19.4.1: PPID Flashcards
1
2
3
4
5
6
7
8
Where is CRH produced? What does it do?
- CRH is produced in the hypothalamus
- It acts on the corticotropes in the pars distalis to produce ACTH
Where is TRH produced? What does it do?
- TRH is produced in the hypothalamus
- It acts on the melanotropes in the pars intermedia to produce ACTH
How is ACTH produced in the pars intermedia and pars distalis?
- ACTH is produed via cleavage of POMC in the pars intermedia and pars intermedia
- POMC is cleaved by prohormone convertase 1
- In the pars intermedia only ACTH is further converted by prohormone convertase 2 to produce biologically active molecules e.g. alpha-MSH and CLIP
- In the normal animal, most ACTH is produced by the pars distalis and very little ACTH in the blood comes from the pars intermedia because this is converted into other hormones
The activity of melanocytes and cell division in the pars intermedia is inhibited by
Dopamine from the periventricular neurones (these have cell bodies in the hypothalamus)
* This controls the amount of POMC and ACTH produced
* Dopamine increase -> less ACTH and other peptides
The production of POMC in the pars intermedia can be stimulated by
TRH which travels in the blood (the hypothalamic portal system) from the hypothalamus to pars intermedia
When is the output from the pars intermedia highest?
- Output from the pars intermedia increases with shorter day lengths
- Concentrations of hormones in plasma is greatest during autumn
- When measuring ACTH, we have to take time of year into account
True/false: just like dogs with Cushing’s, in PPID horses, we measure the amount and activity of cortisol.
False
In dogs we look at cortisol.
In horses we look at ACTH.
Which of these is normal?
B is normal
A is grossly abnormal. There may be a single large adenomas or multiple smaller microadenomas in the pars intermedia.
If the pars intermedia becomes enlarged, what other structures could it compress and what effect would this have?
Could compress the hypothalamus and optic chiasm
This could produce clinical signs
How does PPID arise?
- There is loss of dopamine inhibition
- This results in hyperplasia of the pars intermedia
- This leads to increased POMC -> too much ACTH
- This is often slow onset and insidious
What histological findings are there with PPID?
What accumulates in the pars nervosa of horses with PPID?
Lipofuscin
What cortisol level would you expect in a horse with PPID?
Low or slightly increased
Reason behind this is inconclusive.
PPID signalment
- Ponies predisposed
- Animals betweem 18-25 y.o.; at least 7 y.o.
Clinical signs of PPID
- Muscle atrophy esp postural muscles: epaxial, neck, rump, pot belly appearance
- Hair abnormalities: dull coat, retained hair in some locations e.g. jugular furrow, submandibular space, pastern; hypertrichosis
- Dull, lack of energy
- Poor performance
- Regional adiposity
- Metabolic shifts: hyperinsulinaemia and laminitis
- Secondary bacterial infections e.g. sinusitis, skin infections, foot abscesses, bronchopneumonia
- Hyperhidrosis/anhidrosis
- PUPD (mild and uncommon)
True/false: horses with PPID can have a higher parasite burden than expected.
True
Linked to alpha-MSH
Which sign of PPID is shown here?
Hypertrichosis
Which clinical signs of PPID is shown here?
How do we test for PPID?
Baseline ACTH
TRH
You are suspicious of PPID but the horse’s baseline ACTH was equivocal. What can you do now?
- Re-test
- TRH stim test
What should you consider prior to testing for PPID?
- Stress, excitement, transport and sedation can all affect results
First line treatment for PPID
A horse has not responded as you hoped after 6 months of pergolide for PPID. What can you do now?
- Increase pergolide dose (6ug/kg is extra-label)
- Add cyproheptadine 0.25mg/kg PO BID
- If lack of clinical response: assess concurrent disease (EMS in 33% cases), corrective shoeing, diet
Aside from pergolide and cyproheptadine, what other therapies are available for PPID?
How does pergolide work?
It is a dopamine agonist (dopamine inhibits the pars intermedia)
What side effects are associated with pergolide?
- Generally very well tolerated
- Most common side effect: decreased appetite at start of treatment
- Resolve this by stopping treatment for a few days, then giving half dose, and then gradually increasing back up to full dose
- Other side effects: anorexia, lethargy, mild CNS signs e.g. depression and mild ataxia, sometimes diarrhoea and colic and rarely sweating
How often will you recheck a horse with PPID after starting treatment?
- Test bloods a week/ a month later -> assess basal ACTH levels
- Assess resolution of clinical signs, fewer episodes of laminitis etc.
- Assess BCS, perform clinical exam
