The equine metabolic syndrome peripheral Cushing's syndrome.

Certain management practices tend to promote the development of obesity (metabolic syndrome) in mature horses as they enter their teenage years. These management practices include the provision of starch-rich (high glycemic index) and fat-supplemented rations to healthy horses that are relatively inactive. Some horse breeds and ponies appear to be genetically predisposed to metabolic syndrome. The accretion of intra-abdominal adiposity by equids is associated with the development of insulin insensitivity (hyperinsulinemia), glucose intolerance, dyslipidemia, hypertension, and insidious-onset laminitis. Omental adipocytes are metabolically active, secreting free fatty acids and hormonally active mediators including cortisol, leptin, and resistin that might contribute to persistence and worsening of insulin refractoriness and the obese phenotype. We have hypothesized that obesity-associated laminitis arises as a consequence of vascular changes and a hypercoagulable state, similar to the development of atherosclerosis in human type 2 diabetes. Several molecular mechanisms that might serve to explain the development of insulin insensitivity as a result of excessive adiposity have been incriminated. Little investigation into the relationship between obesity, insulin insensitivity, and laminitis in horses has been reported to date. Insulin sensitivity and glucose tolerance can be improved by dietary restriction and exercise aimed at reversing omental obesity. Management practices that promote the development of obesity are likely initiated during the first 10 years of the horse's life. Veterinarians and horse owners must recognize that mature-onset obesity in adult horses is associated with a risk for development of laminitis. Obesity and insulin insensitivity might be prevented if horse owners can be educated to feed rations with a relatively lower glycemic index to inactive horses. Investigative research pertaining to the development of antiobesity drugs for human patients is continuing. Greater than 30 new pharmaceuticals are in various stages of research. However, it will likely take many years before any of these drugs are shown to be useful and safe in horses. Lifestyle changes in the form of diet and exercise patterns are still the crux of therapy for both human and equine patients.     

Use of trilostane for the treatment of pituitary-dependent hyperadrenocorticism in a cat

Hyperadrenocorticism occurs much less frequently in cats than in dogs and, at present, is more difficult to manage successfully. This report documents the use of the steroid synthesis inhibitor trilostane for the treatment of hyperadrenocorticism in a domestic shorthaired cat with pituitary-dependent disease. Although trilostane was able to alleviate the severity of the clinical signs and was well tolerated, the cat subsequently died of renal failure secondary to a fungal infection of the urinary tract.     

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.     

Adrenal necrosis in a dog receiving trilostane for the treatment of hyperadrenocorticism

Clinical and biochemical changes suggestive of hypoadrenocorticism were observed in a 10-year-old male neutered Staffordshire bull terrier shortly after beginning therapy with trilostane for the treatment of hyperadrenocorticism. The dog's condition was stabilised with intravenous fluids, fludrocortisone and prednisolone. An exploratory laparotomy and excisional biopsy of the left adrenal gland were performed. Histopathological analysis showed adrenal cortical necrosis with reactive inflammation and fibrosis. Trilostane is a reversible inhibitor of steroid synthesis and this complication has not been reported previously. Clinicians should be aware that trilostane therapy may result in adrenal necrosis but that prompt treatment might correct a life-threatening situation.     

The use of trilostane for the treatment of alopecia X in Alaskan malamutes

Three Alaskan malamutes with hair loss and slightly elevated blood concentrations of 17-hydroxyprogesterone after stimulation with adrenocorticotropic hormone (ACTH) were treated with trilostane. Trilostane, an inhibitor of 3 beta-hydroxysteroid dehydrogenase, was given twice daily at a dose of 3.0 to 3.6 mg/kg per day orally for 4 to 6 months. Routine ACTH stimulation tests were performed over 8 months to evaluate the degree of adrenal function suppression. Treatment with trilostane led to complete hair regrowth in all three dogs within 6 months. No adverse effects associated with trilostane were recognized.     

Pituitary pars intermedia dysfunction: equine Cushing's disease.

PPID in older equids has become a major health concern of horse owners. In response, equine practitioners have made greater efforts at understanding, diagnosing, and treating this disorder. Although PPID is recognized to be a different form of pituitary-dependent hyperadrenocorticism than is seen in canine or human patients, relatively little is known about the pathophysiology and natural progression of the disease. At present, the diagnosis is best supported by manifestation of characteristic clinical signs and endocrinologic test results, preferably a supportive DST result. Treatment must focus on improving overall health care, including body clipping, dentistry, and nutrition. As the condition progresses, administration of pergolide or a combination of pergolide and cyproheptadine is currently considered the best medical treatment. The time point at which medication should be added to improved health care and management changes is not currently known, but loss of body condition and development of hyperglycemia suggest more advanced PPID that would likely benefit from drug therapy. Whether medical treatment needs to be continuous or could be intermittent is also unknown. As the demand for treatment of affected equids continues to increase, clinical response and endocrinologic testing data as well as pharmacologic data for currently used drugs and other agents should be expected. Similarly, novel medical, and perhaps surgical, treatment strategies for this condition should also be anticipated in the future.     

Interpretation of laboratory tests for canine Cushing's syndrome

Hypercortisolism (HC) is a common disease in dogs. This article will review the laboratory tests that are available for diagnosis of HC and laboratory tests for differentiating between causes of HC. An emphasis will be made on the clinical process that leads to the decision to perform those tests and common misconceptions and issues that arise when performing them. To choose between the adrenocorticotropic hormone (ACTH)-stimulation test and the low-dose dexamethasone suppression test (LDDST), the advantages and disadvantages of both tests should be considered, as well as the clinical presentation. If the index of suspicion of HC is high and other diseases have been appropriately ruled out, the specificity of the ACTH stimulation test is reasonably high with an expected high positive predictive value. Because of the low sensitivity, a negative result in the ACTH stimulation test should not be used to rule out the diagnosis of HC. The LDDST is more sensitive but also less specific and affected more by stress. A positive result on the urine cortisol:creatinine ratio does not help to differentiate HC from other diseases. A negative result on the urine cortisol:creatinine ratio indicates that the diagnosis of HC is very unlikely. The LDDST is useful in differentiating pituitary-dependent HC from an adrenal tumor in about two thirds of all dogs with HC. Differentiation of HC from diabetes mellitus, liver diseases, and hypothyroidism cannot be based solely on endocrine tests. Clinical signs, imaging studies, histopathology, and response to treatment should all be considered.     

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.     

Nutritional considerations for equine rhabdomyolysis syndrome

Exertional rhabdomyolysis represents a syndrome of typically recurrent exercise‐associated muscle damage in horses that arises from a variety of aetiologies. Major advances have been made in recent years in our understanding of the pathophysiology of equine rhabdomyolysis syndrome (ERS), and a few specific causative genetic defects have been identified. Despite the fact that there is no single procedure or set of procedures (including diet and management) that can guarantee against further episodes of ERS, appropriate management of susceptible individuals, including nutrition, may help to reduce the likelihood, severity or frequency of future episodes. Whilst the dietary advice can be more specific and targeted for those with a known intrinsic muscle problem, for all affected individuals, regardless of the underlying cause, a balanced diet (which is suitable for the individual), together with a well‐designed exercise programme, should be the initial management target. This paper will briefly review the condition and give general nutrition and management advice.     

Serum insulin concentrations in horses with equine Cushing's syndrome: response to a cortisol inhibitor and prognostic value

REASONS FOR PERFORMING STUDY: Serum insulin concentration and its use as a prognostic indicator in horses with equine Cushing's syndrome (ECS) have been poorly documented. OBJECTIVES: To examine daily insulin variations in horses with ECS and the effect of treatment using trilostane, a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase. Further, we aimed to examine the relationship between baseline serum insulin concentration and survival in horses with ECS. METHODS: Basal serum insulin concentrations were measured in 20 confirmed ECS cases by taking blood at regular 4 h intervals for 24 h (1200, 1600, 2000, 2400, 0400 and 0800 h) before treatment (Day 0) and 10 days, and 30 days and 1-2 years after the onset of trilostane therapy. The temporal pattern of insulin was analysed using a linear mixed model approach, and the prognostic value of measurements on Day 0 assessed using receiver-operating characteristic analysis. RESULTS: Horses with ECS showed a diurnal pattern of serum insulin concentration, highest value at 1200 h, and this pattern was not altered by treatment with trilostane. Furthermore, despite a mild increase of serum insulin concentrations after 10 days of trilostane therapy, insulin concentration was unaffected in the long-term. Low serum insulin concentrations at the beginning of the trial were significantly associated with improved survival to 1-2 years. The 1200 h sampling before treatment had the highest prognostic value for prediction of survival with a sensitivity and specificity of at least 90% for serum insulin at < 62 and > 188 microu/ml to predict survival and nonsurvival, respectively. CONCLUSIONS AND POTENTIAL RELEVANCE: Insulin is a useful prognostic indicator for ECS, but potentially large variations can occur throughout a 24 h period, indicating a single sample may not be representative. Serum insulin concentration did not increase over 1-2 years in horses receiving trilostane therapy.     

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).     

Efficacy of a portable oxygen concentrator with pulsed delivery for treatment of hypoxemia during equine field anesthesia

ObjectiveHypoxemia is common during equine field anesthesia. Our hypothesis was that oxygen therapy from a portable oxygen concentrator would increase PaO₂ during field anesthesia compared with the breathing of ambient air.Study designProspective clinical study.AnimalsFifteen yearling (250 – 400 kg) horses during field castration.MethodsHorses were maintained in dorsal recumbency during anesthesia with an intravenous infusion of 2000 mg ketamine and 500 mg xylazine in 1 L of 5% guaifenesin. Arterial samples for blood gas analysis were collected immediately post-induction (PI), and at 15 and 30 minutes PI. The control group (n = 6) breathed ambient air. The treatment group (n = 9) were administered pulsed-flow oxygen (192 mL per bolus) by nasal insufflation during inspiration for 15 minutes PI, then breathed ambient air. The study was performed at 1300 m above sea level. One-way and two-way repeated-measures anova with post-hoc Bonferroni tests were used for within and between-group comparisons, respectively. Significance was set at p ≤ 0.05.ResultsMean ± SD PaO₂ in controls at 0, 15 and 30 minutes PI were 46 ± 7 mmHg (6.1 ± 0.9 kPa), 42 ± 9 mmHg (5.6 ± 1.1 kPa), and 48 ± 7 mmHg (6.4 ± 0.1 kPa), respectively (p = 0.4). In treatment animals, oxygen administration significantly increased PaO₂ at 15 minutes PI to 60 ± 13 mmHg (8.0 ± 1.7 kPa), compared with baseline values of 46 ± 8 mmHg (6.1 ± 1 kPa) (p = 0.007), and 30 minute PI values of 48 ± 7 mmHg (6.5 ± 0.9 kPa) (p = 0.003).ConclusionsThese data show that a pulsed-flow delivery of oxygen can increase PaO₂ in dorsally recumbent horses during field anesthesia with ketamine-xylazine-guaifenesin.Clinical relevanceThe portable oxygen concentrator may help combat hypoxemia during field anesthesia in horses.