Prognostic factors in dogs with common causes of proteinuria.

INTRODUCTION: Little is known about the prognostic value of increased urine protein to creatinine ratios (UPC) comparing different underlying diseases in dogs. Therefore, between 2014 and 2015, dogs with a UPC of 2,0 or higher measured were retrospectively analysed at least once. They were divided into groups of the most common underlying diseases, namely primary glomerulopathy, Cushing's disease, leishmaniasis and in a group of different diseases. Possible prognostic factors, like UPC at time of diagnosis, creatinine, urine specific gravity, albumin and haematocrit, were assessed. Eighty-nine dogs with severe proteinuria were included in the study. Median time of survival was 42 days. UPC and time of survival did not differ significantly between the groups. Among the dogs with primary glomerulopathy, identified significant risk factors for death included increased UPC (p=0,03), increased creatinine (p.

INTRODUCTION: On sait peu de choses sur la valeur pronostique de l'augmentation du rapport protéines/créatinine urinaires (UPC) en fonction des différentes maladies sous-jacentes chez le chien. Par conséquent, entre 2014 et 2015, les chiens ayant une UPC de 2,0 ou plus ont été étudiés rétrospectivement au moins une fois. Ils ont été divisés en groupes des maladies sous-jacentes les plus courantes, à savoir la glomérulopathie primaire, la maladie de Cushing, la leishmaniose et dans un groupe de maladies diverses. Les facteurs pronostiques possibles, comme l'UPC au moment du diagnostic, la créatinine, le poids spécifique de l'urine, l'albumine et l'hématocrite, ont été évalués. Quatre-vingt-neuf chiens présentant une protéinurie sévère ont été inclus dans l'étude. La durée médiane de survie était de 42 jours. L'UPC et le temps de survie ne différaient pas significativement entre les groupes. Parmi les chiens atteints de glomérulopathie primaire, les facteurs de risque de décès significatifs identifiés comprenaient une UPC élevée (p=0,03), une créatinine élevée (p.

Altered Serum Thyrotropin Concentrations in Dogs with Primary Hypoadrenocorticism before and during Treatment.

BACKGROUND: Thyrotropin (TSH) can be increased in humans with primary hypoadrenocorticism (HA) before glucocorticoid treatment. Increase in TSH is a typical finding of primary hypothyroidism and both diseases can occur concurrently (Schmidt's syndrome); therefore, care must be taken in assessing thyroid function in untreated human patients with HA. OBJECTIVE: Evaluate whether alterations in cTSH can be observed in dogs with HA in absence of primary hypothyroidism. ANIMALS: Thirty dogs with newly diagnosed HA, and 30 dogs in which HA was suspected but excluded based on a normal ACTH stimulation test (controls) were prospectively enrolled. METHODS: cTSH and T4 concentrations were determined in all dogs and at selected time points during treatment (prednisolone, fludrocortisone, or DOCP) in dogs with HA. RESULTS: cTSH concentrations ranged from 0.01 to 2.6 ng/mL (median 0.29) and were increased in 11/30 dogs with HA; values in controls were all within the reference interval (range: 0.01-0.2 ng/dL; median 0.06). There was no difference in T4 between dogs with increased cTSH (T4 range 1.0-2.1; median 1.3 µg/dL) compared to those with normal cTSH (T4 range 0.5-3.4, median 1.4 µg/dL; P=0.69) and controls (T4 range 0.3-3.8, median 1.8 µg/dL; P=0.35). After starting treatment, cTSH normalized after 2-4 weeks in 9 dogs and after 3 and 4 months in 2 without thyroxine supplementation. CONCLUSIONS AND CLINICAL RELEVANCE: Evaluation of thyroid function in untreated dogs with HA can lead to misdiagnosis of hypothyroidism; treatment with glucocorticoids for up to 4 months can be necessary to normalize cTSH.

Detection of 'Candidatus Neoehrlichia mikurensis' and other Anaplasmataceae and Rickettsiaceae in Canidae in Switzerland and Mediterranean countries.

INTRODUCTION: 'Candidatus Neoehrlichia mikurensis' is an emerging tick-borne zoonotic agent that primarily affects immunocompromised human patients. Dogs and foxes are frequently exposed to ticks, and both species are in close proximity to humans. This is the first study to systematically investigate the occurrence of 'Candidatus Neoehrlichia mikurensis' in Canidae in Europa. We analyzed 1'739 blood samples from dogs in Switzerland, Italy, Spain and Portugal and 162 blood samples from free-ranging red foxes (Vulpes vulpes) in Switzerland. All samples were tested using a previously described multiplex real-time PCR for the Anaplasmataceae family, the 'Candidatus Neoehrlichia' genus and the 'Candidatus Neoehrlichia mikurensis' species. All Anaplasmataceae positive samples were subsequently tested using specific real-time PCRs for Anaplasma phagocytophilum, Anaplasma platys, Ehrlichia canis and Rickettsia helvetica. Among the tested animals, one dog from Zurich tested positive for 'Candidatus Neoehrlichia mikurensis'. The 12-year old West Highland white terrier had been splenectomized 3 months prior to the blood collection and presented with polyuria/polydipsia. Fanconi syndrome was diagnosed based on glucosuria with normoglycemia and hyperaminoaciduria. A. platys and E. canis were detected in 14/249 dogs from Sicily and Portugal; two of the dogs were coinfected with both agents. Four Swiss foxes tested positive for A. phagocytophilium. R. helvetica was detected for the first time in a red fox. In conclusion, 'Candidatus Neoehrlichia mikurensis' infection should be considered in sick dogs, particularly when immunocompromised. The pathogen seems not to be widespread in Canidae in the investigated countries. Conversely, other Anaplasmataceae were more readily detected in dogs and foxes.

INTRODUCTION: 'Candidatus Neoehrlichia mikurensis' est un agent de zoonose transmis par les tiques qui gagne en importance et concerne principalement les patients immunosupprimés. Les chiens comme les renards sont souvent concernés par des morsures de tiques et vivent en contact étroit avec les êtres humains. Dans le présent travail, nous étudions pour la première fois systématiquement la présence de 'Candidatus Neoehrlichia mikurensis' chez les canidés en Europe. Les échantillons sanguins analysés provenaient de 1'739 chiens de Suisse, d'Italie, d'Espagne et du Portugal ainsi que de 162 renards (Vulpes vulpes) de Suisse. Tous les échantillons ont été examinés avec un test de PCR multiplex en temps réel déjà publié quant à la présence d'agents de la famille des Anaplasmataceae, du genre 'Candidatus Neoehrlichia' et de l'espèce 'Candidatus Neoehrlichia mikurensis'. Les échantillons positifs aux Anaplasmataceae ont ensuite été testés avec un test PCR en temps réel spécifique quant à Anaplasma phagocytophilum, Anaplasma platys, Ehrlichia canis und Rickettsia helvetica. Parmi les échantillons examinés se trouvait celui d'un chien de Zürich qui était infecté par 'Candidatus Neoehrlichia mikurensis'. Ce West Highland White Terrier de 12 ans avait été présenté pour polyurie/polydipsie; il avait été splénectomisé trois mois avant la prise de l'échantillon. Au vu d'une glycosurie et d'une hyperaminoacidurie accompagnées d'une glycémie normale, on a posé le diagnostic de syndrome de Fanconi. A. platys et E. canis ont été mis en évidence chez 14/249 chiens provenant de Sicile et du Portugal; deux chiens étaient infectés par les deux agents pathogènes. Quatre renards suisses étaient positifs à A. phagocytophilium et R. helvetica a été trouvé pour la première fois chez un renard. En résumé, on peut dire qu'une infection à 'Candidatus Neoehrlichia mikurensis' chez un chien malade doit être prise en considération comme diagnostic différentiel, particulièrement chez les anomaux immunosupprimés. Toutefois cet agent n'est pas très répandu chez les canidés des pays examinés, contrairement aux autres Anaplasmataceae spp. qui ont été trouvées plus souvent chez les chiens et les renards.

Lack of association between clinical signs and laboratory parameters in dogs with hyperadrenocorticism before and during trilostane treatment.

INTRODUCTION: Trilostane therapy, the treatment of choice for pituitary- dependent hyperadrenocorticism (HAC) in dogs, is monitored by assessing resolution of clinical signs and measuring adrenocortical reserve capacity with an ACTH-stimulation test. The aim of this prospective study was to evaluate agreement between clinical signs reported by owners and cortisol or ACTH concentrations before and during trilostane therapy (starting dose 1-2 mg/kg once daily). A questionnaire on signs of HAC was used and a clinical score calculated as the sum of the 9 questions. Eighteen questionnaires at diagnosis and 97 during therapy were filled out by owners of 32 dogs. An ACTH-stimulation test was performed at each reevaluation. There were weak correlations between abdominal girth, appetite or weight gain and cortisol concentrations during therapy. However, the clinical score did not correlate with cortisol or cACTH values. In 50% of dogs, trilostane application had to be changed from once daily to twice daily during the study. Clinical signs reported by owners matched poorly with cortisol or cACTH concentrations at any time point. If low-dose trilostane is used, treatment frequency often has to be increased.

INTRODUCTION: Le traitement au trilostane, médicament de choix dans les cas d'hyperadrénocorticisme hypophyso-dépendant chez le chien, est évalué sur la base de la disparition des symptômes cliniques et des résultats des tests de stimulation à l'ACTH. Le but de la présente étude prospective était de comparer les symptômes cliniques (évalués par les propriétaires) avec les concentrations de cortisol et d'ACTH endogène avant et durant un traitement au trilostane (dose initiale 1­2 mg/kg, 1× par jour). On a utilisé un questionnaire composé de 9 questions relatives aux symptômes cliniques sur la base desquels on a calculé un score clinique total. Dix-huit questionnaires ont été remplis au moment du diagnostic et 97 durant le traitement par les propriétaires de 32 chiens. Un test de stimulation à l'ACTH a été réalisé lors de chaque contrôle. Il existait de faibles corrélations entre le périmètre abdominal, l'appétit et la prise de poids et les taux de cortisol durant le traitement. Le score clinique total n'était toutefois pas corrélé avec les concentrations de cortisol ou d'ACTH. Chez la moitié des chiens, la dose de trilostane a du être répartie en deux prises journalières. Les symptômes cliniques jugés par les propriétaires montraient une mauvaise corrélation avec les taux de cortisol et d'ACTH durant le traitement au trilostane. Si on dose ce médicament de façon faible, il y a souvent lieu d'augmenter la fréquence des prises.

Hemoglobinuria-related acute kidney injury is driven by intrarenal oxidative reactions triggering a heme toxicity response.

Intravascular hemolysis can result in hemoglobinuria with acute kidney injury. In this study we systematically explored two in vivo animal models and a related cell culture system to identify hemoglobinuria-triggered damage pathways. In models of stored blood transfusion and hemoglobin (Hb) exposure in guinea pigs and beagle dogs we found that hemoglobinuria led to intrarenal conversion of ferrous Hb(Fe(2+)) to ferric Hb(Fe(3+)), accumulation of free heme and Hb-cross-linking products, enhanced 4-hydroxynonenal reactivity in renal tissue, and acute tubule injury. These changes were associated in guinea pigs with activation of a renal cortex gene expression signature indicative of oxidative stress and activation of the unfolded protein response (UPR). Tubule cells of hemolytic animals demonstrated enhanced protein expression of heme oxygenase and heat shock protein and enhanced expression of acute kidney injury-related neutrophil gelatinase-associated lipocalin. These adverse changes were completely prevented by haptoglobin treatment. The in vivo findings were extrapolated to a MS-based proteome analysis of SILAC-labeled renal epithelial cells that were exposed to free heme within a concentration range estimate of renal tubule heme exposure. These experiments confirmed that free heme is a likely trigger of tubule barrier deregulation and oxidative cell damage and reinforced the hypothesis that uncontrolled free heme could trigger the UPR as an important pathway of renal injury during hemoglobinuria.

Cortisol Response in Healthy and Diseased Dogs after Stimulation with a Depot Formulation of Synthetic ACTH.

BACKGROUND: The ACTH stimulation test is used to evaluate the adrenocortical reserve. Recently, the availability of the synthetic ACTH formulation was limited, causing major problems in clinical practice. OBJECTIVES: The objective of this study was to evaluate poststimulation peak cortisol concentrations and the duration of the stimulatory effect of a depot ACTH preparation in dogs. ANIMALS: Twenty-two healthy dogs, 10 dogs with suspected hypoadrenocorticism (HA) and 15 dogs with suspected hyperadrenocorticism (HC). METHODS: Prospective study. An ACTH stimulation test using a synthetic depot tetracosactide, administered intramuscularly (5 µg/kg or at least 0.1 mL) was performed. Blood samples for determination of cortisol were taken immediately before and 1, 2, 3, 4, 6, and 24 hours after stimulation. RESULTS: Peak cortisol concentrations were reached after 2-4 hours in all dogs. Cortisol concentrations 1 hour after stimulation were >9 µg/dL in all healthy dogs and >5 µg/dL in all dogs in which HA was excluded. None of the dogs with HA showed a cortisol-increase above the detection-limit of the assay. After 6 hours, cortisol concentrations had decreased in the healthy and HC group and were back to baseline after 24 hours. CONCLUSIONS AND CLINICAL IMPORTANCE: The depot formulation can be used in place of the short-acting ACTH to evaluate the adrenocortical reserve. Blood for peak cortisol concentrations should be drawn 3 hours after stimulation in cases in which HC is suspected; in HA-suspected cases, blood sampling can take place after 1 hour. As the stimulatory effect is gone after 24 hours, interference with other hormonal tests is unlikely after that time.

Evaluation of the Cortisol-to-ACTH Ratio in Dogs with Hypoadrenocorticism, Dogs with Diseases Mimicking Hypoadrenocorticism and in Healthy Dogs.

BACKGROUND: The adrenocorticotropic hormone (ACTH) stimulation test is the gold standard for diagnosing hypoadrenocorticism (HA) in dogs. However, problems with the availability of synthetic ACTH (tetracosactrin/cosyntropin) and increased costs have prompted the need for alternative methods. OBJECTIVES: To prospectively evaluate the cortisol-to-ACTH ratio (CAR) as a screening test for diagnosing canine HA. ANIMALS: Twenty three dogs with newly diagnosed HA; 79 dogs with diseases mimicking HA; 30 healthy dogs. METHODS: Plasma ACTH and baseline cortisol concentrations were measured before i.v. administration of 5 µg/kg ACTH in all dogs. CAR was calculated and the diagnostic performance of ACTH, baseline cortisol, CAR and sodium-to-potassium ratios (SPRs) was assessed based on receiver operating characteristics (ROC) curves calculating the area under the ROC curve. RESULTS: The CAR was significantly lower in dogs with HA compared to that in healthy dogs and in those with diseases mimicking HA (P < .0001). There was an overlap between HA dogs and those with HA mimicking diseases, but CAR still was the best parameter for diagnosing HA (ROC AUC 0.998), followed by the ACTH concentration (ROC AUC 0.97), baseline cortisol concentration (ROC AUC 0.96), and SPR (ROC AUC 0.86). With a CAR of >0.01 the diagnostic sensitivity and specificity were 100% and 99%, respectively. CONCLUSION AND CLINICAL IMPORTANCE: Calculation of the CAR is a useful screening test for diagnosing primary HA. As a consequence of the observed overlap between the groups, however, misdiagnosis cannot be completely excluded. Moreover, additional studies are needed to evaluate the diagnostic reliability of CAR in more dogs with secondary HA.

Urinary and plasma catecholamines and metanephrines in dogs with pheochromocytoma, hypercortisolism, nonadrenal disease and in healthy dogs.

BACKGROUND: Diagnosis of pheochromocytoma (PC) is based on a combination of clinical suspicion, finding an adrenal mass, increased plasma, and urine concentrations of catecholamine metabolites and is finally confirmed with histopathology. In human medicine, it is controversial whether biochemically testing plasma is superior to testing urine. OBJECTIVES: To measure urinary and plasma catecholamines and metanephrines in healthy dogs, dogs with PC, hypercortisolism (HC), and nonadrenal diseases (NAD) and to determine the test with the best diagnostic performance for dogs with PC. ANIMALS: Seven PC dogs, 10 dogs with HC, 14 dogs with NAD, 10 healthy dogs. METHODS: Prospective diagnostic clinical study. Urine and heparin plasma samples were collected and stored at -80°C before analysis using high-pressure liquid chromatography (HPLC) coupled to electrochemical detection or tandem mass spectrometry were performed. Urinary variables were expressed as ratios to urinary creatinine concentration. RESULTS: Dogs with PC had significantly higher urinary normetanephrine and metanephrine:creatinine ratios and significantly higher plasma-total and free normetanephrine and plasma-free metanephrine concentrations compared to the 3 other groups. There were no overlapping results of urinary normetanephrine concentrations between PC and all other groups, and only one PC dog with a plasma normetanephrine concentration in the range of the dogs with HC and NAD disease. Performances of total and free plasma variables were similar. Overlap of epinephrine and norepinephrine results between the groups was large with both urine and plasma. CONCLUSION AND CLINICAL IMPORTANCE: Measurement of normetanephrine is the preferred biochemical test for PC and urine was superior to plasma.

Use of plasma renin activity to monitor mineralocorticoid treatment in dogs with primary hypoadrenocorticism: desoxycorticosterone versus fludrocortisone.

BACKGROUND: Measurement of plasma renin activity (PRA) is the gold standard for monitoring mineralocorticoid treatment in humans with primary hypoadrenocorticism (PH). OBJECTIVES: To compare PRA in dogs with newly diagnosed PH, dogs with diseases mimicking PH, and healthy dogs, and evaluate measurement of PRA to monitor therapeutic effects in dogs with PH treated with different mineralocorticoids. ANIMALS: Eleven dogs with newly diagnosed PH (group 1), 10 dogs with diseases mimicking PH (group 2), 21 healthy dogs (group 3), 17 dogs with treated PH (group 4). METHODS: In group 1, PRA was measured before treatment and at different times after initiating treatment. In groups 2 and 3, PRA was measured at initial presentation only. In group 4, no baseline PRA was obtained but PRA was measured once or every 1-6 months during treatment. Mineralocorticoid treatment consisted of fludrocortisone acetate (FC) or desoxycorticosterone pivalate (DOCP). RESULTS: Plasma renin activity before treatment was increased in dogs with PH compared to normal dogs and dogs with diseases mimicking PH with median activity of 27, 0.8, and 1.0 ng/mL/h, respectively. In dogs with PH, PRA decreased and normalized with mineralocorticoid treatment using DOCP but not with FC. In dogs treated with DOCP, PRA was lower than in dogs treated with FC. Plasma sodium concentrations were higher and potassium concentrations were lower with DOCP treatment compared to FC treatment. CONCLUSION AND CLINICAL IMPORTANCE: Plasma renin activity is a reliable tool for monitoring mineralocorticoid treatment. DOCP treatment more effectively suppresses PRA compared to FC in dogs with PH.

Urinary corticoid concentrations measured by 5 different immunoassays and gas chromatography-mass spectrometry in healthy dogs and dogs with hypercortisolism at home and in the hospital.

BACKGROUND: Determination of the urinary corticoid-to-creatinine ratio (UCCR) is an important screening test in the diagnosis of hypercortisolism (HC). However, urinary cortisol metabolites interfere with cortisol measurement in immunoassays, leading to decreased specificity. Gas chromatography-mass spectrometry (GC-MS) is considered the gold standard for steroid hormone analysis, because it provides a high level of selectivity and accuracy. OBJECTIVES: To prospectively compare the UCCR of healthy dogs and dogs with HC determined by 5 different immunoassays and by GC-MS and to evaluate the influence of veterinary care on UCCR. ANIMALS: Twenty healthy dogs; 18 dogs with HC. METHODS: Urine was collected in the hospital and again after 6 days at home. Three chemiluminescence immunoassays (Access 2, Beckmann; Immulite 2000, DPC Siemens, with and without trichloromethane extraction) and 2 RIAs (Utrecht in house; Access Beckmann) were used. GC-MS analyses were performed with Agilent 6890N/5973N. Urinary corticoid concentrations were related to urinary creatinine concentrations. RESULTS: Immunoassay results were significantly higher compared to GC-MS results. Evaluation of bias plots and clinical assessment made on the basis of the assay results of each dog indicated substantial disagreement among the assays. Sensitivity varied from 37.5 to 75% and with selected assays was lower in samples from day 6 compared to day 0. GC-MS was not superior to the immunoassays in discriminating healthy from HC dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Considerable variation must be anticipated comparing different urinary cortisol assays. Establishing an assay- and laboratory-specific reference range is critical when using UCCR.

Evaluation of aldosterone concentrations in dogs with hypoadrenocorticism.

BACKGROUND: Some dogs with primary hypoadrenocorticism (HA) have normal sodium and potassium concentrations, a phenomenon called atypical Addison's disease. The assumption that the zona glomerulosa and aldosterone secretion in these dogs are normal seems widely accepted; however, aldosterone measurements are missing in most published cases. OBJECTIVES: To measure aldosterone in dogs with HA with and without electrolyte abnormalities and to determine the time point of aldosterone peak concentrations during ACTH stimulation. ANIMALS: Seventy dogs with HA, 22 dogs with diseases mimicking HA, and 19 healthy dogs. METHODS: Prospective study. Blood samples were taken before and 60 minutes after injection of 250 µg ACTH in all dogs. Additional blood samples were taken 15, 30, and 45 minutes after ACTH in 7 dogs with HA and in 22 with diseases mimicking HA. RESULTS: Baseline and ACTH-stimulated aldosterone was significantly lower in dogs with HA than in the other groups. Aldosterone was low or undetectable in 67/70 dogs with HA independently of sodium and potassium levels. In 3 dogs, sodium/potassium concentrations were normal; in 1 dog, sodium was normal and potassium decreased. In all 4, ACTH-stimulated aldosterone concentrations were below the detection limit of the assay. Aldosterone concentrations were not different at 30, 45, or 60 minutes after ACTH administration. CONCLUSION AND CLINICAL IMPORTANCE: Cortisol and aldosterone secretion is compromised in dogs with HA with and without electrolyte abnormalities. The term atypical Addison's disease, used for dogs with primary HA and normal electrolytes, must be reconsidered; other mechanisms allowing normal electrolyte balance without aldosterone should be evaluated in these dogs.

Comparison of two treatment regimens with trilostane in dogs with pituitary-dependent hyperadrenocorticism.

Trilostane is used to treat dogs with pituitary-dependent hyperadrenocorticism (PDH). In our institution, it was initially dosed based on bodyweight (BW) categories, since April 06 it is dosed per kg BW. Our objectives were to compare effectiveness, number of dose adjustments and side effects of the two dose regimens in dogs with PDH. Dogs of group 1 (28 dogs) received trilostane based on BW categories (< 5 kg, 30 mg; 5 - 20 kg, 60 mg and > 20 kg, 120 mg; SID); dogs of group 2 (20 dogs) received 2 - 5 mg/kg SID. Treatment goal was a post-ACTH cortisol of 1 - 2.5 and 1.5 - 5.4 µg/dl in group 1 and 2, respectively. Starting doses were significantly higher in group 1 and stayed higher until re-check at 4 - 7 months. Baseline and post-ACTH cortisol were significantly decreased compared to pre-treatment at all time points in both groups. Significantly more dogs of group 2 (5/20) needed a dose increase at the first re-check and significantly more dogs of group 1 (10/23) a dose reduction at the last re-check. Intermittent discontinuation was necessary in 25 and 10 % of dogs of group 1 and 2, respectively. We conclude that dosing per kg BW results in comparable clinical improvement, decrease in cortisol, but lower risk of side effects.

Le trilostane est en Suisse le seul médicament enregistré pour le traitement de l'hyperadrénocorticisme hypophysaire. Dans les débuts, le trilostane a été dosé dans notre clinique selon les catégories de poids; depuis avril 2006 nous le dosons en fonction du poids exact. Le but du présent travail était de comparer l'efficacité, le nombre d'ajustement de la dose et les effets secondaires des deux schémas de dosage chez des chiens souffrant d'hyperadrénocorticisme hypophysaire. Chez les chiens du groupe 1 (28 chiens), le dosage à été fait de la façon suivante: < 5 kg, 30 mg; 5 ­ 20 kg, 60 mg; > 20 kg, 120 mg; q24h. Les chiens du groupe 2 (20 chiens) recevaient 2 ­ 5 mg/kg q24h. Le but du traitement était d'atteindre un taux de cortisol après ACTH entre 1 et 2.5 ug/dl dans le groupe 1 et entre 1.5 ­ 5.4 ug/dl dans le groupe 2. Les doses initiales étaient significativement plus hautes dans le groupe 1 et restaient plus élevées jusqu'au contrôle après 4 à 7 mois. Les taux de cortisol basal et après ACTH étaient significativement plus bas par rapport à ceux mesurés avant le traitement dans les 2 groupes, et ce à tout moment. La dose a du être augmentée lors du premier contrôle de façon significativement plus fréquente (5/20) dans le groupe 2. La dose a du être réduite lors des derniers contrôles de façon significativement plus fréquente (10/23) dans le groupe 1. Des interruptions de courte durée du traitement ont été nécessaires chez 25 respectivement 10 % des chiens des groupes 1 réspectivement 2. Le dosage du trilostane en fonction du poids en kilo amène une réponse thérapeutique et une chute du taux de cortisol comparables, mais avec moi s d'effets secondaires.

Evaluation of baseline cortisol, endogenous ACTH, and cortisol/ACTH ratio to monitor trilostane treatment in dogs with pituitary-dependent hypercortisolism.

BACKGROUND: The effectiveness of trilostane treatment is currently monitored by regular ACTH stimulation tests, which are time-consuming and expensive. Therefore, a monitoring system without a stimulation protocol and with less client expense would be preferable. HYPOTHESIS/OBJECTIVES: The aim of our study was to evaluate if baseline cortisol, endogenous ACTH (ACTH) concentration or the baseline cortisol to ACTH ratio (cortisol/ACTH ratio) could replace the ACTH stimulation test. ANIMALS: Forty trilostane-treated dogs with pituitary-dependent hypercortisolism (PDH) were included in this prospective study. METHODS: A total of 148 ACTH stimulation tests and 77 ACTH concentrations and cortisol/ACTH ratios were analyzed. Control of cortisol release was classified according to cortisol concentration after ACTH administration as excessive (<1.5 µg/dL; group 1), adequate (1.5-5.4 µg/dL; group 2), or inadequate (>5.4 µg/dL; group 3). RESULTS: Baseline cortisol concentrations had considerable overlap between excessively, adequately, and inadequately controlled dogs. Only baseline cortisol >4.4 µg/dL (in 12% of tests) was a reliable diagnosis of inadequate control. Endogenous ACTH concentrations did not differ between groups. The overlap of the cortisol/ACTH ratio between groups was large. Correct classification was only possible if the cortisol/ACTH ratio was >15, which occurred in 4% of tests. CONCLUSIONS AND CLINICAL IMPORTANCE: To monitor trilostane treatment the ACTH stimulation test cannot be replaced by baseline cortisol, ACTH concentration, or the cortisol/ACTH ratio.

Duration of t4 suppression in hyperthyroid cats treated once and twice daily with transdermal methimazole.

BACKGROUND: Transdermal methimazole is an acceptable alternative to oral treatment for hyperthyroid cats. There are, however, no studies evaluating the duration of T4 suppression after transdermal methimazole application. Such information would be valuable for therapeutic monitoring. OBJECTIVE: To assess variation in serum T4 concentration in hyperthyroid cats after once- and twice-daily transdermal methimazole administration. ANIMALS: Twenty client-owned cats with newly diagnosed hyperthyroidism. METHODS: Methimazole was formulated in a pluronic lecithin organogel-based vehicle and applied to the pinna of the inner ear at a starting dose of 2.5 mg/cat q12h (BID group, 10 cats) and 5 mg/cat q24h (SID group, 10 cats). One and 3 weeks after starting treatment, T4 concentrations were measured immediately before and every 2 hours after gel application over a period of up to 10 hours. RESULTS: Significantly decreased T4 concentrations were observed in week 1 and 3 compared with pretreatment concentrations in both groups. All cats showed sustained suppression of T4 concentration during the 10-hour period, and T4 concentrations immediately before the next methimazole treatment were not significantly different compared with any time point after application, either in the BID or SID groups. CONCLUSIONS: Because transdermal methimazole application led to prolonged T4 suppression in both the BID and SID groups, timing of blood sampling does not seem to be critical when assessing treatment response.

Use of insulin glargine in dogs with diabetes mellitus.

The objective of this study was to evaluate the safety and efficacy of insulin glargine in dogs with diabetes mellitus (DM). Twelve client-owned dogs with DM were included. All dogs received insulin glargine every 12 hours for at least six months, re-evaluations were performed after one, two, four, eight, 12 and 24 weeks and included clinical signs, blood glucose curves (BGCs) and measurement of serum fructosamine concentrations. Mean blood glucose concentrations were significantly lower after two weeks of treatment and remained significantly lower for the duration of the study. By week 24, polyuria/polydipsia had improved in 91 per cent of the dogs. No clinical signs that could have been caused by hypoglycaemia were observed. Based on BGCs and remission of the clinical signs for judging the success of the treatment, 58, 33 and 8 per cent of the dogs attained good, moderate and poor glycaemic control by week 24 of the study, respectively. Insulin glargine administered subcutaneously twice daily is a possible and safe method of treatment for dogs with naturally occurring DM. Although only a few studies are available on the use of other types of insulin in dogs, their success rate is somewhat greater than that with insulin glargine.

[FeLV infection in the cat: clinically relevant aspects]. / Die FeLV-Infektion der Katze: Praxis-relevante Aspekte.

The feline leukemia virus (FeLV) is a retrovirus of the domestic cat that was described almost 50 years ago. The FeLV-infection may lead to fatal diseases in domestic and small wild cats. The use of efficacious diagnostics assays and vaccines led to a reduction of the FeLV prevalence; however, FeLV still poses a problem for the cat presented with the infection. This article aims to describe recent developments in diagnostics and findings in the infection pathogenesis that are clinically relevant.

Adrenocorticotropic hormone, but not trilostane, causes severe adrenal hemorrhage, vacuolization, and apoptosis in rats.

Adrenal necrosis has been reported as a complication of trilostane application in dogs with hyperadrenocorticism. One suspicion was that necrosis results from the increase of adrenocorticotropic hormone (ACTH) during trilostane therapy. The aim of the current study was to assess the effects of ACTH and trilostane on adrenal glands of rats. For experiment 1, 36 rats were divided into 6 groups. Groups 1.1 to 1.4 received ACTH in different doses (60, 40, 20, and 10 µg/d) infused subcutaneously with osmotic minipumps for 16 wk. Group 1.5 received saline, and group 1.6 received no therapy. For experiment 2, 24 rats were divided into 3 groups. Group 2.1 and 2.2 received 5 and 50 mg/kg trilostane/d orally mixed into chocolate pudding for 16 wk. Eight control rats received pudding alone. At the end of the experiments, adrenal glands were assessed for necrosis by histology and immunohistochemistry; levels of endogenous ACTH and nucleosomes were assessed in the blood. Rats treated with 60 µg ACTH/d showed more hemorrhage and vacuolization and increased numbers of apoptotic cells in the adrenal glands than rats treated with 20 or 10 µg ACTH/d, trilostane, or control rats. Rats treated with 60 µg ACTH/d had a higher amount of nucleosomes in the blood compared with rats treated with 10 µg ACTH/d, trilostane, or saline. We conclude that in healthy rats ACTH, but not trilostane, causes adrenal degeneration in a dose-dependent manner. Results of this study support the hypothesis that adrenal gland lesions seen in trilostane-treated dogs are caused by ACTH and not by trilostane.

Urinary catecholamine and metanephrine to creatinine ratios in dogs with hyperadrenocorticism or pheochromocytoma, and in healthy dogs.

BACKGROUND: Urinary catecholamines and metanephrines are used for the diagnosis of pheochromocytoma (PHEO) in dogs. Hyperadrenocorticism (HAC) is an important differential diagnosis for PHEO. OBJECTIVES: To measure urinary catecholamines and metanephrines in dogs with HAC. ANIMALS: Fourteen dogs with HAC, 7 dogs with PHEO, and 10 healthy dogs. METHODS: Prospective clinical trial. Urine was collected during initial work-up in the hospital; in dogs with HAC an additional sample was taken at home 1 week after discharge. Parameters were measured using high-pressure liquid chromatography and expressed as ratios to urinary creatinine concentration. RESULTS: Dogs with HAC had significantly higher urinary epinephrine, norepinephrine and normetanephrine to creatinine ratios than healthy dogs. Urinary epinephrine, norepinephrine, and metanephrine to creatinine ratios did not differ between dogs with HAC and dogs with PHEO, whereas the urinary normetanephrine to creatinine ratio was significantly higher (P= .011) in dogs with PHEO (414, 157.0-925.0, median, range versus (117.5, 53.0-323.0). Using a cut-off ratio of 4 times the highest normetanephrine to creatinine ratio measured in controls, there was no overlap between dogs with HAC and dogs with PHEO. The variables determined in urine samples collected at home did not differ from those collected in the hospital. CONCLUSION AND CLINICAL IMPORTANCE: Dogs with HAC might have increased concentrations of urinary catecholamines and normetanephrine. A high concentration of urinary normetanephrine (4 times normal), is highly suggestive of PHEO.

Salivary cortisol concentrations in healthy dogs and dogs with hypercortisolism.

BACKGROUND: Measurement of salivary cortisol is a useful diagnostic test for hypercortisolism (HC) in humans. OBJECTIVES: To determine whether measurement of salivary cortisol concentration is a practical alternative to plasma cortisol to diagnose HC, to validate the use of salivary cortisol, and to examine the effect of time of day and sampling location on salivary cortisol. ANIMALS: Thirty healthy dogs and 6 dogs with HC. METHODS: Prospective, observational clinical trial including healthy volunteer dogs and dogs newly diagnosed with HC. Salivary and plasma cortisol concentrations were measured with an immunoassay analyzer. Intra- and interassay variability, linearity, and correlation between salivary and plasma cortisol concentrations were determined. RESULTS: The required 300 microL of saliva could not be obtained in 88/326 samples from healthy dogs and in 15/30 samples from dogs with HC. The intra-assay variability for measurement of salivary cortisol was 5-17.7%, the interassay variability 8.5 and 17.3%, and the observed to expected ratio 89-125%. The correlation (r) between salivary and plasma cortisol was 0.98. The time of day and location of collection did not affect salivary cortisol concentrations. Dogs with HC had significantly higher salivary cortisol values than healthy dogs (10.2 +/- 7.3 nmol/L versus 1.54 +/- 0.97 nmol/L; P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: The ROCHE Elecsys immunoassay analyzer correctly measured salivary cortisol in dogs. However, a broad clinical application of the method seems limited, because of the large sample volume required.

Urinary catecholamine and metadrenaline to creatinine ratios in dogs with a phaeochromocytoma.

Urinary adrenaline (epinephrine), noradrenaline, dopamine, metadrenaline (metanephrine) and normetadrenaline to creatinine ratios were measured from spot samples of seven client-owned dogs with a histologically confirmed phaeochromocytoma. Urine was collected on day 0 in the hospital in six dogs, and additionally on days 2, 6 and 7 after discharge in two of these dogs. In one dog, urine was sampled on day 7 only. Samples were also collected from 10 healthy control dogs on days 0, 1 and 7. In dogs with phaeochromocytomas, normetadrenaline:creatinine ratios at all time points ranged from 103 to 6430 nmol/mmol. From day 0, ratios of samples taken at the hospital (range 157 to 925 nmol/mmol) were significantly higher (P<0.0012) compared with control samples (range 14 to 91 nmol/mmol). The highest normetadrenaline:creatinine ratios were found in two dogs with bilateral phaeochromocytomas. Adrenaline:creatinine and noradrenaline:creatinine ratios were also significantly increased (P<0.016) in dogs with a phaeochromocytoma at day 0 compared with controls, although the difference was less pronounced than that between controls and dogs with a phaeochromocytoma for the normetadrenaline:creatinine ratio. Urine normetadrenaline:creatinine ratios may be useful in the diagnosis of canine phaeochromocytomas.