Canine Hypoadrenocorticism

What is canine hypoadrenocorticism?

Canine hypoadrenocorticism (Addison’s disease) is a rare endocrine disorder. The adrenal glands, which sit on top of the kidneys, produce hormones that control blood pressure, heart rate, and the body’s response to stress. In dogs with hypoadrenocorticism, these hormones are not produced in the normal amounts, leading to a wide range of symptoms.

The most common symptoms of canine hypoadrenocorticism are vomiting, diarrhea, dehydration, loss of appetite, and weakness. Other symptoms can include changes in behavior (e.g., becoming more aggressive or fearful), a pot-bellied appearance, and a decreased ability to fight infections. In severe cases, dogs may go into shock and die.

Hypoadrenocorticism can be caused by a number of things, including infection, cancer, and certain medications. It can also be inherited. If your dog shows any of the above symptoms, it is important to take him to the vet for a thorough examination.

Treatment for canine hypoadrenocorticism usually involves lifelong administration of hormone replacement therapy. This can be done with medication or, in some cases, with a surgically implanted device. Both primary and secondary forms of this disease occurs while a life-threatening illness, with proper diagnosis and therapy, the prognosis for long-term survival is good. With treatment, most dogs will do well and enjoy a good quality of life.

General Key Points: Hypoadrenocorticism is not common in dogs and is rare in cats.

Two forms of canine hypoadrenocorticism

There are two distinct forms of chronic primary hypoadrenocorticism reported in dogs:

• The “classical” involves deficiencies of cortisol and aldosterone and electrolyte disturbances are present. In the atypical form, also called glucocorticoid deficient hypoadrenocorticism, electrolyte disturbances are not present at time of initial diagnosis but may develop later in the course of the illness.
• Latrogenic secondary hypoadrenocorticism is very similar to the atypical form of the primary disease.

The clinical signs of hypoadrenocorticism are not specific and may suggest a myriad of other diseases. Clinical signs include depression, anorexia, weight loss, vomiting, diarrhea, gastrointestinal hemorrhage, and mild abdominal pain. Regurgitation may be present in some dogs secondary to megaesophagus. Most animals are dehydrated which may be severe.

The disease is much more common in female dogs (68% of cases) and in dogs < 5 years old.2 While any breed of dog may be affected, the disease is more common in mixed breeds, Labrador retrievers, Rottweilers, German shepherds, standard and miniature poodles.

In cats, the clinical signs are also very non-specific and include anorexia, weight loss, vomiting and depression. There is a single report of hypoadrenocorticism caused by adrenocortical lymphoma in cats.

Physical examination findings are not helpful unless the animal has bradycardia secondary to hyperkalemia. Pulse rates may be very slow, normal or increased and quality is reduced.

The differential diagnosis includes acute and chronic renal failure, inflammatory bowel disease, chronic liver disease and pseudo- Addison’s disease (hyperkalemia and hyponatremia associated with trichuriasis).

Clinical pathological findings

• Hematology
  PCV: normal, increased, decreased (non- regenerative anemia occurs in chronic cases)
  Leukogram: usually normal but eosinophilia and lymphocytosis in face of stress is supportive of diagnosis
• Biochemistries
  Blood glucose: < normal in 25% of cases
  BUN: azotemia is common and can be severe

Electrolytes are abnormal in 70-80% of cases but are normal in atypical cases: Sodium < 135 mEq/L, potassium > 5.6 mEq/L, and chloride < 90 mEq/L.

Calcium levels may be increased (>12.5 mg/dl) secondary to increased renal reabsorption of Ca==.

Concurrent liver disease (chronic active hepatitis; hepatic fibrosis) has been reported in some dogs. Most common findings were decreased albumin (90% of cases), decreased cholesterol (70% of cases), increased ALT/ALP (60% of cases) and microhepatica (100% of cases).

Urinalysis is usually normal except for inability to maximally concentrate urine.

A mild metabolic acidosis is usually present but rarely requires treatment.

ECG abnormalities: K=potassium K+ at 5.6-6.5: bradycardia, peaked T waves K+ at 6.6-7.5: wide QRS and decreased R wave K+ at 7.0-8.5: decreased of absent P waves K+ > 8.5: ventricular premature contractions, ventricular fibrillation, asystole

Thoracic radiographs may reveal microcardia or megaesophagus.5

ACTH stimulation test is used to confirm diagnosis. The pre ACTH sample may be low normal or below normal. Following ACTH administration, little or no response is found. Take baseline sample for cortisol; administer 0.25 mg Cortrosyn (Organon Pharmaceuticals) IV or IM and take second sample 1 hour later.

Key Etiologic and Pathophysiologic Points:

Clinical signs result from deficiencies of cortisol and/or aldosterone secondary to adrenal cortical necrosis or atrophy.

In primary hypoadrenocorticism, immune mediated adrenalitis results in adrenocortical destruction. Circulating antiadrenal antibodies have found in some dogs and in one report both antiadrenal and antithyroid antibodies were in one dog (type-II polyglandular syndrome). Acute adrenal necrosis can occur in a variety of diseases but this is rare in dogs and cats.

Lymphoma affecting the adrenal glands of cats can cause hypoadrenocorticism.

Secondary hypoadrenocorticism can be caused by long-term glucocorticoid therapy (systemic and topical), mitotane, and adrenalectomy. Glucocorticoid therapy suppresses the release of ACTH, which leads to atrophy of the zona fasiculata (zone producing cortisol).

Aldosterone deficiency causes

Hyponatremia and hyperkalemia Hyponatremia results in decreased extracellular fluid and severe hypotension. Due to chronic sodium wasting in this disease, renal medullary hypertonicity is reduced which leads to an inability to maximally concentrate urine despite dehydration.

Hyperkalemia has serious depressive effects on myocardial function including bradycardia, sinoatrial arrest, atrial fibrillation, and decreased cardiac output. HYPERKALEMIA must be viewed as a potentially life threatening emergency.

Cortisol deficiency causes

Inability to mount normal response to stress Vomiting, diarrhea, anorexia and weight loss Gastrointestinal hemorrhage may occur in some cases resulting in presentation of acute hemorrhagic gastroenteritis.

Abdominal pain may be present in some dogs.

Hypoglycemia

The net effect is creation of a very hypotensive disease process. GFR is greatly reduced leading to severe pre-renal azotemia and inability to maximally concentrate urine despite severe hypotension and dehydration.

The etiology of reversible megaesophagus in this disease is not known. It occurs in dogs with or without hyperkalemia or hypercalcemia indicating that deficiency of cortisol may play a role.3

Key Therapeutic Points:

The initial goals for therapy of acute adrenal crisis include:

Reverse hypotension, correct electrolyte imbalances, treat cardiotoxicity and hypoglycemia if present.

Fluid therapy: Intravenous 0.9% NaCl is the fluid of choice. Initially, NaCl is infused at 50-60 ml/kg per hour. If hypoglycemia is present, add 50% glucose to NaCl for final concentration of 5%.

The ACTH stimulation test is then performed. Intravenous, water-soluble glucocorticoids are then administered. Prednisolone sodium succinate (4-6 mg/kg) is recommended as a bolus over 2-4 minutes and is repeated every 4-6 hours. Once the animal begins to respond, dexmethasone can be used IV at a dose of 0.25 – 0.50 mg/kg every 8-12 hours.

When diuresis begins, administer mineralocorticoids (see below). A word of caution! Overaggressive correction of hyponatremia can result in diffuse CNS disease.

Treatment of chronic typical adrenal insufficiency

Correct dehydration and hypotension with either 0.9% NaCl or lactated Ringers solution Give prednisolone/prednisone at 0.10-0.30mg/kg twice a day orally or IM if vomiting persists.

Administer mineralocorticoids:

Microcrystalline desoxycorticosterone pivalate (DOCP, Percorten-V, Ciba-Geigy Animal Health) has well studied in dogs.1,8,9 The dose is 2.2 mg/kg IM and is repeated every 20-30 days depending on electrolyte concentrations. Dogs usually stabilize at 1.56 to 1.69 mg/kg every 25 days.2

Fludrocortisone (Florinef acetate, ER Squibb and Sons), 0.01 mg/kg divided bid is also effective but seems inferior to DOCP in many cases.

Final doses are determined by following serum electrolyte levels.

Treatment of atypical hypoadrenocorticism: oral prednisone is usually effective but some dogs may eventually develop mineralocorticoid dependency.

Key Drugs, Dosages and Indications

DOCP- mineralocorticoid 1.5 – 2.2 mg/kg Q 20-30 days IM primary hypoadrenocorticism

Florinef- mineralocorticoid. glucocorticoid0.01 mg/kg Q 12-24 hours oral primary hypoadrenocorticism

Key Prognostic Points:

The animals at greatest risk for death as those with serum potassium levels above 8.0 mEq/L In most cases, long term survival (> 4 years) is expected.

Summary

You should suspect hypoadrenocorticism when:

There is unexplained weight loss, depression, or anorexia

There is chronic and unexplained GI disease including hemorrhagic gastroenteritis

Dogs or cats are ADR and you cannot find any other explanation

Signs that develop following sudden withdrawal from chronic steroid administration

Hypoglycemia is identified

References/Suggested Reading

Peterson ME, Greco DS, Orth DN: Primary hypoadrenocorticism in ten cats. J Vet Intern Med 1989;3:55-58

Kintzer PP, Peterson ME: Treatment and long-term follow-up of 205 dogs with hypoadrenocorticism. J Vet Intern Med 1997;11:43-49.

Lifton SJ, King LG, Zerbe CA: Glucocorticoid deficient hypoadrenocorticism in dogs: 18 cases (1986-1995). J Am Vet Med Assoc 1996;209:2076- 2081.

Medinger TL, Williams DA, Bruyette DS: Severe gastrointestinal tract hemorrhage in three dogs with hypoadrenocorticism. J Am Vet Med Assoc 1993;202:1869-1872.

Bartges JW, Nielson DL: Reversible megaesophagus associated with atypical primary hypoadrenocorticism in a dog. J Am Vet Med Assoc 1992;201:899-891.

Parnell NK, Powell LL, et al: Hypoadrenocorticism as the primary manifestation of lymphoma in two cats. J Am Vet Med Assoc 1999;214:1208-1211.

Graves TK, Schall WD, et al: Basal and ACTH- stimulated plasma aldosterone concentrations are normal or increased in dogs with trichuriasis- associated pseudohypoadrenocorticism. J Vet Intern Med 1994;8;287-289.

Brady Ca, Vite CH, Drobatz KJ: Sever neurologic sequelae in a dog after treatment of hypoadrenal crisis. J Am Vet Med Assoc 1999;215:22-225.

Lynn RC, Feldman EC, Nelson RW: Efficacy of microcrystalline desoxycorticosterone pivalate for treatment of hypoadrenocorticism in dogs. J Am Vet Med Assoc 1993;202:392-396.

Kaplan AJ, Peterson ME: Effects of desoxycorticosterone pivalate administration on blood pressure in dogs with primary hypoadrenocorticism. J Am Vet Med Assoc 1995;206:327-331.