Hyperlipaemia and the Endocrine System

Donkey specific reference ranges for adrenocorticotropic hormone (ACTH) and insulin have been developed by The Donkey Sanctuary. These are for donkeys aged 3-20 years of age and the ACTH ranges are seasonally adjusted.

The range was validated using the TOSOH AIA-360 analyser.

HYPERLIPAEMIA

The pathophysiological process is triggered in response to a negative energy balance resulting in mobilisation of fats from adipose tissue. Although this is a normal response to a fasting state, in hyperlipaemia the rate of lipolysis exceeds the rate of uptake of triglycerides into peripheral tissue for use as an energy substrate. The accumulation of plasma triglycerides results in fatty infiltration of organs such as the liver, pancreas and kidneys, which can in turn lead to multiple organ failure.

Pathophysiology

The mobilisation of fats from adipose tissue is under hormonal control but can also be influenced by cytokines such as granulocyte macrophage colony stimulating factor (GM-CSF) and tumour necrosis factor α (TNF-α), which are produced in inflammatory diseases. Stimulation of β-receptors by catecholamines and release of cortisol also promote lipolysis.
 

• Any condition or circumstance that reduces appetite will stimulate lipolysis.
• Donkeys are inherently insulin resistant and obesity predisposes to insulin resistance. Insulin resistance facilitates lipolysis.
• Stress results in the release of cortisol and catecholamines, which promote lipolysis.
• Cytokines promote lipolysis and inhibit very low density lipoprotein (VLDL) clearance by inhibiting lipoprotein lipase-induced uptake into adipose tissue. The resultant imbalance between release of fatty acids and uptake into peripheral tissue causes hyperlipaemia.

Epidemiology

Hyperlipaemia is unlikely to occur in the absence of a predisposing risk factor. The following factors have been identified and are generally related to the presence or development of an insulin resistant state:

• species – donkeys and native ponies are most at risk
• obesity
• pregnancy – increased energy demands particularly in the last trimester
• lactation – increased energy demands
• inadequate exercise
• older age
• gender – females have a higher predisposition.

Irrespective of these risk factors, it is usually a specific event that acts as a trigger to tip the donkey into a negative energy balance, which activates the lipolysis pathway. Hyperlipaemia may be primary or secondary to the event. Secondary hyperlipaemia can occur if there is concurrent disease, which has led to a negative energy balance. Primary hyperlipaemia is caused by a stressor such as:

• excessive/extreme dieting
• management changes
• transport
• loss of a companion
• stress/anxiety
• cereal feeding
• anorexia/reduced appetite
• unexplained weight loss.

In many cases where donkeys are anorexic or losing weight there will be an underlying disease process resulting in secondary hyperlipaemia. In a recent study 72% of donkeys presenting with hyperlipaemia had a concurrent disease (Burden et al, 2011). The presence of disease rather than the specific disease process appears to be the trigger factor, which could be due to a combination of anorexia/reduced appetite, exacerbation of insulin resistance, and presence of inflammatory mediators. The presence of dental disease has been found to be a risk factor in itself.

Clinical examination

Because a negative energy balance is key to the development of hyperlipaemia, information about appetite should be obtained from the owner as well as being observed as part of the examination.

The digestible energy content of the diet of pregnant and lactating female donkeys should also be examined to ensure it is sufficient to meet their increased energy demands. The general suitability of the diet and bedding should also be assessed, because paper bedding and cereal feeding are risk factors for hyperlipaemia. It is also important to identify any other stressors that may have occurred in the preceding few weeks, because there is often a delay between the trigger factor and manifestation of clinical signs. Clinical signs are often non-specific and may be related to the primary disease process.

Signs that are often present include:

• dullness
• anorexia/reduced appetite
• reduced gut motility/ileus
• reduced faecal output – dry, mucous covered faeces
• halitosis.

A full clinical examination should be carried out to identify any primary disease process, including a rectal examination both to assess faecal output and to identify any gastrointestinal abnormalities. Studies have reported that 18% of colic cases had secondary hyperlipaemia (Duffield et al, 2002).

In view of the potential sequelae of pancreatitis, signs of endotoxaemia should also be assessed. The Donkey Sanctuary have found that the most common concurrent diseases have been reported as colic, respiratory disease, laminitis and renal disease.

Diagnosis

Hyperlipaemia should be suspected whenever presented with an inappetant and/or sick donkey. However, due to the non-specific nature of clinical signs, a blood sample to measure serum triglycerides is required to confirm the diagnosis.

• Take blood early during the examination. Grossly cloudy serum or plasma may be obvious, which enables prompt treatment prior to knowing an exact value for triglycerides.
   

• The Donkey Sanctuary’s normal range for serum triglycerides is 0.6– 2.8 mmol/l (53.4–249.2 mg/dl).
• Liver parameters are also likely to be elevated although it can be difficult to determine whether this is cause or effect because high circulating levels of triglycerides can lead to the development of fatty liver disease.
• Other biochemical and/or haematological abnormalities may give an indication of the primary disease process or the development of pancreatitis.

Treatment

The restoration of a positive energy balance is of utmost importance in the treatment of hyperlipaemia. In addition, it is vital to identify the instigating cause for the hyperlipaemia and to treat this promptly.

Restoring positive energy balance

The restoration of a positive energy balance will stimulate endogenous insulin secretion and switch off lipolysis.

Exact energy requirements for sick donkeys are not known. However, reversal of hyperlipaemia can often be achieved with 60—70kJ/kg bwt/ day even though this is lower than maintenance requirements.

Provision of the energy requirements for reversal of hyperlipaemia can be planned depending on levels of triglyceride.

• In mild cases, support may be given by dosing or in-feed glucose at 1-2g/kg bwt 2 to 3 times a day.
• Enteral feeding may be sufficient where triglycerides are modestly increased (less than 10 mmol/l) and there is some evidence of voluntary food intake and an absence of major concurrent disease.

• Pelleted high-fibre feeds or a ground oat instant breakfast cereal (for example, Ready Brek 1.5 MJ/100g) can be mixed with water, electrolytes and glucose and administered 2 to 3 times a day through a small bore nasogastric tube. Pre- and probiotics can also be added.

• Where triglycerides are more markedly elevated: higher than 10 mmol/l, it may be possible to administer boluses of intravenous fluids in the home. Mix:
  • 3L of an isotonic crystaloid fluid such as Hartmann’s with
  • Dextrose at 1-2ml/kg bwt and
  • Duphalyte (solution of B-vitamins, electrolytes, amino-acids and dextrose) at 1—2ml/kg bwt
• In some cases a combination of enteral feeding and intravenous fluids provides the best outcome.
• In more severe cases, donkeys have the best chance of recovery if hospitalised and administered parenteral nutrition.

Parenteral nutrition should be considered when the donkey does not significantly improve after 48 hours.

The following protocol should be undertaken in hospital conditions because it requires close monitoring. Where possible an infusion pump should be used and regular monitoring of glucose levels performed.

• In the field a less intensive regime may provide sufficient levels to restore normal triglycerides in many of the less severe cases. Use:
  • Hartmann’s drip at 60ml/kg/day with
  • 5% dextrose added at 1-2ml/kg and
  • Duphalyte (solution of B-vitamins, electrolytes, amino-acids and dextrose) at 100mls/50kg bwt.

Maintaining some voluntary food intake improves the prognosis.

Appetite can be stimulated by offering the donkey:

• treats such as chopped apples, grated carrots, bananas (particularly the skin) and mints
• cut brambles or allowing the donkey to browse in hedgerows – this can be effective in mild cases and during the recovery period
• flavour enhancers such as peppermint cordial, dried or fresh mint, ginger and fruit juices such as cherry, apple and carrot.

Pain and anti-inflammatory medication

• Remember that inappetent donkeys are also at risk of gastric ulceration, which can be exacerbated by the use of non-steroidal anti-inflammatories, so gastro-protection with a therapeutic dose of omeprazole or other effective agents is recommended.
• Pain will often result in inappetence, so if there is any suspicion that the donkey is in pain ensure that analgesic therapy is sufficient to control any signs of pain, which can be very subtle.
• As inflammatory mediators can stimulate lipolysis and inhibit VLDL clearance, if any inflammatory disease such as enterocolitis or peritonitis is suspected, the use of anti-inflammatory medication is recommended at dosing intervals suitable for donkeys.
• In view of the risk of endotoxaemia associated with the development of pancreatitis, flunixin may be the anti-inflammatory of choice in many cases.

Prognosis

A successful outcome is more likely if intervention is rapid and energy supply is restored by enteral and/or parenteral feeding alongside appropriate treatment of any underlying condition.

The Donkey Sanctuary has found a mortality rate of 48.5%. The clinical outcome is, however, dependent on the severity of hyperlipaemia such that the survival rate dropped to 30% in donkeys with triglycerides greater than 15mmol/l. It has also been found that donkeys with normal body condition are more likely than obese donkeys to survive while donkeys with concurrent disease were less likely to survive.

Prevention of hyperlipaemia

Be aware of and, where possible, avoid the risk factors and potential stressors associated with hyperlipaemia.

• Maintain a fit and healthy body condition score (Donkey BCS 2.5 -3).

• Apply an appropriate preventative health programme including dental care, parasite control, regular foot care and vaccination.
• Ensure appropriate exercise is encouraged, even in older donkeys, either by walking in hand or through creative use of moveable fencing.

PITUITARY PARS INTERMEDIA DYSFUNCTION (PPID)

Pituitary pars intermedia dysfunction (PPID), also known as Cushing’s disease, is recognised in donkeys. Hirsutism and curliness of the coat are less frequently seen in the PPID donkey than in the horse or pony. Clinical signs may include:

• high internal and external parasite burdens; individual donkeys with consistently high faecal worm egg counts may be affected by PPID
• poorly healing wounds or recurrent infections
• recurrent, acute or unrecognised laminitis
• weight loss and loss of muscle mass
• behaviour and demeanour change; for example, owners may report a donkey ‘slowing up’ or lacking in energy.

At present, PPID in donkeys is diagnosed based upon the results of diagnostic testing in combination with clinical signs. Basal adrenocorticotropic hormone (ACTH) measurement is the primary diagnostic test.

Donkey specific reference ranges for ACTH testing have been set by The Donkey Sanctuary and can be found at the start of this chapter.

Supportive care, remedial farriery and pergolide medication are the mainstay of treatment.

Pergolide treatment

If there is a high index of suspicion of PPID based upon test results and signs then pergolide therapy is justified.

Clinicians should begin pergolide treatment based on the same dosages as those given for horses and ponies. But be aware that:

• it is important to ensure accurate weight estimation and dosage

• pergolide may not be licensed or authorised for use in donkeys and owners must be advised and relevant regulation followed.

Pergolide can be associated with anorexia and secondary hyperlipaemia. Donkeys must be monitored closely, particularly when commencing treatment.

Monitoring the response to treatment by repeated ACTH testing, and adjusting the pergolide dose, should be undertaken as in horses and ponies.

EQUINE METABOLIC SYNDROME (EMS)

EMS should be considered in donkeys where risk factors are found. Donkeys are potentially more insulin resistant than horses and ponies, and obesity and laminitis are common in many companion donkeys. Acute or recurrent laminitis in an overweight donkey may be indicative of EMS. Clinicians should be aware that fat deposits may be localised, for example to the neck and rump, particularly in older donkeys.

As in horses and ponies, dynamic challenge tests may be of most diagnostic value, particularly if a basal insulin result is equivocal. Adiponectin testing in donkeys is not currently thought to be useful.

Donkey specific reference ranges for insulin testing have been developed by The Donkey Sanctuary and can be found at the start of this chapter.

Treatment follows the same guidelines as for horses and ponies. An overweight donkey should have a carefully managed diet programme to facilitate appropriate weight loss without risking hyperlipaemia.

Exercising a donkey with EMS can be challenging as these animals are often sedentary. The owner should be encouraged to exercise their donkey by gentle walking in hand and regular turn out onto bare pasture, once laminitis is under control.

Medication may be used in challenging cases, where diet change and exercise combined with appropriate weight loss alone have been ineffective.