Has your dog recently been diagnosed with Cushing’s Disease? Has your dog’s veterinarian talked to you about testing for Cushing’s Disease? Let’s talk!
What is Cushing’s Disease?
Cushing’s Disease, or hyperadrenocorticism (HAC), is a condition of increased circulating cortisol in the body. Cortisol is the body’s natural steroid that is very important for maintaining many normal processes. Cortisol is produced by the adrenal glands, which are little glands that sit next to the kidneys and produce cortisol, adrenaline, and many other hormones.
There are two primary types of HAC recognized in dogs: pituitary dependent (PDH) and adrenal dependent (ADH). Like many hormone processes in the body, there is tight control on how much of a hormone is being produced.
Adrenocorticotropic hormone (ACTH) is secreted from the pituitary gland in the brain. This hormone regulates the secretion of cortisol from the adrenal glands. When enough cortisol has been released into the blood stream, the adrenal glands decrease the amount of cortisol being made, which decreased the production of ACTH.
Pituitary Dependent (PDH)
Pituitary dependent hyperadrenocortcism occurs when a small, benign tumor forms in the pituitary gland and produces an abundance of ACTH, which stimulates the adrenal glands to produce cortisol. The tumor cells do not have an “off switch”. This results in the adrenal glands becoming enlarged due to continued pressure to produce more and more cortisol.
Adrenal Dependent (ADH)
In ADH, excess cortisol is produced due to a tumor on one of the adrenal glands. Just like the tumor cells in the pituitary gland, the adrenal tumor cells do not have an “off switch” and they continuously produce large concentrations of cortisol.
Symptoms of Cushing’s Disease
The biggest telltale sign of Cushing’s Disease in dogs is an increase in urination and drinking. Dogs with Cushing’s disease also have an increased appetite. The fur may become thin and does not grow back normally after being clipped. The skin on the belly can become thin and they start to develop a big, round belly (pot belly). Dogs with Cushing’s Disease may also have high blood pressure and, if severely affected, may develop blood clots in the lungs or legs.
There can also be some changes noted on blood work before the above clinical signs become obvious. Cushing’s Disease can cause increases in liver enzymes, change in the number of white blood cells present. Cushing’s Disease may be discussed after routine lab has discovered a newly increased liver enzyme.
Diagnosis of Cushing’s Disease
Diagnosis of Cushing’s disease is not always straightforward. If you present your older dog to the veterinarian for an increase in drinking and urination, the minimal lab work that is recommended is a complete blood count (CBC), chemistry panel, and a urinalysis. If the history, physical exam, and initial blood work results suggest Cushing’s Disease, special tests may be recommended.
Urine Creatine Ratio test
A urine cortisol creatinine ratio is a screening test for Cushing’s that can be done without having to bring your dog to the veterinary office. If this test is negative, your dog does not have Cushing’s Disease. If the test is positive, then further testing is needed.
ACTH Stimulation test
An ACTH stimulation test takes 1 hour to perform: a blood sample is taken, a small amount of synthetic ACTH hormone is injected and another blood sample is taken 1 hour later. Cortisol levels are obtained and if the second cortisol is elevated Cushing’s Disease is diagnosed.
Low Dose Dexamethasone Suppression test
A low dose dexamethasone suppression test takes 8 hours to perform. Blood samples are drawn at 0, 4, and 8 hours after receiving a small dose of synthetic steroid (dexamethasone). Cortisol levels are also measured.
An abdominal ultrasound is often recommended during work up for Cushing’s Disease. Ultrasound is useful to determine if the adrenal glands are enlarged and to differentiate between pituitary dependent or adrenal dependent Cushing’s Disease.
Specific testing for Cushing’s disease may not be recommended if your dog only has changes on basic lab work but no clinical signs of Cushing’s because how Cushing’s is treated in dogs.
Treatment for Cushing’s Disease
Treatment for pituitary dependent Cushing’s includes use of oral medication and the goal is to treat the clinical signs (increased drinking, urination, appetite, skin/fur changes). Direct treatment of the benign brain tumor is not usually done. This would involve radiation therapy or, rarely, surgical removal of the pituitary gland.
The medication of choice for treating Cushing’s is trilostane (Vetoryl®). Trilostane blocks the production of cortisol in the adrenal glands resulting in less circulating cortisol and a decrease in clinical signs. Treatment is started based on weight and can be started once or twice a day. There is significant variation in response to the medication and close monitoring is required. ACTH stimulation tests have traditionally been recommended for monitoring (7-14 days after starting treatment, 1 month later, 3 months later, then every 6 months). The goal is to reach a cortisol level between 2-5 but more importantly, the clinical signs should be controlled.
Adrenal dependent Cushing’s Disease can be treated with surgical removal of the mass. Adrenal masses have a 50% chance of being benign or malignant and there are no tests before surgery to make that differentiation. Complete removal of the abnormal adrenal glands may be curative. However, removal of an adrenal gland requires advanced surgical skills and close anesthetic monitoring. Following surgery dogs require intensive care and long term follow up. The normal adrenal gland that is left is atrophied and is not able to make enough cortisol to maintain normal body processes. Supplementation with steroids is required for weeks to months following surgery.
When surgery is not possible, then control of the clinical signs of Cushing’s Disease may still be managed with medications: trilostane or mitotane. Treatment and monitoring with trilostane remains the same as for treatment of pituitary dependent Cushing’s. Mitotane treatment was used for many years as the treatment of choice for Cushing’s Disease before trilostane was available. Mitotane is a cytotoxic medication and destroys the cortisol producing cells in the adrenal gland. Very tight control of dosing and monitoring is controlled. Dosing can result in complete obliteration of cortisol producing cells and can result in the opposite condition called Addison’s disease. However, with an adrenal tumor this cytotoxic effect is taken advantage of to destroy some of the cancerous tissue. Again, close monitoring is required to titrate the dose carefully.
Important of Diagnosing & Treating Cushing’s Disease in Dogs
Testing, treatment, and monitoring of Cushing’s Disease is expensive and time consuming. However, if Cushing’s Disease is not treated the described clinical signs will progress impacting the dog’s and the family’s quality of life. The risk of developing a blood clot increase and secondary effects of high blood pressure may result.