THE 49th BEVA congress took
place at the ICC in Birmingham
from 8th to 11th September.
The first session, on endocrinology,
was chaired by Alex McSloy of the RVC
and the first paper, “Diagnosis and
treatment of PPID and metabolic
syndrome”, was given by Nicola
Menzies-Gow.
PPID (pituitary pars intermedia
dysfunction) is found in older horses
and ponies, with no breed or age
predilection but ponies are affected
more often than horses.
The signs are familiar:
hairiness, weight loss, a
tendency to laminitis,
reduced resistance to
disease, energy loss and
polydipsia/polyuria.
Diagnosis is made
more difficult by the
variation in plasma
cortisol level that is
found in normal
animals. Cortisol is
higher in the morning
than in the evening and
in autumn many
normal animals have
cortisol levels that are
above the reference
range.
There are several
different tests for PPID but none is
foolproof. Cortisol levels of PPID
animals may not always be raised and a
painful condition such as laminitis will
cause a rise in cortisol. Urine
cortisol/creatinine ratio around 30
usually indicates PPID; normal values
are around 10 but there is a large grey
area in between these values.
Screening test
Insulin levels are not useful: normal
ponies can be somewhat insulin-
resistant and so have a high insulin level
and the level at the time of testing is
influenced by feed and exercise. Plasma
ACTH is useful as a screening test: it is
usually increased in PPID but again,
levels tend to rise in autumn so there
can be false positives.
The dexamethasone suppression test
was regarded as the best test but it can
give false positives, especially in autumn.
False positives also occur with the TRH
stimulation test and the refinement of
combining the dexamethasone
suppression test with the TRH
stimulation test is more difficult to carry
out and no more helpful.
Treatment of PPID usually starts
only when the clinical signs cause the
animal distress, for example when it
becomes laminitic. The dopamine
agonist, pergolide, is the most widely
used drug. It is given at 1-5mg per
animal per day by mouth. The starting dose is decreased gradually at 4-6 week
intervals to the lowest effective dose.
Depression, diarrhoea, anorexia and
colic have been noted as side effects.
If pergolide fails to control the
symptoms, cyproheptadine, the
serotonin antagonist, given at
0.25mg/kg once daily by mouth is likely
to be effective. The cortisol synthesis
inhibitor, trilostane, will only reduce the
clinical signs caused by excess circulating
cortisol. It is given at 0.5-1.0mg/kg and
it works in about 80% of cases.
Very fat animals may be
suffering from equine metabolic syndrome,
especially if they have
abnormal bulges of fat
around the tail head,
crest and shoulders or
if they have laminitis
or mares are infertile.
This condition is
characterised by insulin
resistance which can
be demonstrated by
fasting and resting the
horse overnight and
then measuring blood
glucose and insulin
levels.
Raised levels indicate insulin resistance. Weight
reduction is the key to treatment. This can be achieved by altering the diet.
Grain should not be fed and oil should
be avoided though a vitamin and
mineral supplement can be given as the
animal should be maintained on 1.5-2%
of the target bodyweight of hay. This
hay should contain not more than 10%
of starch and sugar combined and can
be soaked for up to 16 hours to reduce
soluble carbohydrate.
Regular light exercise helps the
animal to lose weight and brings in an
insulin-independent uptake of glucose
by the skeletal muscle which reduces the
hyperglycaemia. Thyroxine at 0.1mg/kg
once daily by mouth increases metabolic
rate and metformin has helped fat
ponies but not larger fat mares. The
dose rate is 15mg/kg twice daily by
mouth.
Recent research suggests that the
bioavailabity of metformin is low and
that the half life is very short: this may
explain its inconsistencies.
Obesity
BEVA has always been interested in
sharing areas of research which cover
conditions which occur both in humans
and horses. Dr Jeremy Tomlinson of
the University of Birmingham
specialises in endocrinology, diabetes
and metabolism and gave us his views
on “Metabolic syndrome in humans –
aetiology and treatment”.
Over 23% of the UK population is
obese, and Birmingham is the UK’s
fattest and least exercised city. It is
feared that the outcome of the current
childhood obesity epidemic may be a
swathe of early deaths.
Treatment of obesity is complex but
the immediate message to his patients is
“eat less, exercise more”.
Complex process
Research shows that there is
dysregulation of the hypothalamo-
pituitary-adrenal axis in obese and
metabolic syndrome patients but blood
cortisol levels remain normal. Enzyme
dysregulation in liver, muscle and
adipose tissue has been proposed as
part of the mechanism.
Adipose tissue itself is an endocrine
organ which reaches a state of low
grade inflammation in obesity. This
drives the complex pathogenic process
which includes an increase of insulin
resistance. Studies with twins have
shown that obesity is more heritable
than adult height.
Regular exercise needs to be permanent: once it
stops, insulin resistance
comes back so life-style
modification is one of
the foundations for the
treatment of obesity.
The pharmacological
approach has been
thwarted by the
withdrawal of drugs
such as sibutramine as
they had unwanted
cardiovascular and
cerebrovascular effects.
Orlistat is now the
only licensed anti-obesity drug available
here but research to find safe,
efficacious new drugs is in progress.
Vascular complications
Nicola Menzies-Gow continued Dr
Tomlinson’s theme in her paper on
“Vascular complications of obesity”.
Adipose tissue is the largest endocrine
organ in the body and it secretes a
variety of immunomodulatory
molecules known as adipokines. These
are important regulators of the
physiology of the immune system, the metabolic system and the vascular
system.
In obesity, more nutrient is stored in
the adipose tissue and it goes into a pro-
inflammatory state. This is probably
started by tumour necrosis factor alpha
and it leads to increased secretions by
the adipokines that modulate vascular
tone, nutritive blood flow and insulin
sensitivity. Insulin-mediated
vasoconstriction is increased. Overall
there is a chronic low-grade inflammatory state and
endothelial dysfunction.
This condition
appears to be involved
in the development of laminitis.
Arteries and arterioles fail to dilate
as they should in
response to stimuli
which means that
nutrients and
hormones find it
more difficult to
reach distal tissues.
There is a shortage of bioavailable nitric oxide which is a
strong vasodilator and this sets in train reactions which lead to the
activation of many genes which are
involved in inflammation.
Vasoconstriction is accompanied by
platelet activation and leucocyte
adhesion to the wall of the blood
vessels.
So, in both humans and horses,
research is showing how obesity
involves damage to the vascular
system.
