Cushing's Disease in Cavalier King Charles Spaniels
- What It Is
- Breeders' Responsibilities
- Research News
- Related Links
- Veterinary Resources
The cavalier King Charles spaniel is at increased risk for Cushing's disease, also known as Cushing's syndrome or hyperadrenocorticism. It is a serious, genetic disorder which produces excess hormones from the adrenal glands. If not promptly treated, it can lead to life-threatening disorders.
The adrenal glands produce hormones which help regulate weight, mineral balance, the structure of connective tissue, some white blood cell production, and skin health.
Cushing's disease is caused by either an adrenal cortical tumor (a tumor of the cortisol-producing cells of the adrenal gland) or pituitary tumors (which produce excessive amounts of ACTH -- adrenocorticotrophic hormone, the hormone which causes the adrenal glands to produce cortisol), with the result that an excess of cortisol is released in the cavalier's body. These tumors are, of course, forms of cancer.
Addison's disease is hypoadrenocorticism, the opposite of Cushing's disease. For general information about Addison's disease, see this webpage.
Symptoms include excessive drinking (polydipsia) and urination (polyuria), increased appetite (polyphagia), panting, symmetrical hair loss (alopecia), hard, calcified lumps in the skin (calcinosis cutis) and discoloration, lethargy, muscle weakness, and susceptibility to skin and urinary infections. Victims also develop bulging, sagging bellies, due to decreased muscle strength and the redistribution of fat from body storage areas to the abdomen. Left untreated, Cushing's disease can lead to life-threatening disorders such as diabetes, congestive heart failure, and liver and kidney failure, and to chronic problems of hypothyroidism, and infections of the skin, ears, gums, eyes, or bladder.
Cushing's disease can be diagnosed by laboratory tests of blood and urine, including a urine cortisol/creatinine ratio test, an ACTH stimulation test, and low and high dose dexamethasone suppression (LDDS) tests. Once diagnosed, tests can also determine if it is caused by pituitary gland tumors or an adrenal gland tumor.
Surgery can cure an adrenal cortical tumor that has not spread to other areas of the body. However, about half of adrenal tumors are malignant and may have already spread. Pituitary Cushing's disease cannot be cured, but the treatment can prolong the cavalier's quality of life, but not to increase the lifespan. Drug therapies include lysodren (Mitotane), ketoconazole (Nizoral), anipryl (Deprenyl, Eldepryl, Selegiline, and vetoryl (Modrenal, Trilostane).
There are conflicting reports regarding whether lysodren (Mitotane) may induce hypoadrenocorticism (Addison's disease) in cavaliers. Compare this 2005 report with this 2008 powerpoint presentation, both submitted by Michael E. Herrtage.
Cavaliers diagnosed with Cushing's, or otherwise determined to be pre-disposed to it, should not be bred. Any littermates of breeding stock having Cushing's disease should be taken into consideration. The Canine Inherited Disorders Database (www.upei.ca/~cidd/intro.htm) advises to breed only dogs from families with no history of the disorder. Any cavalier King Charles spaniel intended to be bred should be blood tested for Cushing's disease at least annually, the closer the examination to the breeding the better.
►July 2012: Texas A&M researchers find compounded trilostane may be defective. In a July 2012 report, a team of researchers from Texas A&M University evaluated 96 batches of compounded trilostane products from eight pharmacies. They found a wide variablity in actual drug content, compared to the labels' claims. They determined that the defective products may compromise effective management of patients being treated for hyperadrenocorticism.
Control of Canine Genetic Diseases. Padgett, G.A., Howell Book House 1998, pp. 198-199, 222.
A Comparison of the Survival Times of Dogs Treated with Mitotaneor Trilostane for Pituitary-Dependent Hyperadrenocorticism. E.N. Barker, S. Campbell, A.J. Tebb, R. Neiger, M.E. Herrtage, S.W.J. Reid, and I.K. Ramsey. J Vet Intern Med; 2005;19:810–815. Quote: "The survival times of 148 dogs [including 6 cavalier King Charles spaniels] treated for pituitary-dependent hyperadrenocorticism were studied using clinical records from 3UK veterinary centers between 1998 and 2003. Of these animals, 123 (83.1%) were treated with trilostane, while 25 (16.9%) weretreated with mitotane. Treatment groups were compared using t-tests and analysis of variance (or their nonparametric equivalents)and chi-square tests. Survival data were analyzed using Kaplan-Meier survival plots and Cox proportional hazard methods. Therewas no signiﬁcant difference between the population attributes from each center or between treatment groups. The median survival time for animals treated with trilostane was 662 days (range 8–1,971) and for mitotane it was 708 days (range 33–1,399). There were no signiﬁcant differences between the survival times for animals treated with trilostane and those treated with mitotane. In the multivariable model (including drug, center, breed group, weight, diagnostic group, and age at diagnosis), only age at diagnosis and weight were signiﬁcantly negatively associated with survival. Importantly, there was no signiﬁcant effect of drug choice on survival."
Diagnosis and Management of Hypoadrenocorticism. Michael E. Herrtage. 2008. Get PDF version of Powerpoint. Quote: "Mitotane-induced hypoadrenocorticism: breed incidence: higher in Scottish terrier, Cavalier King Charles spaniel, Cocker spaniel, Springer spaniel, and Yorkshire terrier. Age range: range 4 - 10 years; mean 8.4 years."
Use of Computed Tomography Adrenal Gland Measurement for Differentiating ACTH Dependence from ACTH Independence in 64 Dogs with Hyperadenocorticism. M.I. Rodríguez Piñeiro, P. de Fornel-Thibaud, G. Benchekroun, F. Garnier, C. Maurey-Guenec, F. Delisle, D. Rosenberg. J Vet Int Med Sept 2011; 25(5):1066-1074. Quote: "The measurement of adrenal gland size on computed tomography (CT) scan has been proposed for the etiological diagnosis of hyperadrenocorticism (HAC) in dogs. Symmetric adrenal glands are considered to provide evidence for ACTH-dependent hyperadrenocorticism (ADHAC), whereas asymmetry suggests ACTH-independent hyperadrenocorticism (AIHAC). However, there are currently no validated criteria for such differentiation. Objective: The aim of this retrospective study was to compare various adrenal CT scan measurements and the derived ratios in ADHAC and AIHAC cases, and to validate criteria for distinguishing between these conditions in a large cohort of dogs. Results: An overlap was systematically observed between the AIHAC and ADHAC groups for all measurements tested. Overlaps also were observed for ratios tested. For the maximum adrenal diameter ratio derived from reformatted images (rADR), only 1/18 AIHAC dogs had a rADR within the range for ADHAC. For a threshold of 2.08, the 95% confidence intervals for estimated sensitivity and specificity extended from 0.815 to 1.000 and from 0.885 to 0.999, respectively, for AIHAC diagnosis. Conclusion and Clinical Importance: Measurements from cross-sectional or reformatted CT scans are of little use for determining the origin of HAC. However, rADR appears to distinguish accurately between ADHAC and AIHAC, with a rADR > 2.08 highly suggestive of AIHAC."
Pharmaceutical Evaluation of Compounded Trilostane Products. Audrey K. Cook, Cornelia D. Nieuwoudt, and Susan L. Longhofer. J Am Anim Hosp Assoc. Jul/Aug 2012;48(4):228-233. Quote: "Compounded trilostane capsules (15 mg, 45 mg, or 100 mg) were purchased from eight pharmacies and assayed for content and dissolution characteristics. Capsules made in-house containing either inert material or 15 mg of the licensed product and proprietary capsules (30 mg and 60 mg) served as controls. Findings were compared with regulatory specifications for the licensed product. Altogether, 96 batches of compounded trilostane and 16 control batches underwent analysis. In total, 36 of 96 (38%) compounded batches were below the acceptance criteria for content. The average percentage label claim (% LC) for each batch ranged from 39% to 152.6% (mean, 97.0%). The range of average % LC for the controls was 96.1–99.6% (mean, 97.7%). The variance in content of the purchased compounded products was substantially greater than for the controls (234.65 versus 1.27; P<0.0001). All control batches exceeded the acceptance criteria for dissolution, but 19 of 96 batches (20%) of purchased compounded products did not. Mean percent dissolution for the purchased compounded products was lower than for controls (75.96% versus 85.12%; P=0.013). These findings indicate that trilostane content of compounded capsules may vary from the prescribed strength, and dissolution characteristics may not match those of the licensed product. The use of compounded trilostane products may therefore negatively impact the management of dogs with hyperadrenocorticism."
Applied Dermatology: Old or New? A Comparison of Mitotane and Trilostane for the Management of Hyperadrenocorticism. Joel D. Griffies. Compendium. May 2013; 35(5). Quote: "Hyperadrenocorticism (HAC) is a common endocrinopathy in dogs. With better recognition of the disease, more cases are being presented to clinicians for management. Mitotane, a 3- to 4-decade-old therapy, remains a viable and useful option for management of this disease. Thorough education and understanding of the drug are important, however, as the learning curve of how to manage its effects can be significant. Trilostane, a newer option for management of HAC, offers a simplified protocol and, often, smoother and faster control of the disease. ... Both mitotane and trilostane are useful tools in the management of an often insidious chronic disease. While both have pros and cons, the clinician’s comfort level, experience, and understanding of each drug are probably the most important features in deciding which to choose. With proper drug therapy, patient follow-up, and client communication, successful management of HAC can result in significantly improved quality of life for the patient and the owner."