A case-control survey study of environmental risk factors for primary hypoadrenocorticism in dogs.

BACKGROUND: Primary hypoadrenocorticism in dogs is thought to be multifactorial with roles for both genetic and environmental factors. The contributions of environmental factors remain unexplored. OBJECTIVE: Identify environmental and lifestyle exposures associated with primary hypoadrenocorticism in 2 dog breeds with high risk of developing the disease. ANIMALS: Animals were not used in this study. Owners of Standard Poodles (STPDs) and Portuguese water dogs (POWDs) participated in a survey. METHODS: Retrospective case-control study. Dog owners were invited to participate in an online survey through convenience sampling. Questions regarded the demographics, health histories, and indoor/outdoor environments in which their dogs live and play. Responses for dogs with primary hypoadrenocorticism were compared to those without the disease using univariate and multivariate logistic regression models. RESULTS: Five thousand forty-seven responses (358 cases, 4689 controls) met initial inclusion criteria. Significant associations with modest effect size were found for community type, ingestion of canned food, and use of lawn fertilizer in some analysis models. Reproductive (spay/neuter) status exhibited the strongest association with high effect size across all models with adjusted odds ratio (OR) 2.5 (95% confidence interval [CI], 1.4-4.5; P = .003) for spayed females and 6.0 (95% CI, 2.6-13.9; P < .001) for neutered males. CONCLUSIONS AND CLINICAL IMPORTANCE: The large effect size for reproductive status reflects its high potential clinical relevance, whereas modest effect sizes for other environmental variables suggest lower potential clinical relevance. These findings are associations and do not necessarily imply causation. Before any actionable recommendations are warranted, additional evidence regarding biological mechanisms is needed.

Clinical features and long-term management of cats with primary hypoadrenocorticism using desoxycorticosterone pivalate and prednisolone.

BACKGROUND: Primary hypoadrenocorticism (PH) is rare in cats and knowledge about treatment is sparse. OBJECTIVE: To describe cats with PH with a focus on long-term treatment. ANIMALS: Eleven cats with naturally occurring PH. METHODS: Descriptive case series with data on signalment, clinicopathological findings, adrenal width, and doses of desoxycorticosterone pivalate (DOCP) and prednisolone during a follow-up period of >12 months. RESULTS: Cats ranged from 2 to 10 years (median 6.5); 6 cats were British Shorthair. Most common signs were reduced general condition and lethargy, anorexia, dehydration, obstipation, weakness, weight loss, and hypothermia. Adrenal glands on ultrasonography were judged small in 6. Eight cats could be followed for 14 to 70 months (median: 28). Two were started on DOCP doses ≥2.2 mg/kg (2.2; 2.5) and 6 < 2.2 mg/kg (1.5-2.0 mg/kg, median 1.8) q28 days. Both high-dose cats and 4 low-dose cats needed a dose increase. Desoxycorticosterone pivalate and prednisolone doses at the end of the follow-up period were 1.3 to 3.0 mg/kg (median: 2.3) and 0.08 to 0.5 mg/kg/day (median: 0.3), respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Desoxycorticosterone pivalate and prednisolone requirements in cats were higher than what is currently used in dogs; thus, a DOCP starting dose of 2.2 mg/kg q28 days and a prednisolone maintenance dose of 0.3 mg/kg/day titrated to the individual need seems warranted. Small adrenal glands (width < 2.7 mm) on ultrasonography in a cat suspected of hypoadrenocorticism can be suggestive of the disease. The apparent predilection of British Shorthaired cats for PH should be further evaluated.

Evaluation of symmetric dimethylarginine and creatinine in dogs with primary hypoadrenocorticism receiving long-term mineralocorticoid replacement therapy.

OBJECTIVES: To investigate kidney function by determining serum symmetric dimethylarginine (sSDMA) and serum creatinine (sCr) concentrations in dogs with primary hypoadrenocorticism (PH) receiving long-term mineralocorticoid replacement therapy. METHODS: Dogs with PH receiving a minimum of 12 months of either desoxycorticosterone pivalate or fludrocortisone acetate were included in the study provided that banked frozen serum samples were available for sSDMA analysis. sCr concentrations were retrieved from the medical records. In dogs still alive and presented for regular re-evaluations and in newly diagnosed patients, blood was prospectively collected for sSDMA and sCr determination. RESULTS: Thirty-two dogs met the inclusion criteria. The treatment time ranged from 12 to 146 months after initial diagnosis (median, 55.5 months). The majority of dogs had normal sSDMA and sCr concentrations throughout the hormone replacement treatment. Both sSDMA and sCr concentrations were persistently elevated in three of 32 dogs. Further workup confirmed chronic kidney disease (CKD) in all three dogs. CONCLUSIONS: Based on these data, the prevalence of CKD could be higher in dogs with PH receiving long-term mineralocorticoid replacement treatment than in the general dog population. However, additional studies with a larger number of dogs are needed to confirm it.

Genetic characterization of Addison's disease in Bearded Collies.

BACKGROUND: Primary hypoadrenocorticism (or Addison's disease, AD) is an autoimmune disease that results in destruction of the adrenal cortex and consequent adrenal insufficiency. The disease has been described in purebred and mixed breed dogs, although some breeds, including the Bearded Collie, are at increased risk for AD. Candidate gene approaches have yielded few associations that appear to be breed-specific. A single other genome-wide association study reported no significant regions of association for AD in Standard Poodles. The present study aimed to identify genomic regions of association for canine AD in Bearded Collies. RESULTS: Our study consists of the first genome-wide association analysis to identify a genome-wide significant region of association with canine AD (CFA18). Peaks of suggestive association were also noted on chromosomes 11, 16 and 29. Logistic regression analysis supported an additive effect of risk genotypes at these smaller effect loci on the probability of disease associated with carrying a risk genotype on CFA18. Potential candidate genes involved in adrenal steroidogenesis, regulation of immune responses and/or inflammation were identified within the associated regions of chromosomes 11 and 16. The gene-poor regions of chromosomes 18 and 29 may, however, harbor regulatory sequences that can modulate gene expression and contribute to disease susceptibility. CONCLUSION: Our findings support the polygenic and complex nature of canine AD and identified a strongly associated locus on CFA18 that, when combined with three other smaller effect loci, was predictive of disease. The results offer progress in the identification of susceptibility loci for canine AD in the Bearded Collie. Further studies are needed to confirm association with the suggested candidate genes and identify actual causative mutations involved with AD susceptibility in this breed.

[Therapy of primary hypoadrenocorticism in dogs with low dose desoxycorticosterone pivalate]. / Therapie des primären Hypoadrenokortizismus beim Hund mit niedrig dosiertem Desoxycorticosteronpivalat.

OBJECTIVE: Since 2016 the only approved drug for the treatment of primary hypoadrenocorticism (Addisons disease) in dogs in Germany is desoxycorticosterone pivalate (DOCP), namely Zycortal®. The initial dose recommended by the manufacturer is 2.2 mg/kg. Our own experience and select publications raise the suspicion that a distinctly lower initial dose would be sufficient. Mainly cost reduction motivates for dose reduction and with it comes a higher owner motivation and compliance. It was the objective of our retrospective study to show that an initial dose of 1.5 mg/kg DOCP is sufficient for controlling canine hypoadrenocorticism. MATERIAL AND METHODS: Dogs with primary hypoadrenocorticism were included if the initial starting dose was 1.5 mg/kg DOCP subcutaneously. The first, second and the last known dose of DOCP were documented. Electrolyte concentrations at the time of diagnosis as well as 10-14 days after the first injection, on the day of the second injection as well as at the last known injection were recorded. A dog was considered medically well-regulated when clinically healthy, sodium and potassium concentrations within the reference ranges, and when the responsible veterinarian did not recommended a dose alteration. RESULTS: All 13 included dogs were clinically healthy after the first or second injection. One dog received 1.6 mg/kg DOCP as last documented dose, all other dogs received ≤ 1.5 mg/kg (median: 1.3, range: 0.4-1.6) DOCP. Eleven dogs were injected once monthly, 2 dogs received injections every 60 days. The dogs were followed at least 7 months (median: 20 months, range: 7-26 months). CONCLUSION AND CLINICAL RELEVANCE: We were able to show that a starting dose of 1.5 mg/kg DOCP (Zycortal®) is sufficient for controlling primary hypoadrenocorticism in dogs. Adjustments of the dose are needed in some dogs. Regular measurement of electrolyte concentrations 10 days after treatment initiation and at the monthly DOCP injection is required for a correct disease management with DOCP.

Suspected bilateral adrenal gland tumour causing primary Addison's disease in a dog.

A 13-year old miniature poodle presented with a 3-day episode of vomiting, anorexia, and lethargy. Lack of micturition had been noted for 2 days. Clinical examination indicated dehydration and a tense, painful abdomen. Laboratory parameters (severe azotaemia, hyperkalaemia, severe hyponatraemia, hypochloraemia, and hyperphosphataemia with glucosuria and proteinuria) were consistent with anuric acute kidney injury (AKI). Abdominal ultrasound revealed bilateral adrenal masses. ACTH stimulation test was diagnostic for Addison's disease. Computed tomography confirmed bilateral adrenal masses and indicated multifocal liver nodules. Additionally, infiltration of the caudal vena cava with partial luminal occlusion was demonstrated. Surgical removal of the adrenal masses with venous plasty intervention and stenting of the vessels deemed unrewarding in this patient in respect to progressed tumour growth with assumed metastatic spread. The dog was treated for Addison's disease and discharged with good overall condition. Eight weeks later, the dog was euthanized due to progressive caudal vena cava occlusion. Whilst hypoadrenocoticism typically affects young to middle aged dogs, in old dogs primary Addison's disease might be caused by neoplastic bilateral adrenal gland destruction. This is the first case report of hypovolaemia leading to AKI secondary to bilateral adrenal masses causing Addison's disease in a dog.

Infecção de trato urinário inferior por Citrobacter sp em cadela com hipoadrenocorticismo / Citrobacter sp lower urinary tract infection in a bitch with hypoadrenocorticism

Citrobacter sp. é um microrganismo frequentemente encontrado em vagina de cadelas, mas corresponde a menos de 3% do total de microrganismos isolados em urocultura. O hipoadrenocorticismo (HA) é uma doença endócrina incomum e que leva a poliúria e hipostenúria. O objetivo deste trabalho é relatar o caso de uma fêmea da espécie canina, da raça Teckel, 11 anos, atendida com queixa de urina de odor alterado há vários dias, além de vômito, diarreia e inapetência há três dias, e poliúria e polidipsia há 2 meses, com histórico de tratamento anterior com mitotano para hiperadrenocorticismo. O diagnóstico foi de ITU por Citrobactersp., além de HA iatrogênico. Como destaques nos exames, relação sódio:potássio de 22,6 foi observada, sugestiva de HA, que foi confirmado por teste de estimulação com ACTH, além de urina inicialmente hipostenúrica (densidade 1,006), o que pode ser atribuído ao washout medular renal devido à hiponatremia causada pelo hipoadrenocorticismo. O tratamento foi feito com amoxicilina associada a ácido clavulânico por 20 dias, além da terapia específica para HA com prednisona e fludrocortisona, que foi continuado. A paciente recuperou-se bem, a densidade urinária aumentou após início do tratamento para HA e não houve recidiva da ITU em período de acompanhamento de 8 meses. Acredita-se que a baixa densidade urinária causada pelo HA tenha sido fator essencial para a ocorrência da ITU por Citrobacter.

Citrobacter sp. is a normal constituent of bitches' vagina, but it is related to less than 3% of total isolated microorganism in uroculture. Hypoadrenocorticism (HA) is an endocrine disease uncommonly diagnosed that leads to polyuria and hypostenuria. The aim of this work is report the case of a Teckel bitch, 11 years old, attended with complaint of altered urinary smell for several days, besides vomiting, diarrhea and inappetence for three days, and polyuria and polydispsia for two months, with previous mitotane treatment for hyperadrenocorticism. The diagnosis was Citrobacter UTI, besides iatrogenic HA. The most important exam results include sodium:potassium ratio of 22.6, suggestive of HA, that was confirmed by ACTH stimulation test. Besides, hypostenuria (urinary specific gravity ­ USG - of 1.006) was noted, attributed to renal medular washout due to hyponatremia seen in HA. Therapy comprised amoxicillin associated with clavulanic acid for 20 days, in addition to specific therapy for AH with prednisone and fludrocortisone. The patient recovery well, USG increased after the beginning of the treatment for HA and there was no UTI reinfection for a 8 month period. It is believed that low USG due to HA was essential for the occurrence of Citrobacter UTI.

Machine learning algorithm as a diagnostic tool for hypoadrenocorticism in dogs.

Canine hypoadrenocorticism (CHA) is a life-threatening condition that affects approximately 3 of 1,000 dogs. It has a wide array of clinical signs and is known to mimic other disease processes, including kidney and gastrointestinal diseases, creating a diagnostic challenge. Because CHA can be fatal if not appropriately treated, there is risk to the patient if the condition is not diagnosed. However, the prognosis is excellent with appropriate therapy. A major hurdle to diagnosing CHA is the lack of awareness and low index of suspicion. Once suspected, the application and interpretation of conclusive diagnostic tests is relatively straight forward. In this study, machine learning methods were employed to aid in the diagnosis of CHA using routinely collected screening diagnostics (complete blood count and serum chemistry panel). These data were collected for 908 control dogs (suspected to have CHA, but disease ruled out) and 133 dogs with confirmed CHA. A boosted tree algorithm (AdaBoost) was trained with 80% of the collected data, and 20% was then utilized as test data to assess performance. Algorithm learning was demonstrated as the training set was increased from 0 to 600 dogs. The developed algorithm model has a sensitivity of 96.3% (95% CI, 81.7%-99.8%), specificity of 97.2% (95% CI, 93.7%-98.8%), and an area under the receiver operator characteristic curve of 0.994 (95% CI, 0.984-0.999), and it outperforms other screening methods including logistic regression analysis. An easy-to-use graphical interface allows the practitioner to easily implement this technology to screen for CHA leading to improved outcomes for patients and owners.

Addison's Disease Secondary to Bilateral Adrenal Gland Metastatic Mammary Carcinoma in a Dog.

A 12 yr old intact female Siberian husky was referred with a 2 wk history of progressive weakness, paraparesis, anorexia, and panting. A 4 cm diameter grade 3 mammary solid carcinoma involving the fifth right mammary gland had been removed 2 days prior to the current visit. While hospitalized, the dog was diagnosed with Addison's disease based on electrolyte disturbances and low serum cortisol levels following adrenocorticotropic hormone stimulation test. An abdominal ultrasound revealed adrenal glands at the upper limit of normal size. Despite treatment, the dog deteriorated and died 4 days after presentation. A postmortem examination revealed a neoplastic infiltrate of epithelial malignant cells in both adrenal glands, popliteal lymph nodes, vertebral bodies, and paralumbar musculature, compatible with metastasis from mammary carcinoma. To our knowledge, this is the first reported case of Addison's disease secondary to metastatic mammary carcinoma in a dog.

Randomised clinical non-inferiority trial comparing two formulations of desoxycortone pivalate for the treatment of canine primary hypoadrenocorticism.

BACKGROUND: This clinical trial compared two formulations of desoxycortone pivalate (DOCP) for treating the mineralocorticoid deficit in dogs with primary hypoadrenocorticism (PH). METHODS: At veterinary clinics in the USA and France, dogs with PH (n=152) were randomised (3:1) to receive approximately monthly treatments with either the test product, Zycortal (Dechra), administered subcutaneously (n=113), or the control product, Percorten-V (Novartis Animal Health), administered intramuscularly (n=39), both at an initial dose of 2.2 mg/kg DOCP. Treatment administrators were unblinded; veterinarians assessing clinical signs were blinded; owners were blinded until at least day 90, the primary end point. Veterinarians assessed treatment outcome based on all of the following: clinical signs; sodium concentrations; potassium concentrations. Dogs received concurrent glucocorticoid therapy throughout the trial. Non-inferiority was assessed using a generalised linear mixed model to compare success rates between groups. RESULTS: Success rates at day 90 were similar between groups (per-protocol population at day 90: Zycortal 87/101, 86.2 per cent, Percorten-V 29/34, 85.1 per cent). Zycortal was non-inferior to Percorten-V as the upper limit of the 95 per cent CI for the difference between groups was 13.6 per cent. Polydipsia and polyuria were the most common clinical observations. CONCLUSION: Both products, in combination with glucocorticoid therapy, were safe and effective in treating PH.

DLA class II haplotypes show sex-specific associations with primary hypoadrenocorticism in Standard Poodle dogs.

Addison's disease (AD) is a life-threatening endocrine disorder that occurs spontaneously in both humans and dogs. Associations between MHC class II genes and AD have been shown in several human studies. Our goal was to identify MHC class II associations with AD in a large population of Standard Poodles, a breed highly predisposed to AD. We sequenced exon 2 of the class II genes DLA-DRB1, DLA-DQA1, and DLA-DQB1 in 110 affected and 101 unaffected Standard Poodles and tested for association with AD. After correcting for population structure, two haplotypes were found to confer risk of developing AD in a sex-specific manner: DLA-DRB1*015:01-DQA1*006:01-DQB1*023:01 in males (x2p = 0.03, OR 2.1) and DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 in females (x2p = 0.02, OR 8.43). Sex-specific associations have been previously described in human populations, but this is the first report of this kind in dogs. Consistent with findings in other studies, we found the DLA-DQA1*006:01 allele (x2p = 0.04) to be associated with AD in males independent of haplotype. In females, the haplotype DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 confers a very high risk for developing AD, although its frequency was rare (9 of 124 females) in our study population. Further studies are warranted to validate the findings of this exploratory dataset and to assess the usefulness of this haplotype as a risk marker for AD in female Standard Poodles. Our results highlight the importance of evaluating MHC class II disease associations in large populations, and accounting for both biological sex and population structure.

Evaluation of a low-dose desoxycorticosterone pivalate treatment protocol for long-term management of dogs with primary hypoadrenocorticism.

BACKGROUND: Lowering the dose of desoxycorticosterone pivalate (DOCP) for the treatment of dogs with primary hypoadrenocorticism (PH) decreases costs and could lead to increased owner motivation to treat their affected dogs. OBJECTIVE: To evaluate the efficacy of a low-dose DOCP treatment protocol in dogs with PH. ANIMALS: Prospective study, 17 client-owned dogs with naturally occurring PH (12 newly diagnosed, 5 previously treated with fludrocortisone acetate [FC]). METHODS: Dogs with newly diagnosed PH were started on 1.5 mg/kg DOCP SC; dogs previously treated with FC were started on 1.0-1.8 mg/kg DOCP SC. Reevaluations took place at regular intervals for a minimum of 3 months and included clinical examination and determination of serum sodium and potassium concentrations. The DOCP dosage was adjusted to obtain an injection interval of 28-30 days and to keep serum electrolyte concentrations within the reference interval. RESULTS: Median (range) follow-up was 16.2 months (4.5-32.3 months). The starting dosage was sufficient in all but 2 dogs and had to be significantly decreased after 2-3 months to a median dosage (range) of 1.1 mg/kg (0.7-1.8). Dogs 3 years of age or younger needed significantly higher dosages compared to older dogs. None of them, however, needed the 2.2 mg/kg DOCP dosage, recommended by the manufacturer. CONCLUSIONS AND CLINICAL IMPORTANCE: A starting dosage of 1.5 mg/kg DOCP is effective in controlling clinical signs and serum electrolyte concentrations in the majority of dogs with PH. An additional dose reduction often is needed to maintain an injection interval of 28-30 days. Young and growing animals seem to need higher dosages.

A longitudinal study of autoantibodies against cytochrome P450 side-chain cleavage enzyme in dogs (Canis lupus familiaris) affected with hypoadrenocorticism (Addison's disease).

Autoantibodies directed against the P450 side chain cleavage enzyme (P450scc) have been recently described in dogs affected with hypoadrenocorticism, consistent with an immune-mediated pathogenesis of this endocrinopathy. In human autoimmune Addison's disease, autoantibodies may have a predictive value, being detectable before clinical signs developing, and have been shown to persist for a period of time after diagnosis. Furthermore, an autoantibody positive status post-diagnosis has been associated with successful remission of Addison's disease following B-cell depletion, suggesting active immunopathology in these cases. The current study was designed to investigate changes in serum P450scc autoantibody status over time in dogs diagnosed with spontaneous hypoadrenocorticism. P450scc autoantibodies were measured using a species-specific radioimmunoprecipitation assay in an initial cohort of 213 dogs, indicating a prevalence of 24%. Thirty two of these dogs had repeat samples (n = 80 in total) available for analysis. Five dogs were consistently P450scc autoantibody positive in all samples, for up to 425 days following first sampling. Three dogs were initially autoantibody positive, then became seronegative at later time points. One dog, a 1 year old female entire standard poodle, was initially negative for P450scc autoantibodies, but seroconverted 18 months after diagnosis. The remaining 23 dogs with multiple samples available were consistently P450scc autoantibody negative. Persistence was not associated with sex (p = .673). This study demonstrates persistence of P450scc autoantibodies in a subset of dogs affected with hypoadrenocorticism and seroconversion over one year post-diagnosis. P450scc autoantibody reactivity in human autoimmune Addison's disease has been associated with sex, with females having a higher prevalence, possibly due to P450scc expression in the ovary acting as an additional source of antigenic stimulation. However, there was no sex difference in autoantibody persistence in the dogs affected with hypoadrenocorticism. Autontibody persistence in dogs with hypoadrenocorticism might represent persistent pathology, due to residual antigenic stimulation and autoimmune inflammation in the adrenal gland.

Prednisolone dosages in Addisonian dogs after integration of ACTH measurement into treatment surveillance.

OBJECTIVE: To examine the prednisolone and fludrocortisone dosages in dogs with primary hypoadrenocorticism after integrating endogenous ACTH (eACTH) determination into the surveillance regimen. MATERIALS AND METHODS: The local electronic medical records database was searched for dogs with primary hypoadrenocorticism and a complete follow-up including routine eACTH measurements until stabilisation. Dogs were considered stable if they showed no signs of glucocorticoid deficiency or excess, sodium and potassium were within the laboratory reference limits and no change of prednisolone and/or fludrocortisone dosage was recommended by the clinician. To avoid subclinical glucocorticoid overreplacement prednisolone was routinely reduced in case of eACTH concentrations below the detection limit of the assay. RESULTS: Thirteen client-owned dogs were eligible for inclusion in the study. Stabilisation was achieved after a median (range) of 14 (1-36) months and 4 (2-9) visits. After exclusion of two patients that did not need additional glucocorticoids, the prednisolone dosage was 0.06 (0.02-0.26) mg/kg/day and 9.1 times lower than the starting dose. No correlation was identified between prednisolone dosage in mg/kg/day and bodyweight (rSP = -0.369, p = 0.215). The final fludrocortisone dose was 0.022 (0.013-0.036) mg/kg/day. The median (range) survival time of the dogs that had died during the study period (n = 6) and all dogs was 74.5 (62-98) months and 71 (18-104) months, respectively. CONCLUSION AND CLINICAL RELEVANCE: The integration of eACTH measurement into treatment surveillance helps to optimise glucocorticoid replacement therapy. It supports treatment recommendations and is a particular aid in dogs with ambiguous clinical signs. The results suggest that most dogs on fludrocortisone substitution therapy benefit from additional very low dose prednisolone.

Lymphocyte Subsets in the Adrenal Glands of Dogs With Primary Hypoadrenocorticism.

Primary hypoadrenocorticism, or Addison's disease, is an autoimmune condition common in certain dog breeds that leads to the destruction of the adrenal cortex and a clinical syndrome involving anorexia, gastrointestinal upset, and electrolyte imbalances. Previous studies have demonstrated that this destruction is strongly associated with lymphocytic-plasmacytic inflammation and that the lymphocytes are primarily T cells. In this study, we used both immunohistochemistry and in situ hybridization to characterize the T-cell subtypes involved. We collected postmortem specimens of 5 dogs with primary hypoadrenocorticism and 2 control dogs and, using the aforementioned techniques, showed that the lymphocytes are primarily CD4+ rather than CD8+. These findings have important implications for improving our understanding of the pathogenesis and in searching for the underlying causative genetic polymorphisms.

Altered Serum Thyrotropin Concentrations in Dogs with Primary Hypoadrenocorticism before and during Treatment.

BACKGROUND: Thyrotropin (TSH) can be increased in humans with primary hypoadrenocorticism (HA) before glucocorticoid treatment. Increase in TSH is a typical finding of primary hypothyroidism and both diseases can occur concurrently (Schmidt's syndrome); therefore, care must be taken in assessing thyroid function in untreated human patients with HA. OBJECTIVE: Evaluate whether alterations in cTSH can be observed in dogs with HA in absence of primary hypothyroidism. ANIMALS: Thirty dogs with newly diagnosed HA, and 30 dogs in which HA was suspected but excluded based on a normal ACTH stimulation test (controls) were prospectively enrolled. METHODS: cTSH and T4 concentrations were determined in all dogs and at selected time points during treatment (prednisolone, fludrocortisone, or DOCP) in dogs with HA. RESULTS: cTSH concentrations ranged from 0.01 to 2.6 ng/mL (median 0.29) and were increased in 11/30 dogs with HA; values in controls were all within the reference interval (range: 0.01-0.2 ng/dL; median 0.06). There was no difference in T4 between dogs with increased cTSH (T4 range 1.0-2.1; median 1.3 µg/dL) compared to those with normal cTSH (T4 range 0.5-3.4, median 1.4 µg/dL; P=0.69) and controls (T4 range 0.3-3.8, median 1.8 µg/dL; P=0.35). After starting treatment, cTSH normalized after 2-4 weeks in 9 dogs and after 3 and 4 months in 2 without thyroxine supplementation. CONCLUSIONS AND CLINICAL RELEVANCE: Evaluation of thyroid function in untreated dogs with HA can lead to misdiagnosis of hypothyroidism; treatment with glucocorticoids for up to 4 months can be necessary to normalize cTSH.

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

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.

Prévalence et caractéristiques cliniques de l'hypoadrenocorticisme chez les Montagnes des Pyrénées au sein d'une population référée : 11 cas. L'hypoadrénocorticisme (maladie d'Addison) est une maladie rare dont la prévalence est estimée à 0,06 % à 0,28 % au sein de la population canine générale. L'objectif de cette étude rétrospective est d'évaluer la prévalence et les caractéristiques cliniques de l'hypoadrénocorticisme chez les Montagne des Pyrénées présentés au Centre Hospitalier Universitaire Vétérinaire de l'Université de Montréal entre mars 2005 et octobre 2014. Cent chiens ont été diagnostiqués avec l'hypoadrénocorticisme, représentant 0,38 % (95 % CI : 0,26 % à 0,5 %) de la population canine étudiée. La prévalence la plus élevée est observée pour les chiens Montagnes des Pyrénées (9,73 %, 95 % CI : 9,12 % à 10,35 % P < 0,0001), suivie des West Highland white terriers (4,66 %, 95 % CI : 4,24 % à 5,09 %, P < 0,0001), Grand Danois (1,87 %, 95 % CI : 1,6 % à 2,14 %, P < 0,0001), Caniches standards (1,76 %, 95 % CI : 1,5 % à 2,02 %, P = 0,0001), Saint-Bernards (1,72 %, 95 % CI : 1,47 % à 1,98 %, P = 0,018), et les Jack Russell terriers (1,48 %, 95 % CI : 1,24 % à 1,72 %, P = 0,003). Bien que les caractéristiques cliniques soient non spécifiques, comparativement aux autres chiens atteints d'hypoadrénocorticisme les Montagnes des Pyrénées étaient plus souvent présentés avec une anémie, une azotémie et une éosinophilie, ou encore en hypotension ou cachectique.(Traduit par les auteurs).

Desoxycorticosterone Pivalate Duration of Action and Individualized Dosing Intervals in Dogs with Primary Hypoadrenocorticism.

BACKGROUND: Clinicians alter dosing for desoxycorticosterone pivalate (DOCP) to mitigate costs, but this practice has not been critically evaluated in a prospective clinical trial. HYPOTHESIS/OBJECTIVES: The duration of action of DOCP is longer than 30 days in dogs with primary hypoadrenocorticism (PH). ANIMALS: A total of 53 client-owned dogs with PH. Twenty-four dogs with newly diagnosed PH (Group 1) and 29 dogs with treated PH (Group 2). METHODS: Prospective, multicenter, clinical trial. For phase I, DOCP was administered and plasma sodium and potassium concentrations were measured until the dog developed hyponatremia or hyperkalemia at a planned evaluation, or displayed clinical signs with plasma electrolyte concentrations outside of the reference interval independent of a planned evaluation, thus defining DOCP duration of action. Plasma electrolyte concentrations then were assessed at the end of the individualized dosing interval (IDI; i.e., DOCP duration of action minus 7 days, phase II and at least 3 months after concluding phase II, phase III). RESULTS: The duration of action of DOCP in dogs in phase I with naïve PH (n = 24) ranged from 32 to 94 days (median, 62 days; 95% confidence interval [CI], 57, 65) and previously treated PH (n = 29) from 41 to 124 days (median, 67 days; CI, 56, 72). Overall, the final DOCP dosing interval for all dogs that completed phase II (n = 36) ranged from 38 days to 90 days (median, 58 days; CI, 53, 61). No dog that completed phase III (n = 15) required reduction in the IDI. The DOCP duration of action, independent of group, was not significantly associated with several baseline variables. The median drug cost reduction using IDI was approximately 57.5% per year. CONCLUSION AND CLINICAL IMPORTANCE: The duration of action of DOCP in dogs with PH is >30 days, and plasma sodium and potassium concentrations can be maintained with an IDI >30 days long term.