19.4.1: PPID

Question 1

1

Answer 1

Question 2

2

Answer 2

Question 3

3

Answer 3

Question 4

4

Answer 4

Question 5

5

Answer 5

Question 6

6

Answer 6

Question 7

7

Answer 7

Question 8

8

Answer 8

Question 9

Where is CRH produced? What does it do?

Answer 9

• CRH is produced in the hypothalamus
• It acts on the corticotropes in the pars distalis to produce ACTH

Question 10

Where is TRH produced? What does it do?

Answer 10

• TRH is produced in the hypothalamus
• It acts on the melanotropes in the pars intermedia to produce ACTH

Question 11

How is ACTH produced in the pars intermedia and pars distalis?

Answer 11

• 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

Question 12

The activity of melanocytes and cell division in the pars intermedia is inhibited by

Answer 12

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

Question 13

The production of POMC in the pars intermedia can be stimulated by

Answer 13

TRH which travels in the blood (the hypothalamic portal system) from the hypothalamus to pars intermedia

Question 14

When is the output from the pars intermedia highest?

Answer 14

• 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

Question 15

True/false: just like dogs with Cushing’s, in PPID horses, we measure the amount and activity of cortisol.

Answer 15

False
In dogs we look at cortisol.
In horses we look at ACTH.

Question 16

Which of these is normal?

Answer 16

B is normal
A is grossly abnormal. There may be a single large adenomas or multiple smaller microadenomas in the pars intermedia.

Question 17

If the pars intermedia becomes enlarged, what other structures could it compress and what effect would this have?

Answer 17

Could compress the hypothalamus and optic chiasm
This could produce clinical signs

Question 18

How does PPID arise?

Answer 18

• 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

Question 19

What histological findings are there with PPID?

Answer 19

Question 20

What accumulates in the pars nervosa of horses with PPID?

Answer 20

Lipofuscin

Question 21

What cortisol level would you expect in a horse with PPID?

Answer 21

Low or slightly increased
Reason behind this is inconclusive.

Question 22

PPID signalment

Answer 22

• Ponies predisposed
• Animals betweem 18-25 y.o.; at least 7 y.o.

Question 23

Clinical signs of PPID

Answer 23

• 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)

Question 24

True/false: horses with PPID can have a higher parasite burden than expected.

Answer 24

True
Linked to alpha-MSH

Question 25

Which sign of PPID is shown here?

Answer 25

Hypertrichosis

Question 26

Which clinical signs of PPID is shown here?

Answer 26

Question 27

How do we test for PPID?

Answer 27

Baseline ACTH
TRH

Question 28

You are suspicious of PPID but the horse’s baseline ACTH was equivocal. What can you do now?

Answer 28

• Re-test
• TRH stim test

Question 29

What should you consider prior to testing for PPID?

Answer 29

• Stress, excitement, transport and sedation can all affect results

Question 30

First line treatment for PPID

Answer 30

Question 31

A horse has not responded as you hoped after 6 months of pergolide for PPID. What can you do now?

Answer 31

• 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

Question 32

Aside from pergolide and cyproheptadine, what other therapies are available for PPID?

Answer 32

Question 33

How does pergolide work?

Answer 33

It is a dopamine agonist (dopamine inhibits the pars intermedia)

Question 34

What side effects are associated with pergolide?

Answer 34

• 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

Question 35

How often will you recheck a horse with PPID after starting treatment?

Answer 35

• 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