sugar test
Results of fasting insulin concentrations for PPID
- 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
Treatment for PPID
- FDA approve Pergolide
- Once a day oral medication
Monitoring before and after starting Pergolide
- Perform a baseline test prior to starting and recheck in a month
Improvement in the first 30 days with PPID
- improved attitude
- Improvement of PU/PD
- Increased activity
- Control of hyperglycemia
Improvement in the first 10-12 months with PPID
- Improvement of hair coat abnormalities
- Less pronounced round abdomen
- Decrease infections
- Increased skeletal mass
- Fewer/milder laminitis episode
How should you assess PPID response to treatment and when should you assess it?
- Test used to diagnose PPID should be rechecked at 30 days
- Period of two months rquired before conclusions drawn about change in clinical signs
If adequate lab response…
- 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
If inadequate lab response with good clinical response
- Positive test results at 30 days
- Patient doing well
- Dosage could be held or increased
- Veterinary preference
Inadequate lab response with poor clinical response
- Positive at 30 days and not responding well clinically
- Increase dosage
- Recheck again in 30 days
Other treatment strategies for horses not responding to treatment
- Increase dosage
- Add cyproheptadine
What is the best test for diagnosis of early disease for PPID?
- TRH
