Addisons Disease

Addisons Disease

SPC

 

Two new SPC Vet Members have kindly put together this up to date (May 2020)

piece on Addison's:

Addison’s Disease and Standard Poodles

Introduction
Addison’s disease is a hormonal disease of the adrenal glands, these glands sit just on top of the kidneys, one on each side. The adrenal glands are best known for their role in the ‘fight or flight’ response where they release adrenaline to prepare the body for exertion. In addition to this, the adrenals have other jobs, with each layer of the gland having a different important role. Addison’s disease concerns the outer layers of the adrenal glands called the adrenal cortex. The adrenal cortex is involved in the release of 2 main hormones Cortisol and Aldosterone. The adrenal glands release cortisol when they receive hormones from the pituitary gland in the brain and the cortisol has several important roles in the body such as: regulating blood pressure, regulating metabolism of carbohydrates / proteins and helping the body to deal with stress. Aldosterone’s main function is to make the kidneys reabsorb Sodium from the urine in the kidneys and to excrete Potassium into the urine, from the blood. This is important because water will follow the reabsorbed sodium back into the blood. Thus, aldosterone helps to maintain the blood volume and blood pressure, preventing dehydration. Aldosterone has 2 main triggers for its release: High levels of Potassium in the blood or low blood volume or pressure. When this is detected the kidneys release a chemical called Renin which converts Angiotensinogen (a protein produced in the liver) into Angiotensin I which is then converted into Angiotensin II. This Angiotensin II then raises the blood pressure by many different mechanisms, one of which is by stimulating the adrenal glands to release Aldosterone.
In general, Addison’s disease is considered are relatively rare condition. However, poodles are far more likely to develop the condition due to their genetics and approximately 70% of cases occur in females with most dogs developing the condition in early-middle stages of life. The cause for Addison’s disease in over 95% of cases is thought to be due to the body’s immune system attacking the outer layers of the adrenal gland. As poodles are prone to hormonal diseases this immune-mediated destruction can also occur to other glands causing other hormonal diseases too in what’s called a ‘Polyendocrinopathy’. Other rare causes include: tumours or fungal infections invading the adrenal gland destroying the adrenal cortex, blockages in blood vessels supplying the adrenal cortex such as blood clots or trauma to the adrenal gland. These are very rare causes of Addison’s disease, and poodles are not at higher risk of these causes.
As well as there being different causes of Addison’s disease there are also different types or categories of the disease. Primary Addison’s disease is by far the most common and this condition results from too little Cortisol AND Aldosterone being released by the adrenal gland. Iatrogenic Addison’s disease is another type. Iatrogenic generally refers to a condition that is caused by treating a different condition so can be thought of as a side effect of treating a different condition. This can happen when treating Cushing’s syndrome which is the opposite of Addison’s disease when theres too much cortisol. It can also happen when a dog is being treated with steroids for various different conditions and when the steroids are suddenly stopped without weaning the dose down. The third main type of Addison’s disease is Atypical Addison’s disease. Atypical Addison’s disease is rare and results from too little Cortisol release only. Poodles are primarily predisposed to primary Addison’s disease and atypical Addison’s disease.


Symptoms:
Addison’s disease tends to present itself in 2 main ways. It can either present with chronic symptoms or it can present suddenly with acute symptoms in what’s known as an Addisonian Crisis. Dogs will usually only present with acute symptoms when they’ve had the disease for some time and thus will likely have had some chronic symptoms before the acute crisis.
The symptoms they get are caused by the deficiency in cortisol and aldosterone. The most common chronic signs are:
•    Poor appetite
•    Lethargy
•    Weight loss
•    Vomiting or Regurgitation
•    Weakness
•    Dark black stools or blood in stools
•    Sometimes abdominal pain
•    Drinking and urinating more
These chronic symptoms may also worsen when they are physically or mentally stressed in any way and are known for waxing and waning.

Acute signs of an Addisonian crisis include:
•    Lethargy
•    Weakness
•    Collapsed and not being able to get up
•    Slow heart rate
•    Low blood pressure
•    Vomiting
•    Diarrhoea
•    Abdominal Pain
•    Hypothermia
•    Weak pulses
•    Low blood volume (Hypovolaemia)

As a general rule, Addison’s disease should always be in the back of a clinician’s mind whenever they have a dog that has vague symptoms such as weight loss, weakness or chronic gastrointestinal problems. Another feature that is sometimes seen with Addison’s disease is the symptoms tend to wax and wane and can be intermittent in nature.


Reaching a diagnosis:
There are several tests that can point towards Addison’s disease. The first step in investigating this disease involves a basic blood test with a full haematology (looking at different blood cells) and Biochemistry (looking at organs such as liver and kidneys as well as electrolytes).
Biochemistry: 90% of dogs with Addison’s disease have high potassium levels in the blood and 80% have low sodium in the blood which is due to low aldosterone levels. Clinicians may also use a ratio of sodium to potassium to aid in their assessment. Also the waste products that are excreted in the urine tend to build up in higher levels particularly in acute Addisonian crises because the blood flow to the kidneys is impaired by the low blood volume and low blood pressure caused by a deficiency in cortisol and aldosterone.
Haematology: There can be changes to the different types of white cell counts called an ‘anti-stress leukogram’ which is a pattern that the clinician can look out for.

There are more specific tests that test hormone levels that can confirm the diagnosis once a high suspicion has developed for the condition. There are 2 main hormone tests that can be done. These are: Basal Cortisol and ACTH Stimulation Test. Your clinician will assess which one is most appropriate depending on the level of suspicion for the disease.

Basal Cortisol test is a simple blood test to measure the amount of cortisol in the blood.
ACTH stimulation blood test involves taking 2 blood samples with the injection of ACTH in between the two blood samples to assess the bodies response to ACTH. ACTH is the hormone released from the pituitary gland in the brain which stimulates the adrenal glands to release cortisol. So the test assesses the ability of the adrenal glands to release cortisol when they are told to.


Treatment:
Treatment will depend on whether the dog is presenting with acute or chronic signs. In the case of an acute crisis, these are life threatening and are considered an emergency. The goals of treatment for acute disease are to return the electrolyte levels back to safe levels, improve blood pressure and blood volume and to replace the deficient hormones. Whereas, the treatment goals for chronic cases will involve supplementing the deficient hormones to reduce symptoms and to prevent acute Addisonian crises. Primary and Atypical Addison’s disease cannot be cured unfortunately so these treatments will be life-long.

Acute Treatment (if your dog goes into an Addisonian Crisis):
•    Intravenous fluid therapy with a fast rate drip (to restore blood pressure and blood volume)
•    Intravenous steroids (to replace deficient cortisol and aldosterone to a lesser extent)
•    Intravenous Calcium Gluconate (to protect heart form dangerous electrolyte imbalances)
•    Intravenous dextrose or glucose (to reduce the potassium levels to a safer level)
Once stabilised they can then be started on the long-term treatment which is better at replacing the deficient aldosterone and will also replace the deficient cortisol.

Long-term treatment:
•    Monthly injections with ‘Zycortal’ under the skin which will involve a monthly visit to the vets. This will replace aldosterone to allow your dog to maintain healthy levels of electrolytes and blood pressure.
•    Serial blood tests to check electrolyte balance of sodium and potassium to monitor for the correct dose of Zycortal.
•    Daily oral prednisolone to replace cortisol which will allow your dog to cope with stress, regulate their metabolism and maintain good blood pressure.
•    It is important to communicate with your vet about future events that could be stressful for your dog (fireworks, holidays etc.) as the dosage of prednisolone needed might change as a result of this.

Prognosis:
Prognosis is generally good with an average survival time of 4-5 years. Addison’s dogs can lead completely normal lives thanks to their long-term treatment.
        


Dr. Samuel Goldman MRCVS
Kate Bleasdale (soon to be Dr. and MRCVS)

 

 

For more information on Addison's speak to your Vet, your SPC regional representative or contact David Dennison 07377991101

 Email

The Standard Poodle Club has made a major donation of £1000 towards the vital research project to investigate the rise in numbers of dogs with Addison's Disease. The initiative has been led by the Beardied Collie Breed Council with a major grant from the Kennel Club. With the support of the SPC and others the fundraising target was reached, research commissioned and completed.

Our breed is badly affected and we hoped that this research project's findings would help to understand more about this distressing condition. Unfortunately the results were inconclusive - a lay summary report from Professor Catchpole is below and the full research findings available from the SPC stand at Crufts NEC  at our Champ Show  and Open shows.  

Serological profiling of autoantibodies in canine hypoadrenocorticism

Brian Catchpole BVetMed MSc PhD FRVCS

Professor of Companion Animal Immunology

Lay Summary

Canine Addison’s disease results from autoimmune destruction of the adrenal glands, leading to a deficiency in corticosteroid production. This results in a number of clinical signs, from waxing and waning non-specific illness to collapse and sudden death. In humans, the disease is associated with the presence of autoantibodies in the blood, which target the enzymes involved in steroid synthesis (known as P450scc, 21OH, 17OH and 3βHSD). We previously developed a radio-immunoassay for canine P450scc and demonstrated that a proportion of dogs affected with Addison’s disease were autoantibody positive. The aim of the project was 1) to adapt this assay to a non-radioactive format, 2) to expand the autoantigen panel for use in serological testing and 3) to specifically test serum samples from high risk breeds.

1) We successfully cloned canine p450scc into a new vector and produced recombinant protein containing a nanoluciferase tag, for use in a luciferase immunoprecipitation assay. Serum samples from Addisonian dogs were tested and a proportion of dogs were shown to be positive, similar to that seen with the original radio-immunoassay.

2) We successfully cloned canine 17OH and 3βHSD, although the cloning of 21OH failed. We developed autoantibody assays for these two additional steroid synthesis enzymes and demonstrated that a proportion of Addisonian dogs were positive (10/58 positive for 17OH autoantibodies and 8/53 positive for 3βHSD autoantibodies). Repeat cloning of canine 21OH into a new vector has now been achieved and we will be testing this autoantigen in the luciferase immunoprecipitation assay in the future (with a new MRes research student).

3) Serum samples from 9 Standard Poodles were submitted to the Royal Veterinary College during the course of the project. These were tested for autoantibodies against P450scc, 17OH and 3βHSD. Only one dog was positive and reacted to P450scc only. This is similar to the results found in Bearded Collies, although in the Finnish Laphund, all dogs tested so far have been positive for P450scc autoantibodies. This indicates that there are breed differences in the autoantibody response and suggests that some dogs react to 21OH or some other (as yet unidentified) adrenal autoantigen.

 

Future plans

We will continue the research into autoimmunity in Addison’s disease. We have a new MRes student starting in October 2018 who will be taking on development of the 21OH immunoassay. We will continue to pursue different avenues for sponsorship (e.g. crowdfunding, charities and commercial sources, such as Dechra). The one year MRes programme is a cost effective way of advancing this research programme as well as providing a postgraduate training experience

RADAR 

Addison’s disease in dogs is this on your RADAR?

R - RECOGNITION of the symptoms which include poor appetite, weight loss, lethargy, hind end weakness, irregular heartbeat, shaking, feeling cold, sickness, diarrhoea, ‘depression’ and others. Addison’s mimic many other things and a dog may only have one visible symptom.

A - ACTION if your dog displays any of the above symptoms or something feels ‘not right’ act fast, a dog with under diagnosed Addison’s can go downhill very quickly and even die before a diagnosis is made. Ask your vet to do an ACTH test, the definitive test for Addison’s. Have the electrolytes checked also as these are relevant in distinguishing the type of Addison’s your dog has.

D - DIAGNOSIS MADE VIA THE ACTH TEST

there are two main types of Addison’s

1. Typical Addison’s where a dog’s adrenal glands are unable to produce two hormones aldosterone and cortisol. The electrolytes will be unbalanced with high potassium and low sodium.

2. Dogs with Atypical Addison’s have well balanced electrolytes and only need a cortisol replacement. Some dogs with Atypical, transition to Typical usually within the first few months post diagnosis.

A - ADMINISTRATION of drugs. Once a diagnosis has been made and the dog is stabilised I V fluids may be necessary initially  - dogs with Atypical Addison’s need Prednisolon or similar EVERY day.

Dogs with Typical Addison’s need either a monthly injection of DOCP (Zycortal or Percorten) as well as a daily dose of steroid such as Prednisolone or they need Fludrocortizone tablets every day. The drugs will be necessary for the duration of their lives.

R - REVIEW and aim to optimise the Meds  over the next few months which means checking the electrolytes where applicable to ensure the dog has no unwanted side-effects. Your dog can now enjoy it’s life to the full.

WHEN IN DOUBT CHECK ADDISON’S OUT

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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@2017 Standard Poodle Club.

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