Urinary concentration of corticoids in ponies with hyperlipoproteinaemia or hyperadrenocorticism

The urinary corticoid:creatinine (c:c) ratio was determined in ten pony mares suffering from hyperlipoproteinaemia. The mean (+/- sd) urinary c:c ratio of these ten ponies (47 +/- 31 x 10(-6)) was not significantly different from that of twelve pony mares with a pituitary pars intermedia adenoma (31 +/- 18 x 10(-6). The correlation between the urinary concentration of corticoids and plasma total lipids, and the correlation between the urinary c:c ratio and plasma total lipids in ponies with hyperlipoproteinaemia were not significant (P > 0.05; r = 0.53 and r = 0.008, respectively). Preliminary results favour primary hyperadrenocorticism being associated with hyperlipoproteinaemia. In conclusion, the data presented here suggest that cortisol can contribute to insulin resistance in ponies with hyperlipoproteinaemia.     

Urinary corticoids in the diagnosis of canine hyperadrenocorticism

In 20 healthy experimental dogs the 24 hour urinary corticoid excretion as measured by cortisol radioimmunoassay on two consecutive days varied from 0.5 to 3.3 nmol/kg/24 hours and from 0.3 to 3.6 nmol/kg/24 hours. In 20 dogs with otherwise proven spontaneous hyperadrenocorticism these values varied from 4.4 to 35.7 nmol/kg/24 hours and from 3.6 to 26.8 nmol/kg/24 hours respectively. Corticoid/creatinine ratios in morning urine samples of 28 healthy pet dogs were 1.2 to 6.9 X 10(-6). In 27 dogs with spontaneous hyperadrenocorticism all ratios exceeded the range observed in the healthy pet dogs.     

Urinary glucocorticoid excretion in the diagnosis of hyperadrenocorticism in ferrets

Hyperadrenocorticism in ferrets is usually associated with unaltered plasma concentrations of cortisol and adrenocorticotropic hormone (ACTH), although the urinary corticoid/creatinine ratio (UCCR) is commonly elevated. In this study the urinary glucocorticoid excretion was investigated in healthy ferrets and in ferrets with hyperadrenocorticism under different circumstances. In healthy ferrets and in one ferret with hyperadrenocorticism, approximately 10% of plasma cortisol and its metabolites was excreted in the urine. High-performance liquid chromatography (HPLC) revealed one third of the urinary corticoids to be unconjugated cortisol; the other peaks mainly represented cortisol conjugates and metabolites. In 21 healthy sexually intact ferrets, the UCCR started to increase by the end of March and declined to initial values halfway the breeding season (June). In healthy neutered ferrets there was no significant seasonal influence on the UCCR. In two neutered ferrets with hyperadrenocorticism the UCCR was increased, primarily during the breeding season. In 27 of 31 privately owned ferrets with hyperadrenocorticism, the UCCR was higher than the upper limit of the reference range (2.1 x 10(-6)). In 12 of 14 healthy neutered ferrets dexamethasone administration decreased the UCCR by more than 50%, whereas in only 1 of the 28 hyperadrenocorticoid ferrets did the UCCR decrease by more than 50%. We conclude that the UCCR in ferrets primarily reflects cortisol excretion. In healthy sexually intact ferrets and in ferrets with hyperadrenocorticism the UCCR increases during the breeding season. The increased UCCR in hyperadrenocorticoid ferrets is resistant to suppression by dexamethasone, indicating ACTH-independent cortisol production.     

Urinary excretion of glucocorticoids in the diagnosis of hyperadrenocorticism in cats

In dogs and humans, the measurement of urinary corticoid excretion has become a standard screening test for the diagnosis of hyperadrenocorticism. Mainly because the urinary excretion of cortisol was considered to be very low in cats, its measurement was not used in the diagnosis of hyperadrenocorticism in this species. We therefore studied the urinary excretion of [³H]cortisol and measured the corticoid/creatinine (C/C) ratio in healthy cats and in cats with hyperadrenocorticism in order to evaluate the applicability of this measurement in the diagnosis of feline hyperadrenocorticism. The median urinary excretion of intravenously administered [³H]cortisol was 1.85% (measured as excreted ³H; range, 1.56 to 1.99; n = 4). High-performance liquid chromatography analysis showed a small peak of cortisol and a large peak consisting primarily of conjugates of cortisol and/or its metabolites. The 2.5 and 97.5 percentiles of the urinary C/C ratio in healthy cats were 2 × 10⁻⁶ to 36 × 10⁻⁶ (n = 42). The C/C ratio was significantly higher in six cats with pituitary-dependent hyperadrenocorticism (median, 122 × 10⁻⁶; range 51 × 10⁻⁶; to 272 × 10⁻⁶). The administration of a high dose of dexamethasone (0.1 mg/kg thrice daily per os) led to marked suppression of the C/C ratio in healthy cats (median suppression of the average of the C/C ratio of the first two consecutive days was 92%; range, 74 to 96%; (n = 12), as well as in five cats with pituitary-dependent hyperadrenocorticism. Our results demonstrate that despite the low urinary excretion of injected [³H]cortisol, urinary corticoid concentrations in cats can be measured by radioimmunoassay and that the urinary C/C ratio is a sensitive test in the diagnosis of hyperadrenocorticism in the cat.     

Evaluation of serum 17-hydroxyprogesterone concentration after administration of ACTH in dogs with hyperadrenocorticism

OBJECTIVE: To evaluate serum 17-hydroxyprogesterone (17-OHP) concentration measurement after administration of ACTH for use in the diagnosis of hyperadrenocorticism in dogs. DESIGN: Prospective study. ANIMALS: 110 dogs. PROCEDURE: Serum 17-OHP concentrations were measured before and after ACTH stimulation in 53 healthy dogs to establish reference values for this study. Affected dogs had pituitary-dependent (n = 40) or adrenal tumor-associated (12) hyperadrenocorticism or potentially had atypical hyperadrenocorticism (5; diagnosis confirmed in 1 dog). In affected dogs, frequency interval and borderline and abnormal serum 17-OHP concentrations after ACTH stimulation were determined. Serum cortisol concentrations were assessed via low-dose dexamethasone suppression and ACTH stimulation tests. RESULTS: In healthy dogs, serum 17-OHP concentration frequency intervals were grouped by sex and reproductive status (defined as < 95th percentile). Frequency intervals of serum 17-OHP concentrations after ACTH stimulation were < 77, < 2.0, < 3.2, and < 3.4 ng/mL (< 23.3, < 6.1, < 9.7, and < 10.3 nmol/L) for sexually intact and neutered females and sexually intact and neutered males, respectively. In 53 dogs with confirmed hyperadrenocorticism, serum cortisol concentrations after ACTH stimulation and 8 hours after administration of dexamethasone and serum 17-OHP concentrations after ACTH stimulation were considered borderline or abnormal in 79%, 93%, and 69% of dogs, respectively. Two of 5 dogs considered to have atypical hyperadrenocorticism had abnormal serum 17-OHP concentrations after ACTH stimulation. CONCLUSIONS AND CLINICAL RELEVANCE: Serum 17-OHP concentration measurement after ACTH stimulation may be useful in the diagnosis of hyperadrenocorticism in dogs when other test results are equivocal.     

Urinary cortisol:creatinine ratios in healthy horses and horses with hyperadrenocorticism and non-adrenal disease

Urinary cortisol and creatinine concentrations, and the cortisol:creatinine ratio were compared between 12 healthy horses (group 1), 13 horses with Cushing's disease (group 2), and eight horses with dysautonomia syndrome (equine grass sickness) (group 3). The mean (sd) urinary cortisol concentrations were 112 (55.7), 250 (357) and 864 (526) nmol/litre in groups 1, 2 and 3, respectively; the mean (sd) urinary creatinine concentrations were 18.9 (7.3), 12.0 (6.7) and 45.2 (26.4) nmol/litre in groups 1, 2 and 3, respectively, and the mean (sd) ratios were 6.1 (2.6), 19.8 (23.8) and 21.3 (14.5) (x 10(-6)) in groups 1, 2 and 3, respectively. The urinary cortisol and creatinine concentrations were significantly greater in group 3 than in groups 1 and 2, but the ratios were not significantly different, although there was a trend (P=0.076) towards higher values in groups 2 and 3. A diagnostic cut-off in the cortisol:creatinine ratio for the confirmation of Cushing's disease of more than 6.9 x 10(-6) was associated with a diagnostic sensitivity and specificity of 92.3 and 75.0 per cent, respectively, when compared with healthy horses. However, when group 3 horses were included, a cut-off of more than 7.4 x 10(-6) was associated with a diagnostic sensitivity and specificity of 84.6 and 54.5 per cent, respectively.     

Retrospective evaluation of urinary tract infection in 42 dogs with hyperadrenocorticism or diabetes mellitus or both

A retrospective study was performed to determine the proportion of dogs with hyperadrenocorticism or diabetes mellitus or both that had urinary tract infection (UTI) and to describe clinical and laboratory findings. Dogs with these endocrine disorders were included if results of quantitative urine culture were available and dogs were not receiving antimicrobials. Dogs with positive urine cultures were considered to have UTI and dogs with negative urine cultures were used as controls. Information including history, clinical signs, physical examination findings, and results of laboratory tests and urine culture was extracted from all records. Findings in dogs with UTI were compared with control dogs. There were 101 dogs with hyperadrenocorticism or diabetes mellitus or both that met inclusion criteria; 42 (41.6%) had UTI and 59 (58.4%) did not. UTI was present in 46% of dogs with hyperadrenocorticism, 37% of dogs with diabetes mellitus, and 50% of dogs with both endocrine disorders. There was no association between endocrine group and occurrence of UTI. Escherichia coli was the most common bacteria isolated, and cultures from 29 dogs (69%) showed growth of this organism. Of dogs with UTI, <5% had stranguria, pollakiuria, or discolored urine, whereas 60% had pyuria and 69% had bacteriuria. We conclude that UTIs are common in dogs with hyperadrenocorticism, diabetes mellitus, or both diseases. Clinical signs of UTI, however, are uncommon and results of urinalysis may be normal. Therefore, it is appropriate to recommend urine culture as part of the evaluation of dogs with these endocrine disorders.     

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.     

Plasma theophylline concentration and lung function in ponies with recurrent obstructive lung disease

Six ponies with recurrent obstructive lung disease were studied during two separate 60 min periods while receiving constant equal volume infusions of either aminophylline or sterile water. Dynamic lung compliance, pulmonary resistance, respiratory rate, tidal volume, blood gas tensions and heart rate were measured. Plasma samples were obtained for determination of theophylline concentrations before, and at 10 min intervals during, the infusion period. Excitability was assessed subjectively at these same time periods. The plasma theophylline concentrations in ponies were well predicted by a previously published model of theophylline pharmacokinetics in the horse. Sterile water had no effect on lung function. Aminophylline produced significant changes in lung function compared to baseline values, including a decrease in resistance at 30 min when the mean plasma theophylline concentration was 59 +/- 14 mumol/litre and an increase in compliance at 60 mins at a mean plasma theophylline concentration of 102 +/- 23 mumol/litre. Excitement was noted between 40 and 50 mins in all ponies (mean plasma theophylline concentration 74 +/- 20 and 84 +/- 24 mumol/litre, respectively). Heart rate increased at 50 mins. The therapeutic range for intravenous (iv) theophylline concentration in 'heavey' ponies therefore appears to be between 59 and 84 mumol/litre when aminophylline is administered iv. Below 59 mumol/litre there was no consistent bronchodilator activity and above 84 mumol/litre excitement and tachycardia limited the usefulness of the drug.     

Real time monitoring of propofol blood concentration in ponies anaesthetized with propofol and ketamine

This study examined the pharmacokinetics of propofol by infusion in ponies using an analyser for the rapid measurement of propofol concentrations. The analyser (Pelorus 1000; Sphere Medical Ltd., Cambridge, UK) has a measurement cycle of approximately five minutes. Ten Welsh‐cross ponies (weighing 135–300 kg) undergoing minor procedures were studied after premedication with acepromazine 0.03 mg/kg and detomidine 0.015 mg/kg. Anaesthesia was induced with ketamine 2 mg/kg and diazepam 0.03 mg/kg, and maintained with an infusion of propofol at an initial rate of 0.16 mg/kg/min for the first thirty minutes, after a bolus of 0.3 mg/kg; and ketamine by infusion (20–40 μg/kg/min). Blood samples (<2 mL) were collected prior to, during and after the infusion, and on assuming standing position. Anaesthesia was uneventful; with the duration of infusion 31–89 min. Blood propofol concentrations during the infusion ranged between 1.52 and 7.65 μg/mL; pseudo‐steady state concentrations 3.64–6.78 μg/mL, and concentrations on assuming standing position 0.75–1.40 μg/mL. Propofol clearance and volume of distribution were 31.4 (SD 6.1) mL/min/kg and 220.7 (132.0) mL/kg, respectively. The propofol analyser allows titration of propofol to a given concentration; and may be useful for anaesthesia in animals where kinetics are unknown; in disease states; and where intercurrent therapies affect propofol disposition.     

Determination of the minimum alveolar concentration of isoflurane in Shetland ponies using constant current or constant voltage electrical stimulation

Objective To determine the minimum alveolar concentration (MAC) of isoflurane in Shetland ponies using a sequence of three different supramaximal noxious stimulations at each tested concentration of isoflurane rather than a single stimulation. Study design Prospective, experimental trial. Animals Seven 4‐year‐old, gelding Shetland ponies. Methods The MAC of isoflurane was determined for each pony. Three different modes of electrical stimulation were applied consecutively (2 minute intervals): two using constant voltage (90 V) on the gingiva via needle‐ (CVneedle) or surface‐electrodes (CVsurface) and one using constant current (CC; 40 mA) via surface electrodes applied to the skin over the digital nerve. The ability to clearly interpret the responses as positive, the latency of the evoked responses and the inter‐electrode resistance were recorded for each stimulus. Results Individual isoflurane MAC (%) values ranged from 0.60 to 1.17 with a mean (±SD) of 0.97 (±0.17). The responses were more clearly interpreted with CC, but did not reach statistical significance. The CVsurface mode produced responses with a longer delay. The CVneedle mode was accompanied by variable inter‐electrode resistances resulting in uncontrolled stimulus intensity. At 0.9 MAC, the third stimulation induced more positive responses than the first stimulation, independent of the mode of stimulation used. Conclusions The MAC of isoflurane in the Shetland ponies was lower than expected with considerable variability among individuals. Constant current surface electrode stimulations were the most repeatable. A summation over the sequence of three supramaximal stimulations was observed around 0.9 MAC. Clinical relevance The possibility that Shetland ponies require less isoflurane than horses needs further investigation. Constant current surface‐electrode stimulations were the most repeatable. Repetitive supramaximal stimuli may have evoked movements at isoflurane concentrations that provide immobility when single supramaximal stimulation was applied.     

Cardiopulmonary effects associated with head-down position in halothane-anesthetized ponies with or without capnoperitoneum

Objective To compare the cardiopulmonary effects of the head‐down position, with or without capnoperitoneum, in halothane‐anesthetized horses. Study design Prospective randomized study. Animals Five ponies (four mares, one stallion; bodyweight 302 ± 38.4 kg [mean ± SD]) were used. Methods The ponies were anesthetized with xylazine, guiafenesin, ketamine, and maintained with halothane/oxygen and lungs were ventilated to 40 ± 2 mm Hg (5.3 ± 0.3 kPa) end‐tidal CO₂ tension. After baseline cardiopulmonary measurements, ponies were kept in horizontal position for 30 minutes, then tilted head‐down 30° to the horizontal position for 60 minutes, and then returned to a horizontal position for final measurements. Capnoperitoneum (intra‐abdominal pressure: 12 mm Hg [1.6 kPa]) was introduced after baseline cardiopulmonary measurements, until 5 minutes before the final measurements (treatment INS). Ponies in the control treatment (CON) did not receive capnoperitoneum. Cardiopulmonary data were collected every 10 minutes following the baseline measurements until recovery. Results In the head‐down position, in both treatments, significant decreases were observed in PaO₂, and significant increases were observed in PaCO₂, right atrial blood pressure, arterial to end‐tidal CO₂ gradient, calculated V_d/V_t and ratios. During the head‐down position, in CON there was decreased cardiac index, and in INS, there were decreases in arterial plasma pH and increases in mean systemic arterial and airway pressures. Treatment INS developed ventilation–perfusion mismatch earlier in the study, and had longer recovery times compared to CON. Conclusion Cardiac index and systemic blood pressure appeared to be preserved in INS during the head‐down position, but ventilation–perfusion mismatch appeared earlier with head‐down position and capnoperitoneum. Clinical relevance Healthy ponies tolerate capnoperitoneum at 12 mm Hg (1.6 kPa) intra‐abdominal pressure when tilted head down 30° to the horizontal position.     

Effect of low-dose butorphanol on halothane minimum alveolar concentration in ponies

Minimum alveolar concentration (MAC) for halothane was measured before and after administration of intravenous butorphanol (0.022 and 0.044 mg/kg in bodyweight in nine yearling Shetland ponies. Arterial blood pressure, heart rate, respiratory rate, expired CO2 and rectal temperature was also measured. Even though mean MAC values decreased 10 and 9 per cent after the low and high doses respectively, they were not statistically different from those measured prior to butorphanol. Halothane MAC values increased after butorphanol in two ponies, both animals increasing locomotor activity and demonstrating apparent central nervous system stimulation. No significant differences were seen in any variable measured after butorphanol administration.     

Evaluation of combinations of nalbuphine with acepromazine or detomidine for sedation in ponies

The effect of combinations of nalbuphine (0.3 mg/kg) with either detomidine (10 μg/kg) or acepromazine (50 μg/kg) was investigated in ponies. Nalbuphine enhanced the degree of sedation produced by both sedatives; sedation with detomidine and nalbuphine was profound. Cardiovascular and respiratory effects were mild and could usually be attributed to the effect of the sedative itself. Side effects were minimal and gave no cause for concern. It was concluded that nalbuphine, in combination with acepromazine or detomidine, is a safe and effective sedative for use in ponies.     

Tyzzer's disease in kittens with familial primary hyperlipoproteinaemia

The clinical signs, gross pathology and histopathological findings of three kittens with Tyzzer's disease are described. The three affected kittens were also hyperlipoproteinaemic, being offspring of a hyperlipoproteinaemic sire and a normolipoproteinaemic dam. Two kittens showed clinical signs of acute hepatic disease with severe icterus. Necropsy revealed multiple focal lesions in the liver, myocardium and intestines. Histological examination confirmed the presence of organisms resembling Bacillus piliformis in viable hepatocytes adjacent to necrotic liver tissue. Apart from the hyperlipoproteinaemia no predisposing ‘stress’ factors were identified.     

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.     

Comparison of non-selective adrenocorticolysis with mitotane or trilostane for the treatment of dogs with pituitary-dependent hyperadrenocorticism

Forty-six dogs with pituitary-dependent hyperadrenocorticism were treated with mitotane by the non-selective adrenocorticolysis protocol and 40 were treated twice a day with trilostane. The treatment groups were compared by chi-squared tests, and survival data were analysed using Kaplan-Meier survival plots and a Cox proportional hazard method. The non-selective adrenocorticolysis protocol was very effective (89 per cent), its toxicity was moderate (24 per cent) and there were fewer recurrences (29 per cent) than reported with the classical selective adrenocorticolysis protocol (58 per cent). In a multivariate model, age and bodyweight at diagnosis were significantly negatively correlated with survival time. The median survival time of the dogs treated with trilostane twice a day (900 days) was longer (P=0.05) than that of the dogs treated with mitotane (720 days).