Glucocorticoid-dependent hypoadrenocorticism with thrombocytopenia and neutropenia mimicking sepsis in a Labrador retriever dog

Glucocorticoid-deficient hypoadrenocorticism (GDH) with immune-mediated-neutropenia (IMN) and -thrombocytopenia (IMT) were diagnosed in a 3-year-old Labrador retriever dog. Glucocorticoid-deficient hypoadrenocorticism is rare and diagnostically challenging as clinical signs and laboratory abnormalities are often nonspecific. Immune-mediated cytopenias and other autoimmune disorders, as part of an autoimmune polyglandular syndrome have been reported with hypoadrenocorticism in humans. This is the first reported case of hypoadrenocorticism and bicytopenia in a dog.     

Hypoadrenocorticism in a kindred of Pomeranian dogs

Three adult Pomeranian dogs, full siblings from 2 litters, were diagnosed with primary hypoadrenocorticism following onset of hypoadrenal crisis. Review of the family history revealed the dogs’ maternal grandmother also had hypoadrenocorticism. All 4 dogs were pedigree-certified by the American Kennel Club. An inherited basis for hypoadrenocorticism is proposed in these Pomeranian dogs.     

Heritability and complex segregation analysis of hypoadrenocorticism in the standard poodle

The heritability of hypoadrenocorticism (Addison's disease) was evaluated in 778 standard poodles with known Addisonian phenotypes. Addisonian status was confirmed clinically by adrenocorticotropic hormone (ACTH) challenge and 8.6 per cent of the poodles enrolled in the study were classified as being Addisonian. Hypoadrenocorticism affected both sexes with equal probability (P > 0.1). The most common coat colours had a negligible effect on the incidence of hypoadrenocorticism (P > 0.09), although red coat colour had a significant impact on the disease, probably due to the relatively small numbers of dogs with that coat colour. The heritability of hypoadrenocorticism in the standard poodle was estimated to be 0.75. Complex segregation analyses suggested that hypoadrenocorticism in the breed is influenced by an autosomal recessive locus. Clarification of both the heritability and mode of inheritance of hypoadrenocorticism in the standard poodle allows for better-informed breeding decisions.     

Calcium metabolism in eight dogs with hypoadrenocorticism

Hypoadrenocorticism is a well-described endocrinopathy in dogs that results from deficient production and secretion of glucocorticoids and/or mineralocorticoids. Although hyperkalaemia, hyponatraemia and hypochloraemia are the most common electrolyte disturbances, hypercalcaemia also occurs in approximately 30 per cent of cases. The pathogenesis of hypercalcaemia in dogs with hypoadrenocorticism is unknown. This case series reports ionised calcium, parathyroid hormone, parathyroid hormone-related protein and vitamin D metabolite concentrations that were measured in eight dogs with concurrent hypercalcaemia and hypoadrenocorticism. Ionised calcium was increased in five of seven dogs with hypercalcaemia associated with hypoadrenocorticism. Parathyroid hormone, parathyroid hormone-related protein and 1,25 dihydroxyvitamin D concentrations were within their reference ranges in seven of eight dogs, six of seven cases and six of seven dogs, respectively. This case series highlights that hypercalcaemia associated with hypoadrenocorticism is rarely associated with increases in plasma parathyroid hormone, parathyroid hormone-related protein or serum 1,25 dihydroxyvitamin D concentrations.     

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.     

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.     

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.     

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.     

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.     

Treatment and Long-Term Follow-up of 205 Dogs With Hypoadrenocorticism

Results of long-term treatment were evaluated in 200 dogs with primary hypoadrenocorticism and 5 dogs with spontaneous secondary hypoadrenocorticism. Fludrocortisone acetate initially was used for mineralocorticoid replacement in 190 of the dogs with primary hypoadrenocorticism. The daily dose of fludrocortisone required in these dogs increased significantly during the treatment period (median, 2.6 years) from an initial median dose of 13.1 μg/kg to a final dose of 22.6 μg/kg. In 27 of the 200 dogs, mineralocorticoid therapy was changed from fludrocortisone to desoxycorticosterone pivalate (DOCP) because of adverse effects, poor response, or financial considerations. The dose of DOCP required in the 33 dogs (27 dogs plus 6 dogs initially given DOCP) increased significantly during the treatment period (median, 3.5 years) from an initial median dose of 1.56 mg/kg to a final dose of 1.69 mg/kg; the interval between DOCP injections ranged from 14 to 35 days (median, 30 days). The dose of prednisone administered to the dogs with primary hypoadrenocorticism decreased significantly from an initial median dose of 0.3 mg/kg to a final dose of 0.2 mg/kg; the drug was discontinued in 22 dogs due to adverse effects. The 5 dogs with secondary hypoadrenocorticism received only glucocorticoid replacement therapy (prednisone) at initial and final daily dosages of 0.41 mg/kg and 0.25 mg/kg, respectively, during a median treatment period of 4.4 years. More than 80% of the dogs were considered to have a good to excellent response to therapy. The median survival time of all 205 dogs was 4.7 years. There were no differences in response to treatment or survival between dogs treated with fludrocortisone and those receiving DOCP, or between dogs with primary hypoadrenocorticism and those with secondary hypoadrenocorticism.     

Hypoadrenocorticism in small animals

The diagnosis and treatment of hypoadrenocorticism can be one of the greatest challenges faced by veterinary practitioners, as Addison's disease may have many faces and many presentations. Although the disease is most often diagnosed in dogs, cats may also suffer from Addison's disease. The practitioner must have a high index of suspicion to make a diagnosis of hypoadrenocorticism. This index of suspicion is based on knowledge of the common signalment, history, physical examination, and laboratory findings. Diagnosis of hypoadrenocorticism is supported by appropriate choice of diagnostic endocrine tests that are described in detail in this article. Once a diagnosis of hypoadrenocorticism has been made, expedient treatment is of foremost concern. Timely treatment using fluids, corticosteroids, and supportive care will ensure a successful outcome; the emergency treatment of Addison's is covered briefly in this article and fully in another article in this issue. The purpose of this review was to describe the clinical diagnosis and chronic treatment of hypoadrenocorticism in dogs and cats.     

Clinicopathologic findings resembling hypoadrenocorticism in dogs with primary gastrointestinal disease

Nine dogs with primary gastrointestinal disease had clinical and laboratory findings resembling hypoadrenocorticism. The dogs had histories of anorexia, weakness or lethargy, diarrhea, vomiting, and weight loss. Hypothermia, dehydration, and emaciation also were detected on physical examination. Hyponatremia, hyperkalemia, and abnormally low Na/K ratios were found on laboratory evaluation, but results of ACTH-response tests were not compatible with hypoadrenocorticism. The primary diagnoses were trichuriasis and salmonellosis in 2 dogs, trichuriasis in 5 dogs, and perforated duodenal ulcer in 2 dogs. Most dogs responded to medical or surgical treatment of their primary gastrointestinal disease, and the original electrolyte abnormalities resolved. These findings emphasize the importance of the ACTH-response test in the diagnostic evaluation of dogs with clinicopathologic findings similar to those of hypoadrenocorticism.     

Use of basal serum or plasma cortisol concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (2000-2005)

OBJECTIVE: To determine whether basal serum or plasma cortisol concentration can be used as a screening test to rule out hypoadrenocorticism in dogs. DESIGN: Retrospective case-control study. ANIMALS: 110 dogs with nonadrenal gland illnesses and 13 dogs with hypoadrenocorticism. PROCEDURES: Sensitivity and specificity of basal serum or plasma cortisol concentrations of either 2 microg/dL that are not receiving corticosteroids, mitotane, or ketoconazole are highly unlikely to have hypoadrenocorticism. However, if the basal cortisol concentration is 相似文献   

Ultrasonographic evaluation of the adrenal glands in six dogs with hypoadrenocorticism.

The purpose of this study was to determine the value of ultrasonographic characterization of the adrenal glands in dogs with hypoadrenocorticism. Measurements of adrenal glands were obtained in six dogs with hypoadrenocorticism. The adrenal glands on both sides were shorter (range: left adrenal gland length, 10.0 to 19.7 mm; right adrenal gland length, 9.5 to 18.8 mm) and thinner (range: left adrenal gland thickness, 2.2 to 3.0 mm; right adrenal gland thickness, 2.2 to 3.4 mm) than in normal dogs (range: left adrenal gland length, 13.2 to 26.3 mm; right adrenal gland length, 12.4 to 22.6 mm; left adrenal gland thickness, 3.0 to 5.2 mm; right adrenal gland thickness, 3.1 to 6.0 mm). Statistical analysis revealed a significant reduction in size of the left adrenal gland (p less than 0.05) in dogs with hypoadrenocorticism compared to the left adrenal gland in normal dogs. The results of this study show that atrophy of the adrenal glands in dogs with hypoadrenocorticism seems to lead to an ultrasonographic-measurable reduction in size of the adrenal glands.     

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.     

Basal Serum Cortisol Concentration as a Screening Test for Hypoadrenocorticism in Dogs

Background

Measurement of basal serum or plasma cortisol concentration is used as a screening test for hypoadrenocorticism in dogs, but is not well characterized.

Objectives

To evaluate the sensitivity and specificity of basal serum cortisol to detect hypoadrenocorticism in a population of dogs with a clinical suspicion of hypoadrenocorticism.

Animals

Four hundred and fifty dogs with nonadrenal gland illness and 14 dogs with naturally occurring hypoadrenocorticism were included.

Methods

Retrospective case‐control study. The records of all dogs having had an ACTH stimulation test performed between January 2005 and September 2011 at the University of Bristol were reviewed. Dogs were included if the test was performed as a screening for hypoadrenocorticism. The sensitivity and specificity of basal serum cortisol concentration to detect dogs with hypoadrenocorticism were calculated using 2 cut‐offs and compared to the gold standard ACTH stimulation test.

Results

Using a cut‐off of ≤2 μg/dL (≤55 nmol/L), the sensitivity and specificity of basal cortisol to detect hypoadrenocorticism were 100% and 63.3%, respectively, whereas for a cut‐off of ≤1 μg/dL (≤28 nmol/L), the sensitivity and specificity were 85.7% and 91.8%, respectively.

Conclusions and Clinical Importance

Measurement of basal serum cortisol is useful as a screening test for hypoadrenocorticism in dogs using a cut‐off of ≤2 μg/dL (≤55 nmol/L), and the disease is unlikely with a basal serum cortisol >2 μg/dL (>55 nmol/L). A basal serum cortisol ≤2 μg/dL (≤55 nmol/L) cannot be used to diagnose hypoadrenocorticism, and an ACTH stimulation test should be performed in these cases.     

Insulin concentrations in dogs with hypoadrenocorticism

Hypoglycaemia is frequently identified in canine cases of hypoadrenocorticism. Potassium and glucose cellular uptake are intimately linked by insulin. We hypothesized that in canine hypoadrenocorticism, hyperkalaemia would stimulate insulin release as a protective mechanism, translocating potassium from the extracellular compartment to the intracellular compartment and also lower glucose concentrations. Serum insulin concentrations were measured in 11 consecutive cases of canine hypoadrenocorticism which were hyperkalaemic and 33 dogs with non-adrenal illness. There was no significant difference between insulin concentrations in the two populations, and no correlation between insulin and potassium concentration in the hypoadrenal group. Thus, no support for the hypothesis was found, although multiple other factors such as pH and osmolality may be obscuring an effect.     

Inheritance of hypoadrenocorticism in bearded collies

OBJECTIVE: To assess heritability and mode of inheritance for hypoadrenocorticism in Bearded Collies. ANIMALS: 635 Bearded Collies. PROCEDURES: Dogs were classified as affected by hypoadrenocorticism or unaffected. Phenotypic and pedigree data were analyzed. Heritability was estimated by use of Bayesian statistical methods. Regressive logistic models for complex segregation analyses were used to characterize mode of inheritance. RESULTS: Hypoadrenocorticism was diagnosed in 60 (9.4%) dogs. Heritability of hypoadrenocorticism was estimated to be 0.76 with both sexes affected with equal probability. Evaluation of the pedigrees did not support a Mendelian autosomal dominant mode of inheritance. Evidence from the complex segregation analysis for a single locus of large effect on hypoadrenocorticism was not convincing. CONCLUSIONS AND CLINICAL RELEVANCE: Hypoadrenocorticism in Bearded Collies is highly heritable. Although a precise genetic mechanism responsible for inheritance of the disorder remains undetermined, breeding decisions must include consideration of the genetic likelihood of passing on this deleterious disorder to offspring of affected dams and sires.     

Combined hyponatremia and hyperkalemia mimicking acute hypoadrenocorticism in three pregnant dogs

Differential diagnoses for hyponatremia with concurrent hyperkalemia should include hypoadrenocorticism. Renal failure, chylothorax, and gastrointestinal tract disorders may also cause abnormally low serum sodium:potassium ratios. The ACTH stimulation test is the gold standard for diagnosis of hypoadrenocorticism.     

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.