Endocrino

Question 1

What dosage of pergolide mesylate can be used in donkeys?
What is the new hypothesis of absoption?

Answer 1

Pergolide mesylate administration to donkeys at 2 μg/kg bwt orally q24h (same as horses) → well-tolerated, with plasma concentrations similar to or higher than concentrations achieved in horses dosed similarly.
This study provides the first report of oral transmucosal abs° in equids.

Pharmacokinetic properties of pergolide mesylate following single and multiple-dose administration in donkeys (Equus asinus)
evj 2023

Question 2

Which months have the lowest and highest TRH-stimulated ACTH concentrations?

Answer 2

TRH-stimulated ACTH concentrations were lowest in February-May and highest in August-October.

Evaluation of seasonal influences on adrenocorticotropic hormone response to the thyrotropin-releasing hormone stimulation test and its accuracy for diagnosis of pituitary pars intermedia dysfunction
Vet J 2023

Question 3

What is the clinical implications of imprecise sampling time for 10- and 30-min TRH stimulation tests ? Which protocol to prefer ?

Answer 3

10-min protocol : In one report, sampling 1 min early or late resulted in deviation of the ACTH concentration by ≥10% in 75% of horses and led to an erroneous diagnosis of PPID status in 21% horses.
30-min protocol : The gradient of the ACTH response curve to TRH administration is flatter at this time, resulting in less minute-to-minute variation.
⇒ Imprecision of >1 min is likely to be more impactful for the 10-min protocol.

Question 4

What are the potential bone sequelae observed in horses with PPID?

Answer 4

Bone mineral density of lumbar vertebrae (nonweight bearing bones) can be decreased with PPID (L3, L4, L5) and could increase risk of developing pathological fractures. Not observed in weight bearing bones (third metacarpus or metatarsus)

Lumbar vertebral bone density is decreased in horses with pituitary pars intermedia dysfunction
evj 2024

Question 5

What is the relationship between cortisol, ATCH and insulin in aged horses (> 15y) ?

Answer 5

There was no association between ACTH and cortisol.
Positive linear correlation between ACTH and post-OGT insulin in the autumn. In autumn, high ACTH was associated with ID, when no clinical signs of PPID were present.

Association between insulin dysregulation and adrenocorticotropic hormone in aged horses and ponies with no clinical signs of pituitary pars intermedia dysfunction
evj 2023

Question 6

How to interpret ACTH dosage tests in PPID ?

Answer 6

The combination of clinical signs and age informs the index of clinical suspicion prior to diagnostic testing.
Both pre-test probability of disease and season of testing have strong influence on the ability to diagnose PPID using basal ACTH or ACTH after TRH stimulation.
Thus, it should be remembered that the risk of an FP result increases in situations where there is a low pre-test probability.

BEVA primary care clinical guidelines: Diagnosis and management of equine pituitary pars intermedia dysfunction
evj 2024

Question 7

Does plasma ACTH dosage (basal and TRH-stimulation test) rather sensitive or specific?

Answer 7

The specificity of the test outweighs its sensitivity, indicating that low concentrations are more useful to rule out the disease than are high concentrations to confirm the disease.

Question 8

What is the effect of breed on plasma ACTH in equids ?

Answer 8

Breed differences in basal ACTH concentrations have been reported. Some pony breeds, donkeys, and Arabians have higher basal ACTH concentrations than horses, particularly in autumn.
Breed and time of year should be considered when interpreting plasma ACTH concentrations in equids suspected for PPID.

Question 9

Which breeds are predisposed to PPID ?

Answer 9

There is no evidence supporting a breed predisposition to PPID. Breed or type is of limited use for estimating pre-test probability.

Question 10

What is the effect of age on plasma ACTH in equids ?

Answer 10

Association between increasing horse age and increased ACTH concentrations in healthy horses and ponies.

Question 11

What is the prevalence of PPID in horses ?

Answer 11

The prevalence of PPID in equids aged ≥15 years is between 21% and 27%.
Odds of PPID increases by 18% in horses/ponies for every year > 15 years of age

Question 12

What are the clinical signs associated with high clinical suspicion of PPID ?

Answer 12

• Generalised or regional hypertrichosis
• Delayed / incomplete hair coat shedding

Question 13

What are the clinical signs associated with moderate clinical suspicion of PPID ?

Answer 13

• Hyperhydrosis
• Abnormal fat distribution / regional adiposity
• Epiaxial muscle atrophy
• Laminitis
• Weight loss
• Recurrent opportunistic infections
• Behavioural changes / docility / lethargy
• PUPD
• Pot-bellied appearance
• Bulging supra-orbital fat
• Lordosis
• Infertility

Question 14

What is the effect of geographical location on plasma ACTH in equids ?

Answer 14

Significant effect of latitude on ACTH concentration has been reported in both northern and southern hemispheres, reflecting differences in photoperiod.
Latitude-specific reference intervals are required when interpreting ACTH concentrations for PPID diagnosis.

Question 15

What factors influence ACTH concentration in healthy horses?

Answer 15

• Age
• Geographical location
• Season
• Breed

Question 16

What factors are associated with pre-test probability of PPID ?

Answer 16

• Age
• Clinical signs

Question 17

How accurate is the basal ATCH assay in diagnosing PPID?

Answer 17

Basal ACTH concentration in aged horses showing specific clinical signs of PPID will have a high PPV based on a high pre-test probability.
Basal ACTH concentrations in young horses showing few or non-specific signs of PPID will have a lower PPV, based on a low pre-test probability.

Question 18

How accurate is the TRH stimulation test in diagnosing PPID?

Answer 18

Where basal ACTH results fall in the equivocal zone, the TRH stimulation test can be used for further evaluation. It has increased accuracy in the diagnosis of PPID, particularly in subclinical cases.

Question 19

What is the repeatability of TRH-stimulation test in mature horses ?

Answer 19

Good repeatability in non-autumn months when performed at intervals of 2–4 week. However, during the autumn, more variation should be expected.
Smaller response of ACTH to TRH stimulation when repeated within 1 day.
⇒ TRH simulation tests for PPID should not be performed at intervals shorter than 24 h.

Question 20

How does the feeding affect basal ACTH or ACTH response (10 min) to TRH administration for diagnosing PPID ?

Answer 20

Conflicting results
There may be some effect of diet and/or feeding vs fasting on basal plasma ACTH concentrations, and fasting may also be relevant to TRH stimulation tests.
For repeated sampling of the same individual, it is prudent to test under similar dietary conditions.

Question 21

What factors could influence basal ACTH concentration or ACTH response (10 and 30 min) to TRH administration for diagnosing PPID?

Answer 21

• Diet
• Critical illness
• Breed
• Transport or acute stress
• Mild to moderate pain
• Concurrent OST testing
• Coat color ? (Grey horses may have higher basal ACTH than non-grey horses in autumn.)

Question 22

How does BCS affect basal ACTH concentration or ACTH response (10 and 30 min) to TRH administration for diagnosing PPID?

Answer 22

BCS may not impact testing for PPID

Question 23

What are the effects of pergolide on ACTH tests in PPID horses ?

Answer 23

Pergolide treatment lowers basal ACTH concentrations and improves the ACTH response to TRH stimulation in most animals.

Question 24

What are the effects of pergolide on clinical signs of PPID horses ?

Answer 24

Pergolide improves most clinical signs associated with PPID in most animals except laminitis

Question 25

Does PPID have a clinical impact on mares’ reproductive performance?

Answer 25

The reproductive performance of the high ACTH group was significantly lower than the other groups.

Relationship between endogenous plasma adrenocorticotropic hormone concentration and reproductive performance in Thoroughbred broodmares
JVIM 2021

Question 26

Does Chasteberry or cyproheptadine help in PPID horses ?

Answer 26

Chasteberry may improve some clinical signs of PPID but there is no proven effect on ACTH and there is no benefit to adding chasteberry to pergolide therapy.
Combination of cyproheptadine with pergolide is not superior to pergolide alone.

Question 27

What is the clinical efficacy of canagliflozin in ID horses ?
A- Canagliflozin decreased mean insulin concentration during OST, decreased body weight and increased triglyceride concentrations.
B- Canagliflozin decreased mean insulin concentration during OST and decreased body weight of horses, and did not impact triglyceride concentrations.
C- Canagliflozin decreased mean insulin concentration during OST and increased triglyceride concentrations, but did non decrease body weight of horses.
D- Canagliflozin was uneffective in decreasing hyperinsulinemia in ID horses.

Answer 27

A- Canagliflozin decreased mean insulin concentration during OST, decreased body weight and increased triglyceride concentrations.
Canagliflozin is a promising drug for treatment of ID horses that requires future studies.

Short-term effects of canagliflozin on glucose and insulin responses in insulin dysregulated horses: A randomized, placebo-controlled, double-blind, study
jvim 2023

Question 28

What is the clinical efficacy and side effects of ertugliflozin in HAL horses ?

Answer 28

After 30 days of treatment with ertugliflozin, there were:
- a reduction in insulin concentrations,
- lowering of insulin concentration in response to OST,
- improvement in modified Obel laminitis scores,
- increase in median serum triglyceride concentrations, but without any clinical signs of hyperlipaemia,
- 19% of PUPD during treatment.
Clinical efficacy observed by 4 days of TT.

Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses: A case series
eve 2023
Oral sugar test responses to ertugliflozin in ten horses with insulin dysregulation
eve 2024

Question 29

What is the more sensitive and specific test to diagnose ID in ponies between basal insulin concentration, OST and ITT ?
Is this test correlated with risk of laminitis ?

Answer 29

Basal insulin (BI) → Se 52% ; Spe 97% (low sensitivity)
OST → Se 84% ; Spe 60% (low specificity)
ITT → Se 85% ; Spe 88%
But only BI and the OST were associated with laminitis

Evaluation of field-testing protocols to diagnose insulin dysregulation in ponies using a Bayesian approach
vet J 2023

Question 30

Does continuous digital hypothermia effective in the treatment of hyperinsulinemic associated laminitis (HAL) ? What are the suspected mechasnisms ? (3 points)

Answer 30

Continuous digital hypothermia (CDH) prevents lamellar failure in the euglycemic hyperinsulinemic clamp (EHC) model of laminitis. These data add further support for the use of CDH as a first aid treatment for severe acute laminitis associated with hyperinsulinemia in horses.
Suspected mechanisms :
- decrease of pro-inflammatory cytokines and chemokines,
- decrease in lamellar glucose metabolism without affecting glucose concentration,
- decrease perfusion.

Effect of digital hypothermia on lamellar inflammatory signaling in the euglycemic hyperinsulinemic clamp laminitis model
jvim 2020
The effect of continuous digital hypothermia on lamellar energy metabolism and perfusion during laminitis development in two experimental models
evj 2020

Question 31

What is the mechanism of hyperinsulinemic associated laminitis during EHC model ?
A- Laminitis developed without evidence of lamellar hypoperfusion or energy stress. Therapies to improve perfusion are unlikely to affect the initial development of endocrinopathic laminitis.
B- Laminitis developed without evidence of lamellar hypoperfusion, but there was evidence of energy stress. Therapies to improve perfusion are unlikely to affect the initial development of endocrinopathic laminitis.
C- Laminitis developed with evidence of lamellar hypoperfusion, but no evidence of energy stress. Therapies to improve perfusion are likely to affect the initial development of endocrinopathic laminitis.
D- Laminitis developed with evidence of lamellar hypoperfusion and energy stress. Therapies to improve perfusion are likely to affect the initial development of endocrinopathic laminitis.

Answer 31

A- Laminitis developed without evidence of lamellar hypoperfusion or energy stress. Therapies to improve perfusion are unlikely to affect the initial development of endocrinopathic laminitis.

Lamellar energy metabolism and perfusion in the euglycaemic hyperinsulinaemic clamp model of equine laminitis
evj 2020

Question 32

What changes are observed during laminitis models?
A- Hypoaminoacidemia
B- Hyperaminoacidemia
C- No impact of insulin on plasma amino acid concentration
D- Nobody knows

Answer 32

Hypoaminoacidemia develops in EHC and PGI
laminitis models.
This finding may have relevance to laminitis because hypoaminoacidemia affects cell adhesion and cytoskeletal dynamics in human cells.

Plasma amino acid concentrations during experimental hyperinsulinemia in 2 laminitis models
jvim 2021

Question 33

What is the impact of intrasynovial triamcinolone treatment on the incidence of laminitis in a large population of sport horses ?

Answer 33

Intrasynovial triamcinolone acetonide administration does not increase the risk of laminitis in this study population.
A recent knowledge summary found “no conclusive evidence to support a causal association between therapeutic systemic corticosteroid administration and the development of laminitis in healthy adult horses/ponies”.

Intrasynovial triamcinolone treatment is not associated with incidence of acute laminitis
evj 2021

Question 34

What is the prevalence and risk factors associated with laminitis in donkeys ?

Answer 34

Prevalence of laminitis in UK Donkey Sanctuary ∼49%
Risk factors differ from those reported in horses:
- more likely to be younger,
- less likely to get extra feed or have an additional medical problem,
- less likely to have undergone dental work, movement, imaging or surgery in the month preceding the episode.

Cross- sectional study to identify the prevalence of and factors associated with laminitis in UK donkeys
evj 2022

Question 35

What is the current hypothesis regarding the pathophysiology of supporting limb laminitis (SLL) ?

Answer 35

Lamellar inflammatory signaling was higher in tissue from horses subjected to prolonged unilateral weight-bearing, suggesting that these pathways could be relevant to the pathophysiology of SLL.

Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing
jvim 2023

Question 36

Which diagnostic tests best quantify the risk of future laminitis development in nonlaminitic ponies ?

Answer 36

• Basal insulin (unfasted)
• OST (insulin T60 post corn syrup 0,3 mL/kg)
• Adiponectin concentration
• Divergent hoof growth

Predictors of laminitis development in a cohort of nonlaminitic ponies
evj 2023

Question 37

Which assessment is true about vitamin D status in horses ?
A-25(OH)D3 is the predominant metabolite in horses, which is depending on season.
B- 25(OH)D2 is the predominant metabolite in horses, with a seasonal effect and without endogenous production of vitamin D3.
C- 25(OH)D3 is the predominant metabolite in horses, which is independent on season.
D- 25(OH)D2 is the predominant metabolite in horses, which is independent on season.

Answer 37

Answer B
In horses, 25(OH)D2 is the predominant vitamin D metabolite, and there is an apparent lack of endogenous vitamin D3 production. In grazing ponies, 25(OH)D2 concentrations were significantly higher on long days compared to short days.

The effect of season, management and endocrinopathies on vitamin D status in horses
evj 2023

Question 38

prevalence of PPID? age related?

Answer 38

PPID prevalence increases with age, reaching 20% in equids 15 years of age and older and 30% in equids over 30 years of age

Endocrinology group 2023

Question 39

What are the Advanced clinicalsigns in PPID?

Answer 39

Strongly suggestive :
Generalized hypertrichosis.

Suggestive:     - Topline muscle atrophy    - Altered mentation    - Exercise intolerance    - Polyuria/polydipsia    - Recurrent infections

Possible comorbidities:
Infertility
Tendon or ligament laxity
Desmitis / tendonitis
Regional adiposity
Hyperinsulinemia-associated laminitis
Recurrent corneal ulcers
Increased mammary gland secretions

Endocrinology group 2023

Question 40

What are the early subtle CS in PPID?

Answer 40

Strongly suggestive :
Regional hypertrichosis/ delayed shedding .

Suggestive:
- Topline muscle loss
- Change attitude / lethargy
- Decreased performance
- Abnormal sweating (increased or decreased)

Possible comorbidities:
Infertility
Tendon or ligament laxity
Desmitis / tendonitis
Regional adiposity
Hyperinsulinemia-associated laminitis

Endocrinology group 2023

Question 41

Laboratory findings with PPID?

Answer 41

Lymphopenia and/or neutrophilia (in the absence of infection)
Hyperglycemia
Hyperinsulinemia
Hypertriglyceridemia
Hypophosphatemia
High fecal egg count

Endocrinology group 2023

Question 42

What are the consequences of PPID on muscles?

Answer 42

PPID affects muscle condition in horses by causing loss of topline muscle in early stages and topline muscle atrophy in advanced stages.

Endocrinology group 2023

Question 43

What is the procedure for conducting TRH test?

Answer 43

• Collect blood into EDTA tubes at baseline
  
  • Administer 0.5 mg (equids < 250 kg) or 1.0 mg (equids > 250 kg) of TRH intravenously
  • Collect blood samples at 0 and exactly 10 minutes after TRH administration
  • A second sample may also be collected 30 minutes after TRH administration if desired

Endocrinology group 2023

Question 44

How to collect ACTH?

Answer 44

• Collected into EDTA containing tubes
  
  • Kept cool (ice packs or refrigerator) at all times
  • Centrifuged and separated prior to shipping
  • Shipped via overnight mail with ice packs
  • Plasma can be frozen (centrifuged samples only) but avoid freeze-thaw cycles

Endocrinology group 2023

Question 45

ACTH vary with seasons, review it.

Answer 45

PPID Unlikely:
dec-june <15
july-nov <15
august <20
sept-oct <30

PPID likely
dec-june >40
july-nov >50
august >75
sept-oct >90

interprettive zone/grey zone betw! (CS, signalement)

Endocrinology group 2023

Question 46

TRH vary with seasons, review it.

Answer 46

10min post:
Jan-Jun <100 (unlikely ) >200 (likely)
july-dec <100 (unlikely). TRH stimulation testing is most useful to identify negativecases in these months. Not for likely!

30min post:
Jan-Jun <40 (unlikely ) >90 (likely)
july-dec <40 (unlikely). TRH stimulation testing is most useful to identify negativecases in these months. Not for likely!

grey zone betw!

Endocrinology group 2023

Question 47

Factors that influence ACTH level?

Answer 47

Season significantly impacts ACTH concentrations
Breed (arabian and donkeys higher acth at any season VS welsh and shetland higher in autumn)
Stress, excitement, and trailering can result in a transient increase in ACTH concentrations. Samples should not be collected within 30 minutes of trailering or in a visibly excited animal.
Sedation impacts endocrine responses. Diagnostic testing with baseline ACTH concentration should only be performed immediately (within 5-10 minutes) after sedation with xylazine or detomidine, with or without butorphanol.
Low to moderate pain of at least 24 hours duration does not appear to impact diagnostic testing with baseline ACTH or TRH stimulation testing. Testing may be performed in laminitic horses, but it is ideal to postpone until severe pain is controlled.

Endocrinology group 2023

Question 48

How to test an advanced clinical signs, old horse in a suspicion of PPID?

Answer 48

baseline ACTH; if grey zone -> TRH -> if grey zone ->3-6months reassess.
IF hypertrichosis generalized -> no test -> treat directly its ok

if grey zone -> use the lower threshold for diagnosis

Endocrinology group 2023

Question 48

What are the recommendations for the management of PPID horse?

Answer 48

1. Testing for PPID is not recommended in the absence of clinical signs.
2. Assessment for insulin dysregulation should be pursued in all patients with PPID.
3. Clinical signs and endocrine testing should be evaluated 1-3 months after starting treatment, and then every 6-12 months.
4. Special considerations for wellness care in horses with PPID include:
   
   • Regular attention to body condition, hoof care, dentistry, and parasite control
   • Monitoring for bacterial infections
   • Ensuring adequate water availability if polydipsia and polyuria are persistent problems
5. Diet and exercise management for horses with PPID:
   
   • Carefully monitor weight and body condition
   • Feed selection based on body condition score and evidence for insulin dysregulation
   • Obese horses should be placed on a lower energy diet and encouraged to follow an exercise program if soundness permits
   • Horses with insulin dysregulation require lower non-structural carbohydrate feeds and limited access to pasture
   • Monthly monitoring of BCS by owners is recommended

Endocrinology group 2023

Question 48

What are the recommendation for treatment management of a PPID horse?

Answer 48

1. The recommended initial treatment for PPID is Prascend® (pergolide tablets).
2. The initial dosage of Prascend® (pergolide) for PPID treatment is 2 mcg/kg (0.5 mg for a 250 kg pony and 1.0 mg for a 500 kg horse).
3. If there’s no improvement in clinical signs or laboratory results, the pergolide dose can be gradually increased (1-2ug/kg) then reassess (same season) 1-3months-> if persistant therefore its a refractory case
4. Strategies used for refractory cases include:
   
   • Gradually increasing pergolide to 4-6 mcg/kg (> 4 being off label)and adding cyproheptadine (0.25 mg/kg PO BID or 0.5 mg/kg PO SID)
   • OR gradually increasing pergolide to 10 mcg/kg (off label)
5. In the event that a horse on pergolide treatment misses a dose, ACTH concentrations may begin to increase within 48 hours.

the most important is the clinical signs

Endocrinology group 2023

Question 48

How to test a mild or early clinical signs of a young horse in a suspicion of ppid?

Answer 48

with TRH test. If grey zone -> reassess in 3-6months. Do not forget insulin.
IF grey zone -> use the upper threshold for the diagnosis

Endocrinology group 2023

Question 49

Does pergolide prolonge lifespan ?

Answer 49

No but improve quality of life

Endocrinology group 2023

Question 50

How does TRH affect the pars intermedia in horses with PPID?

Answer 50

TRH stimulates receptors on melanotropes in the pars intermedia, leading to increased secretion of proopiomelanocortin (POMC)-derived peptides, including ACTH. This response is exaggerated in horses with PPID compared to healthy controls

General knowledge. Evaluation of seasonnal influence on ACTH response to TRH test and its accuracy for diagnosis PPID

Question 51

How do seasonal variations affect ACTH responses to the TRH stimulation test in horses?
During which months are TRH-stimulated ACTH concentrations typically lowest and highest?
Why is TRH stimulation testing not recommended year-round?

Answer 51

• Seasonal variations significantly impact ACTH responses, with higher concentrations observed during autumn months (August-October) and lower concentrations during late winter and spring (February-May)
• TRH-stimulated ACTH concentrations are typically lowest from February to May and highest from August to October.
  • Due to marked seasonal variability, TRH stimulation testing is not recommended year-round as it can lead to a high probability of false positive results during certain months, particularly in autumn

Evaluation of seasonnal influence on ACTH response to TRH test and its accuracy for diagnosis PPID

Question 52

How does the specificity and sensitivity of TRH-stimulated ACTH compare to basal ACTH throughout the year?**

Answer 52

• The specificity of both basal and post-TRH ACTH is generally higher than sensitivity. However, TRH stimulation has improved diagnostic accuracy over basal ACTH, although its sensitivity does not significantly increase year-round

Evaluation of seasonnal influence on ACTH response to TRH test and its accuracy for diagnosis PPID

Question 53

What are the potential side effects observed after TRH administration in horses?

Answer 53

• Potential side effects include transient coughing, flehmen response, and yawning after administration

Endocrinology group 2023

Question 54

A 22-year-old Thoroughbred gelding presents with a history of delayed shedding and mild lethargy. You decide to perform a thyrotropin-releasing hormone (TRH) stimulation test to evaluate for pituitary pars intermedia dysfunction (PPID). You perform the test once and get equivocal results. You’re considering repeating the test in 2 weeks. Which of the following statements is most accurate regarding the repeatability of the TRH stimulation test?
A) The test has excellent repeatability in both winter and autumn
B) The test has excellent repeatability in winter but poor repeatability in autumn
C) The test has poor repeatability in winter but excellent repeatability in autumn
D) The repeatability of the test is not affected by season

Answer 54

The correct answer is B.

2021 Repeatability of a thyrotropin-releasing hormone stimulation test for diagnosis of pituitary pars intermedia dysfunction in mature horses

Question 55

Based on the content of the document “Clinical implications of imprecise sampling time for 10- and 30-min thyrotropin-releasing hormone stimulation tests in horses,” here’s a clinical exam question:

A veterinarian is performing a thyrotropin-releasing hormone (TRH) stimulation test on a 20-year-old mare suspected of having pituitary pars intermedia dysfunction (PPID). The veterinarian administers TRH and plans to collect blood samples at 10 and 30 minutes post-administration. Due to an emergency, the veterinarian is delayed in collecting the samples.

Which of the following statements is most accurate regarding the impact of imprecise sampling times on the interpretation of TRH stimulation test results?

A) A delay of up to 5 minutes for both the 10- and 30-minute samples will not significantly affect the test’s diagnostic accuracy.

B) The 10-minute sample is more sensitive to timing errors than the 30-minute sample.

C) Collecting the 30-minute sample at 35 minutes will lead to falsely elevated ACTH concentrations.

D) Delays in sample collection always result in falsely low ACTH concentrations.

E) The impact of imprecise sampling times is uniform across all seasons.

Answer 55

The correct answer is B.

Imprecise sampling changed PPID
diagnostic classification for 3/27 (11 [4–28] %) horses for both protocols. Using the
30-min protocol as a reference, 1/12 (8 [1–35] %) horses returned a negative test
result and 5/12 (42 [19–68] %) horses returned equivocal test results that would be
considered positive in practice due to the presence of supportive clinical signs. Conclusions: Overall, the impact of imprecise sampling was not significantly different
between the 10- and 30-min TRH stimulation test protocols. However, diagnostic
classification for PPID would have varied between the 10- and 30-min protocols in
this population, if clinical signs had been ignored. Precise timing during TRH stimulation
tests and contextual interpretation of ACTH concentrations remain fundamental
for the diagnosis of PPID. However,
imprecision of >1 min is likely to be more impactful for the
10-min protocol. There was diagnostic disagreement between the
10- and 30-min protocols, whereby 50% of horses classified as PPID
positive by the 30-min protocol would have been identified as not
positive by the 10-min protocol if clinical signs had not been taken
into account for the PPID classification

Explanation: The study found that the 10-minute sample is more sensitive

2023 Clinical implications of imprecise sampling time for 10- and 30-min thyrotropin-releasing hormone stimulation tests in horses

Question 56

Based on the content of the attached document, here’s a clinical exam question:

A 20-year-old mare presents with subtle signs of pituitary pars intermedia dysfunction (PPID), including mild hypertrichosis and decreased performance. You decide to perform a thyrotropin-releasing hormone (TRH) stimulation test to evaluate for PPID. You administer 1 mg of TRH intravenously and plan to collect a blood sample at exactly 10 minutes post-administration. However, due to an unexpected interruption, you collect the sample at 11 minutes instead.

Which of the following statements is most accurate regarding the impact of this 1-minute delay on the test results?

A) The delay will have no significant effect on the ACTH concentration or test interpretation.
B) The ACTH concentration will likely be higher than if sampled at 10 minutes.
C) The ACTH concentration will likely be lower than if sampled at 10 minutes.
D) The effect of the delay is unpredictable and equally likely to increase or decrease the ACTH concentration.
E) The delay invalidates the test results, necessitating a repeat test on another day.

Answer 56

The correct answer is C.

Explanation: The study found that late sampling (11 minutes) yields a lo

2022 Effect of early or late blood sampling on thyrotropin releasing hormone stimulation test results in horses

Question 57

In a clinical audit assessing the management of pituitary pars intermedia dysfunction (PPID) in equids, it was found that out of 459 animals with available records, 51.7% were classified as positive for PPID based on basal plasma adrenocorticotropic hormone (ACTH) concentrations. Among these positive cases, what percentage initiated treatment with pergolide mesylate as per the recommended guidelines?
A) 78.7%
B) 51.7%
C) 11.3%
D) 37.1%

Answer 57

Correct Answer: A) 78.7%

The audit revealed that 78.7% of the animals classified as positive for PPID (n=185 out of 235 positive cases) were treated with pergolide mesylate, indicating a significant adherence to treatment recommendations for this condition

Only 77.7% (n160/206) of pergolide-treated animals had documented PPID m

2022Management of pituitary pars intermedia dysfunction in practice: A
clinical audit

Question 58

How does the pre-test probability of PPID influence diagnostic testing strategies?

Answer 58

Both pre-test probability of disease and season of testing have strong influence on the ability to diagnose PPID using basal ACTH or ACTH after TRH stimulation. The risk of a false positive result increases in situations where there is a low pre-test probability

2023 BEVA primary care clinical guidelines: Diagnosis and management of equine pituitary pars intermedia dysfunction

Question 59

What could be the risk for a horse to be PPID for the musculoskeletal system?

Answer 59

Significant decrease in bone mineral density (BMD) of lumbar vertebrae compared to age-matched controls -> increase the risk of pathological fractures. The decrease in BMD was observed in both trabecular and cortical bone of the lumbar vertebrae.
No differences were found in BMD of weight-bearing bones (third metacarpus and third metatarsus) between PPID+ and control groups. PPID may be associated with an increased risk of pathological fractures, particularly in non-weight bearing bones1
.The observed decrease in BMD appears to be a consequence of the endocrinopathy rather than age-related osteoporosis, as evidenced by the comparison with age-matched controls.
This finding adds to the list of potential clinical problems associated with PPID and may warrant consideration in the management of affected horses.

2023 Lumbar vertebral bone density is decreased in horses with
pituitary pars intermedia dysfunction

Question 60

A 12-year-old Welsh pony presents with a body condition score of 8/9 and a history of difficulty losing weight. The owner reports no previous episodes of laminitis but is concerned about the pony’s risk. Which of the following diagnostic tests would be most appropriate to assess the pony’s risk of developing laminitis, and what result would indicate an increased risk?
A) Complete blood count
B) Serum chemistry panel
C) Basal insulin
D) Radiographs of the front feet
E) ACTH stimulation test

Answer 60

C basal insulin

Basal insulin concentration was found to be a significant predictor of c

2020 Clinical insights: Equine obesity

Question 61

Which field test for insulin dysregulation has the best combination of sensitivity and specificity in ponies?

Answer 61

the insulin tolerance test (ITT) had the best combination of sensitivity (0.85) and specificity (0.88) for diagnosing insulin dysregulation in ponies. However, only the basal insulin and oral sugar test were associated with laminitis.

Evaluation of field-testing protocols to diagnose insulin dysregulation in ponies using a Bayesian approach

Question 62

Does sirolimus administration reduce insulin responses in horses with insulin dysregulation?

Answer 62

Yes, this study found that sirolimus administration reduced insulin responses in both healthy horses and those with experimentally-induced insulin dysregulation.
A single dose decreased the insulin response to oral glucose at 24 hours, and 7 days of treatment reduced exaggerated insulin responses in horses with dexamethasone-induced insulin dysregulation.

Minimal effect on glucose concentration

Effect of sirolimus on insulin dynamics in horses

Question 63

Is ertugliflozin effective in reducing insulin concentrations and improving laminitis scores in horses with hyperinsulinemia-associated laminitis?

Answer 63

This preliminary study suggests that ertugliflozin is effective in reducing insulin concentrations and improving laminitis scores in horses with hyperinsulinemia-associated laminitis. After 30 days of treatment, median insulin concentrations decreased significantly and median laminitis scores improved substantially. However, the study lacked a control group and had a short follow-up period.
Median triglycerides increased from 0.6 to 1.4 mmol/L at 30 days before declining
19% of horses had polyuria/polydipsia, no other adverse effects noted

Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses

Question 64

Do hyperinsulinemic Icelandic horses identified by oral glucose test also demonstrate insulin resistance on a modified 2-step insulin response test using porcine zinc insulin?

Answer 64

This study found that while 6/12 Icelandic horses were identified as hyperinsulinemic by the oral glucose test, all 12 horses were classified as insulin resistant by the modified 2-step insulin response test using porcine zinc insulin. However, glucose reduction during the IRT was similar between hyperinsulinemic and non-hyperinsulinemic horses, suggesting that the established cut-off for insulin resistance may not be appropriate when using porcine zinc insulin in Icelandic horses.

Comparison of a modified 2-step insulin response test performed with porcine zinc insulin and an oral glucose test to detect hyperinsulinemic Icelandic horses

Question 65

How does the function of the enteroinsular axis differ in horses with equine metabolic syndrome compared to healthy horses?

Answer 65

In horses with EMS, there appears to be increased glucose uptake from the intestines, possibly due to an intestinotrophic effect of GLP-2. This leads to higher glucose levels stimulating more insulin secretion. Additionally, there is likely an exaggerated incretin effect, where gut hormones like GLP-1 and GIP further stimulate insulin release from the pancreas beyond just the glucose effect. This results in post-prandial hyperinsulinemia in horses with ID.

Equine metabolic syndrome: Role of the enteroinsular axis in the insulin response to oral carbohydrate

Question 66

Does phenylbutazone administration improve insulin sensitivity in horses with insulin dysregulation?

Answer 66

The study found that phenylbutazone administration in horses with ID decreased both glucose and insulin concentrations in response to an OGT. This suggests that phenylbutazone may improve insulin sensitivity in these horses, as lower insulin levels were needed to handle the glucose load. However, the exact mechanism is unclear and further research is needed to confirm this effect and understand its clinical implications.

Effect of phenylbutazone on insulin secretion in horses with insulin dysregulation

Question 67

Can the HMGA2:c.83G>A variant be used as a genetic marker to identify ponies at increased risk for insulin dysregulation?

Answer 67

The study found that the HMGA2:c.83G>A variant was associated with both decreased height and higher basal insulin concentrations across pony breeds. Ponies with at least one copy of the A allele had significantly higher insulin concentrations compared to G/G individuals. This suggests that the HMGA2:c.83G>A variant could potentially be used as a genetic marker to identify ponies at increased risk for insulin dysregulation. However, as insulin dysregulation is a complex trait influenced by multiple genes and environmental factors, this single variant alone may not be sufficient for accurate risk prediction.

Evaluation of an HMGA2 variant contribution to height and basal insulin concentrations in ponies

Question 68

Can a panel of baseline metabolites accurately predict insulin dysregulation in horses without the need for an oral glucose test?

Answer 68

The kynurenine:tryptophan ratio increased over time during the OGT, suggesting induction of low-grade inflammation.
High insulin response was associated with lower arginine and carnitine concentrations. The study found that a predictive model using only baseline samples performed well with as few as 7 distinct metabolites, achieving a sensitivity of 86% and specificity of 88%. This suggests that it may be possible to develop a screening tool to identify insulin-dysregulated horses using only a baseline blood sample, without the need for an oral glucose test. However, this was a proof-of-concept study with a small sample size, so larger validation studies would be needed before such a test could be implemented clinically.

Metabolic changes induced by oral glucose tests in horses and their diagnostic use

Question 69

A 15-year-old horse presents with progressive weight loss over 6 months, lethargy, and mild intermittent lameness. Blood tests reveal hypercalcemia and elevated parathyroid hormone (PTH) levels.
What is the most appropriate diagnostic approach to confirm a suspicion of primary hyperparathyroidism?

Answer 69

The most appropriate diagnostic approach would be to combine ultrasonography and technetium-99m sestamibi scintigraphy.
Justification:
This approach is justified by data from paper 2 (Gorenberg et al., 2020) which reports that:
Ultrasonography has a sensitivity of 54% (7/13 cases)
Technetium-99m sestamibi scintigraphy has a sensitivity of 81% (13/16 cases)
The combination of both techniques has a success rate of 90% (9/10 cases)
Furthermore, the described clinical signs (weight loss, lethargy, lameness) correspond to signs reported in 71% of cases (12/17) for weight loss and are consistent with other signs mentioned in paper 1 (Johnson and Townsend, 2023).

Diagnosis and treatment of confirmed and suspected primary hyperparathyroidism in equids: 17 cases (1999–2016)

Question 70

A 15-year-old Miniature Horse is diagnosed with primary hyperparathyroidism confirmed by imaging. The owner is hesitating between surgical excision and chemical ablation. Which therapeutic option would you recommend and why?

Answer 70

Answer: Chemical ablation by ultrasound-guided ethanol injection would be recommended.

Justification:
This recommendation is based on information from paper 3 (Colmer et al., 2022) which reports:
A 100% success rate for ethanol ablation in the presented case
Complete short-term resolution and normalization of calcium and PTH levels at 30 months follow-up
Fewer risks and complications compared to surgery
Additionally, paper 2 (Gorenberg et al., 2020) indicates that surgical excision has an overall success rate of only 50% (5/10 cases), although this rate reaches 100% (5/5 cases) for single adenomas located at the thoracic inlet.
Chemical ablation therefore presents a better benefit/risk ratio, particularly for a Miniature Horse where anatomical constraints may complicate surgery.

Treatment of primary hyperparathyroidism in a Miniature Horse using chemical ablation of abnormal parathyroid tissue localized by 3-phase computed tomography

Question 71

What pharmacological treatment options are available from human medicine hyperpathyroidism that could be interesting to think about in equine, and how do they affect biochemical markers and bone mineral density (BMD)?

Answer 71

1Bisphosphonates:
Increase BMD, especially in the lumbar spine
Decrease bone turnover markers
No significant change in serum calcium or PTH
2Denosumab:
Increases BMD
Decreases bone turnover markers (transiently)
Decreases serum calcium
Increases serum PTH
3Cinacalcet:
No significant change in BMD
Increases bone turnover markers
Decreases serum calcium and PTH
4Combination therapy (e.g., cinacalcet + denosumab):
Increases BMD
Decreases bone turnover markers
Decreases serum calcium
Causes transient increases in PTH
The choice of treatment depends on the patient’s specific needs, with cinacalcet being particularly effective for lowering serum calcium and PTH, while bisphosphonates and denosumab are more beneficial for improving BMD. Combination therapy may provide more comprehensive management of both biochemical markers and BMD.

Primary hyperparathyroidism in horses: What can we learn from human medicine?

Question 72

In a 12-year-old dressage horse diagnosed with pituitary pars intermedia dysfunction (PPID) and presenting with mild lameness, what are the most important factors to consider in developing a comprehensive management plan to maintain athletic performance and reduce the risk of complications?

Answer 72

Endocrine management:
Initiate pergolide treatment for PPID
Monitor insulin levels, as 16% of horses with PPID also have insulin dysregulation (ID)
Lameness evaluation:
Assess for **suspensory ligament injury, as it’s the site of greatest soft tissue injury in equine athletes (approx. 14% overall, >25% in dressage horses)
Consider that PPID is associated with higher suspensory ligament degeneration
Exercise and diet plan:
Implement low-intensity exercise to improve insulin sensitivity and improved the ratio between neck circumference and height at withers
Consider a low-starch diet
Laminitis prevention:
Monitor closely for signs of laminitis, as it’s secondary to high insulin in EMS or PPID
Be aware of the 34.1% recurrence rate within 2 years for hyperinsulinemia-associated laminitis
Muscle and back health:
Address potential muscle wasting along the topline, which can affect saddle fit and cause back pain
Implement dynamic mobilization exercises, as pergolide treatment alone doesn’t improve muscle mass in PPID horses
Be aware that 74% of horses with back pain were lame, and 32% of lame horses had back problems
Regular monitoring:
Conduct frequent body condition scoring**, as over 30% of horses in some regions are overweight or obese
Monitor for signs of systemic inflammation, which is linked to obesity and common in EMS/ID

A one-health lens offers new perspectives on the importance of endocrine disorders in the equine athlete

Question 73

In a 15-year-old overweight pony with suspected insulin dysregulation, how does the diagnostic accuracy and ease of administration of the new GC pellets (DysChEq™) compare to the traditional oral glucose test via nasogastric tube?

Answer 73

Based on the study results, the new GC pellets (DysChEq™) offer comparable diagnostic accuracy to the traditional oral glucose test via nasogastric tube, with several advantages in ease of administration:
Palatability: The GC pellets showed excellent palatability, with all horses in the study consuming them completely (acceptance score of 1 for all horses). This high acceptance rate ensures more reliable test results.
Ease of administration: The pellets can be fed directly to the horse, eliminating the need for nasogastric tubing, which is more invasive and may cause stress to the animal.
Standardization: The GC pellets have a defined carbohydrate composition, providing more consistent results compared to variable corn syrup formulations used in traditional tests.
Correlation with tube OGT: Insulin concentrations at 120 minutes showed a significant correlation between the GC pellets and tube OGT (r=0.717; P<0.001), indicating comparable diagnostic accuracy.
Discrimination ability: The study demonstrated that the GC pellets could effectively discriminate between healthy and insulin dysregulated horses.
Safety: No evidence of laminitis or colic was observed throughout the study period, suggesting a good safety profile for the GC pellets.

Palatability, glycemic, and insulinemic responses to various carbohydrate formulations: Alternatives for the diagnosis of insulin dysregulation in horses?