CUSHING

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CUSHINGS DISEASE and OTHER METABOLIC DISEASES

• Nicholas Frank, DVM, PhD, DACVIM
• Assistant Professor
• Large Animal Internal Medicine

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Laminitis and Hormonal Disorders
Too much grain
Colic Diarrhea
Lush pasture
Cushings Disease
LAMINITIS Founder
OBESITY
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LAMINITIS CUSHINGS DISEASE

• Possible cause if 10 to 20 years old
• Likely cause if over 20 years old
• Estimated that more than 70 of horses over 20
  years of age have Cushings disease

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What To Look For Body Condition

• Too FAT in places
• Cresty neck
• Fat pads at tail head
• Bulging fat pads above eyes
• And too THIN in places
• Ridge along back or swayed back
• Ribs showing
• Losing leg muscle mass
• Rounded abdomen (pot-bellied)

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What To Look For Hair Coat

• Long hair in places
• Back of legs
• Curlier hair
• Neck or sides
• Takes longer to shed out
• Patches of long hair in early summer
• Long curly hair coat that never sheds

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What To Look For Lethargy

• Mellowing with age?
• Doesnt want to be ridden

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What To Look For Infections

• More prone to sole abscesses
• White line disease
• Gets every respiratory disease that comes through
  the barn
• Tooth root abscesses
• Sinus infections

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What To Look For Drinking/Urinating

• Seems to drink more water than before
• (filling up buckets more often)
• Stall is wetter than before
• Stall smells worse than before

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Other Associated Conditions

• Osteoporosis
• Delayed wound healing
• Central nervous system dysfunction
• Persistent lactation
• Infertility
• Hindlimb suspensory breakdown

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Cortisol

• Is the stress hormone
• FIGHT or FLIGHT
• Released from adrenal glands (near
  to kidneys)
• Acts to provide fuel for flight (glucose)
• Reduces inflammation

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Cortisol and Laminitis

• Reduces blood supply by constricting arteries
• Weakens attachments
• Impairs ability to repair damage
• Alters glucose delivery to hoof cells

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Pituitary Gland Tumor
Microadenoma if lt 1 cm in size Macroadenoma if gt
1 cm in size
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Pituitary Gland Hormones
ACTH tells adrenal glands to release
cortisol TSH stimulates release of thyroid
hormones LH and FSH sex hormones (normal
cycle) Growth hormone normal growth Prolactin
milk production Oxytocin milk let down ADH
concentrate urine
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CUSHINGS
CRH
ACTH
CORTISOL
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Routine Laboratory Testing

• Elevated blood glucose levels
• Shift in white blood cell pattern
• Insulin concentrations are sometimes high
  (tolerance test recommended)
• Seen with other conditions
• Higher in ponies and obese horses
• Vary with time and diet

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Serum Cortisol

• Resting cortisol is NOT helpful
• Loss of daily rhythm
• Usually higher in morning hours
• Lower in afternoon and evening
• Cushings diagnosed if less than 30 difference
  between morning and evening samples

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Cortisol Rhythm as a Diagnostic Test
UT Research 2003 Four healthy mares assessed
every 2 weeks for 8 weeks
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Plasma ACTH

• Cushings disease if plasma ACTH concentration is
  above 10 pmol/L (45 pg/ml)
• Suspect Cushings if above 7.5 pmol/L (35
  pg/ml)
• Advantage one-time sampling
• Disadvantage grey area in normal/abnormal
• Can be used to assess treatment

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Dexamethasone Suppression Test

• Measure blood cortisol before injection
• Inject 0.04 mg/kg dexamethasone
• Measure blood cortisol 24 hours later
• Suppression to below 10ng/ml is normal
• You should be aware that, in very rare cases,
  injecting dexamethasone may cause an episode of
  laminitis

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HEALTHY
CRH
ACTH
DEXAMETHASONE
CORTISOL
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Time 24h
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CUSHINGS
CRH
ACTH
DEXAMETHASONE
CORTISOL
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Time 24h
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TRH Response Test Inject TRH and then measure
cortisol over 60 minutes
TRH
Cushings
Healthy
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Cyproheptadine

• Site of action Brain
• Mechanism Decreases chemicals that speed up
  the pituitary
• Dose Variable (look at response)
• Response More active
• Milder bouts of laminitis, Sheds out
• Negatives Only at high doses
• (drowsy or wobbly)

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Pergolide

• Site of action Brain
• Mechanism Increases chemicals that slow
  down the pituitary
• Dose Variable (look at response)
• Response Same as cyproheptadine
• Negatives Only at high doses
• Go off feed, colic

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HypothyroidismPeripheral CushingsMetabolic
SyndromeDiabetes
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Obesity
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Diet-Induced Obesity

• A horses diet contains little fat (lt 5) and
  should contain limited soluble carbohydrate
• Human high fat/high cholesterol diet
• (American diet contains 40 fat)

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Obesity-Associated Laminitis

• Affects delivery of glucose to cells of hoof
• (insulin resistance)
• Diabetes-like changes in blood vessels
• Increases inflammation
• Lowers ability to respond to changes
• More affected by switch to lush pasture
• Consistent foot care is more important

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Hypothyroidism

• Previously associated with obesity, lethargy,
  poor performance, laminitis, rhabdomyolysis, and
  infertility
• Deficiency of biologically active thyroid hormone

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Effects of Hypothyroidism (gt12 months)

• Edema
• Skin abnormalities
• Not lethargic
• Not obese
• No cresty necks
• No laminitis
• No muscle disease

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Diagnosis Routine Measures

• Serum total T3 concentration (UT)
• Serum total T4 concentration (UT)
• Free hormones (MSU)
• Problems
• Low when any other disease is present
• Low if on phenylbutazone
• Low in obese horses
• Low in horses with Cushings disease

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Getting More Reliable Information

• Measure another hormone called TSH
• Currently only available for research
• Real hypothyroidism (experimental)
• High serum TSH concentrations
• Other types of hypothyroidism
• Low serum TSH concentrations
• Perform a TRH response test

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Treating Obesity-Associated Laminitis

• Reduce caloric intake
• Discontinue grain
• Limit access to pasture (avoid very green grass)
• Feed hay
• Increase exercise (often limited by laminitis)
• Supplements

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Levothyroxine (Thyro-L)

• Type Synthetic T4 (12mg per tsp)
• Action Supplies additional hormone
• Dose Commonly use 1-2 tsp/d
• 80 tsp/lb 20-25/lb 0.25-1.25/d
• Response More active. Laminitis?
• T4 levels to high-normal range
• Negatives No TSH monitoring available.
  Changes in heart muscle

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• SUPPLEMENTS
• Thyro-L (Lloyd, Inc. funded study)
• Reduces weight
• Improves insulin sensitivity (short-term)
• Magnesium
• Dietary CaMg increased to 21
• Mg deficiency is risk factor for type 2 diabetes
• Chromium tripicolinate
• Lowers insulin concentrations (ponies)

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• Chasteberry (Vitex agnes castus) Hormonize
• Actions against insulin and prolactin
• Advanced Protection Formula (APF)
• Contains Siberian ginseng (and chasteberry?)
• LaminaSaver
• Restaurex is the active ingredient found
  exclusively in Figuerola Laboratories'
  LaminaSaver. Restaurex major role it to support
  the body's ability to enhance new cell
  regeneration during founder/laminitis.
• www.figuerola-labs.com

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University of Tennessee Obesity Research (UT Fat
Camp)http//www.vet.utk.edu/cemr

• Began Summer 2003
• Six obese horses examined to date
• Comparing obese and normal weight horses
• Less than 15 years old
• Calorie-restricted diets
• More prone to laminitis
• Do not have Cushings disease
• Insulin resistant

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Questions
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ACTH Synthesis in the Pituitary Gland
PROHORMONE
?MSH
ACTH
ßLPH
aMSH
CLIP
?LPH
ß endorphin
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• ACTH and CLIP
• Laminitis
• Increased drinking and urinating
• Infections (sole abscesses)

?MSH
ACTH
ßLPH
aMSH
CLIP
?LPH
ß endorphin
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• MSH Melanocyte stimulating hormone
• Long curly haircoat
• Not shedding properly

?MSH
ACTH
ßLPH
aMSH
CLIP
?LPH
ß endorphin
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• ß endorphin
• Lethargy
• More pain tolerance

?MSH
ACTH
ßLPH
aMSH
CLIP
?LPH
ß endorphin