Cushing’s disease, or hyperadrenocorticism, is a common endocrine disease of dogs. It generally affects middle-aged dogs, especially Beagles, Boston Terriers, Boxers, Dachshunds, and Miniature Poodles.
There are two types of Cushing’s disease:
- Pituitary-dependent Cushing’s disease
A benign pituitary tumor secretes excessive amounts of adrenocorticotropic hormone (ACTH). This excessive ACTH leads to increased cortisol release from the adrenal glands.
- Adrenal-dependent Cushing’s disease
In this condition, a functional adrenal mass produces excessive cortisol.
In dogs, approximately 85% of Cushing’s disease cases are pituitary-dependent and 15% are adrenal-dependent.
Diagnosing Cushing’s disease in dogs
Clinical signs of Cushing’s disease in dogs include polyuria, polydipsia, polyphagia, weight gain, “pot-bellied” appearance, lethargy, panting, and dermatologic conditions. Routine bloodwork often shows elevations in alkaline phosphatase (ALP) and alanine transferase (ALT), as well as hypercholesterolemia.
The diagnosis of Cushing’s disease is complex, with many different tests available. Each test has its unique pros and cons, meaning that diagnosis of Cushing’s disease is not always straightforward. The most commonly-performed tests to diagnose Cushing’s disease include the following:
- Urine cortisol creatinine ratio (UCCR)
This test is sensitive but not specific. A dog with a normal UCCR can be assumed to be free of Cushing’s disease, but a dog with an abnormal UCCR requires further testing to confirm the diagnosis.
- Low-dose dexamethasone suppression test (LDDS)
This is often regarded as the screening test of choice for Cushing’s disease, because in addition to being relatively sensitive and specific, it can often help distinguish whether a patient has pituitary-dependent or adrenal-dependent Cushing’s disease.
- Adrenocorticotropic stimulation test (ACTH Stim)
This test can also be used as a screening test for Cushing’s disease. It has higher specificity than the LDDS, but does not aid in determining whether Cushing’s disease is pituitary-dependent or adrenal-dependent.
Depending on the results of the screening tests, a differentiating test may be required to determine whether a dog has adrenal-dependent Cushing’s or pituitary-dependent Cushing’s. Differentiating tests include high-dose dexamethasone suppression test, endogenous plasma ACTH testing, and imaging of the adrenal glands.
Conventional treatments: surgery and medications
In the 15% of dogs diagnosed with adrenal-dependent Cushing’s disease, the recommended treatment is adrenalectomy of the affected adrenal gland. In many cases, the contralateral adrenal gland has atrophied due to the high cortisol production of the affected gland; therefore, dogs may require careful monitoring in the early postoperative period.
Furthermore, the anaesthetic management for adrenalectomies presents unique challenges because of the high incidence of complications. Proper equipment and preparation for anticipated problems, including availability of resuscitative fluids and short-acting drugs, is recommended to minimize the risks of negative outcomes.
Corticosteroid supplementation may be needed postoperatively, until the remaining adrenal gland regains normal function.
Dogs with pituitary-dependent Cushing’s are treated with one of two medications: mitotane or trilostane. Mitotane is the conventional treatment for Cushing’s disease; it is an adrenolytic agent that is given at higher doses during an induction phase, then in lower doses during a maintenance phase. Mitotane must be given with caution, because overdosage can lead to hypoadrenocorticism (Addison’s disease), which may be irreversible.
Trilostane, in contrast, is a newer drug; it works by inhibiting steroids with minimal adverse effects. In the years since its introduction, trilostane has become the preferred treatment for pituitary-dependent Cushing’s disease because of its minimal side effects.
Can diet changes help manage Cushing’s in dogs?
A phenomenon known as “meal-induced hyperadrenocorticism” has been identified in dogs, although it is relatively rare. In these dogs, a genetic defect results in glucagon inhibitory peptide (GIP) receptors being expressed in the adrenal glands.
Glucagon inhibitory peptide is produced by the stomach during every meal; in dogs with meal-induced hyperadrenocorticism, this GIP acts on the aberrant adrenal receptors, resulting in the production of cortisol. While this type of Cushing’s disease is associated with eating, however, it is not associated with any characteristics of the pet’s diet.
Dogs with meal-induced hyperadrenocorticism will release cortisol when any type of food enters the stomach; therefore, diet change is insufficient to manage this condition. Meal-induced hyperadrenocorticism is managed by giving trilostane at meal times to block the action of cortisol.
Some pet owners attempt to manage the signs of Cushing’s disease by feeding a low-carbohydrate, high-protein diet. The philosophy behind this recommendation is two-fold. First of all, Cushing’s disease is thought to be associated with the inflammatory process, which some pet owners believe is exacerbated by high-carbohydrate foods. Secondly, there is significant overlap between Cushing’s disease and diabetes; it is thought that both conditions may benefit from reduced dietary sugar.
Reviewing the literature in both human and veterinary medicine, there is no evidence to support the claim that Cushing’s disease can be managed through the use of a low-carbohydrate diet. While anecdotal evidence abounds on the internet, there have been no controlled studies to demonstrate the efficacy of this treatment.
Although such a diet is unlikely to harm an otherwise-healthy pet, it is best used in conjunction with conventional therapies — not in place of conventional therapies.
Cushex, flaxseed lignans, milk thistle… do herbal supplements work?
Clients who search the internet may learn of, and ask about, a herbal supplement called Cushex. This supplement is made of dandelion, burdock, astragalus, licorice, eleuthero root, vegetable glycerine, and deionized water. The manufacturer of Cushex does not, however, provide any information about what quantities of these substances are contained in the supplement, nor on its proposed mechanism of action.
Some clients report that their pet’s signs of Cushing’s disease resolve with the use of this supplement, but this could be due to a placebo effect and there is little information available on the true safety or efficacy of Cushex.
In addition to these concerns, the company that manufactures Cushex is not a member of the National Animal Supplement Council (NASC), which is an organization that helps to ensure the safety and quality of pet nutritional supplements. Therefore, even veterinarians who are experienced in and comfortable with alternative therapies typically recommend avoiding Cushex.
Melatonin is a supplement that has been used in the management of Cushing’s disease, with varying degrees of success. Human studies have indicated that low melatonin levels are a characteristic of Cushing’s disease. While this is regarded to be an effect of hyperadrenocorticism and not a cause, some feel that melatonin supplementation may help decrease the clinical signs of Cushing’s disease.
Flaxseed lignans have also been used for the management of Cushing’s disease in dogs. While there is little evidence of efficacy, flaxseed lignans are phytoestrogens that compete with estradiol at receptors. Flaxseed lignans have less biological activity than estradiol; therefore, they may mediate some of the effects of the increased sex hormone production that can occur in Cushing’s disease.
Preliminary studies in Germany have suggested that milk thistle may also play a role in managing Cushing’s disease. While widespread studies of milk thistle in Cushing’s disease have not been reported, there may be some benefit to this therapy. Other alternative therapies, such as colloidal silver, have not been shown to have a benefit in the treatment of Cushing’s disease.
If a client wishes to incorporate alternative therapies in the treatment of Cushing’s disease, they should pursue a consultation with a veterinarian who specializes in alternative medicine. In general, these veterinarians recommend the use of herbal supplements such as Si Miao San and other alternative therapies as a complement to conventional Cushing’s therapy.
While many clients may be interested in alternative therapies for Cushing’s disease, there is little evidence to support the use of these treatments as a sole therapy. In most cases, alternative therapies are beneficial as an adjunct to appropriate medical therapy, not a replacement.
Clients who wish to pursue alternative therapies should be referred to a veterinarian who is well-versed in the appropriate use of these treatments.
Sources and additional reading
- Greco D. Cushing Disease (Hyperadrenocorticism). Merck Veterinary Manual. Retrieved from https://www.merckvetmanual.com/endocrine-system/the-pituitary-gland/cushing-disease-hyperadrenocorticism
- Johnson C. 2016. Meal-induced hyperadrenocorticism in dogs: not to be overlooked. Retrieved from http://veterinarymedicine.dvm360.com/meal-induced-hyperadrenocorticism-dogs-not-be-overlooked
- Soszyński P, et al. 1989. Decreased Melatonin Concentration in Cushing’s Syndrome. Horm Metab Res. 21(12): 673-674.
- Clinical Endocrinology Service. Treatment Option Considerations for Hyperadrenocorticism in Dogs. College of Veterinary Medicine/University of Tennessee. Retrieved from https://vetmed.tennessee.edu/vmc/dls/Endocrinology/Documents/Treatment%20Considerations.pdf
- Jebold M, et al. 2015. A C–terminal HSP90 inhibitor restores glucocorticoid sensitivity and relieves a mouse allograft model of Cushing disease. Nature Medicine, 9 February.
- McCullough L. 2017. Integrative Approach to Cushing’s Disease. Innovative Veterinary Care. Retrieved from https://ivcjournal.com/integrative-approach-cushings-disease/