Naturally occurring hyperadrenocorticism (HAC) is an endocrine disorder resulting from the excess production of cortisol or
other adrenal hormones by the adrenal cortex. The clinical syndrome was first documented in people by Dr. Harvey Cushing in
1932 and is also known as Cushing's syndrome. Hyperadrenocorticism in dogs is one of the most common endocrinopathies in
small animal practice, and it is also one of the most complicated to diagnose, treat and monitor clinically. Complications
can arise from the effects of the disease on many systems, or from therapy. Some of the major complications include hypertension,
bacterial infections, urinary calculi, congestive heart failure, pancreatitis, biliary disease, diabetes mellitus, thromboembolic
disease, and nervous system signs. This discussion will focus on hypercoagulability, biliary changes, hypertension, and neurologic
Hypercoagulability and Thromboembolism
Thromboembolic complications including pulmonary thromboembolism (PTE), resulting from hypercoagulability in dogs with HAC
increase mortality rate, and are therefore one of the most serious complications of the disease. Studies in people and in
dogs have documented many changes to the hemostatic system, mainly changes that contribute to hypercoagulability. In one study
in dogs levels of procoagulant factors II, V, VII, IX, X, XII and fibrinogen were significantly increased in dogs with HAC.
In addition, antithrombin was decreased and thrombin-antithrombin complexes were increased. Abnormalities in Von Willebrand's
Factor and platelet activity have been noted in other studies. Recently investigators have used thromboelastography to document
a global tendency to hypercoagulability, but failed to detect a statistically significant difference compared to control dogs.
Signs associated with thromboembolism can relate to any organ system. The most common signs are associated with the respiratory
and nervous systems. Pulmonary thromboembolism is considered to be the most common site. Definitive diagnosis can be difficult,
but presumptive diagnosis can be made through clinical signs, testing and response to therapy. Routine testing (CBC, chemistry,
urinalysis) is non specific but abnormalities that have been noted include anemia, elevated white cells, ALP, ALT, BUN, and
creatinine. Decreases in sodium, potassium and albumin have also been noted. Thoracic radiographs may reveal pleural effusion,
loss of detail, alveolar infiltrates, cardiomegaly and enlargement of the main pulmonary artery associated with PTE. Thoracic
radiographs may also be essentially normal. Echocardiography can also be used to gain evidence for thromboembolism, but results
in dogs are variable. Arterial blood gas results are consistent with hypoxemia, mainly attributed to a ventilation-perfusion
mismatch. Tests that have been used to confirm thromboembolic disease in dogs include pulmonary angiography, ventilation-perfusion
scans, and MRI. Tests used to attempt to confirm a thrombotic tendency include measurement of the procoagulant and anticoagulant
factors, measurement of d- dimers, thrombin-antithrombin complexes, and thromboelastography.
The highest risk for thromboembolism is around the time of surgery, for those dogs where surgery is indicated. The goals of
therapy are to reverse the prothrombotic state and to alleviate the hemodynamic and pulmonary consequences that are life-threatening.
There is little scientific evidence regarding anticoagulant therapy in regards to efficacy in preventing thrombosis, and duration
that therapy is necessary for a particular patient considered at risk for thrombosis. Options include antiplatelet therapy
(example ultra low dose aspirin) and anticoagulant therapy (example low molecular weight heparin). For thromboembolic disease
that has already occurred there is also the potential for use of fibrinolytic agents.
In recent years the problem of biliary mucoceles in dogs has been described and analyzed, and has become the most prevalent
gall bladder disease in dogs. It is associated with breed predispositions (e.g. Shetland Sheepdogs), hyerlipidemia/hypercholesterolemia
due to a variety of underlying diseases and feeding a high fat diet.Dogs with hyperadrenocorticism appear to be more prone
to developing gall bladder mucoceles as a complication of the metabolic alterations that occur with HAC. In one study 23%
of dogs with hyperadrenocorticism (PDH) were noted to have biliary mucoceles.