Endocrine 2025 HPA Axis Disorders in LAs

Previously known as “Equine Cushing’s” but now known as:

Pituitary Pars Intermedia Dysfunction = PPID

not the same as human or canine Cushing’s!

Equine PPID is 100% of the time a __ problem in horses!

a pituitary problem

PPID is COMMON in what age of horses? Associated with what equine health problems?

• 20% of horses over age 15

• 30% of horses over age 30!

• basically older horses

Associated health problems

• weight loss

• tendon and ligament injuries

• infections

• laminitis

How does loss of dopaminergic inhibition happen in patients with PPID?

genetic predisposition?

Normal aging change - associated with oxidative stress?

Chronic inflammation? perhaps sequelae to obesity or insulin dysregulation?

What does the HPA axis look like in health? How does it respond?

stressor initiates cascade of responses that lead to the production of Cortisol which then is used as a negative feedback loop to stop production at the hypothalamus and pituitary steps.

Within the pituitary gland what hormones are produced and provide negative feedback?

Within the pars distalis - production of ACTH - stimulates adrenal cortex to make cortisol. Cortisol then used as negative feedback to stop production at the hypothalamus and pars distalis.

Within the pars intermedia - production of alpha-MSH CLIP - causes various cellular effects. When the hypothalamus is activated: produces CRH and Dopamine. Dopamine is the negative feedback here.

What does the HPA axis pathway look like in a patient with PPID?

Lack of dopamine negative feedback! Pars intermedia constantly making ACTH via the alpha-MSH! Therefore too much ACTH produced!

PPID clinical presentation

• think older horse

• abnormal shedding or excessive hair growth (hirutism)

• sweating disturbance - too little or too much sweat

• weight loss + muscle loss - might be masked by abnormal fat distribution

• tendon/ligament injuries

• chronic/recurrent laminitis

• increased susceptibility to infections

• maybe PUPD

Performing bloodwork on a suspected PPID horse, what abnormalities are you looking for?

• Stress leukogram - SMILED

• hyperglycemia (mild)

• maybe increased liver enzymes

• maybe UTI

Diagnosis for PPID is often done with:

clinical judgement!

strongly suspcious clinical signs: hypertrichosis/shedding changes, weight loss, laminitis, middle aged horse

What test could you use to screen for PPID? Can this be used to diagnose PPID?

Basal ACTH

CANNOT use this test for PPID diagnosis - several factors could affect the sample and cause false positive results

To interpret basal ACTH - you have to consider season! In the fall months basal ACTH seems to be the highest

Basal ACTH tests must be used in conjunction with

clinical signs and signalment

also comparing to time of the year - the ranges are different

What test is no longer conducted to diagnose PPID? Gives false positive in the fall.

DST dexamethasone suppression test - suppresses eACTH and cortisol

take pre sample, give Dex IM, then post sample

post sample should have higher than 1 mcg/dL to be PPID supportive

however test is specific but not sensitive!

Aside from ACTH basal test, which other diagnostic test can you use to check for PPID?

TRH stimulation test (thyrotropin releasing hormone)

TRH will cause increase in ACTH from pituitary so patients with PPID will have a SUPER increased response

more sensitive and specific in early disease stages but still be cautious if testing in the fall

True or false: Testing glucose for insulin resistance is diagnostic for PPID.

False: not diagnostic for PPID but important to test and manage insulin resistance

If the diagnostics are not confirming PPID but there are clinical signs, when should pets be retested?

What is the ideal PPID management? Is it an option for horses?

Removal of affected pituitary tissue

but not an option for horses

Medication management: decrease secretion of POMC-peptides

Using pergolide - a dopamine agonist

How often should PPID patients be retested? What clinical signs should be looked out for?

Hypoadrenocorticism in horses is not that common but transient HPA axis insuffiency is described in

premature foals

septic neonatal foals

horses with colic/systemic inflammation (SIRS)

horses undergoing intense exercise/training

Critical illness-related corticoidsteroid insufficiency (CIRCI)

What is CIRCI?

What are the 3 major pathophysiologic events of CIRCI?

Suppression of part(s) of the HPA axis by infection

altered cortisol metabolism

tissue resistance to glucocorticoids

What are diagnostic approaches to diagnose CIRCI?

Measurement of resting hormone concentrations can be hard to interpret

Dynamic testing is best choice! - ACTH stim test!

There is no perfect test for PPID but

TRH stim test is the best currently. If not able to do that, Basal ACTH is pretty good too. Watch out for fall season as this fluctuates ACTH levels!

True or False: you can use compounded pergolide to treat PPID

False! Only use Prascend!

CIRCI is common in septic foals and should be diagnosed with? What is the recommended treatment option?

ACTH stimulation test

Rx: time, sepsis management, ± low dose hydrocortisone