A deficiency in adrenocortical hormones is seen most commonly in young to middle-aged dogs and occasionally in horses. The disease may be familial in Standard Poodles, West Highland White Terriers, Great Danes, Bearded Collies, Portuguese Water Dogs, and a variety of other breeds. The cause of primary adrenocortical failure usually is unknown, although most cases probably result from an autoimmune process. Other causes include destruction of the adrenal gland by granulomatous disease, metastatic tumor, hemorrhage, infarction, adrenolytic agents (mitotane), or adrenal enzyme inhibitors (trilostane).
Many of the functional disturbances of chronic adrenal insufficiency are not highly specific; they include recurrent episodes of gastroenteritis, a slowly progressive loss of body condition, and failure to respond appropriately to stress. Although hypoadrenocorticism is seen in dogs of any breed, sex, or age, idiopathic adrenocortical insufficiency is most common in young female adult dogs. This may be related to its suspected immune-mediated pathogenesis.
A reduction in secretion of aldosterone, the principal mineralocorticoid, results in marked alterations of serum levels of potassium, sodium, and chloride. Potassium excretion by the kidneys is reduced and results in a progressive increase in serum potassium levels. Hyponatremia and hypochloremia result from renal tubular loss. Severe hyperkalemia may result in bradycardia and an irregular heart rate with changes in the ECG. Some dogs develop a pronounced bradycardia (heart rate ≤50 bpm) that predisposes to weakness or circulatory collapse after minimal exertion.
Although the development of clinical signs is often unnoticed, acute circulatory collapse and evidence of renal failure frequently occur. A progressive decrease in blood volume contributes to hypotension, weakness, and microcardia. Increased excretion of water by the kidneys, because of decreased reabsorption of sodium and chloride, results in progressive dehydration and hemoconcentration. Emesis, diarrhea, and anorexia are common and contribute to the animal’s deterioration. Weight loss is frequently severe. Similar clinical signs are seen in cats with hypoadrenocorticism.
Decreased production of glucocorticoids results in several characteristic functional disturbances. Decreased gluconeogenesis and increased sensitivity to insulin contribute to the development of moderate hypoglycemia. In some dogs, hyperpigmentation of the skin is seen because of the lack of negative feedback on the pituitary gland and increased ACTH release. Atypical Addison disease has been reported in dogs and is associated with hypocortisolemia with normal electrolytes. Clinical signs are similar to those seen in dogs with both glucocorticoid and mineralocorticoid insufficiency.
The most common abnormality in dogs is bilateral idiopathic adrenocortical atrophy, in which all layers of the cortex are markedly reduced in thickness. The adrenal cortex is reduced to one-tenth or less of its normal thickness and consists primarily of the adrenal capsule. The adrenal medulla is relatively more prominent and, with the capsule, makes up the bulk of the remaining adrenal glands.
All three zones of the adrenal cortex are involved, including the zona glomerulosa, which is not under ACTH control; however, no obvious pituitary lesions have been seen in dogs with idiopathic adrenal cortical atrophy.
A destructive pituitary lesion that decreases ACTH secretion is characterized by severe atrophy of the inner two cortical zones of the adrenal gland; the zona glomerulosa remains intact.
A presumptive diagnosis is based on the history and supportive (although not specific) laboratory abnormalities, including hyponatremia, hyperkalemia, a sodium:potassium ratio of <25:1, azotemia, mild acidosis, and a normocytic, normochromic anemia. Severe GI blood loss has also been reported. Occasionally, mild hypoglycemia is present. The hyperkalemia results in ECG changes: an elevation (spiking) of the T wave, a flattening or absence of the P wave, a prolonged PR interval, and a widening of the QRS complex. Ventricular fibrillation or asystole may occur with potassium levels >11 mEq/L.
Differential diagnoses include primary GI disease (especially whipworm infection), renal failure, acute pancreatitis, and toxin ingestion. For definitive diagnosis, evaluation of adrenal function is required. After obtaining a baseline blood sample, ACTH (gel or synthetic) is administered. Gel preparations are administered IM, and a second blood sample is obtained 2 hr later. Synthetic preparations are administered IM or IV with a second blood sample 1 hr later. Baseline (resting) cortisol concentrations >2.5 mcg/dL effectively exclude the diagnosis of hypoadrenocorticism, whereas values <2.5 mcg/dL require the use of ACTH stimulation testing to confirm the diagnosis. Affected dogs have low baseline cortisol levels, and there is little response to ACTH administration in classic and atypical cases. This test can be completed in most animals before replacement hormone therapy is started.
An adrenal crisis is an acute medical emergency. An IV catheter should be inserted, and an infusion of 0.9% saline begun. If the dog is hypoglycemic, the saline should include 2.5%–5% dextrose. The hypovolemia is corrected rapidly by administering 0.9% saline (60–70 mL/kg over the first 1–2 hr). Urine output should be assessed to determine whether the dog is becoming anuric. Fluids should be continued, at a rate appropriate to match ongoing losses, until the clinical signs and laboratory abnormalities have resolved.
Prednisolone sodium succinate (22–30 mg/kg) or dexamethasone sodium phosphate (0.2–1 mg/kg) may be used in the initial management of shock. Dexamethasone will not interfere with cortisol measurements during the ACTH stimulation test. Prednisolone or prednisone should be given at 1 mg/kg, bid, for the first few days of therapy and then at 0.25–0.5 mg/kg/day. Mineralocorticoid replacement therapy (see below) is also begun to help with electrolyte imbalances and hypovolemia. Electrolytes, renal function, and glucose should be monitored regularly to assess response to therapy.
In cases of severe, nonresponsive hyperkalemia, 10% glucose in 0.9% saline can be given for 30–60 min to increase potassium movement into the cells. Regular insulin (0.25–1 U/kg) administered IM will enhance glucose and potassium uptake, but 10% glucose (20 mL per unit of insulin) should be administered IV concurrently to avoid hypoglycemia.
For longterm maintenance therapy, the mineralocorticoid desoxycorticosterone pivalate (DOCP) is administered at 2.2 mg/kg, IM or SC, every 25–28 days. Electrolytes should be measured at 3 and 4 wk after the first few injections to determine the duration of action. Alternatively, fludrocortisone acetate is administered PO at 10–30 mcg/kg/day. Serum electrolytes should be monitored weekly until the proper dose is determined. Some dogs (especially dogs on DOCP) also require daily oral glucocorticoid therapy to adequately control clinical signs. Replacement doses of prednisone (0.2–0.4 mg/kg/day) are required in ~50% of dogs. Additional glucocorticoid supplementation may be required (2–5 times maintenance) during times of illness or stress. Dogs with atypical Addison disease require only replacement doses of prednisone, although it is recommended that electrolytes be monitored every 3 mo for the first year after diagnosis. Dogs with chronic hypoadrenocorticism should be reexamined every 3–6 mo.
Treatment of horses with hypoadrenocorticism is similar—aggressive replacement of fluids, steroids, and glucose if needed in an adrenal crisis. Supportive therapy and rest are indicated in cases of chronic Addison disease.