What Are Health Conditions My Poodle Might Face? How May I Be Sensitive To Potential Signs Of Dis-ease?
Be aware of health conditions your dog might face as Nature has it's say and be sensitive to potential signs of disease. Often, the sooner the problem gets addressed, the better chance your dog will have at living a long and happy life. We highly recommend pet insurance for preparedness. see Great Products
POISONING IN HAWAII: BE AWARE OF TOAD POISONINGS
Giant Marine Toad, Bufo marinus L., Poisoning in Hawaii: Symptoms and Treatment
Julie Ann Luiz, College of Agriculture, Forestry and Natural Resource Management, University of Hawai’i at Hilo, 200 W. Kawili St., Hilo, Hawaii 96720- 4091
INTRODUCTION
Toad poisonings are very common in tropical and subtropical regions of the United States, such as Hawaii, Florida and Texas. There are various forms of toad poisonings, but one of particular concern in Hawaii is called Bufo Toxicosis. Bufo marinus L. is a species of toad introduced to the southern states and Hawaii approximately 50 years ago for insect control (Beasley et al., 1999). The common names associated with Bufo marinus L. are Cane toad, Giant toad, Marine toad, Giant Marine toad, South American Cane toad and Dominican toad.
During evening hours, many dogs and some cats mouth the toads and become poisoned. The toxicity can be serious and life-threatening if not addressed and treated properly.
TOXIC PRINCIPLE
B. marinus produces a toxin containing bufagins, bufotoxins, bufotenins as well as other compounds (Beasley et al., 1999). These toxic agents are digitalis- like and are similar to heart medications such as digoxin, which can often cause severe cardiac abnormalities such as ventricular fibrillation. The toxin is produced within the parotid glands, or self-defense glands of the toad, located behind the neck extending over the shoulders. The toxin can be manually expressed during a threat from a predator through numerous dermal pin hole
openings (Brubacher et al., 1996). People or animals unaware of a toad in the area may be exposed through open wounds, although the threat is commonly toward animals mouthing the toads. Interestingly enough, the species of toad in Florida produces a more potent toxin. Statistics show that mortality ratings in Hawaii and Texas of exposed and untreated dogs are 5%, whereas Florida case mortality is close to 100% (Beasley et al., 1999).
CLINICAL SIGNS
Clinical signs are dependent upon the amount of toxin that is absorbed by the animal and the length of time since exposure to the toad. In general, toxicosis can cause cardiac arrhythmias, increases in blood pressure and hallucinations. Soon after exposure, the owner may notice their pet experiencing severe head shaking, pawing at its mouth as if irritated, a foul odor and hypersalivation. If untreated, the toxicosis may progress with clinical symptoms of incoordination, vomiting, diarrhea and an increase in respiration rate. Severe cases may lead to blindness and convulsions (Beasley et al., 1999). Death results from a critical form of a cardiac arrhythmia called ventricular fibrillation that has been reported to occur quickly within 15 minutes from the time of exposure (Balarz et al., 1986). The clinical signs mentioned above were evident in 33 canine cases and 2 feline cases seen in a practice located in Hawaii. TREATMENT
Owners of pets exposed to B. marinus secretions can prevent absorption of the toxin into mucous membranes by first rinsing out the mouth of the animal with copious amounts of water. Usually, a garden hose is recommended to
accomplish this. It is important to direct the nose of the animal downwards to allow the water along with the toxin to flow out of the mouth. Do not allow the animal to drink or swallow the flushing water; hence the water is contaminated with the toxin and can be absorbed at the lower mucous membranes of the gastrointestinal tract. At this time, the owner should seek veterinary advice. At the veterinarian’s discretion, the animal may need further professional treatment. Usually, activated charcoal and a saline cathartic is given orally and repeated after 2 hours to bind the toxin within the gastrointestinal tract (Sakate et al., 2000). The veterinarian may elect to hospitalize the patient while monitoring the heart via electrocardiography (ECG or EKG). During the hospitalization, the treatment may consist of supportive intravenous fluid therapy to maintain hydration. Medical therapy may be necessary to control cardiac arrhythmias and to control convulsions. Unfortunately, there is no specific antidote for Bufo toxicosis. Prevention measures to reduce the risk of exposure can be undertaken by simply removing the toads from a fenced yard with the use of proper equipment and protection.
PROGNOSIS
For most pets, especially those in Hawaii, the prognosis is good with treatment. However, Bufo marinus can be fatal.
LITERATURE CITED
1. Beasley V, Dorman D, Fikes J, et al. Bufo toxicosis – toad poisoning. In: Beasley V, ed. A systems affected approach to veterinary toxicology. St. Louis, MO: Mosby, 1999; 776-777.
2. Brubacher J, et al. Treatment of toad venom poisoning with digoxin specific fragment. In: Chest 1996; 110:1282-1288.
3. Balarz T, Hanig JP, Herman EH. Toxic responses of the cardiovascular system. In: Casarett LJ, Doull J. Toxicology: the basic science of poisons. 3rd ed. New York: MacMillan, 1986; 387-411.
4. Sakate M, Lucas de Oliveira PC. Toad envenoming in dogs: effects and treatment. In: J. Venom. Anim. Toxins 2000; 6:1590-1599.
Giant Marine Toad, Bufo marinus L., Poisoning in Hawaii: Symptoms and Treatment
Julie Ann Luiz, College of Agriculture, Forestry and Natural Resource Management, University of Hawai’i at Hilo, 200 W. Kawili St., Hilo, Hawaii 96720- 4091
INTRODUCTION
Toad poisonings are very common in tropical and subtropical regions of the United States, such as Hawaii, Florida and Texas. There are various forms of toad poisonings, but one of particular concern in Hawaii is called Bufo Toxicosis. Bufo marinus L. is a species of toad introduced to the southern states and Hawaii approximately 50 years ago for insect control (Beasley et al., 1999). The common names associated with Bufo marinus L. are Cane toad, Giant toad, Marine toad, Giant Marine toad, South American Cane toad and Dominican toad.
During evening hours, many dogs and some cats mouth the toads and become poisoned. The toxicity can be serious and life-threatening if not addressed and treated properly.
TOXIC PRINCIPLE
B. marinus produces a toxin containing bufagins, bufotoxins, bufotenins as well as other compounds (Beasley et al., 1999). These toxic agents are digitalis- like and are similar to heart medications such as digoxin, which can often cause severe cardiac abnormalities such as ventricular fibrillation. The toxin is produced within the parotid glands, or self-defense glands of the toad, located behind the neck extending over the shoulders. The toxin can be manually expressed during a threat from a predator through numerous dermal pin hole
openings (Brubacher et al., 1996). People or animals unaware of a toad in the area may be exposed through open wounds, although the threat is commonly toward animals mouthing the toads. Interestingly enough, the species of toad in Florida produces a more potent toxin. Statistics show that mortality ratings in Hawaii and Texas of exposed and untreated dogs are 5%, whereas Florida case mortality is close to 100% (Beasley et al., 1999).
CLINICAL SIGNS
Clinical signs are dependent upon the amount of toxin that is absorbed by the animal and the length of time since exposure to the toad. In general, toxicosis can cause cardiac arrhythmias, increases in blood pressure and hallucinations. Soon after exposure, the owner may notice their pet experiencing severe head shaking, pawing at its mouth as if irritated, a foul odor and hypersalivation. If untreated, the toxicosis may progress with clinical symptoms of incoordination, vomiting, diarrhea and an increase in respiration rate. Severe cases may lead to blindness and convulsions (Beasley et al., 1999). Death results from a critical form of a cardiac arrhythmia called ventricular fibrillation that has been reported to occur quickly within 15 minutes from the time of exposure (Balarz et al., 1986). The clinical signs mentioned above were evident in 33 canine cases and 2 feline cases seen in a practice located in Hawaii. TREATMENT
Owners of pets exposed to B. marinus secretions can prevent absorption of the toxin into mucous membranes by first rinsing out the mouth of the animal with copious amounts of water. Usually, a garden hose is recommended to
accomplish this. It is important to direct the nose of the animal downwards to allow the water along with the toxin to flow out of the mouth. Do not allow the animal to drink or swallow the flushing water; hence the water is contaminated with the toxin and can be absorbed at the lower mucous membranes of the gastrointestinal tract. At this time, the owner should seek veterinary advice. At the veterinarian’s discretion, the animal may need further professional treatment. Usually, activated charcoal and a saline cathartic is given orally and repeated after 2 hours to bind the toxin within the gastrointestinal tract (Sakate et al., 2000). The veterinarian may elect to hospitalize the patient while monitoring the heart via electrocardiography (ECG or EKG). During the hospitalization, the treatment may consist of supportive intravenous fluid therapy to maintain hydration. Medical therapy may be necessary to control cardiac arrhythmias and to control convulsions. Unfortunately, there is no specific antidote for Bufo toxicosis. Prevention measures to reduce the risk of exposure can be undertaken by simply removing the toads from a fenced yard with the use of proper equipment and protection.
PROGNOSIS
For most pets, especially those in Hawaii, the prognosis is good with treatment. However, Bufo marinus can be fatal.
LITERATURE CITED
1. Beasley V, Dorman D, Fikes J, et al. Bufo toxicosis – toad poisoning. In: Beasley V, ed. A systems affected approach to veterinary toxicology. St. Louis, MO: Mosby, 1999; 776-777.
2. Brubacher J, et al. Treatment of toad venom poisoning with digoxin specific fragment. In: Chest 1996; 110:1282-1288.
3. Balarz T, Hanig JP, Herman EH. Toxic responses of the cardiovascular system. In: Casarett LJ, Doull J. Toxicology: the basic science of poisons. 3rd ed. New York: MacMillan, 1986; 387-411.
4. Sakate M, Lucas de Oliveira PC. Toad envenoming in dogs: effects and treatment. In: J. Venom. Anim. Toxins 2000; 6:1590-1599.
BLOAT
Be aware of health conditions your dog might face and be sensitive to potential signs of disease. Often, the sooner the problem gets addressed, the better chance your dog will have at living a long and happy life.
Symptoms To Watch For In Your Dog: Excessive Drinking
Dogs cannot tell us when something is bothering them, and I doubt that they would even if they could. Dogs are just not the type to go around complaining about things.
That's why it's important that we watch for signs and symptoms of disease. Generally, any change in your dog's body, behavior, actions or routine is telling you something. Some of the signs can be quite subtle and easily overlooked or dismissed. Paying attention to early symptoms can save your dog a lot of suffering and give him the best chance for a successful recovery.
Today we'll take a look at excessive thirst/drinking.
I was talking to a friend about post-op issues her dog was having after an extracapsular repair of her ACL. During our discussion she mentioned that in the snow they noticed that her dog's urine was clear, with no color to it at all, and she asked whether it was something to worry about.
I asked if her dog was drinking a lot. It turned out that her dog had been unusually thirsty and drinking large amounts of water since her surgery three months ago!
Excessive drinking is a symptom that should be taken seriously.
What constitutes excessive drinking?
Any change in your dog's drinking or eating habits should be noted. Drinking more than usual without an obvious explanation—such as hot weather or exercise—should not be dismissed. Do you have to fill the water bowl more often lately? Does your dog urinate more frequently? Talk to your veterinarian.
Take it seriously. Depending on other symptoms, excessive drinking can be a sign of a number of conditions, including
Early diagnosis can mean the difference between treatment success or failure.
Symptoms To Watch For In Your Dog: Excessive Drinking
Dogs cannot tell us when something is bothering them, and I doubt that they would even if they could. Dogs are just not the type to go around complaining about things.
That's why it's important that we watch for signs and symptoms of disease. Generally, any change in your dog's body, behavior, actions or routine is telling you something. Some of the signs can be quite subtle and easily overlooked or dismissed. Paying attention to early symptoms can save your dog a lot of suffering and give him the best chance for a successful recovery.
Today we'll take a look at excessive thirst/drinking.
I was talking to a friend about post-op issues her dog was having after an extracapsular repair of her ACL. During our discussion she mentioned that in the snow they noticed that her dog's urine was clear, with no color to it at all, and she asked whether it was something to worry about.
I asked if her dog was drinking a lot. It turned out that her dog had been unusually thirsty and drinking large amounts of water since her surgery three months ago!
Excessive drinking is a symptom that should be taken seriously.
What constitutes excessive drinking?
Any change in your dog's drinking or eating habits should be noted. Drinking more than usual without an obvious explanation—such as hot weather or exercise—should not be dismissed. Do you have to fill the water bowl more often lately? Does your dog urinate more frequently? Talk to your veterinarian.
Take it seriously. Depending on other symptoms, excessive drinking can be a sign of a number of conditions, including
- Diabetes mellitus
- Cushing's syndrome
- Addison's disease
- Liver or kidney disease
- A potentially life-threatening uterine infection
- and other serious conditions
Early diagnosis can mean the difference between treatment success or failure.
Clinical Diagnosis and Treatment of Hypoadrenocorticism in Dogs Addison's Disease
Introduction
The diagnosis and treatment of hypoadrenocorticism (Addison's disease) can be one of the greatest challenges faced by veterinary practitioners. The purpose of this review is to describe the clinical diagnosis and treatment of hypoadrenocorticism in dogs and cats.
Hypoadrenocorticism is a result of deficient secretion of both mineralocorticoids (aldosterone) and glucocorticoids.1 Naturally-occurring primary hypoadrenocorticism is usually caused by immune-mediated destruction of the adrenal cortex in both cats and dogs;1-4 however, lymphomatous infiltration of the adrenals has been reported as a cause of hypoadrenocorticism in cats.5 Secondary hypoadrenocorticism, in which the pituitary gland produces inadequate amounts of adrenocorticotrophic hormone (ACTH), can be caused by chronic steroid therapy or less commonly by tumors, trauma, or congenital defects of the pituitary gland.1 Secondary hypoadrenocorticism is rare in both dogs and cats. Hypoadrenocorticism, which is glucocorticoid deficient only (hypocortisolemia), has been termed "atypical" Addison's disease.6-9 Secondary hypoadrenocorticism is always atypical and primary hypoadrenocorticism can be atypical in the early stages of the disease prior to destruction of the zona glomerulosa.
Signalment, Clinical Signs and Laboratory Abnormalities
Canine hypoadrenocorticism is most often diagnosed in young female dogs (70%) of any breed. 1,2,8 However, hypoadrenocorticism has been reported in families of Leonbergers and standard poodles suggesting a genetic basis in some breeds.10,11 Young cats of any breed or sex can also develop hypoadrenocorticism.4,5
Historical findings compatible with hypoadrenocorticism include intermittent vomiting, diarrhea, weight loss, lethargy, depression, anorexia, and weakness.1-9 There may be a history of vomiting or diarrhea responsive to non-specific treatment, such as intravenous fluids, only to have signs reoccur several days to weeks later.
Often the clinical signs come and go (waxing and waning) periodically. As the disease progresses, the animal may present with collapse, hypothermia, shaking, polyuria, and polydipsia,. Hair loss and melena are unusual historical findings. Signs of megaesophagus, such as regurgitation and weight loss, have been reported uncommonly in dogs with both typical and atypical hypoadrenocorticism.1, 12 Differential diagnoses for the common clinical signs consistent with hypoadrenocorticism include inflammatory bowel disease, intestinal parasitism (trichuriasis), bilious vomiting syndrome, and renal disease.1,2,13 A comparison of clinical signs hypoadrenocorticism in cats and dogs is shown in Table 1 and a comparison of typical and atypical hypoadrenocorticism in dogs is listed in Table 2.
Physical examination of animals in an acute Addisonian crisis reveals weak pulses, bradycardia, prolonged capillary refill time, severe mental depression, and profound muscle weakness.1,2 Clinical features which should heighten the index of suspicion of hypoadrenocorticism include a normal or slow heart rate in the face of circulatory shock, previous response to corticosteroid or fluid therapy, and a"waxing and waning" course of disease prior to collapse.
Classic electrolyte abnormalities, such as hyponatremia, hyperkalemia, hypochloremia, and sodium to potassium ratios of less than 20 to 1, are highly suggestive of primary hypoadrenocorticism.1,2 However, gastrointestinal disease (trichuriasis), acute renal failure, post-renal azotemia and abdominal/thoracic effusions (third space) are additional differential diagnoses. 1,2,13,14 Azotemia and hyperphosphatemia also attend primary hypoadrenocorticism making it difficult to differentiate from acute renal failure. Azotemia associated with hypoadrenocorticism may be prerenal as a result of dehydration , hypovolemia or gastrointestinal hemorrhage.1,15
Hypercalcemia may be observed in up to 30% of dogs with hypoadrenocorticism as a result of hemoconcentration.16 Metabolic acidosis results from decreased hydrogen ion secretion in the renal distal tubule, increased generation of acids secondary to reduced tissue perfusion, and renal retention of organic acids.1,2 Hypoalbuminemia has been described in associated with hypoadrenocorticism; however, a cause and effect relationship has not been defined. 2,17 Animals with glucocorticoid deficiency only, will not show classic electrolyte imbalances, but may present with hypoglycemia as a result of impaired gluconeogenesis and glycogenolysis.1,5,6
Hematological findings include mild normocytic normochromic (non-regenerative) anemia; however, if the animal is dehydrated the underlying anemia may be masked. The absence of a stress leukogram is a subtle but important feature of atypical hypoadrenocorticism.6,7,9 The presence of a normal or elevated eosinophil or lymphocyte count in a stressed animal should be viewed with suspicion for hypoadrenocorticism, particularly atypical Addison's disease. Eosinophilia and lymphocytosis are seen in 20% and 10% of dogs with primary hypoadrenocorticism, respectively. 1,2
Urine specific gravity is frequently low and is attributed to medullary washout (inadequate medullary gradient due to sodium depletion) and decreased medullary blood flow.1 Dilute urine in the face of azotemia and hyperkalemia may easily be mistaken for acute renal failure. Hormonal assays are required to confirm the presence or absence of adrenal disease and to differentiate between hypoadrenocorticism and renal failure.
Electrocardiography, ultrasound and radiographic findings
If bradycardia is present, an electrocardiogram may be helpful in the diagnosis of hypoadrenocorticism, especially when serum electrolytes are not immediately available. Classic electrocardiographic findings reported with hyperkalemia include prolonged QRS complexes, decreased R wave amplitude, increased T wave amplitude ("spiked" T waves), and prolonged or absent p waves.1 Sinoatrial standstill is the most common arrhythmia noted. Electrocardiagraphic changes should not be used to determine the exact serum potassium concentrations because serum potassium concentrations do not directly correlate with specific EKG changes; however, the EKG is useful in an emergency setting. Radiographs may demonstrate signs associated with volume depletion or decreased tissue perfusion, such as microcardia, narrowed vena cava, and hypoperfused lungs. Megaesophagus has been reported uncommonly in dogs with both typical and atypical hypoadrenocorticism.1,2,12 Ultrasound cannot be routinely used to identify "small" adrenals, particularly since the right adrenal may be difficult to image in normal animals.
Diagnostic testing
Diagnosis of primary hypoadrenocorticism is based on clinical signs, classic electrolyte imbalances, and confirmation with an ACTH response test. To perform the test, a serum sample is obtained before, 30 minutes (cats) and 1 hour (cats and dogs) after intravenous administration of synthetic ACTH (cosyntropin; 0.5 mg/kg).1,2 Administration of a single dose of dexamethasone sodium phosphate prior to obtaining baseline or one hour post ACTH cortisol samples will not interfere with the test. However, administration of prednisolone will interfere with the ACTH response test because prednisolone will cross react with the cortisol assay.2 If corticosteroids have already been administered, one can wait 24 hours and perform the ACTH response test after the short-acting corticosteroids have dissipated.2 Endogenous plasma ACTH may be measured to determine if the hypoadrenocorticism is primary or secondary. This specimen must be collected in an EDTA tube, spun within an hour of sampling and stored in plastic prior to the administration of any corticosteroids.2
Dogs and cats with primary hypoadrenocorticism will exhibit a subnormal response to ACTH administration. The baseline cortisol concentration is usually low or undetectable and the post-ACTH cortisol concentration is also low or undetectable. Endogenous plasma ACTH concentrations are dramatically increased in animals with primary hypoadrenocorticism (> 100 pg/ml) as a result of loss of negative feedback to the pituitary caused by decreased serum cortisol concentrations.1,2 In the case of secondary hypoadrenocorticism, which is caused by a pituitary deficiency of ACTH, the endogenous ACTH concentrations are typically decreased (<20 pg/ml).1 The response to exogenous ACTH is diminished, but not as dramatically as for primary hypoadrenocorticism. Baseline cortisol and post-ACTH cortisol concentrations may be in the normal range.
Therapy: Acute adrenal crisis
Acute adrenocortical insufficiency is a life-threatening emergency; therefore, therapy must be initiated immediately. Treatment of the Addisonian crisis consists of four parts: 1) fluid therapy and electrolyte stabilization, 2) glucocorticoid replacement therapy 3) treatment of gastrointestinal hemorrhage, and 4) mineralocorticoid replacement therapy.1,2,15,18
Of primary importance is rapid administration of large volumes of intravenous fluids; 0.9% NaCl is the fluid of choice. Fluid delivery is best accomplished using a jugular catheter. Blood samples for a complete blood count (CBC), chemistry profile, and resting cortisol level can be obtained through a central jugular catheter prior to initiating therapy. Rapid administration of intravenous fluids restores blood volume and improves renal perfusion which decreases serum potassium concentration via dilution and promotion of renal potassium excretion.1,2,18 However, if hyperkalemia persists, serum potassium can be rapidly decreased by intravenous administration of regular (crystalline) insulin and glucose (0.03 to 0.06 units/lb; for every unit of insulin given, 4 ml 50% dextrose) or intravenous administration of 10% calcium gluconate (0.4 to 1 mg/kg over a 10 - 20 minute period) to counteract the effects of elevated potassium on the heart.1,18
Glucocorticoid therapy, using ultra-short acting corticosteroids such as dexamethasone sodium phosphate (2-4 mg/kg) or prednisolone sodium succinate (15-20 mg/kg), should be instituted immediately.18 Dexamethasone may be preferred in animals that require immediate glucocorticoid administration as it will not interfere with the cortisol assay; in addition, a single dose of short-acting corticosteroid will not suppress the hypothalamic pituitary adrenal axis.2 Some Addisonian dogs may hemorrhage into the gastrointestinal tract because because of poor intestinal perfusion caused by shock..2,15 Treatment of anemia secondary to severe gastrointestinal hemorrhage should include blood transfusion coupled with gastrointestinal protectants.
Rapid correction of hyovolemia with 0.9% NaCl is usually sufficient to correct most electrolyte abnormalities, however, oral mineralocorticoid supplementation with fludrocortisone acetate (Florinef) can be instituted as soon as vomiting ceases. Metabolic acidosis often resolves after fluid therapy; however, severe acidosis (pH < 7.1) may be treated with sodium bicarbonate.18 Hypoglycemia, if present and symptomatic, should be treated with a slow intravenous bolus of 50% dextrose (0.5 - 1.0 ml/kg).1,18
Maintenance therapy and Prognosis
Mineralocorticoid supplementation, using oral fludrocortisone (Florinef Ò, 15-20 mg/kg/day PO q 24 hr) or deoxycorticosterone pivalate (DOCP, 2.2 mg/kg q 25 days) should be initiated after the results of dynamic adrenal testing confirm a diagnosis of hypoadrenocorticism. Glucocorticoid supplementation (0.22 mg/kg) must be given with DOCP as this drug has no glucocorticoid activity.19 Fludrocortisone, on the other hand, does provide some glucocorticoid activity; therefore, additional prednisolone supplementation is only required in about 50% of dogs.1, 19 All dogs should receive additional corticosteroids during periods of stress (i.e. elective surgery).
Cats with hypoadrenocorticism are managed with injectable corticosteroids such as Depo-Medrol (10 mg/cat q 3-4 weeks) and DOCP (12.5 mg/cat q 3-4 weeks).4 Most dogs require DOCP every 25-35 days and most cats require DOCP every 30 days.19 Monitoring of serum electrolytes should be used to determine the optimal dosing interval. Addisonian animals receiving DOCP should be monitored every 3 weeks until the dosage and interval of administration is determined and dogs receiving fludrocortisone should be monitored weekly until electrolytes become normal. In patients with normal potassium, but low sodium concentrations, sodium chloride tablets supplementation has been recommended in the past; however, the cause of the hyponatremia should be investigated and a thorough thyroid evaluation (TT4, cTSH) should be undertaken (see polyendocrine gland failure in small animals). Signs of DOCP toxicity include hypokalemia, hypernatremia, polydipsia and polyuria; however, DOCP toxicity is very difficult to induce.20
The practitioner may want to consider cost and size issues with regard to choosing between Florinef and DOCP. 19 In large breed dogs (> 25 kg), DOCP may be a more economical choice. In a recent study looking at the response of Addisonian dogs to treatment, it was found that fewer than 20% of the dogs required the manufacturer's recommended dose (2.2 mg/kg q 25 days) of DOCP. Therefore, if cost is a consideration, an initial dose of 1.5 mg/kg q 25 days can be administered and the response to therapy monitored. In the same study, adverse effects (iatrogenic Cushing's) occurred in almost one third of the dogs receiving fludrocortisone and necessitated a change to DOCP.19
Prognosis
The long-term prognosis for animals treated for hypoadrenocorticism, once an adrenal crisis is controlled, is excellent with 80% of the dogs having a good to excellent response to therapy.19 Furthermore, the median survival time in one study was 5 years and very few of the dogs died of complications associated with hypoadrenocorticism.19
With appropriate glucocorticoid and/or mineralocorticoid replacement therapy, dogs and cats with hypoadrenocorticism should be expected to live a normal life.
The importance of life-long therapy must be emphasized to the owners, as well as the potential for increasing glucocorticoid requirements during stressful situations.
Introduction
The diagnosis and treatment of hypoadrenocorticism (Addison's disease) can be one of the greatest challenges faced by veterinary practitioners. The purpose of this review is to describe the clinical diagnosis and treatment of hypoadrenocorticism in dogs and cats.
Hypoadrenocorticism is a result of deficient secretion of both mineralocorticoids (aldosterone) and glucocorticoids.1 Naturally-occurring primary hypoadrenocorticism is usually caused by immune-mediated destruction of the adrenal cortex in both cats and dogs;1-4 however, lymphomatous infiltration of the adrenals has been reported as a cause of hypoadrenocorticism in cats.5 Secondary hypoadrenocorticism, in which the pituitary gland produces inadequate amounts of adrenocorticotrophic hormone (ACTH), can be caused by chronic steroid therapy or less commonly by tumors, trauma, or congenital defects of the pituitary gland.1 Secondary hypoadrenocorticism is rare in both dogs and cats. Hypoadrenocorticism, which is glucocorticoid deficient only (hypocortisolemia), has been termed "atypical" Addison's disease.6-9 Secondary hypoadrenocorticism is always atypical and primary hypoadrenocorticism can be atypical in the early stages of the disease prior to destruction of the zona glomerulosa.
Signalment, Clinical Signs and Laboratory Abnormalities
Canine hypoadrenocorticism is most often diagnosed in young female dogs (70%) of any breed. 1,2,8 However, hypoadrenocorticism has been reported in families of Leonbergers and standard poodles suggesting a genetic basis in some breeds.10,11 Young cats of any breed or sex can also develop hypoadrenocorticism.4,5
Historical findings compatible with hypoadrenocorticism include intermittent vomiting, diarrhea, weight loss, lethargy, depression, anorexia, and weakness.1-9 There may be a history of vomiting or diarrhea responsive to non-specific treatment, such as intravenous fluids, only to have signs reoccur several days to weeks later.
Often the clinical signs come and go (waxing and waning) periodically. As the disease progresses, the animal may present with collapse, hypothermia, shaking, polyuria, and polydipsia,. Hair loss and melena are unusual historical findings. Signs of megaesophagus, such as regurgitation and weight loss, have been reported uncommonly in dogs with both typical and atypical hypoadrenocorticism.1, 12 Differential diagnoses for the common clinical signs consistent with hypoadrenocorticism include inflammatory bowel disease, intestinal parasitism (trichuriasis), bilious vomiting syndrome, and renal disease.1,2,13 A comparison of clinical signs hypoadrenocorticism in cats and dogs is shown in Table 1 and a comparison of typical and atypical hypoadrenocorticism in dogs is listed in Table 2.
Physical examination of animals in an acute Addisonian crisis reveals weak pulses, bradycardia, prolonged capillary refill time, severe mental depression, and profound muscle weakness.1,2 Clinical features which should heighten the index of suspicion of hypoadrenocorticism include a normal or slow heart rate in the face of circulatory shock, previous response to corticosteroid or fluid therapy, and a"waxing and waning" course of disease prior to collapse.
Classic electrolyte abnormalities, such as hyponatremia, hyperkalemia, hypochloremia, and sodium to potassium ratios of less than 20 to 1, are highly suggestive of primary hypoadrenocorticism.1,2 However, gastrointestinal disease (trichuriasis), acute renal failure, post-renal azotemia and abdominal/thoracic effusions (third space) are additional differential diagnoses. 1,2,13,14 Azotemia and hyperphosphatemia also attend primary hypoadrenocorticism making it difficult to differentiate from acute renal failure. Azotemia associated with hypoadrenocorticism may be prerenal as a result of dehydration , hypovolemia or gastrointestinal hemorrhage.1,15
Hypercalcemia may be observed in up to 30% of dogs with hypoadrenocorticism as a result of hemoconcentration.16 Metabolic acidosis results from decreased hydrogen ion secretion in the renal distal tubule, increased generation of acids secondary to reduced tissue perfusion, and renal retention of organic acids.1,2 Hypoalbuminemia has been described in associated with hypoadrenocorticism; however, a cause and effect relationship has not been defined. 2,17 Animals with glucocorticoid deficiency only, will not show classic electrolyte imbalances, but may present with hypoglycemia as a result of impaired gluconeogenesis and glycogenolysis.1,5,6
Hematological findings include mild normocytic normochromic (non-regenerative) anemia; however, if the animal is dehydrated the underlying anemia may be masked. The absence of a stress leukogram is a subtle but important feature of atypical hypoadrenocorticism.6,7,9 The presence of a normal or elevated eosinophil or lymphocyte count in a stressed animal should be viewed with suspicion for hypoadrenocorticism, particularly atypical Addison's disease. Eosinophilia and lymphocytosis are seen in 20% and 10% of dogs with primary hypoadrenocorticism, respectively. 1,2
Urine specific gravity is frequently low and is attributed to medullary washout (inadequate medullary gradient due to sodium depletion) and decreased medullary blood flow.1 Dilute urine in the face of azotemia and hyperkalemia may easily be mistaken for acute renal failure. Hormonal assays are required to confirm the presence or absence of adrenal disease and to differentiate between hypoadrenocorticism and renal failure.
Electrocardiography, ultrasound and radiographic findings
If bradycardia is present, an electrocardiogram may be helpful in the diagnosis of hypoadrenocorticism, especially when serum electrolytes are not immediately available. Classic electrocardiographic findings reported with hyperkalemia include prolonged QRS complexes, decreased R wave amplitude, increased T wave amplitude ("spiked" T waves), and prolonged or absent p waves.1 Sinoatrial standstill is the most common arrhythmia noted. Electrocardiagraphic changes should not be used to determine the exact serum potassium concentrations because serum potassium concentrations do not directly correlate with specific EKG changes; however, the EKG is useful in an emergency setting. Radiographs may demonstrate signs associated with volume depletion or decreased tissue perfusion, such as microcardia, narrowed vena cava, and hypoperfused lungs. Megaesophagus has been reported uncommonly in dogs with both typical and atypical hypoadrenocorticism.1,2,12 Ultrasound cannot be routinely used to identify "small" adrenals, particularly since the right adrenal may be difficult to image in normal animals.
Diagnostic testing
Diagnosis of primary hypoadrenocorticism is based on clinical signs, classic electrolyte imbalances, and confirmation with an ACTH response test. To perform the test, a serum sample is obtained before, 30 minutes (cats) and 1 hour (cats and dogs) after intravenous administration of synthetic ACTH (cosyntropin; 0.5 mg/kg).1,2 Administration of a single dose of dexamethasone sodium phosphate prior to obtaining baseline or one hour post ACTH cortisol samples will not interfere with the test. However, administration of prednisolone will interfere with the ACTH response test because prednisolone will cross react with the cortisol assay.2 If corticosteroids have already been administered, one can wait 24 hours and perform the ACTH response test after the short-acting corticosteroids have dissipated.2 Endogenous plasma ACTH may be measured to determine if the hypoadrenocorticism is primary or secondary. This specimen must be collected in an EDTA tube, spun within an hour of sampling and stored in plastic prior to the administration of any corticosteroids.2
Dogs and cats with primary hypoadrenocorticism will exhibit a subnormal response to ACTH administration. The baseline cortisol concentration is usually low or undetectable and the post-ACTH cortisol concentration is also low or undetectable. Endogenous plasma ACTH concentrations are dramatically increased in animals with primary hypoadrenocorticism (> 100 pg/ml) as a result of loss of negative feedback to the pituitary caused by decreased serum cortisol concentrations.1,2 In the case of secondary hypoadrenocorticism, which is caused by a pituitary deficiency of ACTH, the endogenous ACTH concentrations are typically decreased (<20 pg/ml).1 The response to exogenous ACTH is diminished, but not as dramatically as for primary hypoadrenocorticism. Baseline cortisol and post-ACTH cortisol concentrations may be in the normal range.
Therapy: Acute adrenal crisis
Acute adrenocortical insufficiency is a life-threatening emergency; therefore, therapy must be initiated immediately. Treatment of the Addisonian crisis consists of four parts: 1) fluid therapy and electrolyte stabilization, 2) glucocorticoid replacement therapy 3) treatment of gastrointestinal hemorrhage, and 4) mineralocorticoid replacement therapy.1,2,15,18
Of primary importance is rapid administration of large volumes of intravenous fluids; 0.9% NaCl is the fluid of choice. Fluid delivery is best accomplished using a jugular catheter. Blood samples for a complete blood count (CBC), chemistry profile, and resting cortisol level can be obtained through a central jugular catheter prior to initiating therapy. Rapid administration of intravenous fluids restores blood volume and improves renal perfusion which decreases serum potassium concentration via dilution and promotion of renal potassium excretion.1,2,18 However, if hyperkalemia persists, serum potassium can be rapidly decreased by intravenous administration of regular (crystalline) insulin and glucose (0.03 to 0.06 units/lb; for every unit of insulin given, 4 ml 50% dextrose) or intravenous administration of 10% calcium gluconate (0.4 to 1 mg/kg over a 10 - 20 minute period) to counteract the effects of elevated potassium on the heart.1,18
Glucocorticoid therapy, using ultra-short acting corticosteroids such as dexamethasone sodium phosphate (2-4 mg/kg) or prednisolone sodium succinate (15-20 mg/kg), should be instituted immediately.18 Dexamethasone may be preferred in animals that require immediate glucocorticoid administration as it will not interfere with the cortisol assay; in addition, a single dose of short-acting corticosteroid will not suppress the hypothalamic pituitary adrenal axis.2 Some Addisonian dogs may hemorrhage into the gastrointestinal tract because because of poor intestinal perfusion caused by shock..2,15 Treatment of anemia secondary to severe gastrointestinal hemorrhage should include blood transfusion coupled with gastrointestinal protectants.
Rapid correction of hyovolemia with 0.9% NaCl is usually sufficient to correct most electrolyte abnormalities, however, oral mineralocorticoid supplementation with fludrocortisone acetate (Florinef) can be instituted as soon as vomiting ceases. Metabolic acidosis often resolves after fluid therapy; however, severe acidosis (pH < 7.1) may be treated with sodium bicarbonate.18 Hypoglycemia, if present and symptomatic, should be treated with a slow intravenous bolus of 50% dextrose (0.5 - 1.0 ml/kg).1,18
Maintenance therapy and Prognosis
Mineralocorticoid supplementation, using oral fludrocortisone (Florinef Ò, 15-20 mg/kg/day PO q 24 hr) or deoxycorticosterone pivalate (DOCP, 2.2 mg/kg q 25 days) should be initiated after the results of dynamic adrenal testing confirm a diagnosis of hypoadrenocorticism. Glucocorticoid supplementation (0.22 mg/kg) must be given with DOCP as this drug has no glucocorticoid activity.19 Fludrocortisone, on the other hand, does provide some glucocorticoid activity; therefore, additional prednisolone supplementation is only required in about 50% of dogs.1, 19 All dogs should receive additional corticosteroids during periods of stress (i.e. elective surgery).
Cats with hypoadrenocorticism are managed with injectable corticosteroids such as Depo-Medrol (10 mg/cat q 3-4 weeks) and DOCP (12.5 mg/cat q 3-4 weeks).4 Most dogs require DOCP every 25-35 days and most cats require DOCP every 30 days.19 Monitoring of serum electrolytes should be used to determine the optimal dosing interval. Addisonian animals receiving DOCP should be monitored every 3 weeks until the dosage and interval of administration is determined and dogs receiving fludrocortisone should be monitored weekly until electrolytes become normal. In patients with normal potassium, but low sodium concentrations, sodium chloride tablets supplementation has been recommended in the past; however, the cause of the hyponatremia should be investigated and a thorough thyroid evaluation (TT4, cTSH) should be undertaken (see polyendocrine gland failure in small animals). Signs of DOCP toxicity include hypokalemia, hypernatremia, polydipsia and polyuria; however, DOCP toxicity is very difficult to induce.20
The practitioner may want to consider cost and size issues with regard to choosing between Florinef and DOCP. 19 In large breed dogs (> 25 kg), DOCP may be a more economical choice. In a recent study looking at the response of Addisonian dogs to treatment, it was found that fewer than 20% of the dogs required the manufacturer's recommended dose (2.2 mg/kg q 25 days) of DOCP. Therefore, if cost is a consideration, an initial dose of 1.5 mg/kg q 25 days can be administered and the response to therapy monitored. In the same study, adverse effects (iatrogenic Cushing's) occurred in almost one third of the dogs receiving fludrocortisone and necessitated a change to DOCP.19
Prognosis
The long-term prognosis for animals treated for hypoadrenocorticism, once an adrenal crisis is controlled, is excellent with 80% of the dogs having a good to excellent response to therapy.19 Furthermore, the median survival time in one study was 5 years and very few of the dogs died of complications associated with hypoadrenocorticism.19
With appropriate glucocorticoid and/or mineralocorticoid replacement therapy, dogs and cats with hypoadrenocorticism should be expected to live a normal life.
The importance of life-long therapy must be emphasized to the owners, as well as the potential for increasing glucocorticoid requirements during stressful situations.
Research Focuses on Understanding the Genetics Behind Addison's Disease
By Kahu Kāhealani Kawaiolamanaloa Satchitananda
When her Bearded Collie, "Maggie" (Alashaw's Up and At Em,' OA, OAJ, NAC, OJC, CGC) collapsed, Jenny Scheytt of Sterling Heights, Mich., knew something was wrong, so she took the dog to an emergency veterinary clinic. Though the emergency veterinarian who treated Maggie had not seen many cases of Addison's disease, he recognized the possibility partly because Bearded Collies are among the affected breeds.
The veterinarian performed an adrenocorticotropic hormone (ACTH) stimulation test on Maggie, which confirmed the diagnosis. The stimulation test, the only definitive diagnostic tool for Addison's disease, is used to determine whether the adrenal gland produces the corticosteroid hormone cortisol, which is important in regulating metabolism, stress, reproduction and immune system function.
"Prior to Maggie's collapse episode, the only sign that she had Addison's was an occasional lack of appetite," says Scheytt, who breeds Bearded Collies under the Estrella prefix. "In fact, just the weekend before, she had competed in an agility trial. Maggie had never eaten well, especially as a puppy, so I didn't think a lot about it. When she was about 18 months old, I took her to the veterinarian because I was concerned that she was getting thin. A complete blood count analysis did not detect an abnormality."
Reflecting on the events leading up to the diagnosis, Scheytt says, "We were at the agility trial on a Sunday and by Thursday the next week, Maggie started acting weird and not eating. By Friday, she wasn't eating anything and was listless. Within 24 hours, she had totally crashed."
Hypoadrenocorticism, or adrenal insufficiency, is more commonly known as Addison's disease. Named for the British physician Thomas Addison, who described the condition in humans in 1849, Addison's disease is a genetic condition that mimics other illnesses. Signs may occur suddenly and severely or may wax and wane. As a result, dogs with Addison's disease sometimes are mistaken for having conditions such as inflammatory bowel disease, hepatic or liver disease, or acute kidney failure.
Addison's disease first was recognized in dogs in 1953. Although the disorder can occur in any breed, those considered susceptible are Bearded Collies, Great Danes, Leonbergers, Nova Scotia Duck Tolling Retrievers, Portuguese Water Dogs, Standard Poodles, and West Highland White Terriers. Fortunately, dogs can live normal lives when they are monitored and treated with medications.
Malfunctioning adrenal glands are the source of the problem. Located on top of the kidneys, the adrenal glands secrete hormones into the bloodstream. The adrenals have two layers. The outer area, the cortex, produces corticosteroid hormones, such as cortisol, which impacts metabolism and helps the body deal with stress, and aldosterone, which is important in regulating electrolytes. The inner area, the adrenal medulla, is part of the sympathetic nervous system. It produces epinephrine, or adrenaline, and usually is not affected by Addison's disease.
Three types of Addison's disease are recognized: primary, atypical and secondary. The two former types are most likely caused by immune-related damage to the adrenal glands. The secondary type is caused by tumors, long-term steroid use or failure of the pituitary gland to simulate the adrenals with adrenocorticotropic hormone. Identifying the type of Addison's disease through an ACTH stimulation test is important in order to provide proper treatment.
The ACTH stimulation test evaluates a dog's response to the pituitary hormone ACTH. A blood sample is taken, and a dog's resting cortisol level is measured. Then, the dog is injected with a form of ACTH, which tells the adrenals to produce cortisol. After an hour, the blood is drawn again to measure the stimulated cortisol level. A dog that does not respond to the ACTH stimulation with an increase in cortisol hormone level is diagnosed with Addison's disease.
"Most dogs are diagnosed with primary Addison's disease, which means there is a slow degradation of the adrenal cortex over time," says Anita Oberbauer, Ph.D., professor and chairwoman of the Department of Animal Science at the University of California-Davis. "Eventually, there is nothing left of the organ to produce cortisol and aldosterone. The dog's mineral balance and metabolism are disrupted, and that's why the signs are so diffuse."
Addison's disease typically develops in middle-aged dogs between 4 and 6 years old but can appear in dogs as young as 15 weeks or as old as 12. Males and females are equally affected. Maggie, who was 4 1/2 years old, fit the profile.
The veterinarian prescribed a replacement hormone therapy for Maggie that was effective in treating her Addison's disease. "It took about one month before Maggie was her old self again," Scheytt says. "Soon, she was back to doing agility and herding."
Several medications are used to treat Addison's disease. Initially, a mineralocorticoid replaces the aldosterone, the hormone responsible for maintaining electrolyte levels. The mineralocorticoid is replaced with an oral medication, fludrocortisone acetate, or an injectable medication, desoxycorticosterone pivalate. The cortisol normally secreted by the adrenals is replaced with oral prednisone. Monthly costs for medications vary but average around $65.
A Type of Autoimmune Disease
Primary and atypical Addison's disease are autoimmune diseases in which the body creates antibodies to its own adrenal tissues, targeting the cortex for removal by the immune system. The generation of the self-directed antibodies is due to a genetic susceptibility that is likely triggered by unidentified factors, such as the environment or medications. Hypothyroidism is the most frequently reported autoimmune disease in dogs. Signs include thick, oily skin, obesity and lethargy. Other autoimmune diseases can affect functioning of the endocrine glands, bowels, joints, kidneys, heart, lungs, blood and the nervous system.
Symmetrical lupoid onychodystrophy (SLO) is an autoimmune disease that causes dogs to lose claws. Eventually all claws may be lost. Signs include receding quicks, split claws, secondary infection, pain and lameness. Similar to Addison's disease, treatment controls SLO.
Ginny Aulik of Rockford, Ill., describes when her Bearded Collie "Willow" was diagnosed with the condition. "A visit to the veterinarian resulted in a diagnosis of SLO," she says. "Supplements of an omega fatty acid and a pentoxifylline medication known as Trental, which helps to improve blood flow, resolved her lameness and loss of claws."
Aulik's experience with another autoimmune disease in 2002 with her Bearded Collie, CH Desertstorm Secret Formula, who won Best of Breed at Westminster that year, was not as simple. "'Felix' did not have any signs of disease other than toward the end when his topline fell due to pain from kidney disease," she says. "He died in December that year from immune-mediated renal failure. He was diagnosed in June after a wellness checkup indicated high BUN (blood urea nitrogen), creatinine and protein in the urine. He had no other signs of being ill. He romped around just like normal."
Signs of Addison's disease can be ambiguous. "A dog with Addison's disease may seem lethargic, listless or depressed," says Oberbauer. "Owners sometimes say their dog seemed 'off' or 'lost the sparkle in his or her eye.' Lack of appetite is a good indicator, but other signs include vomiting, diarrhea and muscle pain."
Owners may notice a dog having pain in the hind quarters or not being able to jump onto a bed or couch as in the past. Shivering or muscle tremors also are signs.
If the adrenals continue to deteriorate, a dog may have an acute episode or Addisonian crisis.
Potassium levels are elevated, and the heart rate slows and may even stop. Arrhythmia can result, and blood pressure may drop dangerously low.
It often takes a serious incident, such as Maggie's collapse episode, before a diagnosis is made. Researchers indicate a dog with Addison's disease may have depleted 85 to 90 percent of its adrenal hormone reserves before showing clinical signs.
Stress from injuries, exhaustion or severe environmental conditions may trigger the condition.
Making Genetics Progress
Research of the genetics of Addison's disease indicates that the disease is regulated by a major gene inherited in a recessive mode of inheritance, though not necessarily in a simple autosomal recessive inheritance pattern as other factors seem to govern onset of the disease. "This means for Addison's to be passed on, it appears that both the sire and dam have to carry a recessive gene for this disease," says Oberbauer who has studied Addison's disease in dogs since 2001.
Linda Aronson, D.V.M., health chairwoman of the Bearded Collie Club of America and vice president of the Bearded Collie Health Foundation, says, "Presentations at this year's Tufts University genetics conference indicate that 30 to 40 genes may be involved in each autoimmune disease. While some are common to all autoimmune diseases, others are disease-specific. Some genes are protective, and others increase risk.
"Layered on these are the triggers that make a particular animal ill.
These can be environmental, or medications, but most are unknown.
Other factors, such as penetration, expression and epigenetics, also are involved in whether a dog will get sick.
For example, there is a litter of Beardies in the U.K. in which both parents developed Addison's after the puppies were born. All the puppies would be genetically programmed for Addison's if the disease were simple autosomal recessive, yet they are 11 years old now and none has developed Addison's."
Oberbauer's research focuses on identifying the causative gene mutation in Bearded Collies, Great Danes, Leonbergers, Standard Poodles, Portuguese Water Dogs, and West Highland White Terriers.
The AKC Canine Health Foundation has funded the research with support from the Bearded Collie Club of America, Bearded Collie Health Foundation, Poodle Club of America, Leonberger Club of America, Portuguese Water Dog Foundation, and Great Dane Club of America.
"My first Bearded Collie was diagnosed with Addison's in 1989 when there was little information about this disease," says Aronson. "It was a labor of love to find information. By supporting the genetic research, we hope to help advance understanding."
Oberbauer's collaborative research effort involves Äke Hedhammar, professor of small animal medicine at the Swedish University of Agricultural Sciences, and Kerstin Lindblad-Toh, Ph.D., director of Vertebrate Genome Biology at the Broad Institute and professor at Uppsala University. The team is analyzing DNA from Addisonian dogs from around the world to identify the genetic changes responsible for Addison's disease.
Oberbauer and her team have collected and analyzed DNA samples from 1,700 Bearded Collies. The findings indicate that 7 percent of the sample was affected by Addison's disease, slightly higher than the 2 to 4.6 percent reported in a health survey conducted by the Bearded Collie Club of America.
DNA samples they have collected from other breeds also show higher than expected population prevalence, which Oberbauer attributes to interested owners or those with affected dogs submitting samples more frequently than the general public. The prevalence rates for Great Danes, Leonbergers, Portuguese Water Dogs, Standard Poodles and West Highland White Terriers are 8.9 percent, 3.2 percent, 5.9 percent, 15 percent and 17 percent, respectively.
As the research has evolved, Oberbauer has looked for commonalities among autoimmune disorders. "There may be some common genetic regions that confer a greater susceptibility to some of these disorders that may be autoimmune," she says. "Studies of hypothyroidism and Addison's in the Bearded Collie both point to an autoimmune region on chromosome 4. I am optimistic that we will find a marker and possible gene mutation that increase the risk of these diseases."
Discovery of the gene mutation for Addison's disease would help breeders in making breeding decisions. For now, Oberbauer cautiously advises breeders to not disregard dogs with valuable characteristics. "I encourage breeders not to eliminate a potential carrier of Addison's disease, or another autoimmune disorder, if the dog has phenomenal attributes," she says. "You could easily trade one disorder for another.
Any breeding decisions regarding potential carriers must be made by prudently selecting a complementary mate that has very little likelihood of being a potential carrier to minimize affected offspring."
Meanwhile, owners of dogs with Addison's disease cope by monitoring and treating them. Maggie, who is 10 1/2 years old, no longer competes in agility, but she is a healthy, active dog.
"If treated with proper medications, these dogs go on to lead normal lives," Scheytt says.
"Stress can affect Maggie, but I have learned to recognize signs. She should never have another crash."
By Kahu Kāhealani Kawaiolamanaloa Satchitananda
When her Bearded Collie, "Maggie" (Alashaw's Up and At Em,' OA, OAJ, NAC, OJC, CGC) collapsed, Jenny Scheytt of Sterling Heights, Mich., knew something was wrong, so she took the dog to an emergency veterinary clinic. Though the emergency veterinarian who treated Maggie had not seen many cases of Addison's disease, he recognized the possibility partly because Bearded Collies are among the affected breeds.
The veterinarian performed an adrenocorticotropic hormone (ACTH) stimulation test on Maggie, which confirmed the diagnosis. The stimulation test, the only definitive diagnostic tool for Addison's disease, is used to determine whether the adrenal gland produces the corticosteroid hormone cortisol, which is important in regulating metabolism, stress, reproduction and immune system function.
"Prior to Maggie's collapse episode, the only sign that she had Addison's was an occasional lack of appetite," says Scheytt, who breeds Bearded Collies under the Estrella prefix. "In fact, just the weekend before, she had competed in an agility trial. Maggie had never eaten well, especially as a puppy, so I didn't think a lot about it. When she was about 18 months old, I took her to the veterinarian because I was concerned that she was getting thin. A complete blood count analysis did not detect an abnormality."
Reflecting on the events leading up to the diagnosis, Scheytt says, "We were at the agility trial on a Sunday and by Thursday the next week, Maggie started acting weird and not eating. By Friday, she wasn't eating anything and was listless. Within 24 hours, she had totally crashed."
Hypoadrenocorticism, or adrenal insufficiency, is more commonly known as Addison's disease. Named for the British physician Thomas Addison, who described the condition in humans in 1849, Addison's disease is a genetic condition that mimics other illnesses. Signs may occur suddenly and severely or may wax and wane. As a result, dogs with Addison's disease sometimes are mistaken for having conditions such as inflammatory bowel disease, hepatic or liver disease, or acute kidney failure.
Addison's disease first was recognized in dogs in 1953. Although the disorder can occur in any breed, those considered susceptible are Bearded Collies, Great Danes, Leonbergers, Nova Scotia Duck Tolling Retrievers, Portuguese Water Dogs, Standard Poodles, and West Highland White Terriers. Fortunately, dogs can live normal lives when they are monitored and treated with medications.
Malfunctioning adrenal glands are the source of the problem. Located on top of the kidneys, the adrenal glands secrete hormones into the bloodstream. The adrenals have two layers. The outer area, the cortex, produces corticosteroid hormones, such as cortisol, which impacts metabolism and helps the body deal with stress, and aldosterone, which is important in regulating electrolytes. The inner area, the adrenal medulla, is part of the sympathetic nervous system. It produces epinephrine, or adrenaline, and usually is not affected by Addison's disease.
Three types of Addison's disease are recognized: primary, atypical and secondary. The two former types are most likely caused by immune-related damage to the adrenal glands. The secondary type is caused by tumors, long-term steroid use or failure of the pituitary gland to simulate the adrenals with adrenocorticotropic hormone. Identifying the type of Addison's disease through an ACTH stimulation test is important in order to provide proper treatment.
The ACTH stimulation test evaluates a dog's response to the pituitary hormone ACTH. A blood sample is taken, and a dog's resting cortisol level is measured. Then, the dog is injected with a form of ACTH, which tells the adrenals to produce cortisol. After an hour, the blood is drawn again to measure the stimulated cortisol level. A dog that does not respond to the ACTH stimulation with an increase in cortisol hormone level is diagnosed with Addison's disease.
"Most dogs are diagnosed with primary Addison's disease, which means there is a slow degradation of the adrenal cortex over time," says Anita Oberbauer, Ph.D., professor and chairwoman of the Department of Animal Science at the University of California-Davis. "Eventually, there is nothing left of the organ to produce cortisol and aldosterone. The dog's mineral balance and metabolism are disrupted, and that's why the signs are so diffuse."
Addison's disease typically develops in middle-aged dogs between 4 and 6 years old but can appear in dogs as young as 15 weeks or as old as 12. Males and females are equally affected. Maggie, who was 4 1/2 years old, fit the profile.
The veterinarian prescribed a replacement hormone therapy for Maggie that was effective in treating her Addison's disease. "It took about one month before Maggie was her old self again," Scheytt says. "Soon, she was back to doing agility and herding."
Several medications are used to treat Addison's disease. Initially, a mineralocorticoid replaces the aldosterone, the hormone responsible for maintaining electrolyte levels. The mineralocorticoid is replaced with an oral medication, fludrocortisone acetate, or an injectable medication, desoxycorticosterone pivalate. The cortisol normally secreted by the adrenals is replaced with oral prednisone. Monthly costs for medications vary but average around $65.
A Type of Autoimmune Disease
Primary and atypical Addison's disease are autoimmune diseases in which the body creates antibodies to its own adrenal tissues, targeting the cortex for removal by the immune system. The generation of the self-directed antibodies is due to a genetic susceptibility that is likely triggered by unidentified factors, such as the environment or medications. Hypothyroidism is the most frequently reported autoimmune disease in dogs. Signs include thick, oily skin, obesity and lethargy. Other autoimmune diseases can affect functioning of the endocrine glands, bowels, joints, kidneys, heart, lungs, blood and the nervous system.
Symmetrical lupoid onychodystrophy (SLO) is an autoimmune disease that causes dogs to lose claws. Eventually all claws may be lost. Signs include receding quicks, split claws, secondary infection, pain and lameness. Similar to Addison's disease, treatment controls SLO.
Ginny Aulik of Rockford, Ill., describes when her Bearded Collie "Willow" was diagnosed with the condition. "A visit to the veterinarian resulted in a diagnosis of SLO," she says. "Supplements of an omega fatty acid and a pentoxifylline medication known as Trental, which helps to improve blood flow, resolved her lameness and loss of claws."
Aulik's experience with another autoimmune disease in 2002 with her Bearded Collie, CH Desertstorm Secret Formula, who won Best of Breed at Westminster that year, was not as simple. "'Felix' did not have any signs of disease other than toward the end when his topline fell due to pain from kidney disease," she says. "He died in December that year from immune-mediated renal failure. He was diagnosed in June after a wellness checkup indicated high BUN (blood urea nitrogen), creatinine and protein in the urine. He had no other signs of being ill. He romped around just like normal."
Signs of Addison's disease can be ambiguous. "A dog with Addison's disease may seem lethargic, listless or depressed," says Oberbauer. "Owners sometimes say their dog seemed 'off' or 'lost the sparkle in his or her eye.' Lack of appetite is a good indicator, but other signs include vomiting, diarrhea and muscle pain."
Owners may notice a dog having pain in the hind quarters or not being able to jump onto a bed or couch as in the past. Shivering or muscle tremors also are signs.
If the adrenals continue to deteriorate, a dog may have an acute episode or Addisonian crisis.
Potassium levels are elevated, and the heart rate slows and may even stop. Arrhythmia can result, and blood pressure may drop dangerously low.
It often takes a serious incident, such as Maggie's collapse episode, before a diagnosis is made. Researchers indicate a dog with Addison's disease may have depleted 85 to 90 percent of its adrenal hormone reserves before showing clinical signs.
Stress from injuries, exhaustion or severe environmental conditions may trigger the condition.
Making Genetics Progress
Research of the genetics of Addison's disease indicates that the disease is regulated by a major gene inherited in a recessive mode of inheritance, though not necessarily in a simple autosomal recessive inheritance pattern as other factors seem to govern onset of the disease. "This means for Addison's to be passed on, it appears that both the sire and dam have to carry a recessive gene for this disease," says Oberbauer who has studied Addison's disease in dogs since 2001.
Linda Aronson, D.V.M., health chairwoman of the Bearded Collie Club of America and vice president of the Bearded Collie Health Foundation, says, "Presentations at this year's Tufts University genetics conference indicate that 30 to 40 genes may be involved in each autoimmune disease. While some are common to all autoimmune diseases, others are disease-specific. Some genes are protective, and others increase risk.
"Layered on these are the triggers that make a particular animal ill.
These can be environmental, or medications, but most are unknown.
Other factors, such as penetration, expression and epigenetics, also are involved in whether a dog will get sick.
For example, there is a litter of Beardies in the U.K. in which both parents developed Addison's after the puppies were born. All the puppies would be genetically programmed for Addison's if the disease were simple autosomal recessive, yet they are 11 years old now and none has developed Addison's."
Oberbauer's research focuses on identifying the causative gene mutation in Bearded Collies, Great Danes, Leonbergers, Standard Poodles, Portuguese Water Dogs, and West Highland White Terriers.
The AKC Canine Health Foundation has funded the research with support from the Bearded Collie Club of America, Bearded Collie Health Foundation, Poodle Club of America, Leonberger Club of America, Portuguese Water Dog Foundation, and Great Dane Club of America.
"My first Bearded Collie was diagnosed with Addison's in 1989 when there was little information about this disease," says Aronson. "It was a labor of love to find information. By supporting the genetic research, we hope to help advance understanding."
Oberbauer's collaborative research effort involves Äke Hedhammar, professor of small animal medicine at the Swedish University of Agricultural Sciences, and Kerstin Lindblad-Toh, Ph.D., director of Vertebrate Genome Biology at the Broad Institute and professor at Uppsala University. The team is analyzing DNA from Addisonian dogs from around the world to identify the genetic changes responsible for Addison's disease.
Oberbauer and her team have collected and analyzed DNA samples from 1,700 Bearded Collies. The findings indicate that 7 percent of the sample was affected by Addison's disease, slightly higher than the 2 to 4.6 percent reported in a health survey conducted by the Bearded Collie Club of America.
DNA samples they have collected from other breeds also show higher than expected population prevalence, which Oberbauer attributes to interested owners or those with affected dogs submitting samples more frequently than the general public. The prevalence rates for Great Danes, Leonbergers, Portuguese Water Dogs, Standard Poodles and West Highland White Terriers are 8.9 percent, 3.2 percent, 5.9 percent, 15 percent and 17 percent, respectively.
As the research has evolved, Oberbauer has looked for commonalities among autoimmune disorders. "There may be some common genetic regions that confer a greater susceptibility to some of these disorders that may be autoimmune," she says. "Studies of hypothyroidism and Addison's in the Bearded Collie both point to an autoimmune region on chromosome 4. I am optimistic that we will find a marker and possible gene mutation that increase the risk of these diseases."
Discovery of the gene mutation for Addison's disease would help breeders in making breeding decisions. For now, Oberbauer cautiously advises breeders to not disregard dogs with valuable characteristics. "I encourage breeders not to eliminate a potential carrier of Addison's disease, or another autoimmune disorder, if the dog has phenomenal attributes," she says. "You could easily trade one disorder for another.
Any breeding decisions regarding potential carriers must be made by prudently selecting a complementary mate that has very little likelihood of being a potential carrier to minimize affected offspring."
Meanwhile, owners of dogs with Addison's disease cope by monitoring and treating them. Maggie, who is 10 1/2 years old, no longer competes in agility, but she is a healthy, active dog.
"If treated with proper medications, these dogs go on to lead normal lives," Scheytt says.
"Stress can affect Maggie, but I have learned to recognize signs. She should never have another crash."