What's new with hypoadrenocorticism in dogs (Proceedings)


What's new with hypoadrenocorticism in dogs (Proceedings)

Apr 01, 2010

What we know

Hypoadrenocorticism is an uncommon endocrinopathy, which may be difficult to recognize due to its varied clinical presentation. It is most frequently seen in young to middle-aged female dogs. A number of breeds have a predisposition to develop this disease, including poodles, great Danes, bearded collies, Nova Scotia duck tolling retrievers, west highland white terriers, and basset hounds. Dogs with hypoadrenocorticism present different ways with chronic non-specific illness or in a severe adrenocortical crisis.

Primary hypoadrenocorticism (Addison's disease) is caused by destruction of the adrenal cortex. It is thought to be an immune-mediated process resulting in inadequate glucocorticoid and mineralocorticoid secretion. In dogs with atypical primary hypoadrenocorticism, serum electrolytes are normal but occasionally have hypoglycemia as their only abnormality. Primary hypoadrenocorticism can be iatrogenic (caused by over treatment of hyperadrenocorticism) and permanent. Secondary hypoadrenocorticism results from deficient pituitary ACTH secretion causing inadequate glucocorticoid production. Abrupt withdrawal of long-term and or high-dose glucocorticoids can cause secondary hypoadrenocorticism, as well as, idiopathic ACTH deficiency, tumors of the pituitary gland or hypothalamus.

The zona fasciculate and zona reticularis divide the inner region of the adrenal gland and are responsible for the production of glucocorticoids. The most common clinical signs of glucocorticoid deficiency are anorexia, lethargy, vomiting, diarrhea, weakness, and weight loss. Less common signs are intermittent and can be associated with stressful events such as grooming, boarding or showing. Physical examinations are usually nonspecific. Clinicopathological abnormalities include normocytic, normochromic, non-regenerative anemia, lack of a stress leukogram, hypoalbuminemia, Hypocholesterolemia, hypoglycemia and hyponatremia. Remember to perform a fecal examination in all cases suspected of hypothyroidism because gastrointestinal parasites can cause the same clinical signs and electrolyte disturbances.

The outer zone of the adrenal gland is the zona glomerulosa, which is responsible for the production and secretion of the mineralocorticoid aldosterone. Mineralocorticoids are released in response to hypovolemia triggering the renin-angiotensin system and hyperkalemia directly increasing aldosterone synthesis. The most common signs of mineralocorticoid deficiency are weakness, polyuria/polydipsia, lethargy and or collapse. These are varied and result from hypovolemia, hypotension, hyponatremia and hyperkalemia. A sodium: potassium (NA: K) ratio of 27 is consistent with mineralocorticoid deficiency, although many diseases can alter this ratio.

Dogs with concurrent glucocorticoid and mineralocorticoid deficiency can have a combination of any of the previously mentioned clinical signs. Radiographs may reveal hypovolemia, microcardia, hypoperfused lung fields and microhepatica. Ultrasound examination usually reveals bilateral atrophy of the adrenal glands. ECG evaluations may document hyperkalemia-related rhythms such as atrial standstill, etc.

Although other methods have been proposed for diagnosing of hypoadrenocorticism, the gold standard is the ACTH stimulation test. The absence of an appropriate response is definitively diagnostic for hypoadrenocorticism. The diagnosis of atypical hypoadrenocorticism is also established by documenting subnormal cortisol response to ACTH.

The treatment for an acute crisis is restoring intravascular volume, alleviating hyperkalemia and hyponatremia, replacing glucocorticoids, treatment of hyperkalemic cardiac rhythms and correction of the metabolic acidosis. Volume is more important than type of fluid however 0.9%NaCl is the fluid of choice. This usually alleviates the severe electrolyte cardiac disturbances rapidly. If it does not cardioprotective calcium gluconate should be administered. Glucocorticoids should be administered after an ACTH stimulation test is performed however administration of dexamethasone is rapid and will not interfere with the cortisol assay whereas other glucocorticoids will. Hydrocortisone is the ideal replacement glucocorticoid because it has glucocorticoid and mineralocorticoid activity. High-dose glucocorticoids are not recommended as they may cause or exacerbate gastrointestinal hemorrhage. Oral supplementation can be given as tolerated. Initial aggressive therapy followed by continued monitoring and supportive care is paramount for a favorable outcome.

Long-term management of hypoadrenocorticism is accomplished by replacing the insufficient hormones. There are two options for mineralocorticoid therapy, fludrocortisone and desoxycorticosterone pivalate (DOCP). Fludrocortisone is the most common mineralocorticoid replacement and given orally, twice daily. Serum electrolytes should be monitored every one to two weeks and dose adjustments made accordingly. After stabilization dogs should be evaluated every three to four months. With time and increasing age, many dogs need an increase in the dosage. Some dogs (50%) require supplemental glucocorticoid treatment in addition. DOCP, a repositol form of mineralocorticoid that has a long duration of action and is slowly released over three to four weeks. Serum electrolytes and BUN should be monitored at 14 and 25 days for the first two to three months until the correct dose and frequency are determined. Electrolyte abnormalities trigger dose changes (increase with hyperkalemia/hyponatremia and decrease with hypokalemia/hypernatremia). On average DOCP is administered every 25 days. The owners can administer at home. This is generally less expensive than fludrocortisone. Maintenance glucocorticoid administration is needed indefinitely with increases surrounding stressful situations as DOCP has negligible glucocorticoid activity. With appropriate therapy and owner compliance, the prognosis is favorable.