Cushing's disease: something new, something blue (Proceedings)
Hyperadrenocorticism remains one of the most common endocrine disorders diagnosed in the geriatric dog population. It is a disease that is seen in almost every veterinary practice. Unfortunately, the disease tends to be frustrating to deal with, a definitive diagnosis is at times elusive and therapy can have major adverse side effects. Knowing how to diagnose, what problems hyperadrenocorticism can cause in a patient that justify aggressive therapy, and the advantages and disadvantages of the various treatment modalities can be helpful in determining an appropriate diagnostic and therapeutic plan.
The most common clinical signs of Cushing's disease are quite familiar to practicing veterinarians. Commonly PU/PD, pot-bellied appearance, lethargy, polyphagia, obesity, and panting. In addition, many dermatologic manifestations are seen including alopecia (of the trunk), comedones, thin skin, calcinosis cutis, bruising, hyperpigmentation, pyoderma and seborrhea. Less commonly identified signs include muscle weakness or pseudo-myotonia ("frozen" muscles), polyneuropathies, or rupture of the cranial cruciate ligament. Hypertension is relatively common (50% or greater) though with the lack of blood pressure monitoring devices in many practices it often goes undiagnosed. Pulmonary thromboembolism, recurrent (often asymptomatic) urinary tract infections, proteinuria, pancreatitis, pulmonary mineralization, and calcium oxalate urolithiasis are also often frequently seen with Cushing's disease. Recently it has been noted that many dogs with hyperadrenocortism are hypoxic, whether or not they have mineralization of the lung parenchyma. This can be a serious consequence, leading to distress as well as excess strain on the right side of the heart. Some of the clinical problems caused by Cushing's disease are more bothersome than dangerous. Other clinical problems are life threatening such as thromboembolism or pancreatitis. Still other clinical problems can aggravate other disorders that the patient may have, such as is the case if hypertension is present in a dog with underlying heart disease. This is not an uncommon scenario since older dogs tend to have Cushing's as well as valvular heart disease. Hypertension in a dog with valvular problems can be a factor that leads to more rapid progression of the heart problem as well as difficulties in treating heart failure if it occurs.Diagnosis
One of the most frustrating parts of Cushing's disease is trying to establish a definitive diagnosis. Ideally of course clinical signs should be consistent with hyperadrenocorticism. Basically testing is still divided into screening tests and test to differentiate between pituitary dependent hyperadrenocorticism (PDH) and adrenal tumors (AT). There are differences between labs, so it is advisable to contact them if there are any questions regarding the outcome of testing.
A random cortisol level has no diagnostic value in regard to the diagnosis or exclusion of Cushing's disease. The simplest screening test is a urine cortisol to urine creatinine ratio. False positives occur frequently, however false negatives are rare. As such it is a good test to rule out Cushing's. Even the stress of a visit to the veterinarian will elevate the values and as such it is advisable to have the owner collect the urine prior to presentation at the clinic. Because there are so many false positives, a follow-up test such as a low dose dexamethasone suppression test (LDDS) or ACTH stimulation test should be run. These two tests have advantages and disadvantages. The LDDS has some false positives but few false negatives. It can also lead to differentiating between PDH and AT when 4 and 8-hour samples are taken, one of the reasons it is my preferred screening test. If the cortisol levels drop at 4 and escape to above normal range at 8 hours PDH is present. The ACTH stimulation test has few false positives, but false negatives do occur, especially with adrenal tumors. The combined ACTH stimulation /LDDS test is generally not recommended.
Differentiation tests also have their drawbacks. Not all dogs with PDH will suppress on a high dose dexamethasone suppression test. An endogenous ACTH level is a very good test, however the sample needs to be meticulously handled (contact your lab) which often makes it difficult to run. Abdominal ultrasound can be helpful to rule out tumors as well. At times it is not possible to completely rule out an adrenal tumor.