Endocrino Flashcards

Question

What are the consequences of PPID on muscles?

Answer 1

**PPID** affects muscle condition in horses by causing **loss of topline muscle** in early stages and **topline muscle atrophy** in advanced stages. ## Footnote Endocrinology group 2023

Answer 2

- 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 ## Footnote Endocrinology group 2023

Answer 3

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 ## Footnote Endocrinology group 2023

Answer 4

**PPID unlikely:** (pg/mL) dec-june < 15 july & nov < 15 august < 20 sept-oct < 30 **PPID likely:** dec-june > 40 july & nov > 50 august > 75 sept-oct > 90 interpretive zone/grey zone between (CS, signalement) ## Footnote Endocrinology group 2023

Answer 5

**Baseline ACTH** → if grey zone ⇒ TRH-stimulation test → if grey zone ⇒ re-evaluate in **3-6 months** If **generalized hypertrichosis** → no test, treat directly its ok If grey zone → use the **lower threshold** for diagnosis ## Footnote Endocrinology group 2023

Answer 6

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 ## Footnote Endocrinology group 2023

Answer 7

1. The recommended initial treatment for PPID is Prascend® (pergolide tablets). 2. The initial dosage of Prascend® (pergolide) for PPID treatment is **2 µg/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 (1-2 µg/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 µg/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 µg/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 ## Footnote Endocrinology group 2023

Answer 8

No but improve quality of life ## Footnote Endocrinology group 2023

Answer 9

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

Answer 10

Potential side effects include **transient coughing**, **flehmen** response, and **yawning** after administration. ## Footnote Endocrinology group 2023

Answer 11

**Answer B** In horses, **25(OH)D2** is the predominant vitamin D metabolite (from fungi on grass), 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 → **seasonal effect**. ## Footnote The effect of season, management and endocrinopathies on vitamin D status in horses evj 2023

Answer 12

**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) ## Footnote Lumbar vertebral bone density is decreased in horses with pituitary pars intermedia dysfunction evj 2024

Answer 13

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

Answer 14

The reproductive performance of the high ACTH group was **significantly lower** than the other groups. ## Footnote Relationship between endogenous plasma adrenocorticotropic hormone concentration and reproductive performance in Thoroughbred broodmares JVIM 2021

Answer 15

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

Answer 16

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. ## Footnote 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

Answer 17

**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 of CDH: - decrease of pro-inflammatory cytokines and chemokines, - decrease in lamellar glucose metabolism without affecting glucose concentration, - decrease perfusion. ## Footnote 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

Answer 18

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

Answer 19

**Hypoaminoacidemia** develops in EHC and prolonged glucose infusion laminitis models. This finding may have relevance to laminitis because hypoaminoacidemia affects cell adhesion and cytoskeletal dynamics in human cells. ## Footnote Plasma amino acid concentrations during experimental hyperinsulinemia in 2 laminitis models jvim 2021

Answer 20

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**”. But a recent study showed that **blood insulin and glucose** concentrations **modestly increased** for 48 h following IA triamcinolone injection in horses without ID. Consequences on ID horses ? ## Footnote Intrasynovial triamcinolone treatment is not associated with incidence of acute laminitis evj 2021 Intra-articular triamcinolone acetonide injection results in increases in systemic insulin and glucose concentrations in horses without insulin dysregulation evj 24

Answer 21

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

Answer 22

**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. ## Footnote Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing jvim 2023

Answer 23

- **Basal insulin** (unfasted) - **OST** (insulin T60 post corn syrup 0,3 mL/kg) - Adiponectin concentration - Divergent hoof growth ## Footnote Predictors of laminitis development in a cohort of nonlaminitic ponies evj 2023

Answer 24

The correct answer is B. ## Footnote Repeatability of a thyrotropin-releasing hormone stimulation test for diagnosis of pituitary pars intermedia dysfunction in mature horses jvim 21

Answer 25

The correct answer is C. ## Footnote Effect of early or late blood sampling on thyrotropin releasing hormone stimulation test results in horses jvim 22

Answer 26

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 ## Footnote Management of pituitary pars intermedia dysfunction in practice: A clinical audit Vet J 22

Answer 27

C. Basal insulin ## Footnote 2020 Clinical insights: Equine obesity

Answer 28

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. ## Footnote Equine metabolic syndrome: Role of the enteroinsular axis in the insulin response to oral carbohydrate Vet J 23

Answer 29

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). ## Footnote Diagnosis and treatment of confirmed and suspected primary hyperparathyroidism in equids: 17 cases (1999–2016) evj 20

Answer 30

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

Answer 31

Solanum spp.

Answer 32

- **Age** : very high at **birth** and decrease with age. Foals → x10 than adults - **Gender and breed** : **stallions** TH < mares. **Donkeys** TH > horses. - **Physiologic status** : pregnant mares, lactating mares → increase TH - **Hormones** : endogenous or exogenous **glucocorticoids** → decrease TH release ; **catecholamines** → increase TH. - **Drugs** : goitrogenic substances (antithyroid activity) → **PBZ, sulfonamides, phenothiazines** (ACP)... - **Season and daily rythm** : **cold T°** → ⊕ HPTA ; **diurnal rythmicity** related to diurnal variations of **glucocorticoids** → peak TH around 4 pm. - **Activity** : prolonged exercise can ↘︎ TH. - **Feeding** : high carbohydrates diet → **insulin** release → ↗︎ TH ; **starvation** (negative energy balance) → ↘︎ TH ## Footnote Reed EEG 23

Answer 33

Illness, systemic inflammation, stress and starvation → ↗︎ **pro-inflam. cytokines, glucocorticoids, leptin** → **⊖ HPTA** → **low TH** but this is not hypothyroidism. Also **low TH** concentrations commonly measured in **EMS** (insulin resistance) and **laminitic horses**. Exogenous supplementation of TH (levothyroxine) in obese horses ? Watch out for **iatrogenic hyperthydoidism**. ## Footnote EEG 23

Answer 34

Cold intolerance, low body T°, bradycardia, and haircoat abnormalities. ## Footnote EEG 2023

Answer 35

A diagnosis of **hypothyroidism** is only appropriate when results of a **thyroid function test** confirm that the thyroid gland cannot respond adequately to stimulation. Hypothyroidism should not be diagnosed in horses based on **blood thyroid hormone concentrations alone**. For example, low tT3 and/or tT4 concentrations occur in horses receiving **phenylbutazone**. ## Footnote EEG 23

Answer 36

1- Low serum **tT4** +/- tT3 2- Is there a plausible explanation ? **drugs, stress, starvation...** 3- If no, check serum **free t4 (fT4)** concentration by **equilibrium dialysis method** (only accurate way). 4- If low, perform a **TRH stimulation test**. If no response → **HYPOTHYROIDISM** and treatment with **levothyroxine** might be justified at this point. ## Footnote EEG 23

Answer 37

Little used of this test (cost, availability) Injecting 2.5 to 5 UI of **TSH IV** Normal horses : **T3 peak at 2h** and **T4 peaks at 3-4h** (T3 before T4) Insufficient hormonal response → **primary hypothyroidism** PBZ → no influence **Dexamethasone** → blunts TH response to TSH-stimulation

Answer 38

Widely used method to assess thyroid gland function and PPID The protocol is to collect serum for **baseline serum tT3 and tT4** measurements, administer **1 mg TRH IV**, and then measure the serum **tT3** concentration **2 hours later** and serum **tT4** concentration **4 hours later**. **> x1.5** increases in blood tT3 and tT4 concentrations are normally detected Inadequate TH response → **primary (thyroid)** or **secondary (pituitary)** hypothyroidism. NB : measurement of endogenous TSH is not available in horses. **Tertiary hypothyroidism** = hypothalamic disorder **Side effects** of TRH administration include coughing, muscle fasciculations, chewing, and exhibition of the Flehmen response. ## Footnote EEG 23

Answer 39

Weight loss, hyperexcitability, polyphagia, tachycardia, polydipsia, and **goiter**. ## Footnote EEG 23

Answer 40

Blood tT3 and tT4 concentrations are often 2-3 times higher than normal in hyperthyroidism horses. Exogenous adm° of **T3** → should inhibit **TSH** and **TH** secretion (↘︎ T4). No changes = **primary hyperthyroidism** (adenocarcinoma = functional thyroid gland tumor)

Answer 41

Enlarged thyroid glands (**goiter**) in adult horses are most often caused by **benign adenomas** with **cysts** as a less common cause. These enlarged glands **do not affect thyroid function** and simply require monitoring over time. Functional thyroid gland tumors (**adenocarcinomas**) are rare and usually accompanied by **clinical signs of hyperthyroidism** (e.g., weight loss or agitation on rare occasions). **Ultrasound examination** is the best way to evaluate an enlarged thyroid gland. Tumors may be solid or have a characteristic cystic appearance. **BIOPSY OF THE GLAND IS NOT RECOMMENDED** as the thyroid is an extremely vascular organ that bleeds profusely and percutaneous biopsy samples can be non-diagnostic. ## Footnote EEG 23

Answer 42

**Old horses** from **lightweight breeds**. Most common → **adenoma**, benign, unilateral and not associated with thyroid dysfunction. **Adenocarcinoma** : malignant **Medullary carcicnoma** : hyperthyroidism, old horses Multiple endocrine neoplasia (pheochromocytoma...) ## Footnote Reed

Answer 43

**Transport**, **high-carbohydrate** or fat meals ## Footnote EEG 23

Answer 44

**Low serum tT3 and tT4** concentrations are detected in many **EMS horses and ponies**, and this is to be expected given the endocrine and metabolic disturbances that are components of this syndrome. We can therefore think of **EMS as a nonthyroidal illness**, and blood tT3 and tT4 concentrations are low for this reason. **Levothyroxine** can be administered at a high dose for 3-6 months to accelerate **weight loss** in obese EMS horses, but this is not evidence of hypothyroidism. ## Footnote EEG 23

Answer 45

**Goiter** = enlarged thyroid gland for any reason. Goiter does not imply **hypo- or hyperthyroidism** ! Functional tests are necessary. Main cause of neonatal **hypothyroidism** and goiter : **nutritional** → decreased iodine intake. Poor prognosis. **Congenital goiter** : inadequate or excessive iodine intake by the mare. **Premature and septic foals** : ↘︎ TH but not hypothyroidism → **NTIS**

Answer 46

Unlike adult horses, **hypothyroidism** in **foals** is well documented and results in a cluster of clinical signs. Most of the clinical signs are characteristic of **dysmaturity**, although **prognathism** is unique to **hypothyroidism**. cf photo + **forelimb contracture** Pregnant mares should **not receive high iodine supplements**, not be kept on **fescue pasture** in late gestation, or not be allowed access to plants that contain **goitrogens**. ## Footnote EEG 23

Answer 47

Supra-physiologic thyroxine supplementation caused a **decreased V200** during a standard exercise test and may result in **cardiac arrhythmias (AF ++)**. ## Footnote A randomised, controlled trial to determine the effect of levothyroxine on Standardbred racehorses evj 22

Answer 48

A major concern during **thyroidectomy** is the direct intraoperative visualisation of the **RLN** to avoid **iatrogenic damage**, which has been reported to have a **prevalence of 50% in horses**. Can be avoided by the use of **intraoperative neuromonitoring** of the RLN, a superior method that allows identification and preservation of the nerve. ## Footnote Thyroidectomy facilitated with Harmonic Caliper and intraoperative neural monitoring in three horses eve 23

Answer 49

Inability of horses to sweat in response to appropriate stimulation. **Partial anhydrosis** → most common. Frequent in the tropics and areas with **high T°C and humidity** → prevalence in southern US ∼ 6-20% Not associated with exercise but **environmental conditions** + **genetic component** (familial tendency) NB : **PPID** → anhidrosis

Answer 50

**Drug-induced anhidrosis** → likely cause of hyperthermia in foals treated with **macrolide**, particularly **erythromycin**

Answer 51

**Clinical signs** : depression, anorexia, poor performance, tachypnea, hyperthermia, complete or partial decreased sweating, alopecia... Sweating is due to the stimulation of **β2-adrenergic receptors** by **catecholamines**. Diagnostic test : intradermal injection of **epinephrine** (not specific to β2) or **salbutamol, terbutaline** (specific to β2) → delayed or no sweating response.

Answer 52

Resolving in **3 to 7 days** with **supportive management** : cooling the environment, alcohol baths, cooled IV fluids. Then, dietary modification ? Sodium levothyroxine ? TH increase β2-adrenoreceptor sensitivity.

Answer 53

Ratios of **sweat responses** were higher in treatment horses **2 days after treatment**, compared to baseline, but not 4 weeks after treatment. The efficacy of a traditional Chinese veterinary medicine protocol for anhidrosis treatment with **acupuncture and Chinese herbs** was **low** but **higher in treated horses compared with placebo**. ## Footnote Efficacy of treatment of equine anhidrosis with acupuncture and Chinese herbs is low but higher in treated horses compared with placebo javma 24

Answer 54

The most common presenting complaints were **weight loss** (12/17) and **hypercalcemia** (10/17). ## Footnote Diagnosis and treatment of confirmed and suspected primary hyperparathyroidism in equids: 17 cases (1999–2016) evj 20

Answer 55

The significant correlation identified between **composite pain scale (CPS) score** and **[cortisol]** in medical and surgical colic cases provides physiological validation of pain scores as a **marker of underlying stress in horses with colic**. No significant association was found between CPS score and [ACTH]. ## Footnote Application of an equine composite pain scale and its association with plasma adrenocorticotropic hormone concentrations and serum cortisol concentrations in horses with colic eve 20

Answer 56

**Equine metabolic syndrome** (EMS) is a **collection of risk factors** highly associated with an increased risk of **hyperinsulinemia-associated laminitis** (HAL) and potentially other morbidities. **Insulin dysregulation** (ID) is a consistent feature of EMS and increased **generalized or regional adiposity** is typical. Additional factors present in some animals include altered **adipokine** and **postprandial incretin** concentrations, **hypertriglyceridemia**, and **hypertension**. ## Footnote Equine Endocrino Group 22

Answer 57

**Insulin dysregulation** is detected in all equids with **EMS**. **Insulin dysregulation** is defined as any combination of **basal (resting) hyperinsulinemia**, **postprandial hyperinsulinemia** (response to oral sugar test [OST] or consumed feeds), or **tissue insulin resistance** (IR; hepatic and/or peripheral). Insulin dysregulation is the central endocrine disorder of EMS. ## Footnote Equine Endocrino Group 22

Answer 58

The characteristic histopathological changes of HAL are **stretching and elongation of the lamellae** without disruption of the basement membrane. The most popular theory is that **hyperinsulinemia** induces inappropriate stimulation of **insulin-like growth factor-1 receptors** on **lamellar epidermal cells**. ## Footnote Equine Endocrino Group 22

Answer 59

**HAL** is detected in approximately **30%** of horses with **PPID** and horses **greater than 10 years of age** should be tested for PPID as well as ID. ## Footnote Equine Endocrino Group 22

Answer 60

**Oral sugar test (OST)** to assess **postprandial insulin response**, which reflects a more complete sequence of events including digestion and absorption of sugars, incretin hormone responses, secretion of insulin from the pancreas and risk of HAL. **Insulin tolerance test (ITT)** to assess insulin sensitivity, which focuses solely upon **hepatic and/or peripheral tissue insulin sensitivity**. (cf photo) ## Footnote Equine Endocrino Group 22

Answer 61

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

Answer 62

**Two-step approach to diagnosing ID**: Testing can be performed in two steps if the owner raises concerns about dynamic tests inducing laminitis. - The first step is to measure the **resting (basal) insulin** concentration to screen the horse for **hyperinsulinemia** and assess **laminitis risk** (low Se / high Spe). - If the resting insulin concentration is normal, a **dynamic test** must still be performed as a second step because **resting measures** have **low diagnostic sensitivity**. An OST is also recommended when only mild hyperinsulinemia is detected to estimate **insulin responses** to **grazing on pasture or feeds**. ## Footnote Equine Endocrino Group 22

Answer 63

The **variability** in these data support that **basal and post-prandial blood glucose** responses to an **OGT** are not appropriate as stand-alone diagnostic markers of ID or PPID. However, the **association** between **blood glucose** and **cresty neck score** supports the use of cresty neck score when evaluating animals for ID. ## Footnote Diagnosis of equine endocrinopathies: The value of measuring blood glucose during an oral glucose test Vet J 23

Answer 64

**Adipokines** = cytokines of adipose tissue (**leptin, adiponectin**) - **Leptin** : **Higher leptin** concentrations are associated with **increased adiposity** and metabolic derangement. Useful for providing evidence of increased **internal adiposity**. This hormone is more directly associated with **obesity** than ID. - **Triglyceride** : Hypertriglyceridemia associated with **ID and obesity**, exacerbated by negative energy balance. Hypertriglyceridemia is a **predictor of laminitis risk** in ponies. - **Adiponectin** : Total adiponectin concentrations **< 7.9 ug/mL** are consistent with **EMS** and an increased risk of laminitis. ## Footnote Equine Endocrino Group 22

Answer 65

Insulin concentrations are affected by **season**, with higher concentrations detected in **December, January, and February** in the Northern hemisphere, suggesting a **winter-associated exacerbation of ID**. But neither OST results nor adiponectin varies with season. ## Footnote Equine Endocrino Group 22 Variation in insulin response to oral sugar test in a cohort of horses throughout the year and evaluation of risk factors for insulin dysregulation evj 22

Answer 66

1- **Manage diet** : hay ∼ 1.5% BW in dry matter, NSC content **< 10%** (**NSC** appears to be the **main driver** of the postprandial insulin response), restrict grazing, do not feed grain or treats. Or soak hay in cold water for at least 1h. 2- **Manage exercise** when laminitis is resolved. Low intensity exercise for > 30 min, > 3 times a week. Lack of exercise was a risk factor for ID. 3- **Medical therapy** : - **High-dose levothyroxine** : for cases with weight loss resistance. Administer levothyroxine at a high dose of 0.1 mg/kg daily in the feed. Maximum 3-6 months. - **Sodium-glucose co-transporter 2 (SGLT2) inhibitors** : Used when horses are affected by **laminitis** and **severe ID** are not responding to other measures. **Canagliflozin** (0.5 mg/kg, PO, q24h) and **ertugliflozin** (0.05 mg/kg POq24h). **Hypertriglyceridemia** might develop as a consequence, monitor TG at 7 and 14 days, and then every 1-3 months thereafter. - **Metformin hydrochloride** : For animals with persistent hyperinsulinemia, even after management changes have been followed. The drug is only effective in a **small percentage of horses** and may lose efficacy over time. Administer **30 mg/kg metformin** hydrochloride in the feed or by mouth, ideally **30 minutes prior** to feeding or turnout, up to **3 times daily** ## Footnote Equine Endocrino Group 22 Postprandial insulin responses to various feedstuffs differ in insulin dysregulated horses compared with non-insulin dysregulated controls evj 22 Variation in insulin response to oral sugar test in a cohort of horses throughout the year and evaluation of risk factors for insulin dysregulation evj 22

Answer 67

114 owners **(33.3%**) reported one or more initial adverse effects upon induction onto the medication, particularly **excessive urination** (n = 70, 20.5%), **excessive drinking** (n = 38, 11.1%), **excessive weight loss** (n = 34, 9.9%) and **dullness** (n = 26, 7.6%). **Ertugliflozin** was the most commonly prescribed **SGLT2i** (79.8%), and the most common reasons for treatment were **high insulin concentrations** (84.2%) and **active laminitis** (59.7%). The use of SGLT2i in horses was associated with **excellent rates of owner satisfaction** and owner-reported **improved quality of life** for the horse; however, some adverse effects were observed. ## Footnote Horse owner experiences and observations with the use of SGLT2i for the management of equine metabolic syndrome and hyperinsulinaemia- associated laminitis eve 24

Answer 68

**Metformin treatment** had **no significant effect** on plasma glucose, insulin or C-peptide concentrations at any time point compared with placebo in ID horses. The results **do not support the use of targeted metformin treatment** to reduce post-prandial hyperinsulinaemia in horses with naturally-occurring ID. ## Footnote The effect of pre-dosing with metformin on the insulin response to oral sugar in insulin-dysregulated horses evj 24

Answer 69

In the final multivariable model, **only obesity** (body condition score **≥8**) was associated with **ID**. Because obesity is associated with ID in cold-blooded type horses, objective monitoring of phenotypic markers by owners may be beneficial for health outcomes. ## Footnote Insulin dysregulation in a population of Finnhorses and associated phenotypic markers of obesity jvim 20

Answer 70

Answer B Alpha-2-agonists suppress insulin secretion with transient **hyperglycemia** and **rebound hyperinsulinemia** in metabolically stable horses and ID horses. In ID horses, **detomidine** could minimize hyperinsulinemia when compared to **xylazine**. Alpha-2-antagonist, **vatinoxan**, was effective in **preventing detomidine-induced hyperglycaemia** as well as the subsequent **insulin increase** in horses with ID, and after oral carbohydrate load. ## Footnote Blood glucose and insulin concentrations after alpha-2-agonists administration in horses with and without insulin dysregulation jvim 20 The effects of an alpha-2-adrenoceptor agonist, antagonist, and their combination on the blood insulin, glucose, and glucagon concentrations in insulin sensitive and dysregulated horses Vet J 21 Effects of alpha-2-adrenoceptor agonism and antagonism on equine blood insulin and glucose concentrations after oral carbohydrate load Vet J 24

Answer 71

Results do **not** support an effect of **endocrine status** on **L-lactate** concentrations in blood of ponies. Positive correlation between the insulin response and sphingolipid concentrations → **upregulated sphingolipid** metabolism in **ID horses**. A **high plasma ceramide** concentration can indicate insulin dysregulation in horses. ## Footnote Associations of plasma sphingolipid profiles with insulin response during oral glucose testing in Icelandic horses jvim 21 Influence of endocrine disease on l-lactate concentrations in blood of ponies jvim 21

Answer 72

**Obesity** induced by **high fatty** and low NSC haylage was associated with increase in **blood pressure** and an **increase in serum cortisol**, that was not associated with insulin sensitivity. ## Footnote The effect of diet-induced obesity and pasture on blood pressure and serum cortisol in Standardbred mares evj 21

Answer 73

Our results suggest induction of **low-grade inflammation** during the **OGT**. **Plasma arginine and carnitine** concentrations were **lower** in horses with **high insulin response** and could constitute potential therapeutic targets. Development of screening tools to identify insulin-dysregulated horses using only baseline blood sample appears promising. ## Footnote Metabolic changes induced by oral glucose tests in horses and their diagnostic use jvim 21

Answer 74

**Risk factors** associated with a diagnosis of EMS included **ageing**, **being female**, **more sedentary** main activity, **obesity** (cresty neck score), and shorter periods on pasture during the summer. Clinical manifestations of **hoof growth ring** and **supraorbital fat scores** of 3/3 were more frequent in EMS ponies. Not related to breeding activity. ## Footnote Equine metabolic syndrome in UK native ponies and cobs is highly prevalent with modifiable risk factors evj 21 Epidemiological investigation of insulin dysregulation in Shetland and Welsh ponies in Australia evj 24

Answer 75

**Obese, insulin-dysregulated** horses are **hypercoagulable** compared to healthy controls. ## Footnote Thromboelastography in obese horses with insulin dysregulation compared to healthy controls jvim 22

Answer 76

**Strip grazing** limited pony bodyweight gains and upward changes in morphometric parameters. The **dry matte**r (DM) herbage yield of each paddock was determined, and **paddock length adjusted** to provide **1.5%** of individual pony BW as **herbage DM daily**. ## Footnote Strip-grazing: Reduces pony dry matter intakes and changes in bodyweight and morphometrics evj 22

Answer 77

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** (A/G and A/A) 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. ## Footnote Evaluation of an HMGA2 variant contribution to height and basal insulin concentrations in ponies

Answer 78

**Sirolimus** : aka rapamycin, is an immunosuppressive drug. Yes, this study found that **sirolimus decreased the insulinemic response to glucose** in both healthy horses and those with experimentally-induced insulin dysregulation. Warrants further investigation. Minimal effect on glucose concentration. ## Footnote Effect of sirolimus on insulin dynamics in horses jvim 23

Answer 79

Based on this study, **ID horses** seem to have an apparent **threshold for NSC** of around **0.1 g/kg BW /meal** (NCS < 10% ?), above which significantly **increased insulin responses** are seen compared with non ID horses. ## Footnote Identifying possible thresholds for nonstructural carbohydrates in the insulin dysregulated horse evj 23

Answer 80

The **oral glycemic challenge (GC) pellets** (DysChEq)™ and **GC syrup** can be used as **palatable** and **well-accepted** oral GC tests for assessment of ID in horses. 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. ## Footnote Palatability, glycemic, and insulinemic responses to various carbohydrate formulations: Alternatives for the diagnosis of insulin dysregulation in horses? jvim 23

Answer 81

A **bread-based treat** was offered **twice daily for 10 days**, adding **0.36 g/kg body weight (BW) carbohydrates** (> 0.1 g/kg BW/ meal previously recommended) to the daily diet. The **absorption of D-xylose** increased **1.6-fold** after 10 days of eating the treat. A small amount of additional carbohydrate each day in the form of a **treat** can cause a measurable change in the **enteroinsular responses to eating**. ## Footnote A starch-rich treat affects enteroinsular responses in ponies javma 22

Answer 82

IV tests (**ITT**) mainly focus on **peripheral insulin resistance** (IR), while oral tests (**OGT**) assess **postprandial hyperinsulinemia** (HI), which are different aspects of **ID**. In this study, while 6/12 horses were identified as **HI by the OGT**, all 12/12 horses were identified as **IR by the modified 2-step ITT** underlining the importance, but difficulty in choosing the right diagnostic tool in clinical settings to assess ID. NB : A recent study comparing recombinant regular human insulin and porcine zinc insulin (PZI) showed that when using the **ITT-PZI**, an **adjusted cut-off value** for blood glucose reduction of **40 % at 30 min** resulted in better test performance. ## Footnote Comparison of a modified 2-step insulin response test performed with porcine zinc insulin and an oral glucose test to detect hyperinsulinemic Icelandic horses Vet J 23 Evaluating insulindysregulation in horses: A two-step insulin-tolerance test using porcine zinc insulin Vet J 24

Answer 83

**Phenylbutazone** administration in **horses with ID decreases glucose and insulin concentrations** in response to an **OGT** warranting further investigation of a therapeutic potential of phenylbutazone in the management of **hyperinsulinemia-associated laminitis** beyond analgesia. No significant effect was detected in control horses. ## Footnote Effect of phenylbutazone on insulin secretion in horses with insulin dysregulation jvim 24

Answer 84

**Morphometric measures** such as BCS **do not closely reflect [total adiponectin]**. Circulating **[total adiponectin]** and **[basal insulin]** should be determined in all animals with predisposing factors, regardless of obesity status. ## Footnote Relationships between total adiponectin concentrations and obesity in native-breed ponies in England evj 24

Answer 85

No. No difference in **GLP-1 response** was detected according to **ID or IR** status, despite there being strong positive correlations between GLP-1 and insulin concentrations measured at individual time points. These data **do not support of the use of GLP-1 as an adjunctive diagnostic test for ID or IR**, as defined by conventional intravenous or oral dynamic tests. ## Footnote Investigation of glucagon-like peptide-1 response to six oral carbohydrates in ponies Vet J 24

Endocrino Flashcards

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