You hear about Cushing’s disease occasionally in practice. Do you know what Cushing’s is or how it is treated? This blog will review Cushing’s disease basics.

Cushing’s disease (hyperadrenocorticism) is when the body is producing an excess amount of cortisol (a glucocorticoid). The adrenal glands produce this steroid hormone. There are 3 ways an animal can have Cushing’s disease:

1) Pituitary Tumor- this tumor in the pituitary gland (in the brain) is telling the adrenal glands to make more cortisol (by releasing adrenocorticotropic hormone- ACTH). Because of the tumor, the pituitary cannot stop making ACTH and thus the negative feedback is lost (see image above, courtesy of Wikipedia on negative feedback).  This causes enlargement of both adrenal glands. (This is the most common form of Cushing’s, especially in small breed dogs.)

2) Adrenal Tumor- there is a primary tumor on an adrenal gland. This tumor causes the adrenal gland to continue production of cortisol and is not related at all to the pituitary gland. (This is not as common but is seen mostly in large breed dogs)

3) Iatrogenic- chronic steroid supplementation by the owner- the owner is giving the dog steroids (such as prednisone) and causing the dog to have symptoms of Cushing’s.

Clinical Signs of Cushing’s or increased steroid hormone in the body can include:

1)  increased drinking and urinating (polyuria and polydipsia)

2) increased appetite

3) skin changes- thinning of the skin and/or calcinosis cutis (calcification in the skin), hyperpigmentation, increased incidence of pyoderma (skin infection), and symmetrical alopecia (hair loss)

4) pot-belly appearance from increased abdominal fat deposition

5) increased panting

Cushing’s animals have a higher susceptibility to infections, especially urinary tract infections. Steroids cause insulin resistance, so dogs with Cushing’s are at a higher risk for development of diabetes. Because of the effects on the adrenal glands, Cushing’s patients are sometimes hypertensive (have high blood pressure). Dogs with pituitary Cushing’s disease can sometimes show neurologic or behavioral changes if the tumor in the brain is large enough.

Diagnosis of Cushing’s:

The two most common tests for Cushing’s disease are the ACTH stimulation test and the low-dose dexamethasone test (LDDT). You do not need to know the details of the tests for the VTNE, however, remember that these are tests for Cushing’s. Additionally, the LDDT can sometimes help to differentiate pituitary vs. adrenal Cushing’s. A urine cortisol:creatinine ratio can be used as a screening test only (if it is negative, it rules out Cushing’s disease). Ultrasound to evaluate the adrenal glands can be helpful in some cases.

Treatment Options:

Patients with clinical symptoms may need treatment. Treatment depends on each individual patient and risks should be considered. Not every patient with Cushing’s is treated for the disease. This may depend on age, symptoms, and tolerance of medications. The 2 most common medical treatment options include:

1. Mitotane  (o,p’DDD)- Causes permanent destruction of the adrenal gland. Induction and maintenance therapy must be monitored by ACTH stimulation tests to avoid causing hypoadrenocorticism (Addison’s disease).

2. Trilostane – An oral steroid analogue that inhibits the production of cortisol and aldosterone. Requires similar monitoring but does not cause permanent or physical changes to the adrenal glands. Because of this, trilostane is favored by most practitioners.

Adrenalectomy (removing the adrenal gland(s) via surgery) is not commonly performed due to risk and invasiveness of the surgery. However, for a mass on the adrenal gland, this may be a more viable option.

This week, take a minute to review the physiology regarding blood flow through the heart.

Vessels of the heart:

• Vena Cava- brings de-oxygenated blood from the body to the heart and empties into the right atrium.
• Aorta- largest vessel in the body and carries oxygenated blood from the left ventricle to the body.
• Pulmonary artery- transports the de-oxygenated blood from the right ventricle to the lungs.
• Pulmonary vein- transports oxygenated blood from the lungs to the left atrium.
• Coronary arteries- branch off of the aorta near the top of the heart and carry oxygen to the cardiac muscle tissue.

There are Four Cardiac Chambers:

• Left Atrium- receives oxygenated blood from the lungs via the pulmonary vein. During contraction, blood passes from the left atrium through the mitral valve into the left ventricle.
• Left Ventricle- receives oxygenated blood from the left atrium during contraction. As the blood goes through the mitral valve and into the left ventricle, the aortic valve is closed so that the ventricle may fill. After the ventricles are full, they contract. During contraction, the mitral valve closes to prevent backflow of blood and the aortic valve opens to allow the blood to go into the aorta and out to the body.
• Right Atrium- receives de-oxygenated blood from the body via the vena cava. During contraction blood passes from the right atrium through the tricuspid valve and into the right ventricle.
• Right Ventricle- receives de-oxygenated blood from the right atrium during contraction. As the blood goes through the tricuspid valve and into the right ventricle, the pulmonary valve is closed so that the ventricle may fill. During contraction, the tricuspid valve closes to prevent backflow and the pulmonary valve opens so that blood goes into the pulmonary artery and to the lungs.

What is Vestibular Syndrome?

Vestibular syndrome describes a neurologic condition encompassing specific neurologic symptoms (see below). It can be a peripheral or a central disease and has various causes.

What are the symptoms?

Classically, a head tilt is present. There is often a nystagmus. Patients are nauseous and sometimes have a history of vomiting or not eating. In severe cases they are often non-ambulatory and have a history of falling or rolling to the side (the equilibrium is abnormal).

With peripheral disease, there are no other cranial nerve deficits (except in Horner’s syndrome when CN VII is affected) and no postural reaction deficits. If there is lack of conscious proprioception or other cranial nerve deficits are present, then it is most likely due to a central (brain) lesion. (i.e. decreased gag reflex, decreased tongue movement, decreased facial sensation) Central cases also often have mentation changes.

Peripheral vestibular disease is caused by pathology in the inner ear region. Because of the way the nerves exit from the brainstem, the facial nerve can be affected, and Horner’s syndrome can occur.

 What is the cause of this syndrome?

There are several possible causes:

1)      Idiopathic- often called “old dog vestibular”, the cause is unknown. Patients often recover from the disease with supportive/nursing care within a week.

2)      Neoplasia

3)      Hypertension- a vascular accident or blood clot to the nervous system (often referred to as a “stroke”)

4)      Trauma/inflammatory

5)      Inner ear disease/infection

6)      Drug toxicity (metronidazole)

How is it treated?

1) Patients are placed on an anti-emetic to help with nausea. Meclizine (Dramamine) or maropitant (Cerenia) are most commonly used.

2) Supportive care/nursing care are important to prevent injury.

3) Treat the underlying cause if identified and applicable. (Hypertension, ear disease, metronidazole toxicity, etc.)

Brain imaging using MRI can be helpful to look for an underlying cause so appropriate therapy can be instituted.