THE
PET HEALTH LIBRARY
Addison's Disease (Hypoadrenocorticism)
THESE TWO TERMS WILL BE USED INTERCHANGEABLY THROUGH
THIS TEXT
Adrenal Hormones
|
The adrenal glands are located just atop the kidney
Adrenal
Gland
The cortex
is shown in yellow
|
|
The adrenal gland is so named because it is located just forward
of the kidney (renal means kidney). The center of the gland is called
the medulla and the outer area is called the cortex. While both areas
produce hormones, Addison's disease concerns the hormones produced by
the cortex; these hormones are called corticosteroids.
Corticosteroids are the hormones that enable us to adapt physiologically
to stress. The glucocorticoids (such as cortisol and related synthetics,
prednisone and dexamethasone act on the mechanics of sugar, fat,
and protein metabolism. They gear the metabolism towards the preparation
of burning (rather than storing) fuels so as to be ready for a fight
or flight situation.
The Mineralocorticoids (such as aldosterone and related synthetic
fludrocortisone acetate) influence the electrolytes: sodium and potassium.
As a general biological rule, where there's sodium or salt, there's water.
When the mineralocorticoids circulate as part of the fight or flight
preparation, sodium is conserved in anticipation of blood loss so that
there will be extra fluid in the vascular compartment (spare blood).
When sodium is conserved, potassium is lost as part of the biological
balance. This whole picture of fat mobilization, sodium conservation etc.,
which is part of the fight or flight preparation is far more complex than
can be reviewed here but the bottom line is:
Corticosteroid hormones are needed to adapt to stressful situations
and without these hormones, even small stresses could lead to physiologic
disaster.
Hypoadrenocorticism (Addison's Disease)
In animals with Addison's disease, there is a deficiency of
the corticosteroid hormones. It is unusual to discover the direct cause
of this deficiency unless the patient is taking medications that disrupt
adrenal balance (like Ketoconazole or Lysodren) but, fortunately, the
disease can be managed with the administration of corticosteroid hormones
even if the cause of the deficiency is unknown
Clinical Signs
Patients are usually young (age 4-5 years) female dogs. (This
disease occurs in cats but is very rare.) Predisposed breeds include:
the Great Dane, the West Highland White terrier, all sizes of poodles,
and Portuguese water dogs. At first signs are very vague - listlessness,
possibly some vomiting or diarrhea. Ultimately, the disease results in
a phenomenon known as the "Addisonian crisis." The animal collapses in
shock due to its inability to adapt to the caloric and circulatory requirements
in stress. Blood sugar may drop dangerously low. Potassium levels soar
and disrupt the heart rhythm because there is not
enough conserved sodium to exchange for potassium. Heart rate
slows, and arrhythmias result. The patient may not survive this episode.
Corticosteroid hormones are needed to adapt to stressful
situations and without these hormones, even small stresses could lead
to physiologic disaster.
Approximately 30% of dogs with Addison's disease are diagnosed
at the time of an Addisonian crisis.
Making The Diagnosis
Veterinarians are classically presented with a young animal
in shock. There is usually no history of trauma or toxic exposure so
general treatment for shock is initiated. This consists of rapid administration
of fluids (usually lactated ringers solution, which has little potassium
and a moderate amount of sodium) plus some glucocorticoids. By coincidence,
this also happens to be similar to the specific treatment for Addison's
disease so that often the patient simply recovers without the veterinarian
really knowing why.
The blood panel will come back showing elevations in the renal
parameters (BUN and Creatinine) and thus with the elevated potassium
is suggestive of acute renal failure, a condition with an extremely
poor prognosis. The veterinarian may become suspicious of another diagnosis
as the patient will respond well to fluid administration and most renal
failure patients do not respond as well.
Addison's disease may present in more unusual ways. Inability
to maintain normal sugar levels (ultimately manifesting as a seizure
disorder) may be strongly suggestive of an insulin-secreting pancreatic
tumor but before a major abdominal surgery is planned, it is important
to test for Addison's disease.
Similarly unexpected, regurgitation of undigested food due
to abnormal nerve function in the esophagus (a condition called Megaesophagus)
can be caused ultimately by Addison's disease.
Because of the numerous symptoms Addison's disease can be present
with, Addison's disease has earned the medical nickname "the Great Imitator."
The only definitive test for Addison's disease is the ACTH stimulation
test. The patient receives a dose of ACTH, the pituitary hormone responsible
for the release of corticosteroids in times of stress. A normal animal
will show an elevation in cortisol in response to ACTH while an Addisonian
has no corticosteroids to respond with. This lack of response is diagnostic
for Addison's disease; however, a false positive may be obtained if
corticosteroids have been used in the treatment of the crisis prior
to the test. Only dexamethasone does not interfere with the assay for
cortisol; if any other steroid has been used, the test will not be valid
for at least a couple of days.
Treatment After The Crisis
The most important aspect of treatment for hypoadrenocorticism
is the replacement of the missing mineralocorticoids hormones. One
way to do this is with oral Fludrocortisone Florinef. Florinef is given
usually twice a day at a dose determined by the patient's sodium and
potassium blood tests. At first, these electrolytes are monitored weekly.
When levels seem stable, these blood tests are repeated 2 to 4 times per
year. Often with time, it will be found that the dose of Florinef needed
to control the Addison's disease will increase. This is unfortunate as
the medication is relatively expensive. Since Florinef has glucocorticoid
activity as well as mineralocorticoid activity, it is not necessary to
use additional medications for treatment.
Another way to treat this condition is with an injectable medication
called DOCP (brand name Percorten-V). This treatment is given approximately
every 25 days. Electrolytes are measured prior to injections at first
but testing can usually eventually be tapered to once or twice a year.
There is some feeling among experts that DOCP produces better regulation
of electrolytes than does oral Florinef. Some dogs however, do require
glucocorticoid supplementation (such as a low dose of prednisone).
At the moment, DOCP is only available directly through Novartis
Animal Health. It cannot be ordered through regular veterinary distributors
and, of course, pet owners may not directly order it. Your veterinarian
may obtain DOCP by contacting the Novartis Animal Health Customer Service
Department at: 1-800-332-2761
Salting the patient's food is sometimes recommended to assist
the patient with sodium balance.
What is "Atypical Addison's Disease?"
Approximately one dog in 42 will have a special form of Addison's
disease. Most dogs get Addison's disease when all three layers of the
adrenal gland are destroyed and no corticosteroid hormones can be produced.
With atypical Addison's disease, the problem is not with the adrenal
gland itself but with the pituitary gland, which islocated at the base
of the brain. The normal pituitary gland secretes ACTH adrenocorticotropic
hormone), which stimulates the zona fasciculata and zona reticularis to
produce glucocorticoids. Without this hormone, these two areas of the adrenal
gland atrophy but the zona glomerulosa remains normal. This yields a patient
who cannot regulate blood sugar normally but who is not at risk for an
Addisonian crisis. Diagnosis is still by ACTH stimulation test and an
endogenous ACTH level. Treatment is supplementation of glucocorticoid
hormones, such as prednisone. It should be noted that often these
patients progress to the more typical Addison's disease complete with
electrolyte imbalance.
What is Pacific Rimism?
Dog breeds originating in the Pacific Rim, such as the Akita
and Shiba inu, commonly have elevated potassium levels on blood tests.
This can be very confusing when a patient has symptoms that suggest
Addison's disease. These patients will have normal ACTH Stimulation
test results if they do not have Addison's disease.
Whipworm Infection?
Whipworm infection has been known to create a syndrome nearly
identical to Addisonian crisis, complete with abnormal sodium and potassium
values. These patients will have normal ACTH stimulation tests but because
whipworms only periodically shed eggs, fecal testing may not detect
whipworm infection. If there is any question about whipworm infection,
treatment should be instituted. See details on whipworm infection.
Successful Case Study: Otter
Otter was diagnosed with Addison’s disease and is doing well
today. Otter was nearing the point of Addisonian
crisis but the signs he was demonstrating were so vague that
his regular veterinarian could not pinpoint a diagnosis. Otter’s mom
sought help and was directed to an internal specialist in her area. Otter’s
tests uncovered a clear case of Addison’s disease and proper treatment
was initiated. Now that his hormone deficiency is known, on-going hormone
replacement keeps Otter an active, happy boy.
copyright
2005 - 2007 by the Veterinary Information Network, Inc. All rights
reserved.
This work was originally published by Veterinary
Information Network, Inc. (VIN)
and is republished with VIN's permission.
************************
CANINE
ADDISON'S DISEASE
http://www.petwellness.com
Lack of energy,
vomiting and weight loss in dogs may be symptoms of a number of common
disorders; however, they can also be early signs of a relatively rare
disorder called Canine Addison's Disease (hypoadrenocorticism). Because
it is so easily confused with many other diseases and frequently remains
undiagnosed until the dog collapses from weight loss, weakness or dehydration,
Canine Addison's Disease is often referred to as "The Great Pretender."
If left untreated, the disease can be critical, even fatal.
Canine Addison's Disease occurs when a dog's adrenal glands
do not produce enough hormones and other chemicals that help regulate
many bodily functions, such as metabolism, blood pressure and stress
response. While it is not contagious, it is not fully understood why
dogs develop Addison's. The most likely cause is genetic; however,
other possible causes include infections, immune system disorders and
trauma.
Studies have found that 70% to 85% of dogs with Canine
Addison's Disease are female1 and that the dogs most often affected
are between 4 and 7 years old. Some breeds seem to be affected more
commonly than others. These breeds include Great Danes, Portuguese
Water Spaniels, Rottweilers, Standard Poodles, West Highland White
Terriers and Wheaten Terriers.
Some of the most common signs a pet owner may observe
in a dog with Canine Addison's Disease include:
Most Common Signs
|
Less Frequent Signs
|
Anorexia
Lack of energy
Weakness
Vomiting
Diarrhea
Weight loss
Dehydration
|
Bloody vomit or stool
Excessive thirst or urination
Loss of appetite
Hair loss
Shaking and tremors
|
If your dog shows any of these
signs, consult a veterinarian at once. Chances are, your dog does
not have Addison's, but any discomfort or irregularity should always
be evaluated by a veterinarian.
Although abnormalities may be noted in EKGs and X-rays,
veterinarians generally use laboratory tests to confirm the diagnosis
of Canine Addison's Disease. These may include various blood and
urine tests. Even then, Canine Addison's Disease may escape diagnosis
because the results of the laboratory tests may be similar to those
in dogs with kidney failure.
The ACTH stimulation test provides one of the most accurate
and reliable tests for diagnosing Canine Addison's Disease. For
this test, the veterinarian collects blood samples before and after
giving the patient an injection of a hormone to see how the dog's
body responds.
Most veterinarians will treat Canine Addison's Disease
with a medication that replaces the hormones that the adrenal glands
can no longer produce. Today, the only medication approved by the
FDA* for treating Canine Addison's Disease is PERCORTEN®-V (desoxycorticosterone
pivalate).
It has been demonstrated that PERCORTEN-V is well tolerated
with a low incidence of side effects. In a small percentage of treated
dogs, depression, excessive thirst and urination, digestive, skin
and coat changes, weakness and injection site reactions (pain, abscesses)
may occur. Some of these effects may resolve with adjustments in dose
or interval of PERCORTEN-V or concomitant glucocorticoid administration.
Do not use in pregnant dogs or in dogs that are suffering
from congestive heart disease, severe renal disease or edema. Dogs
with renal failure must be stabilized before receiving PERCORTEN-V.
*NADA #141-029, Approved by FDA.
1. Hardy RM: Hypoadreanal gland disease. In Ettinger
SJ, Feldman EC, editors. Textbook of Veterinary Internal Medicine.
Philadelphia: WB Saunders; 1995. p 1579-1593.
2. Kelch WJ. Canine hypoadrenocorticism (Addision's Disease).
The Compendium, June 1998.
3. Grooters AM. Addision's Disease: Diagnosis and Treatment.
In: North American Veterinary Conference 1998 Proceedings. Gainesville,
FL: Eastern States Veterinary Association; 1998. p 238-242.
4. Tilley LP, Smith FWK: Hypoadrenocorticism (Addison's
Disease). In Tilley LP, Smith FWK, editors. The 5-minute Veterinary
Consult. Philadelphia: Williams & Wilkins, 1997. p 716-717.
5. Peterson ME, Kintzer PP, Kass PH. Pretreatment clinical
and laboratory findings in dogs with hypoadrenocorticism: 225 cases
(1979-1993). Journal of the American Veterinary Medical Association
1996; 208: p 85-91.
© 2006
Novartis Animal Health US, Inc.
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The adrenal glands
are essential for life. They are two small glands which sit next
to the kidneys. Their size does not correlate with their importance.
They secrete a number of hormones essential for normal functioning
as well as survival in stressful situations. Addison’s Disease (named
after it’s discoverer in 1855) means there is insufficient production
of these hormones. It is also called hypoadrenocorticism. Addison’s
disease can be primary: atrophy (dying off) of the adrenal gland or secondary:
a problem with the pituitary gland which secretes hormones that control
growth and activity of the adrenal glands.
Causes
Primary: It is believed that most cases of primary Addison’s
Disease are due to the body’s immune system destroying the adrenal
tissue. The reasons for this are unknown. Other less common causes
include infections, cancer, trauma, drug side effects and various types
of inflammation.
Secondary
This is due to problems with the pituitary gland
which include inflammation, trauma or tumours.
Physiology
The hormones produce by the adrenals can be grouped as
follows:
Mineralocorticoids - aldosterone
Glucocorticoids - cortisol
Primary Sex Hormones - androgens, oestrogens
Stress Hormones - adrenalin (note: the production of these
hormones seems to be unaffected in primary Addison’s Disease)
The main groups we are concerned with are the mineralocorticoids
and the glucocorticoids. The areas of the body that these hormones
influence area as follows:
Mineralocorticoids: control the ability to maintain electrolyte
and water balance in the body
Glucocorticoids: affect nearly every tissue in the body
- promote a sense of well being & stimulate appetite; help control
blood glucose levels; help the kidneys control water & calcium
levels in the blood, help with control of red & white blood cell
numbers.
As you see, without these hormones we have a very sick
animal which will not survive long without treatment.
History
Addison’s is seen mainly in middle aged female dogs. There
seems to be no obvious breed prevalence. The disease usually follows
a waxing and waning course and may be confused with other diseases
as the clinical signs are very non-specific.
Physical signs
The physical signs tend to relate to the lack of these
important hormones. These will include:
weakness, depression, lethargy
anorexia, weight loss
vomiting, diarrhoea
excess drinking or urinating
slow heart rates
abdominal pain
hypothermia
Laboratory Signs
The laboratory signs are more useful in diagnosing Addison’s
and will help to explain the physical signs
Increased Lymphocyte (a type of white blood cell) numbers
Anaemia
Increase serum potassium
Decreased serum sodium
Altered sodium/potassium ratio (Na:K): <27
Increased serum phosphorus
Increased serum calcium
Decreased blood glucose
Increased BUN & Creatinine (indicators of kidney function)
Acidosis (upset in body’s acid/base balance)
Low blood cortisol levels
Xrays may also be done which may reveal a smaller than
normal heart due to the reduction in volume of circulating fluid
in the body as part of Addison’s disease.
If the pet is not too sick, a test called an ACTH stimulation
is performed. As this test takes several hours to complete and sometimes
days for results, treatment for Addison’s Disease can usually be
instituted on other laboratory results.
Treatment
Treatment is normally in two stage:
1. Adrenal Crisis Management
Adrenal Crisis Management is required when we have a very
sick animal with abnormalities as those listed above. Your Vet will
decide what the best course of action is to follow according to each
individual case. This may involve fluid therapy and drugs to help reverse
the changes. Once the animal has recovered to a normal state we can
go onto Maintenance Therapy
2.
Maintenance therapy
Maintenance Therapy
is usually lifelong and involves tablets to replace the hormone that
are deficient: ie glucocorticoids & mineralocorticoids. Your Vet
will decide which medications are best for each case.
Monitoring
Careful monitoring of electrolytes is important throughout
he early stages of Addison's disease management. Your Vet is likely
to give you a list of dates when further blood tests will be needed.
These will usually be quite frequent at first with the intervals between
blood tests gradually increasing.
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ADDISON'S DISEASE OR HYPOADRENOCORTICISM
The Soft-Coated
Wheaten Terrier is one of the breeds listed in veterinary literature
as having a predisposition for Addison's disease. The purpose of
this article is to provide Wheaten owners and breeders with information
about the disease. Increased awareness will lead to early diagnosis
and treatment before the crisis stage of the disease.
Addison's disease is the common name and Hypoadrenocorticism
the commonly used scientific name. Adrenal insufficiency and adrenocortical
hypofunction are less commonly used terms. Addison's disease is the
insufficient production and secretion of hormones (glucocorticoids,
mineralocorticoids and androgens) by the adrenal gland cortex. This
is a disease that if left untreated, leads to death.
Dr. Thomas Addison first described the disease in humans
in 1849. In 1856 it was demonstrated that removal of both adrenal glands
resulted in the death of experimental animals. This proved that these
glands are necessary for the maintenance of life. Addison's disease
in dogs was not reported until 1953.
What causes Addison's disease? To date no one has discovered
the cause or any specific risk factors for this disease. About 80%
of human hypoadrenocorticism is immune-mediated destruction of the
adrenal cortices. Many of the features of canine Addison's disease resemble
those in humans and it is likely that dogs also have this immune-mediated
destruction.
What is Autoimmune disease? Autoimmunity is a misdirected
immune response, in which the body's defenses become self-destructive.
Under normal conditions the body's immune mechanism is able to recognize
its own tissues and chemicals. This recognition of self is called immunologic
tolerance. When tolerance breaks down the body fails to interpret
its own cells as self. Autoimmunity may result from a combination of
factors such as; genetic predisposition, hormonal factors and environmental
triggers such as viral infections and vaccinations. Autoantibodies reactive
to the adrenal cortex are diagnostic of autoimmune Addison's disease and
have been identified in dogs with this disease.
When immune-mediated disease affects the adrenal glands;
it may also affect other glands. Up to 5% of Addisonian dogs have endocrine
failure in the thyroid gland (hypothyroidism), the pancreas (diabetes),
parathyroid gland (hypoparathyroidism) and reproductive disorders (primary
gonadal failure). Addison's disease does not cause other disorders; it
is just that the immune disorder may affect more than one tissue.
Who gets Addison's disease? Addison's disease can occur
in dogs of any age, sex or breed. Current research has shown this
to be primarily a disease of young to middle-aged females as is the
case for most immune-mediated disorders in the dog. Up to 70% of dogs
diagnosed are female. 80% are 7 years of age or younger with the average
age being 4.6 years. Dogs of all breeds are affected, including mixed
breeds. Recent publications describe an increased familial or genetic
predisposition with a possible contribution of triggers as a cause for
the disease in some breeds.
Two examples of familial predisposition are; (1) a group
of related Standard Poodles was studied and ten were found to have
Addison's disease. This group had no pattern of inheritance, but the
prevalence of disease was extremely high compared to the general canine
population. (2) The 1996 Autoimmune Endocrine Health Survey for Bearded
Collies also concluded there was a hereditary Addison's disease that
exists in the Bearded Collie population.
Wheatens and Addison's
Dr. Margaret Slater has just completed a health survey for
the SCWTCA. There were 1246 dogs in the final survey, a total of 4
Wheatens with Addison's.This is 0.6% of the 1246 dogs. She states it
doesn't appear to be very common in the breed.
Dr. Meryl Littman states that the prevalence of Addison's
in SCWT's is really not known. She estimates she knows of over 350
Wheatens with PLE/PLN, but only a dozen or so with Addison's. "So although
there is a predisposition in the SCWT breed, Addison's is still not that
common". She does not know of any pedigrees with a higher incidence
of Addison's, but this needs more study. It appears to be a sporadic
problem within the breed.
There are two types of Addison's disease.
Primary hypoadrenocorticism constitutes the majority
of canine cases. This type originates within the adrenal glands and
is an atrophy or destruction of all layers of the adrenal cortex.
Secondary hypoadrenocorticism is caused by
decreased secretion of hormones by the hypothalamus or the pituitary
glands. Their hormones stimulate the adrenal cortex to release its
hormones. Without these triggering hormones the adrenal glands fail
to function. The adrenal glands are small structures located above each
kidney. They have two main sections: the center or medulla and the outer
area or cortex. Addison's disease concerns hormones called corticosteroids
produced by the cortex.
There are two main types of corticosteroid - glucocorticoids
and mineralocorticoids.
They are needed to adapt to stressful situations and without
them, even small stresses can lead to disaster. Cortisol is the major
adrenal glucocorticoid. It affects every tissue in the body and is
responsible for carbohydrate, lipid and protein metabolism, maintenance
of normal blood pressure, and counteraction of the effects of stress.
To counteract stress cortisol increases glucose levels in the blood,
providing a source of energy for all the body's activities. Abnormal adrenal
glands do not secrete any cortisol causing decreased levels of glucose
to deal with stress. Aldosterone is the major mineralocorticoid and is
responsible for maintaining the levels of minerals, sodium, potassium
and chloride in the body. Aldosterone's affect on the kidneys results in
the maintenance of fluid levels and mineral balance in the body.
The onset of Addison's disease is a gradual process with
85 to 90% of adrenal cells being destroyed before signs of deficient
secretion become obvious. Individual variation exists among dogs so
some dogs show symptoms earlier or later than others. A partial deficiency
syndrome may occur, where the adrenal glands secrete adequate amounts
to maintain a near-normal state. Symptoms only occur during periods of
stress when there are inadequate levels of corticosteroids to deal with
the stressful situation. As destruction progresses secretion is inadequate
even under non-stressful conditions.
This illness appears to affect some dogs episodically. These
dogs fluctuate between appearing normal and quite ill. This waxing-waning
course of illness is not always obvious to owners of affected dogs.
Vague symptoms such as; occasional anorexia, vomiting, and/or diarrhea,
muscle weakness, lethargy and depression are common. The vague symptoms
often have the owner talking him or herself out of a veterinary visit.
Signs of illness are often nonspecific and similar to more common diseases
such as kidney, gastrointestinal and infectious diseases. The mimicking
of other diseases is why Addison's disease is often called the "great
pretender".
Comparisons
of Diseases to which SCWT are Predisposed (4)
|
RD
|
PLN
|
PLE
|
ADDISON'S
|
Age of Onset
|
< 1-3 yrs
|
Mean ~ 6 yrs
|
Mean ~ 4.5 yrs
|
Average 4.3-5.4 yrs
|
Sex Predilection
|
None noted
|
Female: male 1.6
|
Female: male 1.7
|
Female (in general)
|
PU/PD
|
Yes
|
Yes
|
Yes
|
Yes
|
Vomiting/Diarrhea
|
Yes
|
Yes
|
Yes
|
Yes
|
Azotemia
|
Yes
|
Eventually
|
No
|
Possibly (pre-renal)
|
Low albumin
|
No
|
Yes
|
Yes
|
Possibly (melena)
|
Low globulin
|
No
|
No
|
Yes
|
Possibly (melena)
|
Low Na:K ratio
|
Not noted
|
Rarely (-7.0%)
|
Rarely (-7.0%)
|
Yes
|
A hallmark symptom of Addison's disease is impaired tolerance
to stress. Even mild physical or emotional stress can cause an Addisonian
crisis. A healthy dog responds to stress by releasing cortisol. Dogs
with Addison's disease can't do this. Therefore, the physiologic defense
provided by cortisol does not operate. Absence of Aldosterone compounds
the problem with depletion of fluids and impairment of cardiac function.
This leads to eventual circulatory collapse.
What constitutes stress and the amount of stress a dog can
tolerate varies with each dog. Examples of stressors are: elective
surgery such as spaying/neutering, traumatic injuries, infection, vaccinations,
cold weather, or psychological distress such as trips to the veterinarian,
the family packing up for a vacation, being placed in a boarding kennel,
traveling or summer thunderstorms. Stress can be fun things too such
as agility or obedience classes.
Commonly reported symptoms.
Severity can vary dramatically from dog to dog.
Anorexia
Thin/Weight Loss
Depression/Lethargy
Vomiting/Diarrhea
Weakness
Collapse
Shaking and Shivering
Excessive urination with or without excessive thirst
Waxing and Waning Course of Illness
Painful/Sensitive Abdomen
Fatigue/exercise intolerance
The dog may also appear clumsy and unable to climb stairs
or jump on the bed. This may be due to muscle loss or weakness. The
dog does not have the strength to do normal activities. On examination
by the veterinarian the dogs were noted to have;
Mental Depression
Thin/emaciated
Muscular Weakness
Dehydration
Slow weak pulse
Blood in feces
Gastrointestinal hemorrhage
Collapse
Abdominal pain
Pale mucous membranes/anemia
Low temperature
Low blood pressure
Grand Mal Seizure
Addisonian Crisis the Endocrine Emergency. Addisonian crisis
occurs when the dog is in circulatory collapse and shock. The deficiency
of Aldosterone leads to severe depletion of sodium (hyponatremia) resulting
in depletion of body fluids (hypovolemia) and potassium retention
(hyperkalemia). This progresses to collapse, bradycardia (slow heart
rate), hypotension (low blood pressure). and associated cardiac arrhythmias
(abnormal heart beats). In Addison's hypovolemia and shock cause bradycardia
but in other diseases this condition causes tachycardia (fast heart
rate). Deficiency of cortisol causes low blood sugar levels (hypoglycemia).
Hypoglycemic seizures have been reported in dogs with Addison's. Decreased
secretion of gastrointestinal enzymes causes anorexia, nausea, vomiting,
flatulence and diarrhea. These symptoms as well as anxiety, mental depression,
and loss of mental acuity, may also be related to the absence of cyclic
peaks of cortisol.
This crisis may be the first time the owner suspects anything
is wrong and may be fatal if not treated promptly. The goal of emergency
treatment is stabilization with aggressive therapy. Virtually every
dog treated with IV therapy, glucocorticoids, and mineralocorticoids
have shown rapid improvement. There may be a need for intensive monitoring
and therapy for several days to stabilize the dog. Studies have found
that between 33 to 51% of dogs with Addison's were diagnosed during a crisis.
The dog owners stated their dog had signs and symptoms of being unwell,
but they had a difficult time getting a definitive diagnosis. The emotional
trauma to both the dog and its owners, combined with expense are the
primary reasons for early diagnosis before crisis occurs.
Diagnostic Testing: Blood Chemistry Profile: Electrolyte
profiles (Sodium, Potassium, Chloride) are extremely valuable. They
support a tentative diagnosis and are useful in modifying therapy. Balance
of these chemicals is vital to health and abnormal levels can be life
threatening. The diagnostic chemistry profile will have a low sodium
(<135 meq/L) and elevated potassium (>6.0 meq/L). Sodium potassium
ratios are used to identify adrenal insufficiency. Normal ratios are
between 27:1 and 40:1. In primary hypoadrenocorticism the sodium: potassium
ratio will be below 25:1. However, these changes are not present in all
dogs. EKG abnormalities are associated with high potassium and low sodium.
Untreated high potassium can lead to cardiac arrest and death. Other diseases
can cause elevated potassium and/or low sodium. The definitive test for
Addison's disease is the ACTH stimulation test. This test directly assesses
the capacity of the adrenal gland to secrete cortisol and indirectly assesses
Aldosterone secretion. An ACTH stimulation test should be considered in
dogs with signs of weight loss, decreased appetite, and intermittent vomiting
and diarrhea.
Long-term Management of Dogs with Primary Hypoadrenocorticism.
In every case, medications must be administered to maintain the life
of the animal. Treatment is replacement of the hormones with synthetic
glucocorticoids (i.e. Prednisone) and mineralocorticoids (i.e. Florinef
or Percorten V). Therapy usually brings about a rapid recovery, and involves
life-long medications. Steroids do not cure disorders; they just treat
the symptoms. Prednisone may be needed on a regular basis, or at times
when the dog will be in a stressful situation. These medications come
in multiple potencies and forms and have no set or consistent dosage.
They need to be individualized to the severity of the condition and the
patient response. When given in the minimum dose that maintains a therapeutic
response side effects can be kept to a minimum. Key is to remember every
dog is different. Once achieved improvements in the dog's health are usually
maintained.
Florinef (fludrocortisone) is in pill form and has been
used for treatment of dogs with Addison's for over 20 years. Advantages
of this medication are; dosage can be quickly changed to adjust incorrect
doses, most owners can administer tablets and the drug is readily available
at most human pharmacies. Disadvantages are; extremely high doses may
be required which increases the side effects, owner compliance in giving
the medication on a regular basis is often a problem and at high doses
this therapy is expensive.
Percorten V or DOCP (desoxycorticosterone pivalate) is an
injection that is given once every 21 to 30 days. The dog on this
medication may also require low doses of Prednisone. The most common
cause of Percorten treatment failure is insufficient supplemental glucocorticoid
administration. Advantages of this form of treatment are; infrequent
doses of the drug (every 21 to 30 days) improves compliance, most owners
can be taught to administer injections to their dogs and expense is similar
or less in larger dogs. Disadvantages are; the need for supplemental Prednisone,
if the owner is unable to give injections it must be done at a veterinarian's
office at an added expense, pain on injection and the drug is not as readily
available as Florinef and must be purchased at the veterinarian's office.
Most often the veterinarian will try to stabilize the dog on Florinef.
If this is not possible a change to Percorten V (DOCP) is indicated.
The goal is to use the medication that produces the desired effect -
a healthy and happy dog.
One side effect that requires caution is immune system suppression.
Synthetic glucocorticoids produce suppression of the immune system
by suppressing antibody formation. This can lead to compromised resistance
and susceptibility to infection. When vaccinating Addisonian dogs avoid
giving combinations by using separate injections at spaced intervals to
prevent overwhelming the immune system. The owner has to pay close attention
to a dog with this disease by watching for signs and symptoms and changes
in the dog's behavior. These dogs crash quickly! Okay in evening but by
morning all signs and symptoms present. Symptoms that can alert owners
to a problem are; dehydration (touch the dogs gums, if they feel tacky
this is a sign of dehydration, a well hydrated dog has wet slippery gums),
changes in appetite, vomiting and/or diarrhea, appear tired and there is
no tail wagging.
I was fortunate to communicate with four Wheaten owners
whose dogs have Addison's disease. They provided me with detailed
information about their experiences and the health of their dogs.
The course of their disease followed the clinical picture described
in much of the literature I read. If the diagnosis of Addison's disease
is made early, it is controllable with an excellent prognosis. After therapy
stabilizes the condition, the dog can usually lead a normal life with few
if any restrictions. The most important factors are long-term response
to medications and diligent owners and veterinarians. Recognition of the
disease and the cost of treatment seem to be the biggest obstacles to
a successful outcome.
With the health focus for Wheaten breeders and owners on
PLE and PLN we must not forget there are other diseases affecting our
breed. Many of the signs and symptoms are the same. Let us be vigilant
and not overlook other causes of illness as this leads to delayed diagnosis
and treatment of those diseases. This in turn leads to prolonged illness
of our dogs. Addison's disease is another reason to send the dog's information
to the open registry. If there is a hereditary link we need to find and
understand it. I would like to acknowledge the following for their help
in my research: Kathleen Strauser, Exec Director, Canine Addison's Disease
Awareness Collaborative, for information, articles and suggestions; the
owners who submitted information about their dogs and experiences, Dr.
Margaret Slater for correspondence on preliminary data from 1999 SCWT Health
Survey and Dr. Meryl Littman for her correspondence.
Addison's Disease Reference List
I used 46 articles/textbooks and many personal correspondences
to research this topic. Listed are the key references:
Feldman, Edward C. D.V.M. and Nelson, Richard W. D.V.M.
(1996). Canine and Feline Endocrinology and Reproduction (2nd ed.).
Philadelphia: W.B. Saunders Co.
Novartis Animal Health Professional Services. Canine Hypoadrenocorticism:
Diagnosis and Treatment of an Emerging Disease. Greensboro, NC. Novartis
Animal Health US Inc..
Canine Addison's Disease Awareness Collaborative (May 1999).
Addisonian Dog Owners Survey. k9 Addison's Internet Support Group k9Addisons@egroups.com
Littman, Meryl P., (1999). ACIVM Proceedings Wheaten Terrier
PLE-PLN. Proceedings of the 17TH Annual Veterinary Forum, ACIVM 1999,
554-556.
Littman, Meryl P., Dambach, D.M., Vaden, Shelley L. and
Giger, U., (2000). Familial Protein-Losing Enteropathy and Protein-Losing
Nephropathy in Soft Coated Wheaten Terriers: 222 Cases (1983-1997).
Journal Veterinary Internal Medicine 14, 68-80.
Levy, J.K., (1994). Hypoglycemic seizures attributable to
hypoadrenocorticism in a dog. Journal American Veterinary Medicine
Association 204(4), 526-530.
Melian, C. and Peterson, M.E., (1996). Diagnosis and treatment
of naturally occurring hypoadrenocorticism in 42 dogs. Journal Small
Animal Practice (37) 6, 268-275.
Peterson, M.E., Kintzer, P.P. and Kass, P.H., (1996). Pretreatment
clinical and laboratory findings in dogs with hypoadrenocorticism:
225 cases (1979-1993). Journal American Veterinary Medical Association
208(1), 85-91.
Login, Joyce A., (1998). Diagnosis and Treatment of Hypoadrenocorticism
(Addison's Disease). Veterinary Medical Bulletin. Novartis Animal
Health US, Inc.
Kelch, W.J., Lynn, R.C., Smith, C.A. and New, J.C.Jr., (1998).
Canine Hypoadrenocorticism (Addison's Disease). Compendium of Continuing
Education for the Practicing Veterinarian 20(8), 921-935.
Schaer, M., Riley, W.J., Buergelt, C.D., Bowen, D.J., Senior,
D.F., Burrows, C.F. and Campbell, G.A., (1986). Autoimmunity and
Addison's Disease in the Dog. Journal American Animal Hospital Association
22, 789-794.
Report on the 1996 Autoimmune Endocrine Health Survey. Beardie
Bulletin, November 1997. and Sell, Elsa, MD Health Committee Chairperson
(1998). Addison's Update, Beardie Bulletin, May 1998.
About the author: I have a degree in nursing and no veterinary
training. I presented information on Addison's disease for the health
seminar at the Soft-Coated Wheaten Terrier Association of Canada's
National Specialty in June 2000. This article is a small portion of
the information presented. I have tried to make the article informative
without getting too technical. Please contact me if you would like
more information or the complete reference listing.
Copyright
© 1997-2003 Helen Larson
Reprinted with kind permission from Helen Moreland, President,
SCWTCA
The Soft Coated Wheaten Terrier Club of America
All rights reserved
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The diagnosis is in; it’s Addison’s disease. All of us here
at AddisonDogs.com remember hearing those words from our vet.
Sometimes they brought up feelings of sadness, or fear, occasionally
relief to know what’s going on. Then the vet starts talking about
mineralo-somethings and prednisone and DOCP and daily this and monthly
that and soon your head is swimming. You just want your dog back.
That’s how AddisonDogs.com came to be.
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the adrenal glands are
located above the
kidneys
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What is Addison’s disease anyway?
Let’s start with a brief overview of Addison’s disease.
It is the common name for hypoadrenocorticism, or adrenal insufficiency.
It is a disease with symptoms that are common to many other ailments,
making diagnosis difficult and sometimes a process of elimination.
But once Addison’s is correctly diagnosed, a properly treated dog can
live a normal, active life.
The adrenal, one on each kidney, is made up of two layers,
the cortex and the medulla. The outer area, or cortex, secretes
corticosteroid hormones such as cortisol and aldosterone. The
medulla, part of the sympathetic nervous system, secretes epinephrine
(adrenaline), which is generally not affected by Addison’s.
There are three forms of Addison’s disease: primary,
secondary and atypical. Primary and atypical Addison’s are usually
the result of immune mediated damage to the glands. Secondary hypoadrenocorticism
is from failure of the pituitary to stimulate the adrenals with adrenocorticotropic
hormone (ACTH). It is important for you to know which type of
Addison’s disease your dog is being treated for.
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SYMPTOMS
Vomiting
Diarrhea
Lethargy
Depression
Lack of appetite
Tremors or shaking
Muscle weakness
Pain in hind quarters
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I don’t have a diagnosis
– what are the symptoms?
The symptoms of Addison’s disease can be vague. More
importantly, they are similar to the symptoms of many different problems.
Initially, the dog may be listless, or seem depressed. Many dogs
are described as just seeming off, or losing the normal sparkle in
their eye. Lack of appetite is a good indicator. Other symptoms
include gastro-intestinal problems like vomiting and diarrhea.
Pain in the hindquarters, or generalized muscle weakness such as a dog
that can’t jump onto the bed or couch as he has done in the past is not
uncommon. Shivering or muscle tremors may also be present.
The most important thing to remember is that you know your dog better than
anyone. If something seems amiss, have it checked out.
These symptoms may wax and wane over months or years making
diagnosis difficult. If the adrenals continue deteriorating,
ultimately the dog will have an acute episode called an Addisonian crisis.
Potassium levels elevate and disrupt normal function of the heart.
Arrhythmias can result and blood pressure drops to dangerously low levels.
BUN and creatinine levels, generally indicators of kidney function, are
often elevated. At this point many animals are diagnosed with renal
failure, as the kidneys are unable to function properly. Typically
animals are given IV solutions for rehydration, which may produce an almost
miraculous recovery. This too, is a great indication that failure
of the adrenals rather than of the kidneys is creating the symptoms.
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Electrolyte levels are important,
but not a definitive test for Addisons.
____________________
Primary Addison's involves changes
in electrolytes while Atypical and
Secondary do not.
____________________
An ACTH Stim test is the only definitive
test for diagnosing Addison's.
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How can you be sure it’s
Addison’s?
One of the first things to look at when Addison’s disease
is suspected are the electrolyte levels. The two that are of
greatest concern are sodium (Na) and potassium (K). In addition
to looking at these values, it is important to look at the ratio between
the two. This number is derived by dividing K into Na and should
be between 27 and 40. For example, a dog with a Na level of 145
and a K level of 4.5 would have a ratio of 32. A dog in an Addisonian
crisis will typically have a low Na level, elevated K and low ratio. (see
laboratory results for more info)
While electrolyte levels are important indicators, they are
not the definitive test to determine Addison’s disease. In fact,
with secondary and atypical hypoadrenocorticism, electrolyte levels
may not be affected. For definitive diagnosis the dog is given
the ACTH stimulation or response test. This tests the ability of
the adrenal glands to produce the corticosteroid hormone cortisol.
To perform the ACTH stimulation test, an initial blood sample
is drawn and the cortisol level is measured. The dog is injected
with a form of the pituitary hormone ACTH that tells the adrenals
to produce cortisol. After an hour, blood is drawn again, and
the cortisol level measured. Resting cortisol should range from
1-4 μg/dl in the average dog, and should be significantly higher, in the
range of 6-20 μg/dl, post-stimulation. (These numbers may vary depending
on the lab.) If resting cortisol is low and the dog has no or a low response
to the stimulation, the diagnosis is Addison’s disease. Be aware
that some glucocorticoids, such as prednisone, can affect the results of
the ACTH test, while dexamethasone does not.
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Primary Addisons requires the
replacement
medications
of mineralocortioids. ____________________
Atypical and Secondary require
the
replacement of
glucocorticoids
only.
____________________
Atypical Addison's
can
become Primary and requires
careful
monitoring of your dog.
____________________
Addison's dogs require additional
glucocorticods during periods of stress,
injury or surgery.
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Keeping on top of it
There are several medications used to treat Addison’s.
The first type acts as a mineralocorticoid and replaces the aldosterone
– the hormone responsible for maintaining electrolyte levels.
It is replaced with either an oral medication called Florinef ™ (fludrocortisone
acetate) or the injectable Percorten-V™ (desoxycorticosterone pivalate
or DOCP). For dogs that have atypical or secondary Addison’s neither of
these medications are used because the production of aldosterone isn’t
effected and electrolytes remain in balance.
In addition to replacing the aldosterone, the cortisol, or
glucocorticoids, normally secreted by the adrenals must also be replaced.
This is typically done with an oral form of prednisone or hydrocortisone.
With atypical and secondary Addison’s the glucocorticoid is the only
medication given.
The bottom line
While your dog with Addison’s disease will need medications
and monitoring for the rest of his life, most dogs with Addison’s can
return to their favorite activities. You will learn to read your
dog, understand what his stress triggers are and follow your instincts
in his care. Together, you will overcome ADversity and learn from
this experience. You will help your dog lead a normal, active and
fun-filled life.
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Treatment
and Medications
There are several
medications used to treat Addison’s disease. The first type
acts as a mineralocorticoid and replaces aldosterone – the hormone
responsible for maintaining electrolyte levels. It is replaced
with either an oral medication called Florinef ™ (fludrocortisone
acetate) or the injectable Percorten-V™ (desoxycorticosterone pivalate
or DOCP). For dogs that have atypical or secondary Addison’s neither
of these medications are used because the production of aldosterone
isn’t effected and electrolytes remain in balance.
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In addition to aldosterone, the cortisol,
or glucocorticoids, normally secreted by the adrenals must also be
replaced. This is typically done with an oral form of prednisone
or hydrocortisone. During a crisis, the dog may receive an injection
of dexamethasone, a potent and fast-acting glucocorticoid. The dog
may be started initially on high doses of prednisone to facilitate a return
to health. On an on-going basis, the glucocorticoid dose can be reduced
and in some cases eliminated except on an as-needed basis. With atypical
and secondary Addison’s the glucocorticoid is the only medication given.
Mineralocorticoids:
Primary Addison’s disease is treated by replacing the mineralocorticoid,
Aldosterone, with either tablets of Florinef or the injectable Percorten-V.
These medications help maintain the balance of the electrolytes Sodium
(Na) and Potassium (K).
Florinef is the brand name for fludrocortisone acetate.
This medication is also available in its generic form, fludrocortisone
acetate, from compounding pharmacists. It is primarily a mineralocorticoid,
but also has some glucocorticoid activity. The starting dose
recommended by the Merck Veterinary Manual is 0.05 – 0.1 mgs per 10
lbs of bodyweight. Some dogs require significantly higher doses
to maintain normal electrolytes.
The dose may be divided and given twice per day or given
all at once, usually in the morning. A 50-pound dog would take
between 0.25 and 0.5 mgs to start. The brand name Florinef tablets
may be purchased directly from your vet or from a pharmacy. Some
people find it more cost effective and efficient to have the proper
dose of the medication prepared by a compounding pharmacist in capsule,
liquid, or chewable form.
Percorten-V is the brand name for desoxycorticosterone pivalate.
It is an injectable medication with only mineralocorticoid activity.
It does not have any glucocorticoid activity. The dose recommended
by Novartis, the manufacturer, is 0.75 – 1.0 mgs per one lbs. of bodyweight,
given every 21 – 30 days. There are 25 mgs in each ml (or cc)
of the medication.
A 50-pound
dog would receive between 37.5 – 50 mgs or 1.5 – 2.0 mls. Some
dogs are adequately maintained on lower doses, while some dogs require
lower doses to minimize rare side effects. Percorten-V is available
only through a licensed veterinarian, although some veterinary pharmacies
may carry the medication.
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Glucocorticoids
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Glucocorticoids:
The adrenal glands produce cortisol, a glucocorticoid.
It is the hormone measured by the ACTH Stimulation test used to diagnose
Addison’s disease.
All dogs with Addison’s require the supplementation of glucocorticoids
in times of stress. Many need glucocorticoids on a more regular
basis, particularly those on DOCP. Dogs with atypical or secondary
Addison’s only take glucocorticoids.
The most common glucocorticoids are prednisone, hydrocortisone
and dexamethasone. There are additional glucocorticoids such
as prednisolone and methylprednisolone. The Merck Veterinary
manual recommends a prednisone dose of 0.1 – 0.2 mgs/lb. per day.
This is equivalent to 0.4 – 0.8 mgs/lb. per day of hydrocortisone.
However,
some dogs show symptoms of excess glucocorticoids on these doses.
These problems may include excessive drinking and urination, increased
appetite, recurring infections, elevated liver enzymes, panting, restlessness
and even behavioral changes. Because these dogs will be on medications
for the rest of their lives, it is important to fine-tune the dosages
to maximize benefits, while minimizing unwanted side effects. If
you are working to reduce your dogs dose of glucocorticoids, be sure to
work with your vet and lower the amount slowly.
Determining what constitutes stress for your dog, when additional
glucocorticoids are necessary, is very individual. Like people,
dogs find different situations stressful. Stress can be in many
forms, both good and bad, from physical to emotional. For some dogs
a trip to the vet requires extra medication, while for others it could
be houseguests or extra active playtime. Knowing your dog’s triggers is
crucial. It is essential to monitor the dog closely and be prepared
to give extra medication when the need arises
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More about ACTH test
Reading your dogs blood work
Determining Electrolyte Ratio
Electrolyte ratio is determined by dividing the "NA" number
by the "K" number.
145÷ 4.5 = 32
Electrolyte
Calculator
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Laboratory Results
Blood tests:
Addison’s disease is diagnosed through a blood test called
the ACTH Stimulation or Response test. This test is typically
only done once to diagnose the condition. To perform the ACTH
stimulation test, an initial blood sample is drawn and the cortisol
level is measured. The dog is injected with a synthetic form
of the pituitary hormone ACTH that tells the adrenals to produce cortisol.
After an hour, blood is drawn again, and the cortisol level measured.
Resting cortisol should range from 1-4 μg/dl in the average dog, and
should be significantly higher, in the range of 6-20 μg/dl, post-stimulation.
If resting cortisol is low and the dog has no or a low response to the
stimulation, the diagnosis is Addison’s disease. Be aware that
some glucocorticoids, such as prednisone, can affect the results of the
ACTH test, while dexamethasone does not.
At diagnosis, your dog will probably have what’s referred
to as a Super Chem or Chem Panel and CBC (Complete Blood Count) to look
at other important blood values. The results from these blood
tests help to determine if organs such as the kidneys, liver and pancreas
are functioning properly, as well as if any signs of infection are present.
A complete blood test should be completed every 6 months to one year for
a dog with Addison’s disease.
There are two blood test results that are of particularly
interest in Addison’s disease. They are Sodium (Na) and Potassium
(K). The hormone Aldosterone regulates these electrolytes.
In primary Addison’s disease, the adrenal glands don’t produce (enough)
Aldosterone, so it must be replaced with Florinef or DOCP. This
is information that you and your vet will use to monitor the effectiveness
of the mineralocorticoid (DOCP or fludrocortisone). The electrolytes
are checked frequently at the beginning to determine correct medication
levels.
Normal ranges
for these values may vary based on the lab and equipment used.
Typically, the normal level for Sodium is between 139 to 154 mEq/L
and Potassium should be between 3.6 to 5.5 mEq/L. In addition to
looking at these values, it can be helpful to look at the ratio between
the two. This number is derived by dividing K into Na and should
be between 27 and 40. For example, a dog with a Na level of 145 and
a K level of 4.5 would have a ratio of 32. A dog in an Addisonian
crisis will typically have a low Na level, elevated K and low ratio. It
is important to learn at what levels your dog feels his best.
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Common Sense
Disclaimer: AddisonDogs.com does not have a vet on staff nor does
it through its board, list-owners
or list-members provide medical advice. All information is
for educational purposes and is not intended to diagnose or treat.
You are encouraged to visit your vet if you have any
concerns about the health of your animals.
Reprinted with kind permission from
Susan Long
No
material from this website — graphics, photographics, or written material—
may be used without express written permission from AddisonDogs.com.
Diagnosis: Kidney Disease
Or is it?
Josephine Tucker
The difference between
the clinical signs and blood analysis of kidney disease (causing renal
failure) and Addison’s disease is very subtle, that is unless you are
aware of what you are looking for, and then the possibility of primary
Addison’s disease can become so obvious it stares you in the face!
Vets could be forgiven for not recognising the vague, non-specific
clinical signs of Addison’s disease if the consequences of a misdiagnosis
were not so dire. It will most certainly result in the premature
and unnecessary death of your dog.
In just three months, two Addisonian cases I have been involved
in were originally misdiagnosed as definite cases of kidney disease. The
dogs were put on a KD diet (a special veterinary diet for dogs with kidney
disease) and no improvement was seen. Both dogs were deteriorating, and
when Addison’s disease was mentioned to the vets’ they dismissed it. After
the owners were made aware of the clinical signs and typical blood results
of dogs with Addison’s disease, it seemed very possible to them that their
vets had misdiagnosed their dog’s condition. The information gave them enough
courage to challenge their vet’s diagnosis and in both cases this resulted
in a confirmed diagnosis of Addison’s disease, which undoubtedly saved
the dogs’ lives.
These two cases were almost identical, so how many other dogs are
being misdiagnosed and dying needlessly? Many years ago when I
had to take one of my dogs to the Royal Veterinary College, the vet looking
after him told me that in the previous three days, four dogs had been
admitted to the hospital with Addison’s disease. He said if veterinary
surgeons only looked at their text books it would not be necessary for
these dogs to be referred to the vet college! No one is saying that
Addison’s is an easy diagnosis to make, as it shares so many similarities
with kidney disease (and other diseases), but there are tell-tale signs
that not only should the vet be aware of but also the owners, and if these
signs are apparent it should be enough reason to suspect Addison’s disease.
Although Addison’s disease has been diagnosed in a dog as old as
14, it is more likely for an aged dog to have degenerative kidney disease
than Addison’s disease. This article is more relevant to dogs of young
to middle age, as this is when Addison’s disease is more likely to occur,
especially in a breed known to be genetically predisposed to this disease.
Much has been written about Addison’s in the past. This article
is intended to give a brief outline of the disease, concentrate mainly
on the common factors, and more importantly the subtle differences between
kidney disease and Addison’s disease, and how the tell-tale signs can
be identified from the blood results. You don’t have to be a vet or scientifically
minded, just look at the overall picture and be brave enough to challenge
your vet’s diagnosis and ask for an ACTH stimulation test, if for no other
reason than to rule it out and give you peace of mind.
Primary Addison’s disease (hypoadrenocorticism) is the result of
an autoimmune destruction of the adrenal glands. The adrenal glands
produce several hormones; the most important of these are aldosterone
(a mineralocorticoid) and cortisol (a glucocorticoid). Insufficient
production of these hormones alters the electrolyte balance in the body,
in particular the sodium and potassium levels, and can produce clinical signs
such as:
Lethargy, depression, nervousness, weight loss, anorexia (no appetite),
vomiting, weakness (particularly of the back legs), shaking or muscle
tremors, limping, diarrhoea (with or without traces of blood), abdominal
pain, dehydration, excessive thirst and urination, weak pulse, slow heart
rate and abnormal heart rhythm, anaemia (pale gums) and collapse. One important
difference between acute/chronic renal failure and Addison’s disease is,
the heart rate in renal failure is more likely to be fast (Tachycardia)
and in Addison’s disease it is more likely to be slow (Bradycardia).
Signs of the disease are most apparent when the dog is physiologically or
psychologically stressed.
Addison’s disease is progressive and it can take many months before
clinical signs are seen. Sadly, in some cases - if subtle changes are
missed - the first sign can be death. Clinical signs are often vague
to start with and can seem insignificant, but this is a common observation
of the disease. Outward signs wax and wane and respond to fluid therapy
or can worsen with stress. As the autoimmune destruction continues the
adrenal glands will reduce in size until they are unable to produce enough
adrenal hormones to sustain the dog. At this point the clinical signs, and
abnormalities in the blood, are increasing and the dog is at risk of collapse,
and subsequent death. It then becomes a serious veterinary emergency,
and it is very desirable to achieve a diagnosis before this occurs.
Unfortunately, it can become a fight against time to get the vet to even
consider that the dog may have Addison’s disease. A common remark is ‘Oh,
it won’t be Addison’s, we never see it’. Never see it, or never diagnose
it?
If your dog is visiting the vet regularly because of continuing
symptoms, ask for a Complete Blood Count (CBC) and a full biochemistry
blood test to be done, and don’t forget to ask for a printout of the results
for your own records. The printout will show you a list of different chemical
values, some of which are mentioned below. The most important ones
to look at in a case of Addison’s disease are the sodium and potassium levels.
However, not all cases of Primary Addison’s disease will have all the
clinical signs and blood abnormalities, and this has to be borne in mind.
Also, there is a less common condition called Atypical Addison’s disease,
in which the dog is deficient in cortisol only. Cortisol enables the body
to cope with stress, and clinical signs relating to a deficiency may include:
depression, nervousness, anorexia, weak pulse and collapse, particularly
in stressful situations. The adrenal mineralocorticoid hormone
regulates the conservation of sodium and excretion of potassium from
the body. In atypical Addison’s this is less severely affected therefore
the sodium and potassium levels may be within normal range.
Greater than 90% of Primary Addisonian cases will have high potassium
and low sodium values, with a ratio of less than 27. Prior to diagnosis,
Addisonian dogs often show a ratio of less than 23. However, the ratio
alone is only suggestive, and not diagnostic, of Addison’s disease. Individual
electrolyte concentrations can be more reliable. As the disease progresses,
the ratio will drop even further and the dog may collapse and become critically
ill. ¹
Routine Laboratory Abnormalities - Haematology &
Biochemistry
INCREASED:
High Potassium (K)
High Creatinine,
High Urea, (BUN – blood urea nitrogen; or SUN - serum urea nitrogen)
High Urea/creatinine ratio (Azotaemia)
Increased Eosinophils
Increased Lymphocytes
High Bilirubin - in some patients
High Calcium (mild to moderate) – in some patients
ALT- ALP - AST (Mild to moderate increase of liver enzymes) – in
some patients
DECREASED:
Low Sodium (Na)
Low Sodium/potassium ratio (K:Na ratio - less than 27) Addisonian
dogs often have a ratio of <23.
Low Chloride (80% of Addisonian dogs will have low chloride
values)
Low Glucose – in some patients
Low Albumin (moderate to severe) – in some patients
Total white blood cell count (WBC) – in some patients
Red blood cell count (RBC or HCT)
Another possible difference between kidney disease and Addison’s
may be seen in the white blood cells (eg., neutrophils, eosinophils, lymphocytes).
When a dog is poorly he becomes stressed and this is reflected in the
white cells. The neutrophil numbers would be expected to be high/normal
or increased, and the eosinophils and lymphocytes would be decreased or
low/normal numbers. This is called ‘stress leucogram’ and is seen in both
chronic and acute renal failure, but not in Addison’s disease. A dog with
Addison’s disease may show a much lower white cell reading than would be
expected in such a poorly dog. In fact there may even be reverse of
what would normally be expected, eg., low/normal values of neutrophils
and a higher value of lymphocytes and eosinophills (called a ‘reverse stress
leucogram’). ¹ ²
The terms used above might sound a bit too scientific but all of
these values are clearly written on the laboratory report with the reference
range, so it is not difficult to see if something is high or low and you
may be able to build up a picture that may lead to a possible diagnosis.
One point to remember, as Addison’s is a progressive disease, remarkable
values may not be present in the earlier stages. If the problems
are ongoing regularly recheck the subsequent blood results for any of the
above abnormalities.
Points to consider:
Is your dog young / middle aged?
Over a period of time, has your dog experienced several of the symptoms
listed above and has he/she responded well to fluid therapy?
Has your young to middle aged dog been diagnosed with kidney disease?
Is he/she improving on the treatment/diet provided by your vet? If the
answer is no, then consider Addison’s disease.
Do you have a dog whose breed is known to be genetically predisposed
to Addison’s disease?
Do you know of any relatives of your dog who may have been diagnosed
with Addison’s disease or kidney failure at a young age, or other autoimmune
disease? Speak to your dog’s breeder; he/she may be able to give you valuable
information.
Have a Full Serum Biochemistry panel and a Complete Blood Count
test done and ask your vet for a copy of the results for your own records.
Study the results yourself and check for the abnormalities listed above.
If symptoms persist, have a further blood test done to see if there are
any changes, but don’t leave it too long in between (a week or less) as
deterioration seems to quicken in the last stages. Keep each laboratory
report for comparison. Blood testing is never a waste of money (in the long
term it can save you money), and it provides a ‘bench mark’ on which to base
further tests).
What to do if you if your dog continues to deteriorate and you suspect
that he/she may have Addison’s disease.
If your dog is extremely poorly, eg. very lethargic, call your vet
straight away, regardless of the time, or if it is a weekend or Bank holiday.
Tell your vet of your concerns and suspicions. Relay clinical signs
and draw attention to any significant blood results. It is surprising
how many vets miss the significant sodium/potassium clue.
If the breed is genetically predisposed to Addison’s, stress this
to your vet.
The vet should respond by asking you to take your dog to the surgery
immediately. If your vet shares your suspicions he may carry out
an ACTH stimulation blood test. (Unfortunately this is not possible over
a weekend). If your vet does not respond to your concerns then start
making telephone calls until you find one who does. Don’t worry about offending
your existing vet; your dog may be in extreme and immediate danger.
If your dog is too poorly for an ACTH stim test and has typical
electrolyte imbalance usually seen in primary Addison’s disease, then
your vet will need to give life saving treatment, eg., saline (sodium)
intravenous fluids to re-hydrate, and bring down the dangerously high
potassium levels and raise the sodium levels in the blood, and an intravenous
injection of dexamethasone to enable your dog to cope with the stress.
²
NOTE: Dexamethasone is a glucocorticoid but unlike
prednisolone it does not interfere with the ACTH stim test.
Giving intravenous fluids and dexamethasone will hopefully support
your dog until the result of the ACTH stim test is known. Do not
leave your dog without supportive treatment at this critical time.
It wouldn’t be the first time that a dog has died waiting for the results
of the ACTH stim test to come through.
If the result is positive, your dog will be prescribed a mineralocorticoid
hormone called Florine-f. The initial dose is usually on the low
side, and is gradually increased until the sodium and potassium levels
are within normal range and clinical signs have resolved. The treatment
must be given every day for life (usually the dose is split and given twice
a day). For the first few weeks or so your dog will also be on prednisolone
(a glucocorticoid). Once stabilised, there is usually enough glucocorticoid
in Florine-f to control everyday stress levels, so the prednisolone can
be withdrawn. At times of added stress, however, (caused by fireworks or
even going to the groomers etc.,) the owner must give additional prednisolone
to enable the dog to cope with the trauma. These are replacement
doses and are vital to an Addisonian dog’s survival and should not be confused
with higher treatment doses of steroids used to treat inflammatory conditions.
The body is designed to produce these hormones on a supply and demand basis.
An Addisonian dog no longer has the ability to do this and they rely on
the owner to anticipate stressful situations and administer the appropriate
medication. It is not a difficult regime to follow once the dog is stabilised
and you are familiar with the condition.
Initially, blood tests to check electrolytes should be every 5-7
days and as clinical signs improve and blood results return to within normal
limits the tests can become less frequent. Electrolyte blood tests
should still be carried out every 6 months when the dog is stable.
In the United States dogs with Addison’s disease are more often
treated with intramuscular or subcutaneous injections of desoxycorticosterone
pivalate (DOCP – trade name Percorten-V.) Dogs seem to do better
with these injections than with Florine-f. The dosage must be balanced
by effect, both in the amount of the drug given and the interval between
injections. This can range from every 20 to 35 days, but usually
is every 26-28th day. After the initial injection sodium and potassium
levels will be evaluated at 12 and 25 days to determine the size and timing
of the next injection. DOCP has purely mineralocorticoid activity,
and so it is necessary to give a small dose of prednisolone – usually
2.5mg to 5.0mg every 24 or 48 hours.
Many dogs with Addison’s disease also are hypothyroid, and treating
their thyroid problem tends to make treating the Addison’s easier.
Usually the dog will require less Florine-f or DOCP, and will handle
stress better too.
The resolution of both clinical signs and blood results must be
taken into consideration when evaluating the dog’s progress and should
not be used in isolation. Remember in Addison’s disease especially, clinical
signs usually reflect blood results and vice versa, but one may lag behind
the other. If your dog is receiving an appropriate dose of Florine-f (this
can vary from dog to dog) and his/her clinical signs or blood results do
not stabilise after a few months, a full biochemistry blood test to check
kidney/liver function etc., may be useful, or ask your vet for a referral
to an endocrinologist, just in case there is an unidentified, underlying
problem.
If the ACTH stim test does not confirm Addison’s disease, it may
have to be repeated at a later date if clinical signs and blood abnormalities
persist. The result of the ACTH stim test reflects the ‘current’
adrenal function status and may not show a ‘flat line response’- which
is diagnostic of Addison‘s disease - until much later in the disease process.
The good news is that the prognosis for Addison’s disease is usually
excellent. Dogs can go on to live a happy, normal life on daily medication
for many years, living well into old age, 15 or 16 years. It is certainly
a much better prognosis than kidney disease.
There is plenty of general and practical information on Addison’s
disease on the internet, however, if anyone would like further, specific,
information please email jo@cimda.fsnet.co.uk
Reliable information can be obtained by visiting BeaCon’s website on www.beaconforheath.org
Jo Tucker
References:
1. BSAVA Manual of Canine & Feline Clinical Pathology
2. BSAVA Manual of Small Animal Endocrinology
Additional information from Linda Aronson DVM
reprinted with kind permission from Josephine Tucker
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