Equine Endocrinology Flashcards
Obj: Similarities & Differences between PPID & EMS
Obj: Pathogenesis of PPID & EMS
Obj: Role of dopamine in PPID
Obj: Equine Metabolic Syndrome
Obj: Insulin & its role in laminitis
Obj: Diagnostics and treatment of PPID & metabolic Syndrome
Obj: Importance of diet impact on insulin dysregulation (EMS)
What is the function of the Hypothalamus
- 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
Why is Equine Pituitary Pars Intermedia Dysfunction (PPID) “Cushing’s” considered a hypothalamic disorder?
Primary hypothalamic disorder due to dopaminergic neurodegeneration
What are the parts of the Pituitary Gland?
- Pars distalis
- Pars intermedia
- Pars nervosa & infundibular stalk
What is the function of the pars distalis?
- Pleocelluar gland containing 5 cell types
- Somatotrophs - growth hormone
- lactotrophs - prolactin
- Gonadotrophs - LH, FSH
- Thyrotrophs - TSH
- Corticotrophs - Pro-opiomelanocorticotropin (POMC)
How is POMC converted to ACTH
Post-translational processing by the prohormone convertase I
What is the function of the Pars Intermedia?
- 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
How is the Pars intermedia controlled?
- 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
What is the function of the pars nervosa and infundibular stalk?
- 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
What is the cause of Pituitary Pars Intermedia Dysfunction (PPID) in horses?
- Hyperplasia or dysfunction of the pars intermedia results in excessive secretion proopiomelanocortin (POMC) by melanotropes
What are the results of lack of dopaminergic innervation in the pars intermedia?
- Hyperplasia and overproduction of POMC
- Leads to increased production of:
- β-endorphin
- α-MSH (melanocyte stimulating hormone)
- CLIP (corticotropin like peptide)
- ACTH (adrenocorticotropin)
What is the normal function of dopamine in the pars intermedia? How does PPID affect that?
- Normally has a tonic inhibitory control over the pars intermedia
- PPID - dopamine loss in the periventricular nuclei of the hypothalamus
What are the clinical signs of PPID?
- 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
How is PPID diagnosed?
- 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
What must be done with horse blood for Plasma ACTH concentration tests?
- Plasma and blood must be separated within 3 hours of taking sample
What is the treatment for Pituitary Adenomas?
- Peroglide - FDA approved
- Dopamine agonist (DA-2)
- 0.5mg/500kg q24h
- General treatments for improving insulin sensitivity
What are the principle components of Equine Metabolic Syndrome?
- Adiposity
- abnormal fat deposits
- Insulin resistance
- dysregulation
- Laminitis
- clinical to subclinical
What are the clinical signs/classis presentation of EMS?
- 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
Why are EMS horses commonly diagnosed with hypothyroidism?
- EMS horses have low circulating concentrations of thyroid hormones
- glands and stimulation tests are normal
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
- Structural CHO - insoluble fiber in diet (cellulose, hemicelluloses, lingocellulose)
- Genetics: anecdotal reports, “thrifty gene”
- Exercise: lack of exercise → weight gain → insulin resistance
- Hyperinsulinemia experimentally results in laminitis
How is EMS diagnosed
- Signalment and Phenotype
- middle aged, obese, laminitic, w/ normal hair coat
- Documentation of insulin resistance
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
- Resting insulin conc:
-
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
- Fast horse for 3-8hrs
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
- add fat - water soaked beet pulp, rice bran, corn oil
- Low-starch high fat diet
- feed smaller more frequent meals
- Avoid/limit pasture grass
- 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
- Weight loss
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
How is the dopaminergic neurodegeneration in PPID horses similar to Parkinson’s in humans?
- Motor dysfunction
- Nigrostriatal neurons
- Hormonal dysregulation
- Periventricular hypothalamic neurons
Why does laminitis develop?
- Ischemic/Vascular theory
- Mechanical/Traumatic
- Metabolic/Enzymatic
What syndromes are associated with Laminitis?
- PPID & EMS
- Corticosteroids
- Systemic illness (Endotoxemia)
- GI disease, retained placenta
- Toxins - Black Walnut
- Grain Overload
- Idiopathic
Why are horses with PPID PU/PD?
- Hyperglycemia (Osmotic Diuresis)
- Pars Nervosa - Destruction
- lack of ADH
- Cortisol - ADH interference
- Cortisol increases GFR
Why are horses with PPID PU/PD?
- Hyperglycemia (Osmotic Diuresis)
- Pars Nervosa - Destruction
- lack of ADH
- Cortisol - ADH interference
- Cortisol increases GFR
