Electrolyte measurements differ between point-of-care and reference analysers in dogs with hypoadrenocorticism.

INTRODUCTION: Dogs treated for hypoadrenocorticism are monitored through analysis of their blood electrolytes. This is routinely performed with point-of-care analysers and doses of medications are adjusted based on the results. OBJECTIVES: To investigate the performance of two point-of-care analysers (IDEXX Catalyst Dx and IDEXX VetStat) against a reference laboratory method for the measurement of blood sodium, potassium and chloride concentrations, as well as sodium: potassium ratios, in dogs diagnosed with and treated for hypoadrenocorticism. METHODS: Forty-eight dogs were enrolled into a prospective cross-sectional study. Paired blood samples were taken and tested on two point-of-care analysers and at a reference laboratory. Statistical analysis was then performed with Bland-Altman analysis and Passing-Bablok regression. The clinical effects of inaccurate electrolyte analysis were investigated. RESULTS: In total, 329 samples were tested on the Catalyst analyser, while another 72 samples were tested on the VetStat. Passing-Bablok regression identified both proportional and constant bias for some analytes. There was poor agreement between sodium and chloride concentrations on both analysers. Both analysers tended to give higher results than the reference method for all analytes, except for potassium when measured on the VetStat. CLINICAL SIGNIFICANCE: There are inherent differences between the electrolyte concentrations measured by these two point-of-care analysers and reference laboratory methods in dogs with hypoadrenocorticism.

Factors that affect stabilisation times of canine spontaneous hypoadrenocorticism.

The objective of this retrospective study was to examine factors that may have affected the stabilisation times of 50 dogs with spontaneous hypoadrenocorticism that were being treated with fludrocortisone acetate, with particular emphasis on dosing frequency and the concurrent use of prednisolone. Stabilisation was defined as an absence of clinical signs with a sodium:potassium ratio >27:1 and both electrolyte concentrations within a laboratory reference range. It was found that the median time till stabilisation was three months. The frequency of fludrocortisone treatment (once, twice or changed from once to twice a day) had no effect on the stabilisation time. The two groups of dogs that were started and stabilised on once a day or twice a day dosing had a median stabilisation time of two months. However, dogs that failed to stabilise on once a day dosing of fludrocortisone and were then changed onto twice a day dosing then stabilised a median of one month later. Concurrent use of prednisolone resulted in significantly faster stabilisation times. It was concluded that dogs with hypoadrenocorticism should be continued on prednisolone therapy until they are stabilised. If a dog is failing to stabilise on once a day fludrocortisone acetate, a change to twice a day administration could be considered.

A novel method of continuous cage-side monitoring of hyperthyroid cats treated with radio-iodine.

A continuous monitoring system (MGP DM2000X) was assessed for monitoring γ radiation emissions and determining appropriate isolation times for hyperthyroid cats treated with radioactive iodine (I(131)). Daily radiation emitted by 12 cats who had received a range of doses of I(131) (80-200 MBq) was measured and average background radiation readings deducted. The effective half-lives of the I(131) in the cats were found to have a median of 2.54 days (range 1.40-3.24 days). Cats treated with 200 MBq emitted 5 µGy/day more exposure than cats treated with lower doses throughout the study period (P=0.032). All cats were found to emit a total radiation dose exposure less than 100 µGy (range 0-43 µGy) during days 18-21 of isolation. The potential additional dose exposure to owners was calculated at various days that might be considered for the cats to be returned to their owners. Using this provisional data, maximum isolation periods at this institution could be safely reduced to 17 days as long as certain precautions are followed. This preliminary study demonstrated that this novel cage-side monitoring system can be used to calculate the effective half-life of I(131) and to measure γ radiation exposure from treated cats, which may assist other institutions in determining appropriate isolation times for individual cats.

A comparison of factors that influence survival in dogs with adrenal-dependent hyperadrenocorticism treated with mitotane or trilostane.

BACKGROUND: Trilostane is a recognized treatment for canine pituitary-dependent hyperadrenocorticism (PDH); however, its efficacy in dogs with adrenal-dependent hyperadrenocorticism (ADH) is unknown. OBJECTIVES: To examine factors that might influence survival in the medical management of ADH, with particular emphasis on treatment selection. ANIMALS: Thirty-seven animals referred to 4 centers over a period of 12 years that had been diagnosed with ADH and treated with either trilostane (22/37), mitotane (13/37), or both (2/37). METHODS: Retrospective analysis of clinical records. RESULTS: There was no statistically significant difference between the survival times of 13 dogs treated only with mitotane when compared with 22 dogs treated only with trilostane. The median survival time for animals treated with trilostane was 353 days (95% confidence interval [CI] 95-528 days), whereas it was 102 days (95% CI 43-277 days) for mitotane. Metastatic disease was detected in 8 of 37 dogs. There was a significantly lower probability of survival for dogs with metastatic disease when compared with those without metastatic disease (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: The choice of medical treatment for ADH may not have a major effect on survival times. However, the presence of metastatic disease considerably decreases survival time regardless of the choice of medical treatment.

Monitoring the response of canine hyperadrenocorticism to trilostane treatment by assessment of acute phase protein concentrations.

BACKGROUND: Acute phase proteins (APPS) include haptoglobin (Hp), C-reactive protein (CRP) and serum amyloid A (SAA). Increased Hp concentrations may be induced by endogenous or exogenous glucocorticoids in dogs. OBJECTIVES: To assess whether control of hyperadrenocorticism (HAC) affects the concentrations of Hp, CRP, SAA, alkaline phosphatase (ALKP) and cholesterol, to determine whether these analytes can be used to assess control of HAC following trilostane treatment, and whether a combination of these tests offers a valid method of assessing disease control. METHODS: Hp, CRP, SAA, ALKP and cholesterol were assessed in 11 dogs with spontaneous HAC before and after treatment with trilostane. Adequate control of HAC was defined as post-ACTH cortisol less than 150 nmol/l. RESULTS: Significant reductions in Hp, ALKP, cholesterol and SAA (P<0.05) but not of CRP were found after control of HAC. Only Hp, cholesterol and ALKP were moderately informative (Se & Sp>0.7) of disease control when compared to adrenocorticotropin or corticotropin (ACTH) stimulation test. SAA and CRP were unhelpful (Se & Sp<0.7). The analysis of the combination of the analytes did not improve the correlation with ACTH stimulation test. CLINICAL RELEVANCE: Relying on these analytes does not provide additional information over ACTH stimulation test results when assessing control of HAC treated with trilostane.

Persistent isolated hypocortisolism following brief treatment with trilostane.

A 12-year-old male neutered Miniature Poodle with confirmed pituitary-dependent hyperadrenocorticism was treated with trilostane. After three doses, it developed clinical and laboratory changes suggestive of isolated hypocortisolism ('atypical hypoadrenocorticism'), which persisted and progressed for more than 3 months despite immediate withdrawal of the trilostane. The clinical signs of hyperadrenocorticism resolved without further trilostane. After 3 months, prednisolone treatment was started and the clinical signs of hypocortisolism resolved. Prednisolone therapy was required for more than 1 year. Ultrasonography initially demonstrated large hypoechoic adrenal cortices, typical of dogs with hyperadrenocorticism, which then became small and heteroechoic, consistent with the development of adrenal necrosis. Persistent isolated hypocortisolism has not been reported previously as a complication of trilostane therapy. The case is also remarkable for the very short duration of trilostane therapy that elicited this complication. Clinicians should be aware that trilostane therapy may result in adrenal necrosis, even in the very earliest stages of therapy, but prompt action can prevent a life-threatening situation.

Study of the effects of once daily doses of trilostane on cortisol concentrations and responsiveness to adrenocorticotrophic hormone in hyperadrenocorticoid dogs.

The effects of trilostane, a 3beta-hydroxysteroid dehydrogenase inhibitor on basal cortisol concentrations and the results of ACTH stimulation tests in dogs with pituitary-dependent hyperadrenocorticism were investigated. In eight of nine dogs trilostane suppressed the concentration of cortisol below the lower limit of the reference range (<50 nmol/l) for a mean (sd) of 3.5 (2.3) hours during the day, but for no longer than 13 hours. In another 10 dogs, there was a clear difference between the post ACTH cortisol concentrations observed four and 24 hours after the administration of trilostane. Furthermore, in the six dogs whose clinical signs were poorly controlled the post-ACTH concentrations observed four and 24 hours after the administration of trilostane were always higher than the equivalent cortisol concentrations in the four dogs whose clinical signs were controlled. A short duration of drug action may be responsible for the failure of some dogs to respond adequately to once daily trilostane administration.

Association of canine hypothyroidism with a common major histocompatibility complex DLA class II allele.

Dogs exhibit a range of immune-mediated conditions including a lymphocytic thyroiditis which has many similarities to Hashimoto's thyroiditis in man. We have recently reported an association in Doberman Pinschers between canine hypothyroidism and a rare DLA class II haplotype that contains the DLA-DQA1*00101 allele. We now report a further series of 173 hypothyroid dogs in a range of breeds where a significant association with DLA-DQA1*00101 is shown.

A comparison of the survival times of dogs treated with mitotane or trilostane for pituitary-dependent hyperadrenocorticism.

The survival times of 148 dogs treated for pituitary-dependent hyperadrenocorticism were studied using clinical records from 3 UK veterinary centers between 1998 and 2003. Of these animals, 123 (83.1%) were treated with trilostane, while 25 (16.9%) were treated with mitotane. Treatment groups were compared using t-tests and analysis of variance (or their nonparametric equivalents) and chi-square tests. Survival data were analyzed using Kaplan-Meier survival plots and Cox proportional hazard methods. There was no significant difference between the population attributes from each center or between treatment groups. The median survival time for animals treated with trilostane was 662 days (range 8-1,971) and for mitotane it was 708 days (range 33-1,399). There were no significant differences between the survival times for animals treated with trilostane and those treated with mitotane. In the multivariable model (including drug, center, breed group, weight, diagnostic group, and age at diagnosis), only age at diagnosis and weight were significantly negatively associated with survival. Importantly, there was no significant effect of drug choice on survival.

Hyperparathyroidism in dogs with hyperadrenocorticism.

OBJECTIVES: To assess the effect of canine hyperadrenocorticism (HAC) on parathyroid hormone (PTH), phosphate and calcium concentrations. METHODS: PTH concentrations and routine biochemical parameters were measured in 68 dogs with HAC. Ionised calcium was measured in 28 of these dogs. The results obtained were compared with an age- and weight-matched group of 20 hospital patients that did not show signs of HAC. RESULTS: There were significant differences between the PTH, phosphate, alkaline phosphatase, creatinine and albumin concentrations between the two groups. Total and ionised calcium concentrations were not significantly different. Most of the dogs (92 per cent) with HAC had PTH concentrations that were greater than the reference range (10 to 60 pg/ml), and in 23 dogs they were greater than 180 pg/ml. There were significant positive correlations between the PTH and basal cortisol, post-adrenocorticotropic hormone (ACTH) cortisol and alkaline phosphatase concentrations, and also the phosphate and post-ACTH cortisol concentrations. CLINICAL SIGNIFICANCE: Adrenal secondary hyperparathyroidism is a cause of increased PTH concentrations and may be associated with abnormalities in calcium and phosphate metabolism in dogs with HAC. The findings of this study could explain why canine HAC may cause clinical signs such as calcinosis cutis that are associated with altered calcium metabolism.

Canine hyperadrenocorticism: effects of trilostane on parathyroid hormone, calcium and phosphate concentrations.

OBJECTIVES: To determine the effects of treating canine hyperadrenocorticism (HAC) on parathyroid hormone (PTH), calcium and phosphate concentrations in dogs. METHODS: Serum calcium, phosphate and PTH concentrations were analysed in 22 dogs with HAC before treatment with trilostane and at a median of 210 days after commencing treatment. Pretreatment data were compared with data from an age- and weight-matched group of hospitalised patients, and post-treatment data were compared with pretreatment data. RESULTS: PTH and phosphate concentrations were significantly higher in dogs with HAC compared with control dogs. PTH concentrations reduced significantly with treatment, such that there was no longer a difference between the HAC and control groups. Phosphate concentrations also reduced significantly with treatment but there was still a significant difference between those in dogs with HAC and control dogs. Despite no significant difference between calcium concentrations in the pretreatment HAC and control groups, calcium concentrations increased significantly with treatment. CLINICAL SIGNIFICANCE: These results show that adrenal secondary hyperparathyroidism resolves with treatment and suggest that increased calcium and phosphate levels have a role in its pathogenesis.

Haptoglobin concentrations in dogs undergoing trilostane treatment for hyperadrenocorticism.

BACKGROUND: Increased concentrations of haptoglobin (Hp), a moderate acute phase protein, have been demonstrated in dogs with hyperadrenocorticism (HAC). Monitoring serum concentrations of Hp in hyperadrenocorticoid dogs before and after trilostane administration may provide valuable information on the response to therapy. OBJECTIVE: The aim of this study was to measure Hp concentrations in dogs with spontaneously occurring HAC at the time of diagnosis and after treatment with trilostane. METHODS: Serum Hp concentration was measured using an automatic biochemical assay based on Hp-hemoglobin binding and utilizing SB-7 reagent in 12 dogs with spontaneous HAC before and after treatment with trilostane (30 or 60 mg PO q 12-24 h). Post-treatment Hp concentrations were measured at the time the owner reported an improvement in clinical signs. Pretreatment and post-treatment Hp values were compared with reference values and with values from 4 healthy control dogs. RESULTS: Two dogs with HAC had pretreatment Hp values within the reference interval; 10 dogs had moderate (n = 8) or marked (n = 2) increases in Hp concentration. After treatment with trilostane, Hp concentration remained within the reference interval (n = 2), decreased to within the reference interval (n = 3), or remained moderately increased (n = 7; 3-10 g/L). Overall, a significant decrease was observed in Hp concentration after trilostane treatment compared with pretreatment values (P <.005). Both untreated and treated dogs with HAC had significantly higher Hp concentrations (P <.001) when compared with control dogs. CONCLUSIONS: Clinical control of HAC did not closely relate to serum Hp concentration. Further studies are required to assess whether this is because of inadequate control of disease or because a build-up of cortisol precursors or secondary effects of HAC affect Hp concentration.

Thoracic high-resolution computed tomography in the diagnosis of metastatic carcinoma.

Three dogs were presented for investigation of recurrent pyrexia of unknown origin, chronic vomiting and respiratory distress, respectively. One dog was markedly underweight and the other two were cachexic. Physical examination and initial diagnostic tests failed to establish the underlying cause of the presenting signs. Thoracic radiographs were within normal limits for the age of the dog. In each case there was a high index of suspicion for an occult neoplastic process in view of the profound unexplained weight loss present. High-resolution computed tomography (HRCT) of the thorax was performed. The lung fields were divided into three zones for analysis and a novel classification scheme was used to describe the HRCT findings in each zone. Postmortem examination and histopathology confirmed the presence of an infiltrating metastatic carcinoma in all three cases. The HRCT changes correlated closely with the pathological findings. The authors conclude that HRCT of the lung should be considered for pulmonary metastatic screening in the dog and introduce a classification system for HRCT findings, based on terminology used in human medicine.

Diagnosis and management of hepatic copper accumulation in a Skye terrier.

A one-year-old, neutered female Skye terrier presented with anorexia, vomiting, seizures and ascites. Portal venography demonstrated the presence of multiple acquired portosystemic shunts. Hepatic biopsy confirmed the presence of copper accumulation and fibrosis. Treatment included ursodeoxycholic acid therapy, colchicine and oral zinc. To the authors' knowledge, this is the first case report detailing successful management of Skye terrier hepatopathy.

The use of 17-hydroxyprogesterone in the diagnosis of canine hyperadrenocorticism.

A number of dogs are seen with clinical signs consistent with hyperadrenocorticism (HAC), supporting CBC and biochemical findings, but the disease cannot be confirmed with either the ACTH stimulation test or the low-dose dexamethasone suppression test (LDDST). Therefore, another screening test is required to aid diagnosis in these atypical cases of HAC. The aim of this study was to investigate whether measuring 17-hydroxyprogesterone (OHP) concentrations could be used in this role. Plasma cortisol and OHP concentrations were measured in dogs with clinical signs suggestive of HAC before and after administration of exogenous ACTH. In dogs with HAC, plasma OHP showed an exaggerated response to ACTH stimulation. This was seen in both typical cases of HAC with a positive cortisol response to ACTH administration and in atypical cases with negative screening test results. The test can be performed on plasma already taken for a conventional ACTH stimulation test. Post-ACTH OHP concentrations decreased after treatment with mitotane or adrenalectomy. These results suggest that OHP measurements can be used as an aid to diagnose and manage canine HAC.