Pituitary pars intermedia dysfunction Flashcards
(21 cards)
Describe equine PPID.
“PPID is a neurodegenerative disease with loss of dopaminergic inhibitory input to the melanotropes of the pars intermedia”
- Disease of aged horses
- Slowly progressive
- Characterized by excessive production of ACTH
- ACTH excess results excessive cortisol production which results in insulin resistance and a lowered immune system.
NB this can occur WITH equine metabolic syndrome.
pituitary gland Located in
sella turcica
4 lobes of the pituitary:
Neurohypophysis (posterior pituitary):
* Pars nervosa
Adenohypophysis (anterior pituitary):
* Pars distalis
* Pars intermedia
* Pars tuberalis
(tubular sheath extends from the pars distalis and winds around the pituitary stalk)
Describe the activity of pars intermedia.
Pars intermedia has a seasonal rhythm with increased secretion when days shorten (Aug-Oct) in order to adapt to nutritional and metabolic
pressures of cold season.
- Inhibited by dopamine
- Stimulated by thyrotropin-releasing hormone from the hypothalamus.
- Possibly other unknown regulatory factors too.
- secretes α-melanocyte-stimulating hormone (α-MSH), and corticotropin-like intermediate peptide.
POMC = proopriomelanocortin is a hormone
precursor protein, precursor for ACTH, α-MSH/alfa melanocyte stimulating hormone etc.
In the presence of dopamine, secretion of proopiomelanocortin/POMC-derived hormones is decreased.
the pars intermedia of the pituitary gland can secrete ACTH (adrenocorticotropic hormone), but it’s more accurate to say that it produces precursors or fragments of ACTH.
Why does PPID occur?
Hyperplasia in pars intermedia: Single large or many small adenomas.
* Disease previously described as benign
neoplasia.
Now considered to be neurodegenerative disease with loss of dopaminergic inhibitory input to the melanotropes of the PI (hypothalamus doesn’t produce enough dopamine, PI enlarges).
- Precise cause unknown. Pathophysiology similar to human Parkinson’s disease.
- Contribution of oxidative stress?
- Impaired autophagy in the periventricular neurons?
Signalment of a PPID horse.
Very common among old horses and ponies.
* 15-30% among aged horses
* Age is greatest risk factor
* Typically diagnosed in 18-20-years old horses (any
horse older than 10 should be tested if suspicion).
* Hardly ever less than 10 y.
* No breed or sex predisposition
8 Main clinical signs of PPID.
hirsutism
muscle atrophy
laminitis (due to high insulin & high cortisol)
PU/PD
hyperhydrosis
regional adiposity
lethargy
neuro signs (Ataxia, blindness, narcolepsy, seizures)
Hair coat signs of PPID.
- Hirsutism (excessive hair growth)
- Delayed shedding
- Incomplete shedding
- Lightening of the coat color
Pathophysiology of these changes has not been studied but correlation or association has been:
* 90% of horses with hirsutism were PPID positive
* Horses with shedding abnormalities were 5 times
more likely PPID positive
Muscle atrophy signs of PPID.
Sarcopenia: mostly topline (epaxial and gluteal muscles).
* Common in aged horses without PPID as well.
Possible mechanisms:
* hyperglycemia
* insulin resitance
* chronic inflammation
PU/PD signs in PPID.
- In 30% of PPID horses
Causes:
* Pars nervosa compression leads to loss of antidiuretic hormone production.
* High cortisol leads to increased thirst.
* Hyperglycemia and glucosuria lead to osmotic diuresis.
Renal values are normal in these horses and the kidneys can concentrate urine.
Regional adiposity sign in PPID.
- In 15-30% of PPID horses.
- Insulin resistance present in 60% PPID horses.
Typical locations:
* supraorbital fossa
* crest of the neck
* over the tailhead
* mammary/sheath region
Clinical signs: immunosuppression in PPID.
Levels of several immunosuppressive hormones higher in PPID horses.
Secondary infections found in 35% of PPID horses.
- Sinusitis
- dermatophilosis aka rain scald, pictured (caused by the spore-forming bacterium Dermatophilus congolensis)
- pneumonia
- hoof abscesses etc.
- More susceptible to endoparasitism.
!! These are older horses with already age-related reduction of immunity.
NEUROLOGICAL SIGNS in PPID
- Ataxia, blindness, narcolepsy, seizures
6-50% of PPID horses (depending on the studied population!). More common compared to aged horses without PPID.
Bloodwork findings in PPID horses.
- Hyperglycemia – non-specific though
- Increased liver enzymes: GGT, GLDH, AST due to steroid induced hepatopathy. Reported in over 70% of PPID horses.
- Information about secondary diseases present because these horses also often have infections – important to rule out.
Gold standard test for the diagnosis of equine PPID.
There is no gold standard antemortem test. Diagnosis not so straightforward as once thought.
* Slow progressive nature
* Early disease may be not shown by testing
* False positives in autumn (ACTH levels rise)
* One testing strategy not optimal for every individual case.
* Characteristic signs are seen in advanced cases! Not in mild cases.
Potential tests:
* Resting cortisol (unreliable)
* Resting ACTH
* Dexamethasone suppression test
* Thyrotropin releasing hormone stimulation test – best but not available outside USA.
* Combined dexamethasone suppression/ TRH stimulation test.
Describe diagnosis of PPID using plasma ACTH/ α-MSH concentration.
Advantage:
* one sample
* informative
* α-MSH: increased accuracy compared to plain ACTH
Disadvantages:
* season affects results greatly: use seasonal references for ACTH and α-MSH
* ACTH increases also with stress, competition, exercise, disease
* α-MSH not commercially available currently
natural changes in their endocrine system, primarily driven by photoperiod (day length) and preparation for winter. Shortening days (late summer into autumn) stimulate the pars intermedia of the pituitary gland. This part of the pituitary becomes more active and produces more ACTH. Cortisol helps Regulate metabolism (especially fat and energy storage) & Manage stress during colder months.
Describe diagnosis of PPID using the dexamethasone suppression test.
Test principle: dexamethasone inhibits ACTH release from the pars distalis resulting in suppression of cortisol release.
* In PPID horses, cortisol is not suppressed because ACTH is coming from pars intermedia instead, which is not influenced by glucocorticosteroids.
Testing:
* 1. Measure baseline blood cortisol
* 2. Suppress with dexamethasone (0,04mg/kg IM)
* 3. Measure blood cortisol again (20h later)
* Cortisol level over 27 nmol/L (over 10 mg/ml or over 1 ug/dl) is suggestive of PPID.
Previously considered gold standard but will only detect advanced cases.
Describe diagnosis of PPID using the TRH stimulation test.
Test principle: PPID horses have 30-50% increase in serum ACTH and cortisol after administration of TRH.
* No grain for 12 hrs
* Baseline ACTH
* admin. 0.5 to 1 mg TRH IV
* Re-test in 10 minutes
* Normal horses do not respond to TRH administration.
Advantage: safe and fast
Disadvantage: False positives very common; TRH is expensive/unavailable outside the USA.
- Test accuracy can be improved with combined dexamethasone suppression/TRH stimulation but Disadvantage of this: Several samples needed in 24h.
Tx of equine PPID.
- Not curable But is manageable.
- Not preventable
- Associated with ageing
- Early diagnosis and laminitis prevention are key factors.
- drug Pergolide mesylate is used lifelong
- drug Cyproheptadine may be used in combination bu t not on its own
Describe Treatment of PPID using Pergolide mesylate.
- Dopamine receptor agonist
- Decreased POMC peptide production
- Usually started 1mg per horse (start at 2 ug/kg, can go up to 10 ug/kg). Total daily dose up to 5 mg/ horse.
- Titrated to effect by assessing changes in clinical signs.
- Can take months to have an effect
- Recheck ACTH every 6-12 months
- Side effects are uncommon. Most common: anorexia; helps to decrease the dose and increase gradually.
Medication is daily and lifelong – dosage may increase over time (probably because of disease progression).
Treatment of PPID using Cyproheptadine.
- Serotonin antagonist, antihistaminic, antimuscarinic
- Not useful as monotherapy
- Additional drug if maximal doses of pergolide are not effective.
- Be cautious in horses that have neurologic disease/seizures.
In dogs and cats, cyproheptadine is often used as an appetite stimulant.
