Hypoadrenocorticism (Addisons disease) remains challenging to recognize due to the variety of clinical signs that mimic other diseases.
Hypoadrenocorticism (Addison's disease) remains challenging to recognize due to the variety of clinical signs that mimic other diseases. Without timely recognition, life-threatening fluid and electrolyte changes cause acute renal failure, cardiac arrhythmias, hypovolemia, and death. Prompt diagnosis and treatment can avoid life-threatening illness.
Adrenocortical insufficiency in dogs most often results from autoimmune destruction or atrophy of the adrenal glands bilaterally. Less common causes include infarction, surgical destruction; fungal infection, prolonged glucocorticoid therapy, and neoplasia. Cats rarely develop hypoadrenocorticism, and are more likely than dogs to have adrenal dysfunction for reasons other than autoimmune destruction.
Characteristic clinicopathologic abnormalities occur due to absence of glucocorticoid (cortisol) and mineralocorticoid (aldosterone). Absence of cortisol results impairs gluconeogenesis and glycogenolysis causing hypoglycemia, impaired free water excretion adding to hyponatremia through dilution, and decreased vitality as evidenced by poor appetite, lethargy, and impaired mentation. Loss of mineralocorticoid causes sodium and chloride ion wasting (isotonic fluid loss) and potassium ion retention. Ongoing losses of isotonic (sodium-containing) fluid cause lethargy, polyuria, compensatory polydipsia, hypotension, impaired cardiac output, poor renal perfusion, and hypovolemic shock. Hyperkalemia causes muscle weakness and cardiac arrhythmia. Severity of symptoms increases as the disease progresses. Glucocorticoid deficiency can occur without mineralocorticoid deficiency from an adrenal gland disorder (atypical Addison's) or from pituitary dysfunction causing absence of adrenocorticotropic hormone (ACTH) release (secondary Addison's).
Dogs with idiopathic, autoimmune, or atrophic hypoadrenocorticism are typically young to middle aged. Any breed can be affected, and mixed breed dogs are commonly identified with this disease. Labrador retrievers, Rottweiler, German shepherd dogs, Doberman pinschers, Poodles (both standard and miniature) and golden retrievers have all been commonly identified in retrospective case series. Females are more commonly affected than males. Cats rarely get hypoadrenocorticism, and tend to be older at the time of diagnosis. Older dogs, and cats, are more likely to have hypoadrenocorticism from a cause other than immune-mediated gland destruction.
Clinical signs can be separated into those caused by glucocorticoid versus mineralocorticoid deficiency. Definitive diagnosis commonly follows one or more episodes of hospitalization for nonspecific gastroenteritis that responds to intravenous fluid therapy. When the patient is discharged, the patient relapses. Physical examination findings include poor body condition, mental dullness, dehydration, bradycardia, poor peripheral pulse quality, and cardiac arrhythmia. Addisonian crisis is characterized by collapse, severe mental dullness or stupor, severe dehydration, and hypovolemic shock. Most diseases causing hypovolemia result in tachycardia, but in the Addisonian, bradycardia occurs as a result of hyperkalemia.
Complete blood count abnormalities include absence of stress leukogram due to lack of glucocorticoid response in stress. Eosinophilia occurs in 20-25% of cases. The classic electrolyte pattern of hypoadrenocorticism is hyponatremia with concurrent hyperkalemia (sodium: potassium ratio <27). Hypochloremia occurs with hyponatremia. Hyponatremia and hyperkalemia occur with other disease processes, including excessive fluid loss (chylothorax, ascites, severe whipworm infestation), or acute renal failure. Hypercalcemia, azotemia, hypoglycemia, and hypochloremia can occur. Blood gas reveals metabolic acidosis which is typically associated with an increased anion gap. Urinalysis shows isosthenuria in the face of dehydration, as a result of intrinsic renal failure, or from medullary washout. Thoracic radiographs commonly show microcardia. Electrocardiogram (EKG) findings show evidence of hyperkalemia - induced arrhythmia (increased T wave amplitude, short and flattened P wave, bradycardia, heart block, atrial standstill, widened QRS complexes, sine wave QRS pattern, and ventricular asystole or fibrillation).
ACTH stimulation testing definitively identifies cortisol deficiency; however a single subnormal resting cortisol level greater than 2 ug/dl (> 60 mmol/L) can be used to rule out hypoadrenocorticism. ACTH stimulation should be conducted in animals with resting cortisol values < 2 ug/dl. Cortisol levels < 2ug/dl (< 60 mmol/L) on the post-ACTH sample are consistent with hypoadrenocorticism. Aldosterone does not commonly need to be measured for clinical diagnosis since mineralocorticoid deficiency is evidenced by hyponatremia with hyperkalemia. If atypical or secondary Addison's disease is present, electrolytes can be normal, and the disease is diagnosed on the basis of abnormal clinical signs and ACTH stimulation alone. Measurement of ACTH level in the patient with glucocorticoid deficiency only will help to identify pituitary dysfunction (secondary Addison's) from adrenal dysfunction; since ACTH should be maximally stimulated if the pituitary gland is functioning normally.
Treatments to address hypovolemia, hypotension, dehydration, and hyperkalemia are indicated for initial therapy. Goals of fluid therapy include volume resuscitation, rehydration, and correction of hyponatremia and hypochloremia. Isotonic sodium-based, electrolyte solution, preferably 0.9% sodium chloride (NaCl), is indicated for intravenous fluid therapy. Balanced electrolyte solutions are alternatives only in the event that 0.9% NaCl is not available. 0.9%NaCl is the preferred fluid choice due to ongoing wasting of sodium and chloride in the renal tubules in the absence of aldosterone. Fluid dose should be calculated to include maintenance fluid needs, dehydration replacement, and contemporary losses from vomiting or diarrhea. Rapid elevation of sodium with chronic hyponatremia can result in cerebral myelinosis and neurologic dysfunction. Neurologic dysfunction usually occurs 2-3 days after overzealous sodium correction. To avoid neurologic dysfunction, serum sodium should not increase more than 8-12mEq/day.
Serum potassium levels > 7.0 mmol/l can cause progressive cardiac dysfunction, and may necessitate treatment strategies to protect the myocardium and rapidly lower serum phosphorous. Choice of therapy should be based upon the severity of hyperkalemia and arrhythmia. Treatments include calcium gluconate, regular insulin and dextrose, and sodium bicarbonate. Usually, hyperkalemia treatments do not need to be repeated once initial therapy has been administered and intravenous fluid therapy initiated.
Glucocorticoid therapy may be instituted with a rapid-acting product administered intravenously, such as prednisolone sodium succinate at 5-10mg/kg, or dexamethasone sodium phosphate at 0.25-0.50 mg/kg. Prednisone-type drugs interfere with ACTH stimulation since the cortisol assay also detects prednisolone. After the initial therapy, oral prednisone at 0.5 – 1.0 mg/kg/day may be administered. If oral medications are not tolerated initially, dexamethasone may be administered subcutaneously at 0.05 to 0.1mg/kg/day. Chronic glucocorticoid replacement with prednisone should be administered at 0.25mg/kg/day, with dose increase to coincide with stressful events as needed. Glucocorticoid therapy should be adjusted based upon clinical signs of GI upset, lethargy, and weight loss. Polyuria and polydipsia might indicate excessive glucocorticoid administration; however also occurs with mineralocorticoid deficiency. Most patients need maintenance glucocorticoid therapy on a daily basis.
Mineralocorticoid therapy is recommended as soon as administration is practical. Fludrocortisone acetate may be administered at 0.01mg/kg orally twice daily if the patient is not vomiting. Following initial therapy, long-term treatment may be administered at 0.02 mg/kg orally once daily, and increased as needed based upon serum sodium and chloride administration. Alternatively, desoxycortisone pivilate (DOCP) is a slowly absorbed mineralocorticoid administered subcutaneously or intramuscularly at 21-28 day intervals. The dose for DOCP is 2-3 mg/kg per treatment. Mineralocorticoid dose should be adjusted to maintain normal sodium and potassium.
When azotemia and anorexia have resolved, intravenous fluids can be discontinued by tapering dose over a 24 to 48-hour period. The client should be instructed at the time of discharge to monitor for signs of mineralocorticoid deficiency (polyuria, polydipsia, weakness) and of glucocorticoid deficiency (anorexia, vomiting, diarrhea, shaking, weight loss). In stable dogs with hypoadrenocorticism, recheck evaluations should be scheduled three to four times a year to monitor for electrolyte changes. Having a ready supply of medication is imperative.
Long-term prognosis depends upon owner compliance with recommended therapy. With a compliant, observant owner who has been appropriately educated, prognosis can be good to excellent. Treatment is life-long. Renal failure complicates management of hypoadrenocorticism. Episodes of dehydration should be avoided to limit the risk of renal tubular damage and loss. Cost of ongoing therapy is significant, and should be discussed with the owner following stabilization of any life-threatening emergency related to hypoadrenocorticism.
Clinical Signs of Glucocorticoid Deficiency Clinical Signs of Mineralocorticoid Deficiency Weight loss Polyuria/polydipsia Lethargy Hypovolemia/hypovolemmic shock Vomiting Cardiac arrhythmia Diarrhea (often large bowel, herorrhagic) Bradycardia (inappropriate if hypovolemic) Impaired mentation Dehydration Anorexia Mental depression Weakness Nausea Shaking or trembling Hypotension Muscle weakness
Drug Mechanism Dose Onset Duration Calcium gluconate 10% Stabilizes myocardium and cardiac conduction 0.5-1.5 ml/kg IV slowly 1-3 min 30-50 min Sodium bicarbonate K+ redistributes from to the intracellular space 1 mEq/kg IV over 2 min 5-10 min 1-2 hrs Regular insulin plus 50% dextrose Redistribution of K+ to the intracellular space Regular insulin: 0.2 units/kg IV; Dextrose: 2 g/unit insulin IV and 5% dextrose in IV fluid for 6 hours 30 min 4-6 hrs