Date of Award
Doctor of Philosophy
Comparative and Experimental Medicine
John C. New, Jr.
Walter Farkas, Joe Fuhr, Larry Kerr, Al Legendre, Mary Leitnaker
This study of canine hypoadrenocorticism (canine Addison's disease; adrenal insufficiency) used several techniques to determine the incidence and prevalence of the disease and to identify factors associated with its occurrence. These techniques were historical; statistical, including meta-analysis and logistic regression; and epidemiologic, including both case series and case control data. Data were gathered by: extracting the details of cases reported in the veterinary literature, a rudimentary meta-anaylsis; using data obtained by Ciba Animal Health in the clinical trial of the drug microcrystalline desoxycorticosterone pivalate (DOCP); using data obtained from the Veterinary Medical Data Base (VMDB), a data repository of clinical information from colleges of veterinary medicine in the United States - augmented by directly querying VMDB non-participant colleges of veterinary medicine in the United States and Canada; surveying by mail veterinarians enrolled in the Ciba Animal Health clinical trial of DOCP; and surveying by mail l,000 practicing small animal veterinarians selected randomly from the mailing list of the American Veterinary Medical Association.
The historical study focused on how humans first recognized the existence of the adrenal glands, next understood they were involved with disease in humans and other animals, and then developed methods for identifying and treating hypoadrenocorticism. The historical study began with Galen in the second century A.D., continued as human understanding expanded over the centuries, ended with the contemporary understanding of hypoadrenocorticism, and provided a context in which the specific results of the study became meaningful.
Incidence estimates for canine adrenal insufficiency were, depending on the data set used to obtain the estimate, 0.13/1000 dogs/yr, 0.34/1000 dogs/yr, and 0.6/1000 dogs/yr. A point estimate was 0.36/1000 dogs/yr. Prevalence estimates were 3.2/1000 dogs, 1.7/1000 dogs, and 0.6/1000 dogs. A point estimate was 1.8/1000 dogs.
Estimates of the average age (yr) at diagnosis for dogs with hypoadrenocorticism were 4.3, 4.9, and 5.4, again depending on the data set. A point estimate was 4.9. The ages of cases and controls suggested, based on the computation of age-specific odds ratios (OR) and logistic regression, that age was associated with the occurrence of disease and that the probability of disease increased with age.
Female dogs were more likely to be hypoadrenal than males, and neutered dogs of either sex were more likely than intact ones. These conclusions were based on sex-specific incidence estimates, sex-specific OR, and logistic regression. The latter confirmed that sex was a significant factor associated with hypoadrenocorticism in dogs.
Breed was, based on breed-specific OR and logistic regression, a significant factor in whether or not a dog developed adrenal insufficiency. Airedale Terriers, Basset Hounds, Bearded Collies, German Shepherds, German Shorthaired Pointers, Great Danes, Poodles, Saint Bernards, Springer Spaniels, and West Highland White Terriers were at increased risk of disease. Boston Terriers, Boxers, Cocker Spaniels, Dalmatians, Lhasa Apsos, Pit Bull Terriers, Pomeranians, Shetland Sheepdogs, Shih Tzus, and Yorkshire Terriers were at decreased risk. There was less compelling evidence that Labrador Retrievers and Mixed breed dogs were at decreased risk.
Average body weight (kg) estimates for hypoadrenal dogs were 23.4, 24.5, and 19.7, depending on the data set. A point estimate was 22.5. The body weights of cases and controls suggested, based on age-specific OR and logistic regression, that body weight was associated with disease and that the probability of disease increased with body weight.
Hypoadrenal dogs were characterized by hyponatremia, hyperkalemia, and a decreased ratio of serum sodium to potassium concentrations. Point estimates for serum sodium concentration, serum potassium concentration, and serum sodium to potassium concentration ratio were 132.1 meq/L, 6.6 meq/L, and 21.1, respectively. There was evidence that hypoadrenal dogs were seldom normal for all three diagnostic indicators.
Common clinical findings among hypoadrenal dogs were anorexia, vomiting, depression, weakness, weight loss, azotemia, and diarhrea. Though probably affected by measurement bias, there was evidence that dogs with adrenal insufficiency were more likely than dogs from the general population to have anemia, arthritis, cruciate ligament rupture, diabetes mellitus, hepatitis, hypothyroidism, keratoconjunctivitis sicca, megaesophagus, myasthenia gravis, nephritis, and thrombocytopenia.
The study concluded that epidemiologic studies of canine hypoadrenocorticism may use the practicing veterinarian's diagnosis as a case definition rather than require a strict case definition based on the adrenocorticotropic hormone stimulation test. This would produce larger numbers of cases, be less complex, more convenient, and less costly.
Logistic regression of data from the mail survey of veterinarians enrolled in the clinical trial of DOCP indicated that age, breed, sex, and body weight were associated with canine hypoadrenocorticism. The probability of disease increased with age and body weight, was greater in females than males, was greater in neutered than intact dogs, and varied with breed. There was model-dependent evidence of higher order interactions, but the exact nature of these interactions could not be determined. Models were prepared which could predict the relative probability of hypoadrenocorticism in different dogs. It was emphasized that these models undoubtedly overlooked other unknown variables.
Data from the veterinary literature, VMDB, clinical trial of DOCP, and survey of veterinarians enrolled in the DOCP clinical trial were all useful. The mail survey methodology was valuable, and should be a useful tool in veterinary epidemiologic studies. The mail survey of randomly selected veterinarians was a poor method for studying an uncommon disease; this deficiency might be overcome if larger samples were obtained.
Kelch, William James, "Canine Hypoadrenocorticism (Canine Addison's Disease): History, Contemporary Diagnosis by Practicing Veterinarians, and Epidemiology. " PhD diss., University of Tennessee, 1996.