Equine Endocrinology Flashcards
1
Q
Obj: Similarities & Differences between PPID & EMS
A
2
Q
Obj: Pathogenesis of PPID & EMS
A
3
Q
Obj: Role of dopamine in PPID
A
4
Q
Obj: Equine Metabolic Syndrome
A
5
Q
Obj: Insulin & its role in laminitis
A
6
Q
Obj: Diagnostics and treatment of PPID & metabolic Syndrome
A
7
Q
Obj: Importance of diet impact on insulin dysregulation (EMS)
A
8
Q
What is the function of the Hypothalamus
A
- Severs as a translator between the CNS and pituitary gland
- Synthesizes releasing and inhibitory factors responsible for control of hormone release from the adenohypophysis and neurohypophysis
9
Q
Why is Equine Pituitary Pars Intermedia Dysfunction (PPID) “Cushing’s” considered a hypothalamic disorder?
A
Primary hypothalamic disorder due to dopaminergic neurodegeneration
10
Q
What are the parts of the Pituitary Gland?
A
- Pars distalis
- Pars intermedia
- Pars nervosa & infundibular stalk
11
Q
What is the function of the pars distalis?
A
- Pleocelluar gland containing 5 cell types
- Somatotrophs - growth hormone
- lactotrophs - prolactin
- Gonadotrophs - LH, FSH
- Thyrotrophs - TSH
- Corticotrophs - Pro-opiomelanocorticotropin (POMC)
12
Q
How is POMC converted to ACTH
A
Post-translational processing by the prohormone convertase I
13
Q
What is the function of the Pars Intermedia?
A
- Homogenous cell population - melanotrophs
- Contain prohormone convertase I & II
- POMC is cleaved into α-MSH, β-endorphin, corticotrophin-like intermediate peptide (CLIP) and very little ACTH
14
Q
How is the Pars intermedia controlled?
A
- secretory control through tonic inhibition by dopamine w/ additional modulation by serotonin, β-adrenergic and gamma-aminobutyric acid (GABA) inputs
- Dopamine in the pars is released directly from the nerve terminals - originate from periventricular nucleus of the hypothalamus
- Interacts at the D2 receptors of the melanotrophes to decrease POMC production
15
Q
What is the function of the pars nervosa and infundibular stalk?
A
- composed of axons extending from nerve bodies in the hypothalamus and pituicytes
- Oxytocin and ADH (vasopressin) are secreted from the axon terminals directly into circulation
16
Q
What is the cause of Pituitary Pars Intermedia Dysfunction (PPID) in horses?
A
- Hyperplasia or dysfunction of the pars intermedia results in excessive secretion proopiomelanocortin (POMC) by melanotropes
17
Q
What are the results of lack of dopaminergic innervation in the pars intermedia?
A
- Hyperplasia and overproduction of POMC
- Leads to increased production of:
- β-endorphin
- α-MSH (melanocyte stimulating hormone)
- CLIP (corticotropin like peptide)
- ACTH (adrenocorticotropin)
18
Q
What is the normal function of dopamine in the pars intermedia? How does PPID affect that?
A
- Normally has a tonic inhibitory control over the pars intermedia
- PPID - dopamine loss in the periventricular nuclei of the hypothalamus
19
Q
What are the clinical signs of PPID?
A
- Due to:
- Increased ACTH
- Physical destruction of the pars nervosa
- increased circulating concentrations of POMC-derived peptides
- Usually Old horse (~20% of geriatric horses have PPID)
- Long curly hair coat (hypertrichosis)
- thick guard hairs
- failure to shed in spring
- early development of winter coat
- Chronic laminitis
- not all horses with PPID will have hyperinsulinemia & laminitis
- Immunosuppression
- PU/PD/PP
- Hyperhidrosis
- Excessive Cortisol - muscle wasting, hyperlipemia, insulin resistance, abnormal fat deposits, pendulous abdomen
20
Q
How is PPID diagnosed?
A
- CBC - stress leukogram (matrue neutrophilia, lymphopenia)
- Chem - hyperglycemia (150-350), hyperlipemia, mild elevations in liver enzymes
- UA - glucosuria
- Plasma ACTH concentration
- catches Moderate/Advanced PPID
- TRH stimulation
- detects Early PPID
- Overnight Dex Suppression
- PPID fail to suppress endogenous cortisol after Dexamethasone
- No negative feedback from pars intermedia
21
Q
What must be done with horse blood for Plasma ACTH concentration tests?
A
- Plasma and blood must be separated within 3 hours of taking sample
22
Q
What is the treatment for Pituitary Adenomas?
A
- Peroglide - FDA approved
- Dopamine agonist (DA-2)
- 0.5mg/500kg q24h
- General treatments for improving insulin sensitivity
23
Q
What are the principle components of Equine Metabolic Syndrome?
A
- Adiposity
- abnormal fat deposits
- Insulin resistance
- dysregulation
- Laminitis
- clinical to subclinical
24
Q
What are the clinical signs/classis presentation of EMS?
A
- Middle Aged
- BCS >6, can be thin with abnormal fat deposits
- Cresty neck, fat prepuce or mammary glands, fat in supraorbital fossa, above tail head
- Mares - infertility
- Laminitis - wide range - lameness, increased digital pulses, subclinical but divergent rings on feet, changes on radiographs (rotation of P3)
- Hair coats are normal
25
Why are EMS horses commonly diagnosed with hypothyroidism?
* EMS horses have low circulating concentrations of thyroid hormones
* glands and stimulation tests are normal
26
What is the pathogenesis of Equine Metabolic Syndrome
* Exact unknown
* Diet:
* Structural CHO - insoluble fiber in diet (cellulose, hemicelluloses, lingocellulose)
* Fermented in the Large Colon
* Good carbs
* Non-structural Carbohydrates (NSC) - Sugar, starch, fructans
* digested and absorbed in the small intestine
* Insulin is produced in response
* Genetics: anecdotal reports, “thrifty gene”
* Exercise: lack of exercise → weight gain → insulin resistance
* Hyperinsulinemia experimentally results in laminitis
27
How is EMS diagnosed
* Signalment and Phenotype
* middle aged, obese, laminitic, w/ normal hair coat
* Documentation of insulin resistance
28
How is insulin resistance tested for in horses? how are results interpreted ?
* Gold standard - difficult in clinical setting
* **Resting insulin concentration:**
* horse can eat hay (no grain/pasture)
* Avoid stress or testing during concurrent illness/lameness
* Glucose conc. are normal but high end
* May _not_ be sensitive in early cases
* Useful for **Positive** diagnosis, but if insulin is not high, can't rule out EMS
* Resting insulin conc:
* \> 20umol/L = non-diagnostic
* 20-50 umol/L = suspect if clinical signs present
* \>50umol/L = EMS
* **Oral Sugar Test:**
* Fast horse for 3-8hrs
* administer light corn syrup (0.15ml/kg)
* measure glucose and insulin conc at 60-90min
* More sensitive than resting insulin concentration
* Insulin \>45umol/L = EMS
29
How is EMS treated?
* Goal - improve insulin sensitivity
* Weight loss
* Feed hay at 1.5-2% ideal body weight (15-20lbs for 1000lb horse)
* avoid trigger foods
* Avoid/limit pasture grass
* especially during change/dynamic phase (spring, fall, heavy rain)
* Feed hay with low NSC (\<12%)
* soaking in water reduce NSC by 50%
* Grass hay generally best
* In thin horses - feed more calories
1. add fat - water soaked beet pulp, rice bran, corn oil
2. Low-starch high fat diet
3. feed smaller more frequent meals
* exercise - daily, may be limited w/ laminitis
* medication/supplements
* Chromium 5-10mg
* Thyroid Supplementation - for overweight EMS
* weight loss and improved insulin sensitivity
* 48 mg/horse for 3-6 months then wean off slowly
* Metformin (dimethylbiguanide)
* human diabetes type 2 drug - mixed results in studies
30
What cuases dopaminergic neurodegeneration?
* Accumulation of a misfolded protein
* Alpha-synuclein - increase in nerve terminals
* Related to oxidative stress
* Chronic inflammation
* Oxidative Stress
* NOT a reduction in systemic anti-oxidant capacity
31
How is the dopaminergic neurodegeneration in PPID horses similar to Parkinson's in humans?
* Motor dysfunction
* Nigrostriatal neurons
* Hormonal dysregulation
* Periventricular hypothalamic neurons
32
Why does laminitis develop?
* Ischemic/Vascular theory
* Mechanical/Traumatic
* Metabolic/Enzymatic
33
What syndromes are associated with Laminitis?
* PPID & EMS
* Corticosteroids
* Systemic illness (Endotoxemia)
* GI disease, retained placenta
* Toxins - Black Walnut
* Grain Overload
* Idiopathic
34
Why are horses with PPID PU/PD?
* Hyperglycemia (Osmotic Diuresis)
* Pars Nervosa - Destruction
* lack of ADH
* Cortisol - ADH interference
* Cortisol increases GFR
35
Why are horses with PPID PU/PD?
* Hyperglycemia (Osmotic Diuresis)
* Pars Nervosa - Destruction
* lack of ADH
* Cortisol - ADH interference
* Cortisol increases GFR
