Clinical features and heritability of hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers: 25 cases (1994-2006)

OBJECTIVE: To evaluate the clinical features and heritability of naturally occurring hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers (NSDTRs). DESIGN: Retrospective case series. ANIMALS: 25 NSDTRs with hypoadrenocorticism. PROCEDURES: Questionnaires completed by owners of NSDTRs with hypoadrenocorticism and medical records from veterinarians were reviewed for information regarding diagnosis, age at diagnosis, concurrent diseases, age at death, and cause of death. Pedigrees were analyzed for heritability and mode of inheritance of hypoadrenocorticism (including complex segregation analysis of pedigrees of 1,515 dogs). RESULTS: On the basis of results of ACTH stimulation testing, hypoadrenocorticism was diagnosed in 16 female and 9 male NSDTRs (including 6 full siblings). Median age at diagnosis was 2.6 years; the diagnosis was made prior to 2 years of age in 11 dogs. Seventeen dogs had hyponatremia, hyperkalemia, or both, and serum electrolyte concentrations were within reference ranges for 8 dogs at the time of diagnosis. Median survival time after diagnosis for 4 dogs that died or were euthanized as a result of medical causes was 1.6 years. Heritability was calculated at 0.98 with no sex effect, and complex segregation analysis fit a major gene model with an autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL RELEVANCE: In NSDTRs, hypoadrenocorticism was diagnosed at an earlier age, compared with published reports of age at diagnosis among the general dog population. Among the study dogs, 32% had no serum electrolyte abnormalities at the time of diagnosis, and the disease appeared to have an autosomal recessive mode of inheritance in the breed.     

Comparison of classic hypoadrenocorticism with glucocorticoid-deficient hypoadrenocorticism in dogs: 46 cases (1985-2005)

OBJECTIVE: To compare dogs with glucocorticoid-deficient hypoadrenocorticism (GDH) with those with mineralocorticoid- and glucocorticoid-deficient hypoadrenocorticism (MGDH) and determine prevalence, historical and clinicopathologic markers, and outcome of dogs with GDH. DESIGN: Retrospective case series. ANIMALS: 46 dogs with hypoadrenocorticism. PROCEDURES: Records in the veterinary medical database at Purdue University were searched for dogs in which hypoadrenocorticism had been diagnosed at the Veterinary Teaching Hospital from 1985 to 2005. Data pertaining to signalment, history, a minimum clinicopathologic database, treatment, and outcome were collected. Dogs with hypoadrenocorticism were classified as having MGDH if hyponatremia, hyperkalemia, or both were detected and as having GDH if hyponatremia and hyperkalemia were absent. Dogs were excluded if they had ever been treated with mitotane or had been treated with > 1 dose of corticosteroids within a month prior to the ACTH-stimulation test. RESULTS: 35 dogs with MGDH and 11 dogs with GDH met the inclusion criteria. Dogs with GDH were older at the time of diagnosis and had a longer duration of clinical signs prior to diagnosis than those with MGDH. Dogs with GDH were more likely to be anemic, hypoalbuminemic, and hypocholesterolemic than dogs with MGDH. CONCLUSIONS AND CLINICAL RELEVANCE: GDH was more common than reported in a referral hospital population of dogs with primary hypoadrenocorticism. Definitive diagnosis of GDH remains a clinical challenge. Absence of a stress leukogram in dogs with signs of illness (especially relating to the gastrointestinal tract) warrants further investigation. Most dogs with primary cortisol deficiency do not develop mineralocorticoid deficiency.     

Ventricular systolic dysfunction in dogs diagnosed with hypoadrenocorticism

In human patients with hypoadrenocorticism, a secondary dilated cardiomyopathy is noted that has been reported to resolve with replacement steroid therapy. A similar secondary dilated cardiomyopathy in dogs with hypoadrenocorticism has not been previously described. We present three dogs concurrently diagnosed with hypoadrenocorticism and ventricular dilation with systolic dysfunction. Two dogs were presented with clinical signs consistent with biventricular congestive heart failure and a third dog was presented with signs of acute hypoadrenocorticism without congestive heart failure. All dogs recovered to normal cardiac size and function with therapy. Hypoadrenocorticism should be considered as a differential diagnosis in dogs that present with ventricular dilation and systolic dysfunction if there are other indicators in the clinical and laboratory testing. Additionally, a thorough cardiac evaluation should be recommended for dogs that are found to have a heart murmur at the time of diagnosis of hypoadrenocorticism.     

Massive hematuria of nontraumatic renal origin in dogs

Massive hematuria of renal origin was diagnosed in 4 dogs. In all dogs, blood and blood clots were clearly visible in the urine. Serum urea nitrogen and urine concentrating ability were normal. All dogs were anemic, and results of coagulation and platelet function tests were within normal limits. Excretory urography indicated hydroureter and hydronephrosis in all dogs, with filling defects in the bladder attributable to large blood clots in 2 dogs. Cystotomy and catheterization of the ureters enabled identification of one kidney as the source of bleeding in 3 dogs. Unilateral nephrectomy and ureterectomy resolved their hematuria. The results of histologic examination were normal in 2 dogs. The 3rd dog had evidence of pyelitis. Cystoscopy of the 4th dog did not reveal hematuria from either ureter. The dog was not operated on and it continued to have intermittent hematuria.     

Muscle cramps in two standard poodles with hypoadrenocorticism

Two standard poodles were evaluated for painful, episodic muscle cramps affecting their thoracic and pelvic limbs. Both dogs had been diagnosed with hypoadrenocorticism and were being treated with fludrocortisone acetate and prednisone when evaluated for muscle cramps. However, the muscle cramping started approximately 1 month prior to the diagnosis of hypoadrenocorticism. Findings on general physical examination included lethargy and dehydration. Neurological examination was normal between episodes. Serum biochemical abnormalities included hyperalbuminemia, azotemia, hyponatremia, hypochloremia, and hyperkalemia. Altering treatment to desoxycorticosterone pivalate resolved the electrolyte abnormalities and the episodes of muscle cramping in both dogs. The authors conclude that hypoadrenocorticism can be associated with episodes of painful muscle cramping in standard poodles.     

Examination of candidate genes for hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers

Inherited hypoadrenocorticism occurs in some dog breeds including the Nova Scotia Duck Tolling Retriever (NSDTR) and is thought to be due to an immune attack on the adrenal glands. The genetic cause of this disorder in dogs has not been identified; however, many genes have been associated with hypoadrenocorticism and other immune-mediated conditions in humans including AIRE, BAFF, Casp10, CD28, CTLA-4, FASL, PTPN22, and TNFRSF6B. Microsatellite marker loci were analysed for linkage with the disease phenotype in a pedigree of NSDTRs and excluded all genes examined, the exception being CTLA-4, which was neither excluded nor shown to be associated by this analysis. Thus, genes associated with hypoadrenocorticism in humans were not linked with the condition in the dog. Further examination is necessary to identify the genetic cause of inherited hypoadrenocorticism in dogs and this may reveal a novel gene not yet implicated with immune-mediated disease.     

Hyponatremia and hyperkalemia associated with idiopathic or experimentally induced chylothorax in four dogs

Two dogs with idiopathic chylothorax and 2 dogs with experimentally induced (ie, ligation of the cranial vena cava) chylothorax were treated by intermittent thoracic drainage. Of these 4 dogs, 3 that did not have evidence of renal failure had normal or near-normal serum sodium and potassium concentrations before thoracic drainage began, and all 3 developed repeatedly marked hyponatremia and hyperkalemia during thoracic drainage. Another dog became weak and depressed, ostensibly because of hyperkalemia. Serum sodium and potassium concentrations in 1 dog with spontaneous chylothorax returned to normal after chylothorax resolved and thoracic drainage was stopped. The other 3 dogs died or were euthanatized, and the effect of stopping thoracic drainage could not be evaluated. In 3 dogs in which it was measured, normal-to-high plasma cortisol concentration was observed before and after adrenocorticotropin administration, and 2 dogs also had hyperaldosteronemia. Hyponatremia was hypothesized to be caused by sodium loss via thoracic drainage whereas hyperkalemia may have been multifactorial in origin, but probably was attributable, at least, in part to decreased renal potassium clearance.     

Radiographic findings in dogs with naturally-occurring primary hypoadrenocorticism.

Survey radiographs often are obtained in dogs with primary hypoadrenocorticism in adrenal crisis as part of the routine evaluation of a critically ill dog. In this study, standardized methods of cardiac, pulmonary vasculature, and vena cava mensuration were used in 22 dogs with naturally-occurring primary hypoadrenocorticism, and the findings were compared with those in 22 breed-matched, clinically normal dogs. Most (81.8%) untreated dogs with primary hypoadrenocorticism had one or more radiographic abnormalities, including small size of the heart (45.5%), cranial lobar pulmonary artery (36.4%), caudal vena cava (54.5%), or liver (36.4%). Megaesophagus was not found in any of the dogs with hypoadrenocorticism, and therefore, compared to the other common radiographic findings, should be considered a rare finding.     

Multiple endocrine abnormalities in Basenji dogs with renal tubular dysfunction

Three Basenji dogs with renal tubular dysfunction were studied. Hyposthenuria and diminished urine concentrating ability, indicative of nephrogenic diabetes insipidus, were documented. Metabolic acidosis, hyperchloremia, and reduction in glomerular filtration rate also were detected in all dogs. In addition, an exaggerated response to the adrenocorticotropin test and hyperaldosteronism, believed to be secondary to decreased effective circulating blood volume, were detected in all 3 dogs. Thyroxine values were decreased in all dogs and could be correlated with histopathologic changes of the thyroid gland in 2 dogs. Gastropathy and hypergastrinemia were identified in 2 dogs. Diffuse lymphocytic-plasmacytic enteritis was evident in 2 dogs. It was concluded that a urine concentrating defect that may be secondary to hypercortisolism exists in Basenji dogs with renal tubular dysfunction.     

Discospondylitis associated with three unreported bacteria in the dog

Three cases of discospondylitis in the dog, caused respectively by Pseudomonas aeruginosa, Enterococcus faecalis and Staphylococcus epidermidis, are reported. These bacteria have not previously been documented as being the cause of the condition in this species. The neurological involvement was severe in all three cases. Two dogs were paraplegic and one was tetraplegic, and one of the paraplegic dogs had no deep pain on the extremities of both pelvic limbs. All dogs were treated surgically with a satisfactory neurological recovery.     

Clinical evaluation of sodium sulfanilate clearance for the diagnosis of renal disease in dogs

Sodium sulfanilate (ss) clearance time was measured in 13 clinically normal dogs and in 24 dogs with suspected renal disease. The results were compared with those from more routine tests of renal function to assess whether measurement of ss clearance provided additional information about the degree of renal dysfunction. It was concluded that ss clearance is a more sensitive measure of renal dysfunction than is serum creatinine or blood urea nitrogen. Sodium sulfanilate half-life was increased before the complete loss of ability to concentrate urine; however, urine concentrating ability was impaired in some dogs with normal ss clearance. In dogs with glomerular disease, proteinuria developed before increased ss clearances. However, ss clearance was a more reliable method of monitoring the degree of renal dysfunction than was protein concentration in single urine samples.     

Clinical features of hypoadrenocorticism in soft-coated wheaten terrier dogs: 82 cases (1979–2013)

The objective of this retrospective case series, which included 82 client-owned soft-coated wheaten terriers, was to characterize clinical features of hypoadrenocorticism in this breed. Median age at diagnosis was 3.5 years. There was no gender predilection. Clinicopathologic findings included sodium/potassium ratio < 27 (85%), hyperkalemia (76%), hyponatremia (63%), elevated blood urea nitrogen (83%) or creatinine (71%), and hypercalcemia (36%). Nine dogs with normal sodium and potassium (11%) were older and less often azotemic, hyperphosphatemic, or hypercalcemic. Twenty-one dogs (26%) developed protein-losing nephropathy (n = 18) and/or end-stage renal disease (n = 3). Overall median survival time was 5.4 years, but was shorter in dogs with normal sodium and potassium at diagnosis (4.2 years), or those with subsequent protein-losing nephropathy (4.2 years). This population showed no gender predilection, unlike that reported in the general canine population with hypoadrenocorticism, and more comorbid protein-losing nephropathy than in the general soft-coated wheaten terrier population.     

Prevalence of behavioral changes associated with age-related cognitive impairment in dogs

OBJECTIVE: To determine the prevalence of age-related behavioral changes, namely impairment, in a randomly chosen population of dogs. DESIGN: Age-stratified cohort study. ANIMALS: 97 spayed female and 83 castrated male dogs that were 11 to 16 years old. PROCEDURE: Data on possible impairment in 4 behavioral categories (ie, orientation in the home and yard, social interaction, house training, and sleep-wake cycle) linked to cognitive dysfunction were obtained from dog owners, using a structured telephone interview. Hospital records of dogs had been screened to exclude dogs with dysfunction in organ systems that may cause behavioral changes. Dogs with behavioral impairment were those with > or = 2 signs of dysfunction within a category. Dogs with impairment in 1 category were considered mildly impaired and those with impairment in > or =2 categories were considered severely impaired. RESULTS: Age by sex interactions for dogs with impairment in any category were not significant, and, therefore, data on castrated males and spayed females were pooled for analyses across ages. The prevalence of age-related progressive impairment was significant in all categories. The percentage of 11- to 12-year-old dogs with impairment in > or = 1 category was 28% (22/80), of which 10% (8/80) had impairment in > or = 2 behavioral categories. Of 15- to 16-year-old dogs, 68% (23/34) had impairment in > or =1 category, of which 35% (12/34) had impairments in > or = 2 categories. There were no significant effects of body weight on the prevalence of signs of dysfunction in the behavioral categories. CONCLUSIONS AND CLINICAL RELEVANCE: Data collected provide estimates of the prevalence of various degrees of age-related behavioral changes associated with cognitive dysfunction in dogs. Age-related behavioral changes may be useful indicators for medical intervention for dogs with signs of cognitive impairment.     

Use of a low-dose ACTH stimulation test for diagnosis of hypoadrenocorticism in dogs

BACKGROUND: Although definitive diagnosis of hypoadrenocorticism usually is made by an adrenocorticotrophic hormone (ACTH) stimulation test using 250 microg/dog of synthetic ACTH (cosyntropin/tetracosactrin), increased costs have prompted a search for less-expensive diagnostic methods. HYPOTHESIS: A low-dose ACTH stimulation test (5 microg/kg) will distinguish between dogs with nonadrenal illness and hypoadrenocorticism. Additionally, administration of cosyntropin will not affect the results of another ACTH stimulation test performed 24 hours later. ANIMALS: Eight healthy adult dogs and 29 hospitalized dogs with suspected hypoadrenocorticism. METHODS: In this prospective study, each healthy dog received 4 ACTH stimulation tests. Dogs received either 5 microg/kg or 250 microg/dog of cosyntropin on day 1 and the alternate dose on day 2. The opposite dosing sequence was used after a 2-week washout period (days 15 and 16). Dogs with suspected Addison's disease received 2 ACTH stimulation tests, 24 hours apart, using either a dose of 5 microg/kg cosyntropin or 250 microg/dog on the 1st day and the alternate dose on the 2nd day. RESULTS: In healthy dogs, poststimulation cortisol concentrations on days 2 and 16 and days 1 and 15 were equivalent (90% confidence interval [CI]: 86.7-101.2%). In dogs with suspected Addison's disease, mean (+/-SD) cortisol responses to ACTH in the 5 microg/kg dose (16.2+/-7.7 microg/dL) and 250 microg/dog dose (15.9+/-6.3 microg/dL) were statistically equivalent (90% CI: 91.2-105.4%). CONCLUSIONS AND CLINICAL IMPORTANCE: Low-dose ACTH stimulation testing distinguishes between dogs with nonadrenal illness and hypoadrenocorticism. Additionally, the administration of 2 ACTH stimulation tests on consecutive days does not affect results of the second test.     

Diseases of the adrenal cortex of dogs and cats

The most common cause of hypoadrenocorticism in dogs is idiopathic immune-mediated destruction of the adrenal cortex. Other causes include anterior pituitary insufficiency, pituitary or adrenal neoplasia, acute withdrawal of exogenous corticosteroids, and mitotane toxicity. Females are affected more often than males; only 1 feline case has been documented. Animals 2-5 years old are most commonly affected. Clinical signs include lethargy, weakness, weight loss, anorexia, vomiting, diarrhea and bradycardia. Hematologic and biochemical changes can include eosinophilia, lymphocytosis, anemia, hyperkalemia, hyponatremia and hypercalcemia. Diagnosis is by finding negligible resting levels of plasma cortisol and no response to ACTH administration, and a serum Na:K ratio of 20:1 or less. Treatment involves restoring fluid volume, correcting acidosis, and supplementing salt and glucocorticoids. Daily oral use of prednisone at 0.05 mg/kg can safely maintain most affected dogs. Some dogs only require glucocorticoids in stressful situations. Iatrogenic secondary adrenocortical insufficiency (iatrogenic Cushing's disease) may result from a single injection of long-acting glucocorticoids or from long-term use. Clinical signs are the same as for natural hyperadrenocorticism, but endogenous cortisol release is suppressed. Treatment is gradual withdrawal of the offending glucocorticoid and elimination of the cause that initially prompted glucocorticoid therapy.     

Hypoadrenocorticism in a family of Standard poodles

Thirty-one ancestors of a Standard Poodle with hypoadrenocorticism were located. Hypoadrenocorticism had been confirmed in 8 of 32 dogs (25%) by use of ACTH response testing or necropsy. In 2 additional dogs, hypoadrenocorticism was diagnosed on the basis of characteristic clinical signs and serum electrolyte abnormalities consistent with adrenocortical insufficiency. Although an obvious pattern of inheritance was not evident, the high prevalence of hypoadrenocorticism suggested that heredity may have been a factor in the development of idiopathic adrenal insufficiency in dogs of this family.     

Toxicity of aminoglycoside antibiotics.

In cats, aminoclycosides cause vestibular damage followed in a few days by renal damage. The reverse is true in the dog, except that streptomycin causes vestibular damage prior to renal damage. To avoid toxicities, therapeutic doses of aminoglycosides should not be given longer than a week and they should be given cautiously in animals with renal impairment. Failure of the kidneys to eliminate aminoglycosides will result in very high blood levels, even with therapeutic doses, that can cause further renal and vestibular damage. The oral administration of aminoglycosides is seldom dangerous when normal therapeutic doses are employed. Although it is remote, the possibility exists that animals with renal impairment and intestinal obstruction may become intoxicated. Kanamycin is less nephrotoxic to dogs than neomycin and it is less destructive to the auditory nerve than vestibular damage than streptomycin. Gentamicin in cats is twice as toxic to the vestibular apparatus as streptomycin and more toxic to the cochlea than streptomycin or dihydrostreptomycin. Neomycin is more toxic than kanamycin, gentamicin, and streptomycin to both cats and dogs. Amikacin causes renal damage in dogs similar to other aminoglycosides. It also causes vestibular damage.     

Hypercalcaemia in the dog: a study of 40 cases

Forty dogs referred to the University Department of Clinical Veterinary Medicine, Cambridge for medical and oncological conditions between 1985 and 1990 were found to be hypercalcaemia In 18 cases the primary or underlying condition was diagnosed as lymphoproliferative disease with multicentric lymphoma occurring most commonly. Ten dogs were suffering from hypoadrenocorticism (Addison's disease) and two had adenocarcinomas of the apocrine glands of the anal sac. In three dogs a clinical diagnosis of renal dysplasia was made, this diagnosis being confirmed at post mortem examination in one dog. In the remaining cases hypercalcaemia was associated with a primary lung tumour, a thymoma, an osteosarcoma with widespread skeletal metastases, primary hyperparathyroidism due to a parathyroid adenoma, chronic panniculitis, iatrogenic hypoadrenocorticism following mito-tane therapy (one case each] and, in a further case, no diagnosis was reached. The most common clinical signs were inappetence, polyuria/ polydipsia, weakness, vomiting, lethargy and depression. As a group, the dogs with lymphoproliferative disease had a significantly higher mean plasma calcium concentration (4-3 ± 0–7 vs 3–5 ± 0–4 mmol/litre), a significantly lower mean plasma inorganic phosphate concentration (1–5 ± 0–5 vs 2–4 ± 09 mmol/litre) and were significantly older (5-5 ± 2–4 vs 3-3 + 1–8 years) than the dogs with hypoadrenocorticism.     

Canine hypoadrenocorticism: Part I

Hypoadrenocorticism (Addison’s disease) has been referred to as “the great pretender,” due to its ability to mimic other common diseases in the dog and thereby represent a diagnostic challenge. Naturally occurring hypoadrenocorticism is an uncommon canine disease. Young, female dogs are overrepresented. Hypoadrenocorticism typically results from immune-mediated destruction of all adrenocortical layers, resulting in deficiencies of min-eralocorticoids (aldosterone) and glucocorticoids (cortisol). A small number of dogs suffer from glucocorticoid deficiency only. Dogs suffering from hypoadrenocorticism may present in a variety of conditions, from a mildly ill dog to a shocky and recumbent dog. This review discusses etiology, pathophysiology, history, physical examination findings, and diagnostic findings in the Addisonian patient. A follow-up article (Part II) will discuss the definitive diagnosis and management strategies for these patients.