ShapeShapeauthorShapecrossShapeShapeShapeGrouphamburgerhomeGroupmagnifyShapeShapeShapeShape

Conditions common to humans and horses

by
01 October 2010, at 1:00am

MARION McCULLAGH reports on some of the early papers presented at last month’s BEVA congress

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.