Clinical Presentation and Diagnosis
Owners sometimes describe a “waxing and waning” illness. Anorexia (total or partial), lethargy, and weight loss are the most common recognized clinical signs, followed by intermittent gastrointestinal signs, and dehydration.
If the disease remains unrecognized, the signs typically progressively worsen and some dogs eventually present in an acute addisonian crisis. These dogs can exhibit moderate to severe shock. A shock situation accompanied by an inappropriate bradycardia can be an important clue in the suspicion of the disease. Other possible clinical signs include polyuria/polydipsia, abdominal pain, melena and occasionally hematemesis (Lathan 2015; Scott-Moncrieff 2015; Van Lanen and Sande 2014). Important differentials include acute kidney injury, hepatic and gastrointestinal disease.Most dogs present with hyperkalemia and hyponatremia with hypochloremia also commonly observed. Besides these electrolyte abnormalities, azotemia, acidosis, and hypoalbuminemia are frequently observed. Less commonly, a mild hypercalcemia, a mild increase in liver enzymes or hypoglycemia can be seen. Although the biochemical hallmark of primary Addison's disease is hyperkalemia, this can be observed with several other diseases such as renal or gastrointestinal disease and pleural effusion (chylothorax). Atypical cases do not present with the typical electrolyte imbalances and are therefore more difficult to recognize.
Lymphocytosis and eosinophilia can sometimes be observed. In a stress situation, these findings should alert the clinician to the possibility of hypoadrenocorticism. Indeed, lymphopenia and eosinopenia are expected in a sick animal and even finding normal values for eosinophils or lymphocytes in a sick animal can be a hint for the diagnosis of hypoadrenocorticism. Hypoadrenocorticism is also frequently associated with mild nonregenerative normocytic normochromic anemia.
However, following gastrointestinal hemorrhage, a regenerative anemia may be present.Urine specific gravity is often used in clinics to help differentiate prerenal from renal azotemia. However, in cases of hypoadrenocorticism the patient cannot always concentrate its urine even if dehydrated because of the hypoaldosteronism and natriuresis.
Hyperkalemia can cause typical changes in an ECG such as spiked T-waves, shortened Q-T interval, prolongation of the QRS complex, reduction or absence of P-waves and bradycardia. With severe hyperkalemia, ventricular asystole or ventricular fibrillation may also be observed.
Microcardia, small cranial pulmonary artery and caudal vena cava, and occasional mega-esophagus can be observed on survey radiographs. Adrenal ultrasonography can reveal a reduction of size of these glands.
Confirmation of the Diagnosis
No clinical or biochemical abnormalities are pathognomonic for Addison's disease. Basal serum cortisol can be useful as a screening test for hypoadrenocorticism using a cut-off value of≤2μg∕dl. Hypoadrenocorticism is unlikely if basal cortisol is > 2μg∕dl (Bovens et al. 2014). Diagnosis must be confirmed with an ACTH stimulation test. Several protocols have been described, but most often, synthetic ACTH is administered IV and blood samples for cortisol measurements are taken at T0 and after 1 hour. An inadequate increase in cortisol concentration following ACTH administration confirms the diagnosis.
Most glucocorticoid preparations, except dexamethasone, cross-react with most commonly used commercial cortisol assays and cause falsely increased cortisol values. Dexamethasone sodium phosphate can therefore be used as emergency treatment in a suspected acute hypoadrenocorticoid crisis, while the ACTH stimulation test is being performed.
Endogenous ACTH or aldosterone (pre and post exogenous ACTH administration) serum concentrations can be measured to distinguish primary and atypical cases from secondary hypoadrenocorticism. Endogenous ACTH is highly labile and strict sample handling precautions must be followed to prevent in vitro degradation following sample collection (use apportioning or dry ice). Until recently, it was assumed that normal aldosterone concentrations were essential to maintain normal electrolyte values (Baumstark et al. 2014b; Scott-Moncrieff 2015). However, in a recent study describing aldosterone concentration in dogs with hypoadrenocorticism, several dogs with atypical primary HA, also had very low aldosterone concentrations (Baumstark et al. 2014b). These findings suggest that some other mechanism must be involved to maintain normal sodium and potassium serum concentrations in dogs with atypical hypoadrenocorticism.