Equine Endocrine Disease: Cushings and Equine Metabolic

Equine Endocrine Disease:
Cushings and Equine
Metabolic Syndrome
Dr. Martin Furr
Dip ACVIM, PhD
Adelaide C Riggs Professor of Medicine
Acknowledgements to Dr Scott Pleasant for some slides
Endocrine Disease
• “Endocrine system”
– Interacting system of organs that produce
hormones regulating many body functions
– Pituitary, thyroid, adrenal glands, etc.
• 2 most common equine conditions
– Cushings disease
– Equine Metabolic Syndrome/Insulin resistance
syndrome
Equine Cushings Disease
• A syndrome in which there is excessive secretion
of the hormones ACTH (pituitary) and cortisol
(adrenal gland)
– aka equine cushings syndrome, pituitary adenoma,
pars intermedia adenoma,
– Most properly referred to as pituitary pars intermedia
dysfunction (PPID)
• A common clinical syndrome in older horses
– 15-30% of horses > 15 years
– No gender bias, ponies and Morgans more likely
Equine Pituitary Gland
Disease mechanism
• Pituitary gland enlarges
(pituitary adenoma)
• Too much ACTH hormone is
released into the
bloodstream
• Excess cortisol is secreted
from the adrenal glands in
response to the ACTH
• Feedback inhibition of ACTH
by cortisol is blocked
• Clinical signs result from
excess cortisol and other as
yet unidentified hormonal
products
Clinical Signs
• Long shaggy hair coat
(hirsutism)
• Laminitis
• Excessive water
consumption and urination
(polydypsia/polyuria)
• Weight loss and “pot belly”
• Recurrent infections,
blindness, skin infections,
lethargy, hyperhydrosis,
infertility
Diagnosis
• Characteristic clinical signs
– In advanced cases only!
• Characteristic changes in routine labwork (not
always present!):
– High white blood cell count
– Anemia
– High resting glucose concentration
– 45% in one study, 95% in another
– Glucose in urine
Specific Diagnostic Tests
• Resting cortisol
concentrations
• Large horse to horse variation
• Day to day variation
• Not all horses with PPID have
high cortisols
• Cortisol is influenced by many
different things
• Not the best method
Specific Diagnostic Tests
• Resting ACTH
concentrations
• Day to day, horse to horse and
season to season variation
• Better diagnostic value than
cortisol
• 91% accurate for horses
• 80% accurate for ponies
Specific Diagnostic Tests
• Dexamethasone
suppression test
60
Serum Cortisol (ng/ml)
• Baseline blood cortisol
• Suppress with
dexamethasone
• Assay blood cortisol again
70
– Normal cortisol drops
– PPID cortisol does not drop
• 20% error rate(?)
• Multiple samples, expense
50
40
Normal
Abnormal 1
30
Abnormal 2
20
10
0
0
3:00
3:30
4:00
24:00:00
Time Post Dexamethasone
Specific Diagnostic Tests
• Combined
Dexamethasone
suppression/TRH
stimulation test
• Measure cortisol:
– at baseline
– after suppression
– after stimulation
• 85% accuracy
• Multiple blood samples,
expense
Treatment/Management
• PPID is NOT curable- but it is manageable
• Combination of management and drugs
– Good quality feed/nutritional management
– Dental care
– Foot care
– Clip long hair in non-shedders
Drugs for PPID
Pergolide
.5 mg twice per day PO
Monitor ACTH and clinical signs
every 6 weeks
Increase by .5 mg if not controlled
Cost- 1-2$/day
Drugs for PPID
Ciproheptadine
.25 mg/kg per day
Monitor ACTH at 6 weeks
No response- increase the dose to
twice per day
Monitor again
Cost 1$/day
Equine Metabolic Syndrome
• A syndrome of insulin resistance associated
with obesity and pasture associated laminitis
Insulin and Glucose
Insulin
Regulates blood glucose
As glucose goes up- insulin goes up in
response
Insulin stimulates cellular uptake of the
glucose
Blood glucose goes down as a result
Insulin Resistance/Hyperinsulinemia
• insulin resistance (IR): inability of
insulin to result in an appropriate
decrease in blood glucose
• hyperinsulinemia (high blood levels of insulin):
compensatory response which may
maintain a proper insulin – mediated
responses (is an indicator of IR)
Equine Metabolic Syndrome
Clinical Signs
• Obesity and regional adiposity
– Observation, body scoring, scales, or weight tapes
– Cresty neck
• Insulin resistance
• Subclinical or chronic laminitis
– Observation of “founder rings”
– Clinical laminitis
– Radiographs of feet (rotation)
Diagnosis of Insulin Resistance
• Resting blood insulin concentrations
• Resting blood glucose concentrations
• Tests should be done after 6 hours of fed
deprivation
Glucose
Insulin
Interpretation
normal
normal
Normal
normal
high
Compensated IR
high
high
Uncompensated IR
Insulin Resistance
Diagnosis
• Combined glucoseinsulin test
• More sensitive than
resting measurements
• Baseline measurement
• Glucose and insulin
given
• Follow-up blood
samples
Equine Obesity and Insulin
Resistance
Incidence?
What is the evidence for a
connection?
Equine Obesity
• United States Department of
Agriculture has estimated that
approximately 5% of the U.S. horse
population is overweight or obese
• this estimate was based on an owner
survey
(USDA –NAHMS 1998)
Virginia Tech Equine
Obesity Study
Study Objectives
• determine the prevalence of obesity in
a sub-population of mature horses in
Virginia.
• determine the prevalence of
hyperinsulinemia (HI) in these horses
• examine the relationships between
obesity and hyperinsulinemia
(Geor, Pleasant, Thatcher et al – VHIB , VMRCVM, DAPS)
VT Obesity Study
Study Methods
• 300 horses, between 4-20 years of
age (randomly selected from a master list of
approximately 1000 horses)
• Summer 2006 (60 days)
• history gathered, body condition
evaluated (2 evaluators), blood collected
(horses evaluated and blood samples collected
between 6-11 AM, before concentrate meals)
Body Condition Score 1
Poor
• Animal extremely emaciated;
spinous processes, ribs,
tailhead, tuber coxae, and
ischii projecting prominently;
bone structure of withers,
shoulders, and neck easily
noticeable; no fatty tissue can
be felt
Body Condition Score 5
Moderate Condition
• Back is flat (no crease or
ridge); ribs not visually
distinguishable but easily
felt; fat around tailhead
beginning to feel spongy;
withers appear rounded
over spinous processes;
shoulders and neck blend
smoothly into body
Body Condition Score 9
Extremely Fat
• Obvious crease down back;
patchy fat appearing over ribs;
bulging fat around tailhead,
along withers, behind
shoulders, and along neck; fat
along with inner thighs may
rub together; flank filled with fat
Results
Levels of Exercise in the Study Population
200
180
59 %
Number of
160
140
120
100
23 %
80
15 %
60
40
3%
20
0
None
Light
Moderate
Intense
Exercise Regimen
Light: 1-3 hrs per week
Moderate: 3-5 hrs per week
Intense: > 5 hrs per week
Results
Distribution of Horses by Amount of Concentrate/Grain Fed Per Day
160
48 %
Number of Horses
140
120
100
30 %
80
60
12 %
40
7%
20
4%
0
None
>0 but <3
3-5
Concentrate Fed (lbs/day)
6-8
>8
Results
Distribution of Body Condition Categories
47 %
160
Number of Horses
140
32 %
120
100
19 %
80
60
40
20
2%
0
Under Condition
Optimal Condition
Over Condition
Body Condtion
Under Condition = BCS < 4
Optimal Condition = BCS 4-6
Over Condition = BCS 6.5-7
Obese Condition = BCS 7.5-9
Obese Condition
Results
Insulin Concentration versus Body Condition
Geometric mean of Insulin
concn + 1 geometric SD (uIU/ml)
25
20
15
10
5
0
Under Conditioned
Optimal Conditioned
Over Weight
Body Condition
Under Condition = BCS < 4
Optimal Condition = BCS 4-6
Over Condition = BCS 6.5-7
Obese Condition = BCS 7.5-9
Obese
Results
Hyperinsulinemia Within Each Body Condition
160
Number of Horses
140
120
100
Below Baseline
80
Hyperinsulinemic
60
40
20
10.3 %
0%
32 %
1.4%
0
Under Condition
Optimal Condition
Over Condition
Body Condition
Under Condition = BCS < 4
Optimal Condition = BCS 4-6
Over Condition = BCS 6.5-7
Obese Condition = BCS 7.5-9
Obese Condition
Summary
• prevalence of over conditioned/obesity
(BCS 6.5-9) of the study horse population
was 51%
• prevalence of obesity (BCS 8-9) of the
study horse population was 19%
Summary
• 1.4% of optimally conditioned or
underweight horses were
hyperinsulemic
• 10% of overconditioned horses were
hyperinsulinemic
• 32% of obese horses were
hyperinsulinemic
Why do Horses
Become Obese?
% of Required Nutrients Supplied (unrestricted pasture)
300%
250%
200%
150%
Pasture
285%
100%
50%
128%
136%
136%
Ca
P
0%
DE
CP
Pasture Associated Laminitis
Why?
Pasture Associated Laminitis
Nonstructural Carbohydrate (NSC)
Induced Laminitis (starch or fructan:
mechanism of)
• excess nonstructural carbohydrate
enters the large intestine
• lactic acid bacteria population
explosion
• acid kills off other resident bacteria
and damages the intestinal lining
Pasture Associated Laminitis
NSC Induced Laminitis
(mechanism of)
• “substances” enter the blood, travel
to the foot
• causes lamellar inflammation
• clinical signs seen depend on the
amount of laminar damage
Pasture Associated Laminitis
(it’s a little lot more complicated than that!)
Risk Factors:
• high NSC intake from pasture
causes by itself)
(rarely
• generalized obesity and regional
adiposity
• insulin resistance/hyperinsulinemia
Obesity/Regional Adiposity
Increased Risk for PAL
(mechanisms of?)
• increased load on lamellar tissues
• production of a state of “chronic
inflammation”
• altered vascular responses
• induction of IR/hyperinsulinemia
Insulin Resistance/HyperInsulinemia
Increased Risk for PAL (mechanisms of?)
• epidermal cell dysfunction
• pro-inflammatory effects
• vascular dysfunction
 laminar deterioration and laminitis
Treatment of EMS
• If you prevent obesity …..you will
vastly reduce (if not eliminate)
IR/hyperinsulinemia … and Pasture
Associated Laminitis
Prevention of Obesity
• Feed appropriately for the body weight
and amount of exercise
• regularly monitor body condition (monthly)
– Weight tapes, scales, body measurements, condition score
• provide regular exercise
(energy requirements
for light work is 1.25 x maintenance)
Body Measurements
Neck Crest Adiposity
“Cresty Neck”
• Neck circumference
(inches) midway
between the poll and
the withers
• Height at withers
(inches)
• Neck
circumference/height
ratio
– horse > 0.63 = cresty
– ponies > 0.68 = cresty
Body Weight Estimation
Weight (in lbs) = girth (inches) x girth (inches) x
body length (inches) divided by 330
Example:
Girth 73 inches, body length 67 inches
73 x 73 x 67/ 330 = 357043/330= 1082 lbs
Treatment of Obesity
• feed an average quality hay in an amount
equivalent to 2% of desired body
condition/weight
– Weigh the hay, concentrate not usually necessary unless in
moderate to heavy work, or lactating mares
• limit grazing, use grazing muzzles, dry
lots, etc
• exercise
– As permitted by laminitis or other conditions
– Even a little helps!
Grazing Guidelines
• Limit grazing of lush pasture (restriction or
grazing muzzles)
– Spring, early summer
– After a “bloom”
– After a frost
•
•
•
•
Avoid flowering grasses (high sugar)
Graze in early morning before 10 am
Avoid overgrazing (more NSC in lower stems)
Prefer native to improved pastures
How to adjust diet?
Treatment of Obesity: Example
(starting weight = 1200#/starting BCS = 9)
1200# – [(9 – 5) x 50#] = 1000#
Current
BW
Current Desired
BCS
BCS
Estimated
Optimum
BW
*feed 20# of average quality hay daily
Treatment
• Metformin (Glucophage™)
– Improves insulin sensitivity at the tissue level
– Conflicting data at present
• Thyroid hormone supplementation
– Widely advocated, conflicting effectiveness
• Special diets and supplements
– Magnesium, chromium, zinc, clenbuterol,
cinnamon, ginger root, grapeseed extract,
antioxidants
4 months later