Prevalence and clinical features of hypoadrenocorticism in Great Pyrenees dogs in a referred population: 11 cases

Abstract

Naturally occurring hypoadrenocorticism (Addison’s disease) is uncommon, with an estimated prevalence in the canine population between 0.06% and 0.28%. This retrospective study evaluated the prevalence and clinical features of hypoadrenocorticism in Great Pyrenees (GP) dogs presented to the Centre Hospitalier Universitaire Vétérinaire of the University of Montreal between March 2005 and October 2014. During this period, 100 dogs were diagnosed with hypoadrenocorticism, representing 0.38% [95% confidence interval (CI): 0.26% to 0.5%] of the canine population studied. The highest prevalence was observed in GP (9.73%, 95% CI: 9.12% to 10.35%, P < 0.0001), followed by West Highland white terriers (4.66%, 95% CI: 4.24% to 5.09%, P < 0.0001), Great Danes (1.87%, 95% CI: 1.6% to 2.14%, P < 0.0001), standard poodles (1.76%, 95% CI: 1.5% to 2.02%, P = 0.0001), Saint Bernards (1.72%, 95% CI: 1.47% to 1.98%, P = 0.018), and Jack Russell terriers (1.48%, 95% CI: 1.24% to 1.72%, P = 0.003). Although most clinical features were nonspecific, Great Pyrenees dogs were more frequently presented with anemia, azotemia, and eosinophilia, or with hypotension and cachexia compared with dogs of other breeds.

Introduction

Canine hypoadrenocorticism, or Addison’s disease, is an endocrine disorder characterized by inadequate secretion of steroid hormones (glucocorticoid and mineralocorticoid hormones) from the adrenal glands. Adrenal insufficiency is categorized as primary or secondary based on whether the deficit is due to the destruction of the adrenal cortex (primary) or the lack of adrenocorticotropic hormone (ACTH), which normally is produced and secreted by the anterior pituitary gland (secondary) (1–3). Primary hypoadrenocorticism is the most common form in dogs. In humans, an immune-mediated process has been clearly identified and autoantibodies to adrenal cortex and/or 21-hydrolase have been detected in up to 48% to 100% of patients with Addison’s disease (4–6). Although autoimmune destruction of the adrenal cortex has been reported in dogs (7), most dogs with spontaneous hypoadrenocorticism are simply classified as idiopathic (2).

Patients with hypoadrenocorticism are typically presented with nonspecific signs such as lethargy, anorexia, vomiting, diarrhea, weight loss, polyuria, and polydipsia. The severity and duration of these clinical findings vary greatly among dogs. Most dogs have chronic and often intermittent clinical signs, but signs can also be acute. Although hyperkalemia and hyponatremia are classic hallmarks of the disease, these clinicopathologic findings are not present in atypical primary and secondary hypoadrenocorticism which result in a glucocorticoid hormone deficiency alone (1,2). An adrenocorticotropic hormone (ACTH) stimulation test is required for definitive diagnosis of hypoadrenocorticism, but a basal serum or plasma cortisol concentration above 55 nmol/L has been suggested as a cut-off value to rule out hypoadrenocorticism with a sensitivity of 100% (8,9). Treatment of naturally occurring hypoadrenocorticism consists of lifelong hormone replacement, which can be expensive, especially in large breed dogs with mineralocorticoid deficiency.

Naturally occurring hypoadrenocorticism is uncommon in dogs. Its prevalence in the general canine population is estimated between 0.06% and 0.28% (10). Based on large epidemiological studies, certain breeds, including bearded collies, standard poodles, Portuguese water dogs, and Nova Scotia duck tolling retrievers, appear to have an increased risk of developing the disease with reported prevalences of 9.4%, 8.6%, 1.5%, and 1.4%, respectively (2,11–13). Data on increased risk for hypoadrenocorticism are reported in many other breeds including West Highland white terriers (WHWT), Great Danes, soft-coated wheaten terriers, rottweilers, and Saint Bernards (2,14). An autosomal recessive inheritance has been identified in standard poodles and Nova Scotia duck tolling retrievers (13,11).

To our knowledge, this is the first paper reporting an increased risk of developing naturally occurring hypoadrenocorticism in Great Pyrenees dogs. Only 1 case report of a 4-year-old female Great Pyrenees dog diagnosed with hypoadrenocorticism has previously been published. This dog was diagnosed with polyendocrinopathy due to lymphocytic adrenalitis and primary hypophysitis (15). The objective of the present study was to evaluate the prevalence and clinical features of naturally occurring hypoadrenocorticism in Great Pyrenees dogs presented to the Centre Hospitalier Universitaire Vétérinaire (CHUV) of the University of Montreal. We hypothesized that the prevalence of naturally occurring hypoadrenocorticism in Great Pyrenees dogs was significantly higher compared to the prevalence of the disease in the hospital population. We also hypothesised that clinical features in naturally occurring hypoadrenocorticism were similar between Great Pyrenees dogs and dogs of other breeds.

Materials and methods

Selection of cases

Medical records of dogs presented to the CHUV of the University of Montreal between March 2005 and October 2014 were reviewed retrospectively to include dogs with a diagnosis of naturally occurring hypoadrenocorticism. The results of an ACTH stimulation test consistent with naturally occurring hypoadrenocorticism had to be available (pre- and post-ACTH serum cortisol level ≤ 55 nmol/L) for dogs to be included in the study (8,9). Dogs diagnosed before their first presentation to the CHUV or newly diagnosed at the CHUV were included. Dogs were excluded from the study if they had received corticosteroids (oral, parenteral, or topical) in the 4 wk before the ACTH stimulation test, or they were being treated or had previously been treated with trilostane or mitotane. Based on these criteria, client-owned dogs with confirmed hypoadrenocorticism were retrospectively separated into 2 groups: the Great Pyrenees dog group (GP) and the control group (CG), defined as affected dogs of other breeds.

Data collected from the medical record

The following data were collected from the records of all dogs included in the study: breed, gender, age, history, and reason for presentation, physical examination, laboratory findings, and treatment regime at diagnosis and at last evaluation at the CHUV, as well as cause of death (if available). The owners and family veterinarians were contacted by telephone to obtain any missing information.

Statistical analysis

The prevalence of hypoadrenocorticism in the studied population, as well as the prevalence per breed, were calculated and compared using a t-test. In addition, a Bonferroni correction for multiple comparisons was applied, based on the number of comparisons (number of breed, n = 34); P-values <0.05 after Bonferroni correction were regarded as significant. Epidemiologic criteria, age at diagnosis, reason for presentation, clinical and laboratory findings were compared between the 2 groups using a t-test (for continuous variables) or a z-test (for categorical variables). The z-test was used to compare the proportions between the 2 populations. Statistical significance was set at P < 0.05. The 95% confidence interval (CI) for prevalence was calculated with exact tests based on binominal distribution.

Results

Study population

The database search of all dogs presented to the CHUV during the study period (n = 26 450) identified 105 dogs with an ACTH stimulation test consistent with hypoadrenocorticism. Five dogs were excluded from the study: 4 dogs had been treated for hyperadrenocorticism with trilostane or mitotane and 1 dog had received corticosteroids a few days before the ACTH stimulation test. Therefore, a total of 100 dogs with a diagnosis of naturally occurring hypoadrenocorticism were included in our study. Fourteen dogs had already been diagnosed upon first presentation to the CHUV and ACTH stimulation test results were provided by their regular veterinarian. A total of 114 Great Pyrenees dogs were presented to the CHUV during the study period.

In addition to Great Pyrenees dogs (GP: n = 11), 34 breeds (control group: n = 89) were represented among the dogs diagnosed with hypoadrenocorticism (Table 1).

Table 1.

Dogs diagnosed with hypoadrenocorticism presented to the CHUV of the University of Montreal between March 2005 and October 2014

Breed	Number of dogs
Great Pyrenees	11
Control group (N = 89)
West highland white terrier	9
Standard poodle	7
Cross-bred dog	7
Great Dane	7
Miniature poodle	6
Labrador retriever	5
Golden retriever	5
Shih tzu	4
Maltese	4
Jack Russell terrier	4
Yorkshire terrier	2
Saint Bernard	2
Collie	2
Boxer	2
Boston terrier	2
German shepherd	2
Basset hound	2
Beagle	1
Australian shepherd	1
Bichon frisé	1
Border collie	1
German shorthaired pointer	1
Toy poodle	1
Chihuahua	1
Doberman pinscher	1
Lhasa apso	1
Malamute	1
Pomeranian	1
Rottweiler	1
Samoyed	1
Newfoundland	1
Wheaten terrier	1
Tibetan terrier	1
Weimaraner	1

Twenty-four dogs were diagnosed with concurrent diseases: 4 with recurrent cystitis (including 1 GP); 3 with herniated disk (including 1 GP); 2 each with epilepsy, dilated cardiomyopathy, diabetes mellitus (1 of which had concurrent glomerulopathy and the other had concurrent hypothyroidism); 1 each with megaesophagus with secondary bronchopneumonia, sick sinus syndrome, degenerative valvular disease with concurrent hypothyroidism, immune-mediated hemolytic anemia, bladder stone, dirofilariasis, pancreatitis, laryngeal paralysis, chronic kidney disease, glaucoma, hip dysplasia (1 GP).

Prevalence of hypoadrenocorticism per breed

The overall prevalence of hypoadrenocorticism in the study population was 0.38% (95% CI: 0.26% to 0.5%). The prevalence per breed varied between 0.17% and 9.73%, with the highest prevalence observed in GP, which was significantly higher than the overall prevalence of hypoadrenocorticism in our study population (9.73%, 95% CI: 9.12% to 10.35%, P < 0.0001). A significantly higher prevalence was also observed in WHWT (4.66%, 95% CI: 4.24% to 5.09%, P < 0.0001), Great Danes (1.87%, 95% CI: 1.6% to 2.14%, P < 0.0001), standard poodles (1.76%, 95% CI: 1.5% to 2.02%, P = 0.0001), Saint Bernards (1.72%, 95% CI: 1.47% to 1.98%, P = 0.018), collies (1.52%, 95% CI: 1.27% to 1.76%, P = 0.033), Jack Russell terriers (1.48%, 95% CI: 1.24% to 1.72%, P = 0.003), and miniature poodles (1.14%, 95% CI: 0.93% to 1.35% P = 0.004) (Figure 1). After Bonferroni correction, the prevalence of hypoadrenocorticism per breed remained significantly higher than the overall hypoadrenocorticism prevalence in our study population in certain breeds including: GP, WHWT, Great Danes, and standard poodles.

Figure 1.

Prevalence of hypoadrenocorticism and total population of dogs in 8 breeds with a significantly higher prevalence of hypoadrenocorticism compared with the overall prevalence of hypoadrenocorticism at the CHUV during the study, with (*) and without Bonferroni correction.

WHWT — West Highland white terrier

Clinical features of Great Pyrenees dogs with hypoadrenocorticism

The clinical features and epidemiological factors compared between the 2 groups are detailed in Table 2. Median age at diagnosis was not statistically different between GP and the control group (Table 2). Males were over-represented in the control group (P = 0.004) and in the overall canine population seen at the CHUV during the study period (P < 0.0001), but the proportion male/female was not significantly different between these 2 groups (P = 0.61). Similarly, the proportion of males was not significantly different in GP compared with the control group.

Table 2.

Comparison of the proportion of clinical features and epidemiological factors between the 2 groups: Great Pyrenees dogs (GP) and control group (CG)

Criteria	GP	CG	P-value
Epidemiologic factors
Age at diagnosis (y)	3.56 (1.02 to 8.21)	4.85 (0.39 to 11.07)	0.22
Female	4/11	40/100	0.79
Male	7/11	60/100	0.79
Reason for presentation
Lethargy	7/9	48/86	0.18
Anorexia	5/9	41/86	0.66
Gastrointestinal signs	3/9	53/86	0.05
Lameness	3/9	12/86	0.08
Weakness	3/9	18/86	0.36
Weight loss	2/9	14/86	0.64
PU/PD	0/9	10/86	0.24
Shaking	0/9	11/86	0.22
Clinical findings
Hypotension	6/9	14/84	< 0.0001
Cachexia	3/9	7/84	0.0041
Dehydration	3/9	28/84	1
Heart murmur	3/9	18/84	0.36
Abdominal pain	2/9	16/84	0.80
Laboratory findings
Anemia	7/9	31/80	0.01
Eosinophilia	3/8	11/79	0.04
No stress leukogram	5/8	50/79	0.96
Azotemia	8/8	42/81	0.004
Hypoalbuminemia	3/8	22/81	0.49
Hypoglycemia	2/9	10/82	0.33
Hyperphosphatemia	4/8	24/81	0.18
Hyponatremia	7/9	56/81	0.55
Hyperkalemia	7/9	55/82	0.87
Mean Na/K ratio	21.25 (13.9 to 28.2)	23.77 (13.5 to 44.7)	0.26
Hypochloremia	4/9	21/83	0.75

PU/PD = polyuria and polydipsia. Bold numbers indicate P-values < 0.05.

The main reasons for presentation in the GP were lethargy and anorexia, whereas the main reasons for presentation for the dogs in the control group were gastrointestinal signs, lethargy, and anorexia. Great Pyrenees dogs were less frequently presented with gastrointestinal signs than dogs in the control group, but this difference was not significant (P = 0.05). Moreover, GP were significantly more often presented with hypotension (P < 0.0001), defined as a systolic blood pressure < 90 mmHg (measured by Doppler method or petMap blood pressure technology), and cachexia (P = 0.004), defined as a body condition score (BCS) of ≤ 3/9 than were dogs in the control group (Table 2).

There was no significant difference in frequency and severity of serum electrolyte abnormalities between the 2 groups. In both groups, most dogs were presented with typical electrolyte abnormalities, i.e., hyperkalemia (GP: n = 7/9; CG, n = 55/82) and hyponatremia (GP: n = 7/9; CG, n = 56/81). The average Na:K ratio in dogs was not significantly different between the 2 groups (GP: 21.25, CG: 23.77, P = 0.26), neither in dogs with typical hypoadrenocorticism (GP: 18.94, CG: 20.97, P = 0.117). The proportion of atypical hypoadrenocorticism was not significantly different between the 2 groups (GP: n = 2/9, CG: n = 21/82, P = 0.824).

Other major laboratory findings in both groups included azotemia, anemia, lack of a stress leukogram, eosinophilia, and hypoalbuminemia. Compared to the control group, GP were more likely to be presented with azotemia (GP: n = 8/8, CG: n = 42/81, P = 0.004), anemia (GP: n = 7/9, CG: n = 31/80, P = 0.01), and eosinophilia (GP: n = 3/8, CG: n = 11/79, P = 0.04).

The treatment initiated following diagnosis was known for 87 dogs including 9 GP. Following diagnosis, dogs were initially treated with either prednisone alone (GP: n = 2/9, CG: n = 20/78), or prednisone with fludrocortisone (GP: n = 7/9, CG: n = 47/78), or desoxycorticosterone pivalate, DOCP (GP: n = 0/9, CG: n = 11/78). Sixty-seven dogs, including 5 GP, came back to the CHUV for at least 1 revaluation following diagnosis. Treatment at last recheck was known for 61/67 dogs, including 5 GP. Forty-one dogs were treated with fludrocortisone, including 4/5 GP, with an average maintenance dose of 0.025 mg/kg body weight (BW) per day, which was significantly higher than the initial dosage (average: 0.018 mg/kg BW per day, P = 0.042). The increase in dose of fludrocortisone was however not significant when considering the groups separately between the initial dosage at time of diagnosis (GP: 0.020 mg/kg BW per day, CG: 0.019 mg/kg BW per day) and at time of the last recheck (GP: 0.022 mg/kg BW per day, CG: 0.025 mg/kg BW per day). At time of the last recheck, prednisone was administered only as needed during stressful events in 25/61 dogs including 4/5 GP, and administered regularly (daily or every other day) for 36/61 dogs, (including 1/5 GP). In both groups, the maintenance prednisone dosage was significantly decreased compared to the initial dosage (average dosage at time of diagnosis 0.43 mg/kg BW per day and 0.26 mg/kg BW per day at time of the last recheck, P = 0.001). The DOCP dosage was not significantly different for both groups between time of diagnosis and time of last recheck (2.16 mg/kg BW per 25 days and 2.07 mg/kg BW per 25 days, respectively).

The Na/K ratio at time of last recheck was 29.02 in GP and 31.63 in CG, which is not significantly different.

One GP and 2 CG dogs were euthanized at diagnosis. These 3 dogs were presented in hypovolemic shock (weakness, pale mucous membrane, weak pulse and hypotension, tachycardia, and dehydration), and were euthanized for financial reasons. Another dog, presented in shock, was euthanized after 2 d of hospitalization because of lack of significant improvement. All 4 were large breed dogs [1 Labrador retriever (32.5 kg), 1 GP (48.5 kg), and 2 Great Danes (50 and 53.5 kg)].

Discussion

The most important finding of our study is a significantly higher prevalence of hypoadrenocorticism in Great Pyrenees dogs (9.73%) compared with the canine hospital population (0.38%). The prevalence of hypoadrenocorticism was also found to be significantly higher in WHWT (4.66%), Great Danes (1.87%), and standard poodles (1.76%).

The high prevalence of naturally occurring hypoadrenocorticism in Great Pyrenees dogs in a referral center in Quebec, Canada, strongly suggests genetic inheritance of this disease. An inherited susceptibility for Addison’s disease has been demonstrated in standard poodles (11) and suspected in the WHWT, soft-coated wheaten terrier, Great Dane, and other poodle breeds (2,10,14,16,17). Saint Bernards have previously been over-represented (18), but although they had an increased prevalence of hypoadrenocorticism in the current study, this was not statistically significant once the Bonferroni correction was applied. The previously reported prevalence in standard poodles was 8.6%, which is higher than the prevalence in our study for this breed and may be explained by the genetic variance of sires and dams in Quebec. Although the mode of inheritance (auto-somal recessive) has been well-identified in standard poodles (11), it remains unknown in other breeds (19).

The overall prevalence of hypoadrenocorticism in our studied population was 0.38% (95% CI: 0.26% to 0.5%), which is higher compared to previously reported prevalences (0.06% to 0.28%) (10). This difference could be explained by the fact that the study was performed in a secondary and tertiary referral practice.

A female predisposition has previously been described for hypoadrenocorticism, with approximately 70% of affected dogs being female (3); however, no gender predisposition has been demonstrated in the standard poodle, Portuguese water dog, Nova Scotia duck tolling retriever, or bearded collie, nor was this observed in Great Pyrenees dogs in our study. Although males with hypoadrenocorticism were over-represented in both groups (GP: 63%, CG: 60%), the higher proportion of males was significant only in the control group (P = 0.04), and likely reflects the male distribution of the overall canine population of the CHUV during the study period. The median age at time of diagnosis was not significantly different between the 2 groups in our study (GP: 3.56 y, CG: 4.85 y), and was similar to the median age of onset for all breeds (13,20,21).

Clinical signs of hypoadrenocorticism are well-described in the veterinary literature (2,3,22). Although the reasons for presentation, clinical signs, and laboratory findings were non-specific, this retrospective study was able to highlight some specific features in the clinical presentation of Great Pyrenees dogs with hypoadrenocorticism presented at the CHUV. In comparison with Addisonians of other breeds, Great Pyrenees dogs were less frequently presented with gastrointestinal signs, but this difference was not significant, yet more frequently presented with hypotension and cachexia which may reflect misdiagnosis/late diagnosis because Great Pyrenees dogs are not known to be at higher risk of developing hypoadrenocorticism. The main clinical signs in GP were lethargy (77.7%) and anorexia (55.5%). Gastrointestinal signs (diarrhea, vomiting, or regurgitation) were noticed in 33.3% of GP and 61% of dogs in the control group. Findings for our control group are consistent with literature data (vomiting or regurgitation present in 68% to 75% of cases, and diarrhea in 35% of cases) (2,17,20).

Anemia, increased blood urea nitrogen (BUN), and creatinine and eosinophilia were also more common in the Great Pyrenees breed than in other breeds with hypoadrenocorticism. Azotemia is reported in 66% to 95% of dogs with primary hypoadrenocorticism at the time of initial diagnosis (2,3,21,23). In our study, all Addisonian GP were azotemic, which was significantly higher than the control group (51.8%). They were also more frequently anemic than the control group. In the veterinary literature, a mild normochromic nonregenerative anemia is commonly reported in Addisonians (21% to 25% cases) (3,19,20,21). As Great Pyrenees dogs were more frequently presented with hypotension, they could be more prone to have intestinal bleeding and pre-renal azotemia than dogs of the control group.

Although not a consistent feature in Addisonian patients, lack of a stress leukogram can be a valuable finding particularly in glucocorticoid only deficient dogs (17). The lack of a stress leukogram was a common finding in our study (GP: 62.5%, CG: 63%), although less common than the 92% reported in the veterinary literature (17,20,21). Absolute eosinophilia is reported in 10% to 20% of cases (10,17,21,24). In our study, eosinophilia was observed in 37.5% of GP and in only 13.9% of the CG. This difference is surprising since eosinophilia has not been reported in Great Pyrenees dogs in the literature, nor was it observed in the entire Great Pyrenees dog population seen at the CHUV during the time of the study, except in our Addisonian population. Although this suggests that eosinophilia is a common finding in Great Pyrenees dogs with hypoadrenocorticism, no information regarding potential parasitism was recorded, which may be an alternate explanation.

In North America, DOCP is the only mineralocorticoid supplement approved for veterinary use. Because of financial concerns, all of the GP diagnosed with a primary typical hypoadrenocorticism in our study were treated with fludrocortisone, a synthetic glucocorticoid with significant mineralocorticoid activity. The starting dosage of fludrocortisone is usually 0.02 mg/kg BW, divided and given twice daily (10,21,22). The median starting dosage in our study was 0.018 mg/kg BW per day. The dosage of fludrocortisone was significantly increased during follow-up when considering our entire Addisonian population, but no significant difference was observed when evaluating the 2 groups separately. Nevertheless, a tendency for fludrocortisone dosage to be increased was observed in the CG only. Veterinarians were possibly less eager to increase the dosage of fludrocortisone in GP than in dogs of other breeds either because of financial concerns or because of cumulative corticosteroid side effects, given the weight of the GP. There was missing information on the long-term follow-up, and time and cause of death in these cases to support any conclusion.

Although evidence supports a similar autoimmune etiology as in humans leading to the destruction of the adrenal cortex, the pathogenesis of hypoadrenocorticism in dogs is not well- established (21,25). In humans, the enzyme steroid 21-Hydrolase (21OH) has been shown to be a major adrenal autoantigen in Addison’s disease, and 21OH antibodies (21OH-Ab) and/or adrenal autoantibodies are present in 48% to 100% of patients with idiopathic Addison’s disease (4,6,26–30). The genetic factors involved in determining susceptibility to Addison’s disease remain poorly understood, despite numerous studies. However, human leucocyte antigen (HLA) DRB1 is recognized as one of the main susceptibility loci involved, with additional risk provided by the major histocompatibility complex (MHC) class I region (29). Similarly, in dogs, several studies support an immune-mediated process with an immune mediated adrenalitis being the most likely etiology for the majority of spontaneous cases of canine primary hypoadrenocorticism (21,25). Two loci have been identified in Portuguese water dogs on the Canis familiaris (CFA) chromosomes CFA 12 and 37 (12). Another study suggests an association between dog leukocyte antigen (DLA) class II haplotype and the development of hypoadrenocorticism in Nova Scotia duck tolling retrievers (30,31). As Short et al (29) have already emphasized, pedigree dogs, because of their relatively small population and existence for a relatively short time period, have a high linkage disequilibrium and long haplo-types within a breed. This provides a considerable advantage in veterinary medicine compared to human medicine in increasing the potential of identifying novel genes that contribute to canine genetic diseases. Moreover, strong similarities have been shown in the genetic background of hypoadrenocorticism between dogs and humans, thereby enabling dogs to be spontaneous, genetic models for human Addison’s disease (29). The discovery of a new at-risk breed could be helpful to better understand the genetic background of this endocrine disorder.

Further studies are needed to infer a genetic basis of the disease in Great Pyrenees dogs as well as its inheritance rate and mode. The small population of Great Pyrenees dogs in Quebec with a high prevalence of the disease may provide an opportunity to identify the etiology and implicated genes in the breed. Unfortunately, it was not possible to establish the degree of relatedness of the Great Pyrenees dogs in our study.

Limits of this study include those inherent to a retrospective study (i.e., missing data, lack of standardization). Moreover, the population size of Great Pyrenees dogs was small, which can lead to type 2 statistical error. Multiple comparisons were performed between the 2 groups to identify specific clinical features of Great Pyrenees dogs suffering from hypoadrenocorticsm, which can lead to type 1 statistical error. Our results, therefore, need to be confirmed by further studies. Finally, since the study was performed in a referral center, the population studied may not be representative of the general canine population and therefore our results should be considered carefully. The real prevalence of hypoadrenocorticism in the general Great Pyrenees dog population remains unknown and large epidemiological studies are required to obtain more representative values. Nevertheless, our results raise awareness about a breed predisposition.

In conclusion, Great Pyrenees dogs diagnosed with hypoadrenocorticism had a prevalence of hypoadrenocorticism of 9.73% and were over-represented in the study population. Therefore, an inherited susceptibility is suspected. Although clinical features were nonspecific, Great Pyrenees dogs were more frequently presented with signs of hypotension, anemia, azotemia, and eosinophilia. A prospective study is necessary to evaluate the prevalence of hypoadrenocorticism in a larger population of Great Pyrenees dogs and to establish its rate and mode of inheritance. CVJ