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.     

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.     

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.     

Basal and ACTH-Stimulated Plasma Aldosterone Concentrations are Normal or Increased in Dogs With Trichuriasis-Associated Pseudohypoadrenocorticism

We measured plasma concentrations of Cortisol and aldosterone before and after administration of adrenocorticotropin (ACTH) in dogs with trichuriasis. These dogs had physical examination, historical, and serum electrolyte findings suggestive of hypoadrenocorticism; trichuriasisassociated pseudohypoadrenocorticism has been reported previously. We found normal basal and ACTH-stimulated plasma Cortisol concentrations. Basal and ACTH-stimulated plasma aldosterone concentrations were normal in 2 dogs and increased in 3 dogs, suggesting that the electrolyte abnormalities seen in this clinical syndrome are not due to aldosterone deficiency.     

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.     

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.     

Phenol poisoning in three dogs

Three adult dogs were evaluated following oral administration of phenol by the owner. All three dogs experienced severe oral and gastric ulceration. Hematological abnormalities included neutropenia with the presence of toxic neutrophils, thrombocytopenia, and increased muscle enzymes. Endoscopic examination was performed, and biopsies yielded a diagnosis of gastric mucosal necrosis in two of the dogs. Following supportive care, the dogs recovered completely. Phenol is a caustic, highly poisonous derivative of coal tar. The dogs of this report were poisoned inadvertently by their owner who received misinformation concerning the use of this chemical via the Internet.     

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.     

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   

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.     

Cardiac changes induced by excess exogenous growth hormone in juvenile miniature poodles

The transient elevated plasma growth hormone (GH) levels that occur at a young age in giant breed dogs may have consequences in adult life. The aim of this study was to investigate whether excess juvenile GH has consequences for cardiac function and morphology. To simulate the naturally occurring juvenile hypersomatotropism in giant breed dogs, elevated plasma GH and insulin-like growth factor-I (IGF-I) concentrations were induced in six miniature poodles (GH dogs) by daily administration of supraphysiological doses of GH starting at 12 weeks of age. Eight miniature poodles of the same age that received vehicle only served as controls. Cardiac anatomy and function were evaluated by echocardiography. After euthanasia at 21 weeks of age, the hearts were examined for weight, myocyte dimensions and collagen fraction. The hearts of the GH dogs had larger atria (+22%), a thicker left ventricular wall (+21%), greater weight (+84%), and their cardiomyocytes were 15% longer, 25% thicker, and 92% greater in volume than those of control dogs. The mean collagen fraction was also higher in the GH dogs (5.6%) than in the controls (3.1%). In conclusion, excess GH in juvenile miniature poodles resulted in myocardial hypertrophy and increased collagen content. These findings are consistent with observations in acromegalic human patients and in rats treated with GH.     

Sebaceous adenitis in Swedish dogs,a retrospective study of 104 cases

Background

Sebaceous adenitis (SA) is an uncommon, immune mediated skin disease in dogs. The aim was to retrospectively investigate SA in dogs in Sweden with respect to breed, sex and age distribution. A second aim was to retrospectively compare clinical signs in dogs with generalized SA and to estimate the survival after diagnosis in the English springer spaniel, standard poodle and the akita.

Methods

In total 34 Swedish veterinarians contributed with 104 clinically and histologically verified SA cases. Breed, gender and age at diagnosis were registered for each case. The degree of clinical signs at time for diagnosis and at follow-up and information about treatments, concurrent diseases and euthanasia were recorded for the springer spaniels, standard poodles and akitas using a standardized questionnaire.

Results

A total of 104 cases of SA were included; most cases were recorded for the springer spaniel (n = 25), standard poodle (n = 21) and the akita (n = 10). These three breeds, together with the lhasa apso and the chow-chow, were the most common when national registry data from the Swedish Board of Agriculture and Swedish Kennel Club were considered. The mean age at diagnosis was 4.8 years. The proportion of males was 61%. When the springer spaniels, standard poodles and the akitas with generalized signs were compared (n = 51), the spaniels showed significantly more severe clinical signs than the poodles at diagnosis regarding alopecia, seborrhoea, pyoderma and the overall severity of clinical signs. At follow-up, the degree of clinical signs for otitis externa and pyoderma differed significantly between the breeds. The estimated median survival time was 42 months.In dogs where data regarding survival was available at the end of the study (n = 44), SA was reported to be the reason for euthanasia in 14 dogs, whereof 7 within 24 months after diagnosis.

Conclusion

The result of this study implicates that the English springer spaniel is a breed predisposed to SA and that it has more severe clinical signs than the standard poodle. A large proportion of the dogs (spaniel, poodle and akita) investigated regarding survival were reported to have been euthanized to great extent due to the disease.     

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.     

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 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.     

Alopecia in pomeranians and miniature poodles in association with high urinary corticoid:creatinine ratios and resistance to glucocorticoid feedback

The adrenocortical function of pomeranians and miniature poodles with alopecia was tested by serial measurements of the urinary corticoid:creatinine ratio (uccr) and by an oral low-dose dexamethasone suppression test (lddst) and uccr measurements. In most of the dogs there was day-to-day variation in the uccrs of the 10 sequential urine samples, often with values above or below the upper limit of the range of healthy control dogs. In 22 alopecic pomeranians the basal uccrs were significantly higher than in 18 non-alopecic pomeranians, and the values of both groups were significantly higher than those of 88 healthy pet dogs. The uccrs of 12 alopecic miniature poodles were significantly higher than those of healthy dogs. In 12 alopecic pomeranians and eight alopecic miniature poodles the oral lddst revealed increased resistance to dexamethasone. In six non-alopecic pomeranians the uccrs after the administration of dexamethasone were not significantly different from those in seven healthy dogs at the same time. In an oral high-dose dexamethasone suppression test, using 0.1 mg dexamethasone/kg bodyweight, the uccrs of seven alopecic pomeranians and five alopecic miniature poodles decreased to low levels.     

Polyglandular endocrinopathy type II (Schmidt's syndrome) in a Dobermann pinscher

A three‐year‐old, female neutered, Dobermann pinscher was presented for investigation of lethargy, episodic collapse, ataxia and myxoedema. Primary hypothyroidism and primary cortisol‐deficient hypoadrenocorticism were diagnosed based on history, physical examination and compatible hormonal analysis. Increased serum concentrations of thyroglobulin autoantibodies and 21‐hydroxylase autoantibodies indicated an immune‐mediated aetiology. The case was complicated by lymphadenopathy with hand‐mirror lymphocytes, classically identified in lymphoma. A polymerase chain reaction test for antigen receptor rearrangement indicated polyclonality and therefore reactive lymphadenopathy. The dog's clinical signs resolved following introduction of levothyroxine and prednisolone. Prioritising the problem‐based approach in this case facilitated the diagnosis of hypoadrenocorticism in addition to hypothyroidism due to the persistence of clinical signs despite thyroxine replacement. Importantly, atypical adrenal gland dysfunction was not misinterpreted as inadequate therapeutic response to thyroxine supplementation. The observation that polyglandular endocrinopathy type II can occur in dogs suggests that in dogs with a suboptimal response to treatment for hypothyroidism or hypoadrenocorticism comorbid endocrinopathies should be investigated.     

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.     

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.     

Myokymia and neuromyotonia in 37 Jack Russell terriers

The clinical and clinicopathological characteristics, treatment and outcome of vermicular muscle contractions (myokymia) and generalized muscle stiffness (neuromyotonia) in 37 Jack Russell terriers were evaluated retrospectively. Thirty dogs were affected by both disorders, whereas seven were presented with myokymia and never developed neuromyotonia. Clinical signs started at the mean age of 8 months. Except for signs of myokymia and neuromyotonia, clinical and neurological examination was normal in all dogs. Thirty dogs demonstrated typical signs of hereditary ataxia.Changes in serum chemistry included increased creatine kinase, aspartate aminotransferase and alanine aminotransferase concentrations. Electromyographic abnormalities, especially in muscles showing macroscopically visible myokymia, consisted of semirhythmic bursts of doublet, triplet, or multiplet discharges of a single motor unit. The amplitudes varied between 80 μV and 1 mV and occurred with an interburst frequency between 10 and 40 Hz and an intraburst frequency between 150 and 280 Hz.Most dogs were treated with a sodium channel blocker with variable results. Seven dogs died (most likely because of hyperthermia) or were euthanased during a neuromyotonic attack; 15 dogs were euthanased due to worsening of clinical signs, or lack of or no long-lasting effect of medication, and three were euthanased for unknown or unrelated reasons. Nine dogs were lost to follow-up and three were still alive 5–10.5 years after the start of clinical signs. In conclusion, young Jack Russell terriers with myokymia and neuromyotonia should undergo a complete blood and electrophysiological examination. Long-term prognosis is not favourable.