Addison's disease in canines
Encyclopedia
Addison's disease in canines refers to hypoadrenocorticism
Hypoadrenocorticism
Hypoadrenocorticism is a medical term describing a condition of decreased secretion of adrenocorticotropic hormone. It should not be confused with Addison's disease, which is a primary adrenocortical insufficiency....

, or Addison's disease
Addison's disease
Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...

, when it occurs in canines
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...

. The first case of Addison’s disease in dogs was recorded in 1953, over 100 years after it was described in humans by Thomas Addison
Thomas Addison
Thomas Addison was a renowned 19th-century English physician and scientist. He is traditionally regarded as one of the "great men" of Guy's Hospital in London....

.

Description

Addison’s disease is an endocrine system
Endocrine system
In physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"...

 disorder that occurs when the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

s – located above the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

s – fail to produce enough hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

s to keep the body functioning normally. The adrenal glands secrete glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...

s such as cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...

  and mineralocorticoid
Mineralocorticoid
Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...

s such as aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...

; when proper amounts of these are not produced, an animal's metabolic and electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....

 balances may be upset. Mineralcorticoids control the amount of potassium
Potassium in biology
Potassium is an essential mineral macronutrient and is the main intracellular ion for all types of cells.It is important in maintaining fluid and electrolyte balance in the bodies of humans and animals....

, salt and water in the body. This may occur when the animal's pituitary gland fails to secrete ACTH
Adrenocorticotropic hormone
Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...

, the hormone which stimulates the adrenal glands' production of cortisol, or when a disorder causes the body to attack and kill its own tissue ("immune mediated destruction"). The disease is also known as hypoadrenocorticism
Hypoadrenocorticism
Hypoadrenocorticism is a medical term describing a condition of decreased secretion of adrenocorticotropic hormone. It should not be confused with Addison's disease, which is a primary adrenocortical insufficiency....

, adrenal insufficiency, or hypocortisolism. Addison’s disease is fatal if left untreated. The only preventable kind of Addison's disease is that which is caused when a dog is abruptly taken off of a steroid medication.
Abrupt Withdrawal of Steroids
Layer Produces
Zona glomerulosa Mineralcorticoids (aldosterone)
Zona fasciculata Glucocorticoids (cortisol)
Zona reticularis Sex steroids (androgens)


Use of steroids
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...

 means that the adrenal glands do not function fully during the course of the medication. The body senses the levels of the exogenous
Exogenous
Exogenous refers to an action or object coming from outside a system. It is the opposite of endogenous, something generated from within the system....

 steroids in the system and therefore does not signal for additional production.

During this time, the adrenal glands go into a type of dormancy because the steroid medication is doing their work for them. The usual protocol for stopping steroid medications is not to eliminate them suddenly, but to withdraw from them gradually in a "tapering off" process. Doses become less and less frequent prior to the planned cessation of the medication. This tells the body to signal the inactive adrenal glands to go back to producing adrenal hormones. In cases where steroids are abruptly withdrawn, the dormant adrenal glands may not able to be "awakened" and the body will need to have its adrenal glucocorticoid hormones replaced by medication; the mineralcorticoids are not affected by this and do not need replacement therapy. There would be no risk of an Addisonian crisis because mineralcorticoid production remains intact.

All causes for Addison's disease are not yet known. Some are genetic, others appear to be autoimmune related; there are cases caused by various disease processes.

It is thought Addison’s disease occurs much more frequently in dogs than in humans; in fact, it may occur one hundred times more often in the canine population. It mostly affects young to middle-aged female dogs, as the average age at diagnosis being four years old (although it has been found in puppies and dogs up to twelve years old). About seventy percent of dogs that are diagnosed with Addison's disease are female.

Nevertheless, Addison's disease is still relatively uncommon in dogs.

Susceptibility of certain breeds

Certain breeds are more susceptible than others to Addison's disease:
  • Great Dane
    Great Dane
    The Great Dane , also known as German Mastiff or Danish Hound , is a breed of domestic dog known for its giant size...

    s
  • Portuguese water dog
    Portuguese Water Dog
    The Portuguese Water Dog is a breed of working dog as classified by the American Kennel Club. Portuguese Water Dogs are originally from the Portuguese region of the Algarve, from where the breed expanded to all around Portugal's coast, where they were taught to herd fish into fishermen's nets, to...

    s
  • Standard poodle
    Poodle
    The Poodle is a breed of dog. The poodle breed is found officially in toy, miniature, and standard sizes, with many coat colors. Originally bred as a type of water dog, the poodle is highly intelligent and skillful in many dog sports, including agility, obedience, tracking, and even herding...

    s
  • West Highland white terrier
    West Highland White Terrier
    The West Highland White Terrier, commonly known as the Westie, is a Scottish breed of dog with a distinctive white coat. The modern breed is descended from a number of breeding programes of white terriers in Scotland prior to the 20th century...

    s


  • Bearded collie
    Bearded Collie
    The Bearded Collie, or Beardie, is a herding breed of dog once used primarily by Scottish shepherds, but now mostly a popular family companion....

    s
  • Rottweiler
    Rottweiler
    The Rottweiler is a medium to large size breed of domestic dog that originated in Rottweil, Germany. The dogs were known as "Rottweil butchers' dogs" because they were used to herd livestock and pull carts laden with butchered meat and other products to market...

    s
  • Springer spaniel
    Springer Spaniel
    Springer Spaniel refers to two different breeds of dogs, both of which are commonly called simply Springer Spaniel:*English Springer Spaniel*Welsh Springer Spaniel...

    s
  • German Shorthaired Pointer
    German Shorthaired Pointer
    The German shorthaired pointer is a breed of dog developed in the 19th century in Germany for hunting.The breed is streamlined yet powerful with strong legs that make it able to move rapidly and turn quickly. It has moderately long floppy ears set high on the head. Its muzzle is long, broad, and...

    s


  • Soft-Coated Wheaten Terrier
    Soft-Coated Wheaten Terrier
    The Soft-Coated Wheaten Terrier is a breed of dog originating from Ireland. There are four coat varieties: Traditional Irish, Heavy Irish, English, and American...

  • German shepherds
  • St. Bernard
    St. Bernard (dog)
    The St. Bernard is a breed of very large working dog from the Italian and Swiss Alps, originally bred for rescue. The breed has become famous through tales of alpine rescues, as well as for its large size.-Appearance:The St. Bernard is a large dog...

    s
  • Nova Scotia Duck Tolling Retrievers


  • Leonberger
    Leonberger
    The Leonberger is a breed of large dog. The breed's name derives from the city of Leonberg in Baden-Württemberg, Germany. According to legend, the Leonberger was ostensibly bred as a 'symbolic dog' that would mimic the lion in the town crest...

    s

Poodles, Leonbergers, and Nova Scotia Duck Tolling Retrievers are considered the most susceptible.

Several breeds are relatively not susceptible, including American Pit Bull Terrier
American Pit Bull Terrier
The American Pit Bull Terrier is a medium-sized, solidly built, short haired dog whose early ancestors came from England and Ireland...

s, American Staffordshire Terrier
American Staffordshire Terrier
The American Staffordshire terrier is a medium-sized, short-coated American dog breed. In the early part of the twentieth century the breed gained social stature and was accepted by the American Kennel Club as the American Staffordshire Terrier in 1936...

s, Chihuahua
Chihuahua (dog)
The ' is the smallest breed of dog and is so named for the state of Chihuahua in Mexico. Chihuahuas come in a wide variety of sizes, head shapes, colors and coat lengths.-History:...

s, Cocker Spaniels, Golden Retriever
Golden Retriever
The Golden Retriever is a medium-sized breed of dog. They were historically developed as gundogs to retrieve shot waterfowl such as ducks and upland game birds during hunting and shooting parties. As such, they were bred to have a soft mouth to retrieve game undamaged and have an instinctive love...

s, Lhasa Apso
Lhasa Apso
The Lhasa Apso is a non-sporting dog breed originating in Tibet. It was bred as an interior sentinel in the Buddhist monasteries, who alerted the monks to any intruders who entered...

, Schnauzer
Schnauzer
A Schnauzer is a German dog type that originated in Germany in the 15th and 16th centuries. The term comes from Schnauze , the German word for "snout", because of the dog's distinctively bearded snout. The word Schnauzer also means moustache in German; some authorities, such as Encyclopædia...

s, and Yorkshire Terrier
Yorkshire Terrier
The Yorkshire Terrier is a small dog breed of terrier type, developed in the 19th century in the county of Yorkshire, England to catch rats in clothing mills. The defining features of the breed are its size, to , and its silky blue and tan coat...

s.

Diagnosis

Symptoms of Addison's disease in canines can include vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

, lethargy, lack of appetite, tremors or shaking, muscle weakness, low body temperature, collapse, low heart rate, and pain in the hind quarters. Hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...

 can also be present, and intially may appear to be a seizure disorder or an insulin-secreting pancreatic tumor (insulinoma
Insulinoma
An insulinoma is a tumour of the pancreas that is derived from beta cells and secretes insulin.Beta cells secrete insulin in response to increases in blood glucose. The resulting increase in insulin acts to lower blood glucose back to normal levels at which point further secretion of insulin is...

). Symptoms can appear to be those of many other disorders, earning Addison's disease the nicknames of "the Great Mimic" and "the Great Imitator" because of this. It is possible not to see any signs of the disease until 90% of the adrenal cortex is no longer functioning.

Signs that a dog may have Addison's disease include elevated levels of potassium and unusually low levels of sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

 (hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...

) and chloride
Chloride
The chloride ion is formed when the element chlorine, a halogen, picks up one electron to form an anion Cl−. The salts of hydrochloric acid HCl contain chloride ions and can also be called chlorides. The chloride ion, and its salts such as sodium chloride, are very soluble in water...

 (hypochloremia
Hypochloremia
Hypochloremia is an electrolyte disturbance whereby there is an abnormally depleted level of the chloride ion in the blood.It rarely occurs in the absence of other abnormalities.It can be associated with hypoventilation....

). However, not all dogs' electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....

 ratios are affected during an Addisonian episode. Therefore, the only accurate test for Addison's disease in canines is an ACTH stimulation test
ACTH stimulation test
The ACTH stimulation test is a medical test usually ordered and interpreted by endocrinologists to assess the functioning of the adrenal glands stress response by measuring the adrenal response to adrenocorticotropic hormone...

. While most corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...

 drugs will invalidate the results of an ACTH test, Dexamethasone
Dexamethasone
Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...

 may be used in the event of an Addison's emergency without fear of compromising the results of the test.

In general, Addison's disease in canines is underdiagnosed, and one must have a clinical suspicion of it as an underlying disorder for many presenting complaints. Females are overrepresented, and the disease often appears in middle age (four to seven years), although any age or gender may be affected. Genetic continuity between dogs and humans helps to explain the occurrence of Addison's disease in both species.

Dogs with Addison's disease may also have one of several autoimmune disorders. Because it is an endocrine disorder, dogs with Addison's disease may also suffer from neuropathy
Peripheral neuropathy
Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....

 and some endocrine-related eye diseases.

Addisonian crisis

If deterioration of the adrenal glands progresses far enough, a dog may experience an Addisonian crisis, a type of acute episode during which potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...

 levels elevate (hyperkalemia
Hyperkalemia
Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...

) and disrupt normal functions of the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

. Arrhythmia can result and blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

 may drop to dangerously low levels, while the dog's kidneys may cease to function properly. Some 35% of canine Addison's cases are diagnosed as the result of an Addisonian crisis. It is a medical emergency.

Whipworms

Laboratory tests for dogs with whipworms can exhibit the same low sodium and high potassium values found in Addison's disease; their ACTH values, however, will be normal.

Pacific Rimism

Breeds that began in the Pacific Rim, among them Akita
American Akita
The Akita is a large spitz breed of dog originating from the mountainous northern regions of Japan. There are now two separate strains: American, a/k/a "Akita" or "American Akita"; and Japanese, aka "Akita Inu" or "Japanese Akita"...

s and Shiba Inu
Shiba Inu
The is the smallest of the six original and distinct breeds of dog from Japan.A small, agile dog that copes very well with mountainous terrain, the Shiba Inu was originally bred for hunting. It is similar in appearance to the Akita, though much smaller in stature...

s, can tend to have higher potassium values in laboratory tests. For these breeds, the elevated levels are not abnormal. Dogs who do not have Addison's disease will have normal values on ACTH tests.

Typical and atypical Addison's

The adrenal outer layer, or cortex, has three layers; each produces a specific type of steroid.
Adrenal Cortex Layers
Layer Produces
Zona glomerulosa Mineralcorticoids (aldosterone)
Zona fasciculata Glucocorticoids (cortisol)
Zona reticularis Sex steroids (androgens)



In typical Addison's, all of these layers stop functioning; the problem is with the adrenal gland. But in atypical Addison's, the problem is not in the adrenal gland but in the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...

. The gland produces a hormone, ACTH
Adrenocorticotropic hormone
Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...

, (adrenocorticotropic hormone), that signals the zona fasciculata
Zona fasciculata
The zona fasciculata constitutes the middle zone of the adrenal cortex, sitting directly beneath the zona glomerulosa. Constituent cells are organized into bundles or "fascicles"....

 and zona reticularis
Zona reticularis
The zona reticularis is the innermost layer of the adrenal cortex, lying deep to the zona fasciculata and superficial to the adrenal medulla. The cells are arranged cords that project in different directions giving a net-like appearance The zona reticularis is the innermost layer of the adrenal...

 to produce their steroids. When the anterior portion
Anterior pituitary
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...

 of the pituitary is unable to produce ACTH, there is nothing to activate the zona fasciculata and zona reticularis and they stop production of their respective hormones. The zona glomerulosa
Zona glomerulosa
The zona glomerulosa of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the adrenal gland's capsule...

 remains able to produce a normal amount of mineralcorticoids because it is not controlled by ACTH. An atypical Addison's patient does not face the risk of an Addisonian crisis and only needs to have medication to replace the glucocorticoid steroid cortisol. One dog in every 42 diagnosed with Addison's disease will have the atypical or secondary form of the disease where mineralcorticoid production remains intact.


Typical Addison's: problem with the adrenal glands.
Atypical Addison's: problem with the anterior pituitary.




Typical Addison's

Typical Addison's
Layer Produces
Zona glomerulosa Mineralcorticoids (aldosterone)
Zona fasciculata Glucocorticoids (cortisol)
Zona reticularis Sex steroids (androgens)


Atypical Addison's

Atypical Addison's
Layer Produces
Zona glomerulosa Mineralcorticoids (aldosterone)
Zona fasciculata Glucocorticoids (cortisol)
Zona reticularis Sex steroids (androgens)



In some dogs with atypical (secondary) Addison's, the disease progresses to the point where mineralcorticoid replacement is necessary (making them typical or primary Addison's patients), while others retain their ability to continue production of mineralcorticoids for years, requiring glucocorticoid replacement only.


Treatment

Hypoadrenocorticism is treated with fludrocortisone
Fludrocortisone
Fludrocortisone is a synthetic corticosteroid with moderate glucocorticoid potency and much greater mineralocorticoid potency. The brand name in the U.S. and Canada is Florinef.-Uses:...

 (trade name Florinef) or a monthly injection called Percorten-V (desoxycorticosterone pivalate, DOCP) and prednisolone
Prednisolone
Prednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...

. Routine blood work is necessary in the initial stages until a maintenance dose is established.

Most of the medications used in the therapy of hypoadrenocorticism cause excessive thirst and urination. It is absolutely vital to provide fresh drinking water for a canine suffering from this disorder.

If the owner knows about an upcoming stressful situation (shows, traveling etc.), patients generally need an increased dose of prednisone to help deal with the added stress. Avoidance of stress is important for dogs with hypoadrenocorticism. Physical illness also stresses the body and may mean that the Addison's medication(s) need to be adjusted during this time. Most dogs with hypoadrenocorticism have an excellent prognosis after proper stabilization and treatment.
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