How I manage endocrine cases (Proceedings)

Article

Information on thyroid function, pituitary pars intermedia dysfunction, and equine metabolic syndrome in horses.

Thyroid Function

  • ↑ mitochondrial number and size
  • ↑activity of Na,K-ATPase

  • 15% to 40% of your Basal Energy

  • Increased energy expenditure of the cell

  • ↑protein synthesis and catabolism

  • ↑ heat production

  • Stimulate basal metabolic rate

Thyroid Function in the Fetus/Neonate

  • ↑ mental activity and neural development

  • ↑ lung maturation

  • ↑ gastrointestinal function

  • ↑ cardiovascular function

  • ↑ growth and maturation of the skeletal system

Hypothyroidism

Primary

Secondary / Tertiary

  • Problem with conversion of T4 to T3 in peripheral tissues

  • TSH

  • TRH

"False" (Non-thyroidal Illness)

Hyperthyroidism

Factors Affecting Thyroid Levels

Physiologic/pathologic influences

  • NSAID administration

  • Decrease levels for 2 weeks!

  • Corticosteroid administration

  • High energy or protein diets

  • > 30% of Diet Concentrate levels will decrease

  • > 50% then levels decrease to very low levels

  • High zinc or copper diets

  • Food deprivation

  • High intensity exercise

  • Non-thyroidal illness syndrome

What DVM's associate with low thyroid levels

  • Anhidrosis

  • Alopecia

  • Chronic Laminitis

  • Infertility

  • Obesity

  • Orthopedic disease

  • Congenital hypothyroidism/dysmaturity syndrome

Thyroidectomized horses

  • Retarded growth

  • Increased sensitivity to cold

  • Edema of lower legs

  • Decreased feed consumption

  • Weight loss

  • Decreased Cardiac Output

  • Increased blood/plasma volume

Non Thyroidal Illness

  • Low thyroid levels to help decrease metabolic rate

  • Conservation of lean mass

  • Decreased conversion of T4→T3

DIAGNOSTICS

  • Rule out other diseases

  • Sick euthyroid

  • Free T4/T3 and Total T4/T3

  • Free T4 either by Dialysis or Diasorin two

  • IF fT4 and fT3 are normal→ Not hypothyroid

  • Even IF Total T4 and T3 are low

  • If fT4 and fT3 are low then:

  • Repeat test / Rule Out Sick euthyroid

  • Perform TRH stimulation test

  • TRH Stimulation Test

  • No sterile medical preparation available

  • 1mg IV Horse

  • 0.5 mg IV Pony

  • Pre-Sample

  • Post Sample 2 hours Post

  • Look for peak in T3

  • Response to Treatment

Treatments

  • Thyro-L

  • Highest MRD 0.08 mg/kg

  • Minimal Increases of T4 Levels

  • Double MRD

  • 100% increase in T4 levels

  • Treat for 4-6 weeks and re-test if OK

  • Decrease to MRD

  • Routinely do PE and hormone levels every 2-4 months

Pituitary Pars Intermedia Dysfunction (PPID)

  • Pituitary Gland

  • Pars distalis (Anterior Lobe)

  • Somatotrophs: growth hormone

  • Lactotrophs: prolactin

  • Thyrotrophs: Thyroid Stimulating Hormone

  • Gonadotrophs: FSH, LH (or ICSH)

  • Corticotrophs: prohormone proopiomelanocortin (POMC) cleaved to ACTH & LPH

  • Pars intermedia (Intermediate Lobe)

  • Melanotropes: Melanocyte Stimulating Hormone

  • POMC→ β-Endorphin,ACTH and α – MSH

  • ACTH= 2% of Posttranslation

  • Pathogenesis (McFarlane 2006)

  • Oxidative damage in the Hypothalmus

  • Dopamine metabolism produces free radicals

  • Loss of dopaminergic innervation to the PI

  • Increased levels of ACTH, α – MSH , β-Endorphin

  • α – MSH and β-Endorphin

  • Six fold increase in the steroidogenic properties of ACTH

  • Increased ACTH

  • Increased Cortisol Concentrations

  • Loss of Circadian Cortisol Concentrations

  • Melanotropes

  • Insensitive to glucocorticoid feedback

  • Corticotrophs are SENSITIVE to feedback

  • Breed Predilection

  • Morgan and Pony Breeds

  • Can occur in any breed

Clinical Signs

  • Hirsutism

  • Most common clinical sign

  • Pathogenesis?

  • Polyuria/Polydipsia

  • Hyperhidrosis

  • Chronic Laminitis

  • Any older horse (> 13 yrs of age) that develops insidious onset of laminitis should be evaluated for PPID

  • Chronic Infections

  • Exercise Intolerance

Diagnostics

  • Hirsutism

  • Over the fence diagnosis

  • Most accurate way to assess PPID

  • So why do testing on these animals?

  • Monitor response to treatment

  • Unfortunately does not occur until later on in the disease process

  • Endocrine Testing

  • Some are controversial

  • Dexamethasone Suppression Test

  • Look for Suppression of endogenous Cortisol

  • After giving 2mg/100 pounds of Dexamethasone IM

  • Give late afternoon (4pm or 5pm)

  • Take 2nd sample between 10am and noon

  • < 1µg/dl by 19 hours

Dexamethasone Suppression Test

  • Do not like to do in hospital setting

  • Seasonal Variation

  • September to December(Donaldson JVIM 2005)

  • Hypothalamic pituitary axis is very active

  • Metabolically prepare for the winter?

  • Decreased availability of food during the winter

  • Increased weight gain/ Fat deposition

  • Accurate with early disease?

ACTH Plasma Levels

  • Looking for Elevations greater than the reference range for you lab

  • ELEVATION: Supportive of PPID

  • Magnitude DOES NOT EQUAL Severity

  • Single Sample Test!

  • Sample Handling

  • Needs to be cooled

  • Protein can degrade if warm

  • Seasonal Variation (Donaldson JVIM 2005)

  • Sept-Dec

Diurnal Cortisol Level

  • Promoted by BET laboratory

  • NO DATA provided by Peer Review

  • Too much variability

  • I DO NOT ADVOCATE THIS TEST

Dexamethasone and TRH Stimulation

  • Time Consuming

  • Accuracy 81%

  • Histological Findings on 42 Horses

  • DST 71%

  • Good test for earlier stages of the disease?

Dexamethasone and TRH Stimulation

  • FIRST

  • Give Dexamethasone 2mg/100 pounds IM

  • Suppresses Cortisol to "base line" level

  • Similar between PPID and normal horses

  • SECOND

  • 3 hours later give 1mg TRH IV

  • Samples

  • Time 0 : Before TRH is given

  • 30 Minutes after TRH is given

  • 66% increase of Cortisol is suggestive of PPID

  • 24 hours after TRH

  • Lack of suppression of cortisol

  • < 1µg/dl

Fasting Insulin Testing (Dr. Schott)

  • Insulin Resistance

  • Long term Prognosis = GUARDED

TRIAL and ERROR

  • "Early PPID"

  • Vague clinical signs

  • Poor performance

  • Tender Feet

  • Diagnostic Dilemma

Treatments

  • MANAGEMENT

  • Foot Care

  • Clip Hair

  • Nutritional Consult?

  • Equine Senior Feeds

  • High fiber feeding

  • Frequent fecal egg counts

  • Intermittent antibiotic administration

  • Medical

  • Will early intervention prolong my horse's life?

  • NO DATA EXISTS

  • Does it need to be continuous or intermittent?

  • Long term longitudinal studies would be needed

  • My horse is in a Fescue Field, do I need to tx?

  • May contain alkaloids that are dopamine-mimetic agents

  • I still would Tx if clinical signs are persistent

  • PERGOLIDE

  • FIRST ROUND CHOICE (Donaldson JVIM 2002)

  • Best treatment response from 3 independent studies

  • SID

  • 2-6µg/kg PO SID (1mg for 500kg horse)

  • Anorexia?

  • Decrease dose to 0.5 mg orally for 1-2 weeks and then increase to 1mg

  • NO PK studies! In horses or humans!!

  • Compounding vs Non Compounding

Treatments

  • PERGOLIDE

  • Response: 30-60 days

  • Give at least 6 weeks

  • Retest in 90 days

  • DST

  • Per Schott : Only 30% will show normalization

  • ACTH

  • Cyproheptadine

  • Anti-serotonin

  • Serotonin = Secretagogue of ACTH

  • Anti-histamine

  • 0.3 mg/kg PO BID

  • POOR CLINICAL RESPONSE

  • Combined with Pergolide

  • Will work for some cases

  • Vitamin E

  • Antioxidant

  • 5,000 to 10,000 IU Orally SID

Equine Metabolic Syndrome

  • Criteria

  • Insulin Resistance

  • Prior or current laminitis

  • Subclinical laminitis

  • Obesity

  • Regional Adiposity

  • Pre Laminitic Metabolic Syndrome (Dr. Geor)

  • Genetic Factors

  • "Thrifty" genes →Easy Keeper

  • Survival through periods of harshness

  • Natural selection/survival of the fittest

  • IR and Pro-inflammatory state before harsh winter

  • Ossabaw Island Pigs

  • Spanish Colonists

  • Environmental Factors

  • NSC in the pasture

  • Over feeding → Iatrogenic

  • INSULIN

  • Released from the pancreas and helps drive glucose into the cells

  • Major sites for insulin mediated glucose uptake (GLUT 4 transport proteins)

  • Skeletal Muscle

  • Adipose Tissue

  • INSULIN Resistance

  • Failure of the Skeletal muscle or Adipose Tissue to respond appropriately to insulin

  • Compensated Insulin Resistance (Common)

  • Example: Insulin has 1/2 of its normal effect→ Pancreas will respond→ MORE INSULIN

  • Normal "Net Effect"

  • Uncompensated Insulin Resistance (Uncommon)

  • Pancreas "fails"

  • Glucose levels start to rise

  • Diabetes Mellitus : Rarely noted (Advanced PPID?)

  • Not all obese horses have an endocrine disorder

  • Mismanaged(Feeding)

  • Feeding grain

  • Stalled without turnout

  • Overestimated significance of "work"

  • Owner is "at fault"

  • Too much energy in ration = fat

  • Genetically Predisposed

  • Middle Aged Obese Horses

  • Pony's

  • Morgans

  • Paso Finos

  • Saddlebreds

  • Norwegian fjords

  • Tennessee Walkers

  • Arabs

  • QH

  • Typical Signs

  • Laminitis

  • Obesity

  • Infertility

  • Confused with Cushings

  • Confused with "hypothyroidism"

Fat acts like a GLAND

  • Adipokines (> 100 described)

  • Reistin

  • Leptin

  • Obese horses noted elevations

  • "Leptin Resistance"

  • IL-6

  • TNF alpha

  • Oxidative stress → Cushing's?

  • Cortisol

Omental Adipocytes → Special

  • Produce numerous "hormones"

  • 11β-hydroxysteroid dehydrogenase-1

  • Converts Cortisone→Cortisol (Locally)

  • Adipogenesis→IR

  • Net activity is greater during obesity

  • Glucocorticoids tend to provoke MORE adipocytes to express MORE 11β-HSD-1

Insulin Resistance

  • Interference with insulin action at targets

  • Enhanced stimulation for pancreatic insulin production (hyperinsulinemia)

  • Insufficient glucose delivery to target cells

  • Too much glucose for cells that do not depend on insulin (endothelial cells)

Insulin Resistance

  • CAUSES

  • Genetic variance

  • Glucocorticoids

  • Obesity →adipokines

  • Stress

  • Inflammation (cytokines)

  • Dietary factors

  • Mineral/micronutrient imbalances

  • Supplements (glycosaminoglycans) (Dr. Messer)

Consequences

  • Laminitis

  • PPID →Oxidative Stress

  • Thyroid Function

  • Incr. Cortisol will Decr TSH production

  • Chronic Inflammatory State→ Ox. Stress

  • Rhabdomyolysis???

  • Muscle cells and Glucose uptake

  • OCD/Osteoarthritis

Insulin Resistance And Laminitis

  • Endothelium is an organ with a mass equivalent to that of the liver

  • Subjected to high levels of glucose

  • Glucotoxicity → Oxidative stress

Insulin Resistance : What we learned

  • Glucotoxic endotheliopathy

  • Vasospasticity

  • Oxidative stress

  • Pro-inflammatory effects

  • Impaired capillary recruitment

  • MMP-9 expression

  • Glucose starvation/deprivation

DIAGNOSTICS

  • FASTING INSULIN

  • Take off food 12 hours

  • Measure Insulin Levels > 30 µU/mlSuggestive

  • NEED TO REDUCE STRESS!

  • Stress can induce insulin resistance

  • Grass Hay If needed to quiet horse

  • Minimal Glycemic Index

  • Combined Glucose-Insulin Test

  • Dynamic Test

  • Detect Early Cases?

  • 150 mg/kg 50% dextrose Drip

  • Give 0.1 units/kg of regular Insulin

  • After dextrose (immediate)

  • BETTER HAVE EMERGENCY DOSE OF GLUCOSE

  • Combined Glucose-Insulin Test

  • Spike of Glucose

  • Back to base line by 45 minutes

  • Take Glucose Levels

  • Pre-Sample

  • 1,5,25,35,45 Minutes

TREATMENT

  • Diet Changes

  • Remove Concentrates

  • Reduce access to lush pasture

  • Morning grazing

  • DO NOT GRAZE AFTER FROST

  • 5,000 – 10,000 IU Vitamin E?

  • CONSULT A NUTRITIONIST

  • Magnesium Oxide

  • Shown to be effective in rats and humans

  • NOT SHOWN TO BE EFFECTIVE IN THE HORSE

  • Chromium

  • No Data to say it is efficacious?

  • APF and Metformin?

TREATMENT

  • Thro-L

  • 4 teaspoons 1x daily for 1-2 months and then try to decrease

  • Use as a metabolic Stimulant (Some clients have used it for 6-8 months)

  • Can use oats to mix in (Low glycemic index)

TREATMENT

  • Podiatry

Recent Videos
dvm360 Live! with Dr. Adam Christman
Related Content
© 2024 MJH Life Sciences

All rights reserved.