Hypoadrenocorticism

Hypoadrenocorticism occurs in dogs and is rare in cats and other species. Affected dogs are usually young to middle-aged, more often female, and of any breed although Bearded Collie, Great Dane, Nova Scotia Duck Tolling Retriever, Portuguese Water Dog, Rottweiler, Saint Bernard, Standard Poodle, and West Highland White Terrier breeds are at greater risk. The disease is usually due to adrenal gland pathology, most likely immune-mediated destruction of the adrenal cortex. Whereas, with HAC, the clinical signs relate to cortisol excess, the clinical signs with hypoadrenocorticism usually relate to mineralocorticoid lack in addition to cortisol lack. Therefore, affected dogs are often presented severely ill with fluid and electrolyte imbalances, although more subtle signs may have been present for days to weeks. The history may include inappetence, decreased activity, vomiting, diarrhea, weakness, and collapse. Possible physical findings are lethargy, low body weight, weakness, ECF contraction, bradycardia, intestinal hemorrhage, shock, and abdominal pain.

CBC findings

Typical findings on the CBC include mild to moderate nonregenerative anemia which may be masked by volume contraction, lack of stress lymphopenia (in an obviously ill dog) resulting in lymphocyte numbers within or above the RI, and lack of stress neutrophilia, eosinopenia, and monocytosis. Lack of lymphopenia is seen more often than absolute lymphocytosis.

Biochemical panel findings

Lack of mineralocorticoid (aldosterone) results in sodium and chloride wasting by the kidneys and potassium retention. Although a sodium to potassium ratio of <23:1 is suggestive of hypoadrenocorticism, other disorders, particularly renal and gastrointestinal disease, may cause similar electrolyte imbalances, thus the diagnosis of hypoadrenocorticism can never be based on sodium and potassium concentrations and the sodium to potassium ratio alone. Depending on the magnitude of the hyperkalemia, cardiac conduction disturbances can occur and be fatal. Water is lost with the sodium and chloride and dogs may become very hypovolemic. Metabolic acidosis with a high anion gap due to lactic acid accumulation may be seen. Impaired hydrogen ion secretion due to aldosterone lack aggravates the metabolic acidosis. Hypovolemia often leads to prerenal azotemia and renal acid accumulation, which also contributes to the metabolic acidosis.

About 30% of dogs with hypoadrenocorticism are hypercalcemic, possibly due to the lack of cortisol which normally promotes calcium excretion by the kidney. About 20% of affected dogs are hypoglycemic due to the lack of glucocorticoid. Ill/stressed dogs are often hyperglycemic, so normoglycemia may also be a significant finding under these circumstances. Intestinal bleeding is probably caused by both a glucocorticoid lack and the fluid and electrolyte abnormalities that result from mineralocorticoid lack. Intestinal bleeding increases ammonia availability for urea synthesis by the liver, and increased serum urea without the same magnitude of creatinine elevation can be explained by this mechanism in some cases. Less than 20% of dogs with hypoadrenocorticism are hypoalbuminemic although it is not known if this relates to hepatic dysfunction, intestinal losses from enteropathy, hemorrhage, or another unidentified reason.

Urinalysis findings

Urine may be unconcentrated (specific gravity <1.030) despite the prerenal cause of the azotemia. Chronic hyponatremia leads to a loss of the cortico-medullary concentration gradient in the kidneys and an inability to reabsorb water in the collecting ducts. These dogs may have isosthenuria and azotemia typical of primary renal disease, and differentiation between renal disease and hypoadrenocorticism can be difficult under these circumstances. Findings such as lack of a stress lymphopenia, lack of a stress leukogram, hypercalcemia, and hypoglycemia may help point the diagnosis towards hypoadrenocorticism rather than renal failure.

Classification of hypoadrenocorticism

Although primary hypoadrenocorticism (mineralocorticoid and glucocorticoid lack from bilateral adrenocortical destruction) is much more common, secondary hypoadrenocorticism (glucocorticoid lack only, from decreased pituitary release of ACTH) also occurs. Dogs with secondary hypoadrenocorticism have historical, clinical, and laboratory findings consistent with cortisol lack but do not experience fluid and electrolyte disturbances, as mineralocorticoid levels are unaffected. Lymphocytosis or lack of a stress leukogram may be seen on the CBC, and hypoglycemia on the biochemical panel.

There is also a group of hypoadrenal dogs that at the time of initial diagnosis have normal electrolyte concentrations but do not have secondary hypoadrenocorticism. This is called “atypical” or glucocorticoid deficient hypoadrenocorticism. Potential reasons for normal electrolyte concentrations in these dogs include: selective destruction of the ZF and ZR, early stage disease in which destruction of the ZG is not complete, increased salt intake to compensate for sodium loss through the kidneys, and concurrent illnesses that may mask the typical electrolyte abnormalities. A small percentage of these dogs may go on to develop mineralocorticoid deficiency, with corresponding electrolyte abnormalities, weeks to months later. Therefore the absence of hyponatremia and hyperkalemia in a dog with suspected hypoadrenocorticism should not exclude the diagnosis, as both primary and secondary hypoadrenocorticism can be associated with only glucocorticoid lack. Conversely, there are potential causes of hyperkalemia and hyponatremia other than hypoadrenocorticism, such as renal or GI disease; therefore a presumptive diagnosis must be confirmed with an ACTH stimulation test.

Confirmatory testing using ACTH stimulation test

The ACTH stimulation test is performed to confirm the diagnosis of hypoadrenocorticism. The baseline cortisol is usually below the lower limit of detection or at the low end of the RI, and there is a lack of response to ACTH. The baseline cortisol, in itself, yields valuable information since a very ill, stressed dog should not have a low normal or low resting cortisol. Some dogs may require therapeutic glucocorticoid administration before or during the test and in these instances dexamethasone is preferred as it does not affect the test results as compared to some other glucocorticoids.

With secondary hypoadrenocorticism, the adrenal glands do not respond to ACTH stimulation because the chronic lack of ACTH from the pituitary gland leads to adrenal cortical atrophy. Plasma ACTH is expected to be high with primary hypoadrenocorticism and low with secondary hypoadrenocorticism.