ABSTRACT
Changes in neutrophil-to-lymphocite ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been identified in dogs with hypercortisolism (HC), but, no studies have investigated the changes in these inflammatory biomarkers as cost-effective and available parameters for the diagnosis and management of HC. This study was performed to evaluate whether NLR and PLR could be used as biomarkers for the diagnosis and treatment response in dogs with HC. This retrospective study included 67 dogs with HC, 58 dogs with non-adrenal illness (NAI), and 39 healthy dogs. NLR and PLR were compared among the three groups. Cut-off values of NLR and PLR for HC screening and percent change in biomarkers for assessing treatment response were evaluated. In addition, the NLR and PLR were compared before and after trilostane treatment. NLR and PLR were significantly higher in the HC group than in the NAI and healthy groups. The NLR cut-off value of 4.227 had a sensitivity of 67.16% and specificity of 65.52%, and the PLR cut-off value of 285.0 had a sensitivity of 56.72% and specificity of 70.69% for differentiating between dogs with HC and those with NAI, respectively. Furthermore, a significant decline in NLR was observed after treatment in the well-controlled HC group. The cutoff value of percent change in NLR to identify well-controlled HC was -7.570%; sensitivity and specificity were 100% and 63.64%, respectively. Therefore, NLR and PLR might be used cautiously as supportive biomarkers for HC diagnosis, and NLR could be a potential monitoring tool in assessing the treatment response of HC in dogs.
Subject(s)
Biomarkers , Dog Diseases , Neutrophils , Animals , Dogs , Dog Diseases/blood , Dog Diseases/diagnosis , Retrospective Studies , Male , Biomarkers/blood , Female , Lymphocytes , Cushing Syndrome/veterinary , Cushing Syndrome/blood , Cushing Syndrome/diagnosis , Blood Platelets , Sensitivity and Specificity , Dihydrotestosterone/blood , Dihydrotestosterone/analogs & derivatives , Dihydrotestosterone/therapeutic use , Platelet Count/veterinaryABSTRACT
A retrospective cross-sectional study was conducted to assess the frequency of low-dose dexamethasone suppression test (LDDST) patterns in canine patients that had clinicopathologic signs consistent with Cushing's syndrome (CS). Medical records for patients of interest (N = 128) were reviewed between January 2014 and December 2020 to analyse and classify LDDST results based upon the following patterns: lack of suppression, partial suppression, complete suppression, escape, or inverse. Complete suppression, lack of suppression, partial suppression, escape, and inverse patterns were identified in 39.1%, 31.2%, 14.1%, 10.1% and 5.5% of cases respectively. LDDST results were also evaluated with respect to clinical signs, serum alkaline phosphatase (ALP) activity, urine specific gravity (USG) and adrenal ultrasonographic findings. There was no association between LDDST patterns and clinical signs (p = 0.11), increased ALP (p = 0.32), USG (p = 0.33) or adrenal ultrasonographic findings (p = 0.19). In all dogs that demonstrated complete suppression or an inverse pattern, CS was excluded by the attending clinician. The diagnosis of CS was also excluded without further exploration in 23.1%, 7.5% and 5.6% of dogs that demonstrated an escape pattern, lack of suppression and partial suppression pattern, respectively. These results suggest that the clinical significance of LDDST patterns, particularly escape and inverse patterns, are misunderstood by some clinicians, leading them to prematurely exclude the diagnosis of CS.
Subject(s)
Cushing Syndrome , Dexamethasone , Dog Diseases , Dogs , Animals , Retrospective Studies , Dog Diseases/diagnostic imaging , Cushing Syndrome/veterinary , Cushing Syndrome/pathology , Dexamethasone/administration & dosage , Dexamethasone/pharmacology , Male , Cross-Sectional Studies , Female , Ultrasonography/veterinaryABSTRACT
BACKGROUND: Muscle atrophy and intramuscular fatty infiltration, as well as their association with prognosis, have not been quantified in dogs with spontaneous hypercortisolism (HC). OBJECTIVE: To quantitatively evaluate muscle atrophy and IM fatty infiltration in dogs with HC and determine their prognostic impact. ANIMALS: Fifty-three dogs with HC and 66 control dogs without HC. METHODS: Retrospective cohort study. Medical records and computed tomography images obtained between 2014 and 2021 were evaluated. Kaplan-Meier curves and log-rank tests were used to analyze the effect of muscle atrophy and IM fatty infiltration on the prognosis of dogs with HC. RESULTS: Dogs with HC showed lower visually measured cross-sectional area (VCSA) and cross-sectional area based on attenuation (HCSA) than control dogs (median [interquartile range {IQR}]: 50.3 mm2/mm [36.2-67.8] vs 66.7 mm2/mm [48.0-85.9]; P < .001; 30.4 mm2/mm [13.7-57.2] vs 54.8 mm2/mm [39.7-71.5]; P < .001, respectively). Dogs with HC had lower epaxial muscle attenuation (L3HU) than control dogs (median [IQR]: 21.2 Hounsfield [HU] [12.4-28.2] vs 33.2 HU [22.6-43.6]; P < .001). Dogs with HC with lower HCSA or L3HU had shorter survival (median [IQR]: 670 days [222-673] vs 949 days [788-1074], P < .01; 523 days [132-670] vs 949 days [756-1074], P < .01, respectively) but not lower VCSA (median [IQR]: 673 days [132-788] vs 949 days [523 to not applicable]; P = .30). CONCLUSION AND CLINICAL IMPORTANCE: Hypercortisolism in dogs causes muscle atrophy and IM fatty infiltration and is associated with poor prognosis.
Subject(s)
Cushing Syndrome , Dog Diseases , Muscle, Skeletal , Muscular Atrophy , Animals , Dogs , Dog Diseases/pathology , Retrospective Studies , Male , Female , Prognosis , Cushing Syndrome/veterinary , Cushing Syndrome/pathology , Muscular Atrophy/veterinary , Muscular Atrophy/pathology , Muscle, Skeletal/pathology , Adipose Tissue/pathology , Tomography, X-Ray Computed/veterinary , Cohort StudiesABSTRACT
OBJECTIVE: To summarize findings from a case of adrenocortical hemorrhage following tetracosactide injection during ACTH stimulation testing for monitoring of trilostane therapy in a dog. ANIMAL: A 12-year old neutered male dog with adrenal-dependent hypercortisolism. CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES: 4 hours after ACTH stimulation testing, the patient developed vomiting, lethargy, and abdominal pain. Abdominal ultrasound was performed before and after an ACTH stimulation test. Following ACTH stimulation testing, there was progressive bilateral adrenal enlargement and free abdominal fluid had developed. This was considered to be caused by adrenocortical inflammation and hemorrhage secondary to the synthetic ACTH analog, tetracosactide, used during stimulation testing. A resting cortisol performed 5 hours after tetracosactide injection was not consistent with iatrogenic hypoadrenocorticism. TREATMENT AND OUTCOME: The patient was managed with analgesia, IV fluids, and corticosteroids and made a full recovery. CLINICAL RELEVANCE: To the authors' knowledge, this was the first reported case of adrenocortical hemorrhage following administration of a synthetic ACTH analog in a dog. This should be considered as a rare potential complication of ACTH stimulation testing.
Subject(s)
Cushing Syndrome , Dog Diseases , Humans , Male , Dogs , Animals , Cosyntropin/therapeutic use , Cushing Syndrome/chemically induced , Cushing Syndrome/drug therapy , Cushing Syndrome/veterinary , Hydrocortisone/adverse effects , Inflammation/veterinary , Dog Diseases/chemically induced , Dog Diseases/drug therapy , Hemorrhage/veterinaryABSTRACT
Miniature Schnauzer dogs (MSs) are predisposed to both idiopathic hypertriglyceridemia (iHTG) and hypercortisolism (HCort). To our knowledge, the lipoprotein profiles of MSs with iHTG have not been compared to those with HCort. We analyzed cholesterol and triglyceride concentrations and lipoprotein fractions in 4 groups of MSs: normotriglyceridemia (NTG) without concurrent disease (Healthy-NTG), HCort and NTG (HCort-NTG), HCort and HTG (HCort-HTG), and iHTG. Lipoprotein fractions were assessed by lipoprotein electrophoresis and compared between groups. Fifty-one plasma samples were analyzed. Twenty-five dogs had NTG (16 Healthy-NTG, 9 HCort-NTG) and 26 dogs had HTG (7 iHTG, 19 HCort-HTG). Dogs with iHTG or HCort-HTG had significantly higher cholesterol concentrations than Healthy-NTG dogs. Dogs with HCort-HTG had higher cholesterol than HCort-NTG dogs. There was a significantly higher low-density lipoprotein (LDL) percentage in iHTG and HCort-HTG dogs than HCort-NTG dogs. HCort-HTG dogs also had lower high-density lipoproteins (HDL) than HCort-NTG dogs. It was not possible to readily distinguish MSs with iHTG from MSs with HCort-HTG or Healthy-NTG using lipoprotein electrophoresis fractions. The diagnosis of iHTG remains a diagnosis by exclusion.
Subject(s)
Cushing Syndrome , Dog Diseases , Hypertriglyceridemia , Dogs , Animals , Cushing Syndrome/veterinary , Lipoproteins , Hypertriglyceridemia/veterinary , Triglycerides , Cholesterol , Dog Diseases/diagnosisABSTRACT
BACKGROUND: A prediction tool was developed and internally validated to aid the diagnosis of Cushing's syndrome in dogs attending UK primary-care practices. External validation is an important part of model validation to assess model performance when used in different populations. OBJECTIVES: To assess the original prediction model's transportability, applicability, and diagnostic performance in a secondary-care practice in the Netherlands. ANIMALS: Two hundred thirty client-owned dogs. METHODS: Retrospective observational study. Medical records of dogs under investigation of Cushing's syndrome between 2011 and 2020 were reviewed. Dogs diagnosed with Cushing's syndrome by the attending internists and fulfilling ALIVE criteria were defined as cases, others as non-cases. All dogs were scored using the aforementioned prediction tool. Dog characteristics and predictor-outcome effects in development and validation data sets were compared to assess model transportability. Calibration and discrimination were examined to assess model performance. RESULTS: Eighty of 230 dogs were defined as cases. Significant differences in dog characteristics were found between UK primary-care and Dutch secondary-care populations. Not all predictors from the original model were confirmed to be significant predictors in the validation sample. The model systematically overestimated the probability of having Cushing's syndrome (a = -1.10, P < .001). Calibration slope was 1.35 and discrimination proved excellent (area under the receiver operating curve = 0.83). CONCLUSIONS AND CLINICAL IMPORTANCE: The prediction model had moderate transportability, excellent discriminatory ability, and overall overestimated probability of having Cushing's syndrome. This study confirms its utility, though emphasizes that ongoing validation efforts of disease prediction tools are a worthwhile effort.
Subject(s)
Cushing Syndrome , Dog Diseases , Animals , Dogs , Humans , Calibration , Cushing Syndrome/diagnosis , Cushing Syndrome/veterinary , Dog Diseases/diagnosis , Medical Records , Netherlands , United Kingdom , Retrospective StudiesABSTRACT
A 12-year-old neutered male Chihuahua dog was diagnosed with pituitary-dependent hypercortisolism and treated with trilostane. Eighty-nine days later, the dog showed lethargy accompanied by hyponatraemia and hyperkalaemia. Hypoadrenocorticism due to trilostane was suspected, but the result of the adrenocorticotropic hormone stimulation test was not conclusive. Contrast-enhanced ultrasound showed loss of adrenocortical blood flow in both adrenal glands, indicating adrenocortical hypoperfusion and isolated hypoadrenocorticism. Treatment with fludrocortisone acetate improved the condition and electrolyte abnormalities. Thirteen months later, the dog showed alopecia, and an adrenocorticotropic hormone stimulation test revealed increased cortisol concentration, indicating hypercortisolism recurrence. The dog died due to progressive deterioration 22 months after the initial presentation. Post-mortem examination revealed focally extensive necrosis with marked calcification in the parenchyma of the adrenal glands and regeneration of the cells in the zona fasciculata with severe fibrosis. Adrenocortical hypoperfusion detected by contrast-enhanced ultrasound can support the diagnosis of adrenal necrosis and hypoadrenocorticism.
Subject(s)
Adrenal Insufficiency , Cushing Syndrome , Dog Diseases , Dogs , Male , Animals , Cushing Syndrome/veterinary , Adrenal Insufficiency/diagnosis , Adrenal Insufficiency/veterinary , Hydrocortisone/adverse effects , Adrenocorticotropic Hormone/adverse effects , Necrosis/veterinary , Dog Diseases/diagnostic imaging , Dog Diseases/drug therapyABSTRACT
Trilostane and insulin requirements and survival time of dogs with concurrent naturally-occurring Cushing's syndrome (CS) and diabetes mellitus (DM) has not been fully investigated. This retrospective study evaluated trilostane and insulin doses in dogs with concurrent CS and DM compared to dogs with only CS or DM. Additionally, a survival analysis was performed using a Kaplan-Meier survival curve. Survival time was compared through Log-rank test. Cox proportional regression method was used to screen predictor factors of death in dogs with CS, DM or concurrent CS and DM. A total of 95 dogs were included, 47 dogs had CS, 31 dogs had DM and 17 dogs had concurrent CS and DM. After long-term follow-up, dogs with concurrent CS and DM required higher final median doses of insulin than dogs with DM [0.90 (0.73-1.1) vs 0.67 (0.55-0.73) u/kg/12 h; P = 0,002]. Conversely, the median trilostane requirements in dogs with concurrent CS and DM did not differ from the median trilostane requirements of dogs with CS [1.52 (0.76-2.80) vs 1.64 (1.19-4.95) mg/kg/day; P = 0.283]. No statistical difference was found for the median survival time between dogs with CS and dogs with concurrent CS and DM (1245 vs 892 days; p = 0.152). Although, median survival time of dogs with DM was not reached, it was longer than median survival time of dogs with CS and DM (892 days; P = 0.002). In conclusion, diabetic dogs with concurrent CS need higher insulin doses and have a shorter survival time compared to diabetic dogs without CS.
Subject(s)
Cushing Syndrome , Diabetes Mellitus , Dog Diseases , Dogs , Animals , Cushing Syndrome/complications , Cushing Syndrome/drug therapy , Cushing Syndrome/veterinary , Insulin/therapeutic use , Retrospective Studies , Diabetes Mellitus/drug therapy , Diabetes Mellitus/veterinary , Dog Diseases/drug therapy , Hydrocortisone/therapeutic useABSTRACT
BACKGROUND: Radiotherapy (RT) is an effective treatment for dogs presented with neurologic signs caused by pituitary tumors. However, its impact on the outcome of concurrent pituitary-dependent hypercortisolism (PDH) is controversial. OBJECTIVES: Determine whether dogs with PDH have longer survival after pituitary RT compared with dogs with nonhormonally active pituitary masses and to evaluate whether clinical, imaging, and RT variables affect survival. ANIMALS: Ninety-four dogs divided into 2 groups: PDH and non-PDH, based on the presence of hypercortisolism. Forty-seven dogs were allocated to the PDH group and 47 to the non-PDH group. METHODS: Retrospective cohort study in which clinical records of dogs undergoing RT for pituitary macroadenomas between 2008 and 2018 at 5 referral centers were retrospectively evaluated. RESULTS: Survival was not statistically different between PDH and non-PDH groups (median survival time [MST], 590 days; 95% confidence interval [CI], 0-830 days and 738 days; 95% CI, 373-1103 days, respectively; P = .4). A definitive RT protocol was statistically associated with longer survival compared with a palliative protocol (MST 605 vs 262 days, P = .05). The only factor statistically associated with survival from multivariate Cox proportional hazard analysis was total radiation dose (Gy) delivered (P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: No statistical difference in survival was identified between the PDH and non-PDH groups, and longer survival was associated with higher Gy delivered.
Subject(s)
Adrenocortical Hyperfunction , Cushing Syndrome , Dog Diseases , Pituitary ACTH Hypersecretion , Pituitary Neoplasms , Humans , Dogs , Animals , Pituitary Neoplasms/radiotherapy , Pituitary Neoplasms/veterinary , Pituitary Neoplasms/complications , Retrospective Studies , Cushing Syndrome/veterinary , Pituitary ACTH Hypersecretion/radiotherapy , Pituitary ACTH Hypersecretion/veterinary , Pituitary ACTH Hypersecretion/complications , Adrenocortical Hyperfunction/veterinary , Treatment Outcome , Dog Diseases/drug therapyABSTRACT
BACKGROUND: Cushing's syndrome is one of the most common endocrinopathies in dogs. The preferred screening test for spontaneous Cushing's syndrome is the low-dose dexamethasone suppression test (LDDST). The diagnostic value of urinary cortisol:creatinine ratios (UCCR) is questionable. OBJECTIVES: The aim of this study was to determine diagnostic cut-off values for UCCR testing in comparison with LDDST as a clinical reference standard and to calculate the sensitivity and specificity. METHODS: Data from 2018 to 2020 were obtained retrospectively from a commercial laboratory. Both LDDST and UCCR were measured by automated chemiluminescent immunoassay (CLIA). The maximum interval between both tests was 14 days. The optimal cut-off value for UCCR testing was calculated by the Youden index. The sensitivity and specificity of these cut-off values for the UCCR test and LDDST were assessed by Bayesian latent class models (BLCMs). RESULTS: This study included 324 dogs with both UCCR test and LDDST results. The optimal UCCR cut-off value, calculated by the Youden index, was 47.4 × 10-6 . Any UCCR <40 × 10-6 was interpreted as a negative result, 40-60 × 10-6 as values in a gray zone, and >60 × 10-6 as positive. Using the cut-off of 60 × 10-6 , BLCM showed 91% (LDDST) and 86% (UCCR test) sensitivity and a specificity of 54% (LDDST) and 63% (UCCR test). CONCLUSIONS: Considering an 86% sensitivity and a 63% specificity, UCCR testing may be considered a first-line investigation to rule out Cushing's syndrome using CLIA analysis. Urine samples can be collected noninvasively at home by the owner, reducing the potential impact of stress.
Subject(s)
Cushing Syndrome , Dog Diseases , Dogs , Animals , Cushing Syndrome/diagnosis , Cushing Syndrome/veterinary , Creatinine/urine , Dexamethasone , Retrospective Studies , Bayes Theorem , Adrenal Cortex Hormones/urine , Luminescent Measurements/veterinary , Hydrocortisone , Dog Diseases/diagnosis , Dog Diseases/urineABSTRACT
The most common causes of insulin resistance in diabetic dogs are Cushing syndrome, diestrus, and obesity. Cushing-associated effects include insulin resistance, excessive postprandial hyperglycemia, perceived short duration of insulin action, and/or substantial within-day and/or day-to-day glycemic variability. Successful strategies to manage excessive glycemic variability include basal insulin monotherapy and combined basal-bolus insulin treatment. Ovariohysterectomy and insulin treatment can achieve diabetic remission in about 10% of cases of diestrus diabetes. Different causes of insulin resistance have an additive effect on insulin requirements and the risk of progression to clinical diabetes in dogs.
Subject(s)
Cushing Syndrome , Diabetes Mellitus , Dog Diseases , Insulin Resistance , Insulins , Female , Dogs , Animals , Cushing Syndrome/veterinary , Cushing Syndrome/complications , Diabetes Mellitus/veterinary , Dog Diseases/therapyABSTRACT
BACKGROUND: Severe muscle stiffness (SMS) in dogs with hypercortisolism (HC) is uncommon. OBJECTIVES: To evaluate signalment, presentation, treatments, and long-term outcomes of dogs with concurrent HC and SMS. ANIMALS: Thirty-seven dogs. METHODS: Medical records of dogs with HC and concurrent SMS were recruited from 10 institutions. Clinical information, test results, therapeutic responses, and survival times were reviewed. RESULTS: All 37 dogs with HC and SMS had pituitary-dependent hypercortisolism (PDH); 36/37 weighed <20 kg. Signs and test results were typical of PDH aside from SMS, initially diagnosed in all 4 limbs in 9, pelvic limbs of 22, and thoracic limbs of 6 dogs. Hypercortisolism and SMS were diagnosed together in 3 dogs; HC 1-36 months before SMS in 23; SMS 1-12 months before HC in 11. Mitotane or trilostane, given to control HC in 36/37 dogs, improved or resolved HC signs in 28; SMS did not resolve, remaining static or worsening in 31/36 dogs, mildly improving in 5/19 dogs given additional therapies. Progression of SMS included additional limbs in 10 dogs and the masticatory muscles of 2. The median survival time from diagnosis of SMS was 965 days (range, 8-1188). CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent SMS and HC is uncommon, possibly affecting only dogs with PDH. Development of SMS might occur before or after diagnosis of HC. Apart from SMS, the clinical picture and survival time of these dogs seem indistinguishable from those of dogs with HC in general. However, while muscle weakness usually resolves with HC treatment SMS does not.
Subject(s)
Cushing Syndrome , Dog Diseases , Pituitary ACTH Hypersecretion , Dogs , Animals , Cushing Syndrome/complications , Cushing Syndrome/diagnosis , Cushing Syndrome/drug therapy , Cushing Syndrome/veterinary , Dog Diseases/diagnosis , Dog Diseases/drug therapy , Pituitary ACTH Hypersecretion/complications , Pituitary ACTH Hypersecretion/diagnosis , Pituitary ACTH Hypersecretion/drug therapy , Pituitary ACTH Hypersecretion/veterinary , Mitotane/therapeutic use , MusclesABSTRACT
Cushing's syndrome (CS) is a serious endocrine disorder that is relatively common in dogs, but rare in humans. In ~15%-20% of cases, CS is caused by a cortisol-secreting adrenocortical tumour (csACT). To identify differentially expressed genes that can improve prognostic predictions after surgery and represent novel treatment targets, we performed RNA sequencing on csACTs (n = 48) and normal adrenal cortices (NACs; n = 10) of dogs. A gene was declared differentially expressed when the adjusted p-value was <.05 and the log2 fold change was >2 or < -2. Between NACs and csACTs, 98 genes were differentially expressed. Based on the principal component analysis (PCA) the csACTs were separated in two groups, of which Group 1 had significantly better survival after adrenalectomy (p = .002) than Group 2. Between csACT Group G1 and Group 2, 77 genes were differentially expressed. One of these, cytochrome P450 26B1 (CYP26B1), was significantly associated with survival in both our canine csACTs and in a publicly available data set of 33 human cortisol-secreting adrenocortical carcinomas. In the validation cohort, CYP26B1 was also expressed significantly higher (p = .012) in canine csACTs compared with NACs. In future studies it would be interesting to determine whether CYP26B1 inhibitors could inhibit csACT growth in both dogs and humans.
Subject(s)
Adrenal Cortex Neoplasms , Cushing Syndrome , Dog Diseases , Humans , Dogs , Animals , Hydrocortisone , Retinoic Acid 4-Hydroxylase/genetics , Transcriptome , Dog Diseases/genetics , Adrenal Cortex Neoplasms/genetics , Adrenal Cortex Neoplasms/veterinary , Adrenal Cortex Neoplasms/pathology , Cushing Syndrome/complications , Cushing Syndrome/veterinaryABSTRACT
Hypercortisolism is one of the most common endocrine diseases in dogs. In humans, it is clearly associated with a higher risk of cardiovascular events, but studies in dogs are scarce. To investigate the arrhythmogenic risk of dogs with naturally-occurring hypercortisolism (NOHC), indices of variability and instability of the QT interval were retrospectively studied in 38 dogs with NOHC and prospectively studied in 12 healthy dogs: variance (QTv), total instability (TI), short-term (STI) and long-term (LTI), and mean (QTm). Except for QTm, all parameters studied were higher in the NOHC group than in the control group. In addition, STI and QTv showed moderate positive correlation with left ventricle wall thickness. The NOHC group was subdivided according to cortisol suppression pattern in the low-dose dexamethasone suppression test. All electrocardiographic indices of partial and absent suppression patterns were numerically higher than healthy dogs. QTv and TI were lower in the control group than in both NOHC subgroups. LTI and STI were lower in the CG than in the group with the partial suppression pattern. There was no statistical difference between sex groups in any of the electrocardiographic parameters studied. This result might indicate that the etiology of NOHC, and its consequent influence on hypothalamus-pituitary-adrenal axis could interfere on the heterogeneity of ventricular repolarization parameters in different ways, especially in the short-term and the long-term stability; however further studies are necessary to understand the role of cortisol on electrical instability in dogs.
Subject(s)
Cushing Syndrome , Dog Diseases , Humans , Dogs , Animals , Hydrocortisone , Retrospective Studies , Adrenocorticotropic Hormone , Cushing Syndrome/complications , Cushing Syndrome/veterinary , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/veterinaryABSTRACT
OBJECTIVES: This study aims to re-evaluate the low-dose dexamethasone suppression test 8-hour cortisol cut-point for the diagnosis of hypercortisolism in dogs using a solid-phase, competitive chemiluminescent enzyme immunoassay. MATERIALS AND METHODS: Twenty-seven client-owned dogs with naturally occurring hypercortisolism and 30 healthy control dogs were prospectively recruited. Performance of the low-dose dexamethasone suppression test was assessed using sensitivity, specificity and a receiver operating characteristic curve compared to a clinical diagnosis of hypercortisolism including response to treatment. RESULTS: Twenty-four dogs were diagnosed with pituitary-dependent hypercortisolism and three with adrenal-dependent hypercortisolism. In 30 healthy control dogs, 8-hour post-dexamethasone cortisol concentrations ranged from 5.5 to 39 nmol/L. A receiver operating characteristic curve curve constructed from the 8-hour post-dexamethasone cortisol concentrations of hypercortisolism and control dogs demonstrated that the most discriminatory cut-point was more than 39 nmol/L with sensitivity of 85.2% (95% confidence interval, 67.5% to 94.1%) and specificity of 100% (95% confidence interval, 88.7% to 100.0%) and an area under the curve of 0.963. CLINICAL SIGNIFICANCE: The optimal cut-point of more than 36 nmol/L proposed by this study is similar to the currently accepted 8-hour cortisol concentration cut-point for diagnosing hypercortisolism when using a solid-phase, competitive chemiluminescent enzyme immunoassay.
Subject(s)
Cushing Syndrome , Dog Diseases , Dogs , Animals , Hydrocortisone , Dexamethasone , Sensitivity and Specificity , Cushing Syndrome/veterinary , ROC Curve , Dog Diseases/diagnosisABSTRACT
Diagnosis of thyroid and adrenal disease can be confusing. Whereas the definitive diagnosis of hyperthyroidism and hypoadrenocorticism are relatively straightforward, hypothyroidism and naturally occurring Cushing's syndrome (NOCS) are more complicated. In a patient with compatible clinical signs, a single increased tT4 is enough to confirm hyperthyroidism, but a low tT4 alone is never enough to confirm hypothyroidism. A flatline result (post-stimulation cortisol <2 ug/dL) on an ACTH stimulation test (ACTHst) confirms hypoadrenocorticism, but not all dogs with NOCS have increased ACTHst results. This article explains which diagnostics should be pursued for these endocrinopathies, and how to interpret them.
Subject(s)
Adrenal Insufficiency , Cushing Syndrome , Dog Diseases , Hyperthyroidism , Hypothyroidism , Dogs , Animals , Adrenocorticotropic Hormone , Adrenal Insufficiency/diagnosis , Adrenal Insufficiency/veterinary , Cushing Syndrome/diagnosis , Cushing Syndrome/veterinary , Clinical Laboratory Techniques/veterinary , Hyperthyroidism/diagnosis , Hyperthyroidism/veterinary , Hypothyroidism/veterinary , Dog Diseases/diagnosisABSTRACT
Heat stress impacts the immune system of dairy animals by altering the hypothalamic-pituitary-adrenal axis and thyroid function, leading to conditions such as hypothyroidism and hypercortisolism. This study aimed to elucidate the effect of hypothyroidism and hypercortisolism on the response of mammary innate immune function to inflammation caused by Escherichia coli in dairy goats. To induce hypothyroidism and hypercortisolism, we administered 6-n-propyl-2-thiouracil (PTU; for 21 days) and dexamethasone (DEX; for 5 days), respectively, to six goats each; six goats without treatment were used as the control group. After treatment, lipopolysaccharide (LPS) from E. coli O111 was infused into the mammary gland. Somatic cell counts (SCC) and levels of lactoferrin (LF), S100A7, immunoglobulin A (IgA), and interleukin-8 (IL-8) in milk until 7 days after LPS infusion were measured. An increase in SCC after LPS infusion was inhibited in both PTU and DEX groups, and an increase in LF after LPS infusion was inhibited in PTU group, compared with that in the control group. The results of the present study suggest that the recruitment of neutrophils and LF production decreased under hypothyroidism or hypercortisolism, which may be one of the causes underlying increased incidence of mastitis in dairy animals under heat stress conditions.
Subject(s)
Anti-Infective Agents , Cattle Diseases , Cushing Syndrome , Goat Diseases , Hypothyroidism , Mastitis, Bovine , Female , Animals , Cattle , Milk , Lipopolysaccharides , Interleukin-8 , Mammary Glands, Animal , Lactoferrin/pharmacology , Escherichia coli , Propylthiouracil/pharmacology , Hypothalamo-Hypophyseal System , Cushing Syndrome/veterinary , Pituitary-Adrenal System , Goats , Anti-Infective Agents/pharmacology , Immunoglobulin A , Hypothyroidism/veterinary , Dexamethasone/pharmacologyABSTRACT
A 13-year-old spayed female Schnauzer dog with chronic kidney disease (CKD; International Renal Interest Society stage 2, non-proteinuric, normotensive), diabetes mellitus, hypercortisolism and myxomatous mitral valve degeneration (American College of Veterinary Internal Medicine stage B2) presented with electrolyte imbalance that had progressed to hyperkalaemia and hyponatremia, with a sodium to potassium (Na:K) ratio of 19.6. Cortisol levels after the adrenocorticotropic hormone stimulation test were within the therapeutic range, but aldosterone levels were below the reference range; hence, isolated hypoaldosteronism was diagnosed. After administration of deoxycorticosterone pivalate (DOCP), the electrolyte imbalance improved with a Na:K ratio of 27.7. This is the first report of the management of isolated hypoaldosteronism and hypercortisolism using trilostane and DOCP in a dog. This case highlights the importance of recognizing isolated hypoaldosteronism after long-term treatment with trilostane in a canine patient with CKD.
Subject(s)
Cushing Syndrome , Dog Diseases , Hypoaldosteronism , Renal Insufficiency, Chronic , Dogs , Animals , Female , Hypoaldosteronism/diagnosis , Hypoaldosteronism/therapy , Hypoaldosteronism/veterinary , Cushing Syndrome/veterinary , Potassium/therapeutic use , Sodium , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/veterinary , Electrolytes , Dog Diseases/diagnosis , Dog Diseases/drug therapyABSTRACT
The sensitivity of the adrenocorticotropic hormone (ACTH) stimulation test to detect Cushing's Syndrome (CS) using a depot formulation needs to be evaluated. The aims of this study were to propose a reference interval (RI) for cortisol values 1-hour after administration of a low-dose of depot ACTH in healthy dogs, and to evaluate the sensitivity of this test to detect CS, differentiating among types of CS based on ultrasound findings. Forty-one healthy dogs (20 males, 21 females) were prospectively included. Additionally, 90 dogs with CS (31 males, 59 females) were retrospectively included. Dogs with CS were ultrasonographically classified as follows: 44 dogs with symmetrical adrenomegaly consistent with pituitary-dependent hypercortisolism (PDH), 8 dogs with unilateral adrenomegaly and atrophy of the contralateral adrenal gland or unilateral or bilateral adrenomegaly with malignancy features consistent with adrenal-dependent hypercortisolism (ADH), 34 dogs with equivocal adrenal asymmetry (EAA) and 4 dogs with normal adrenal thickness. In healthy dogs, lower and upper limit of the 95% RI for 1-hour post-ACTH cortisol concentration and their 90% confidence intervals, were 4.4 (2.7-5.8) µg/dl and 18.4 (16.5-20.0) µg/dl, respectively. Post-ACTH cortisol concentration was above the RI in 90.0% (ci95%, 76.1-100) of dogs with CS. An elevated post-ACTH cortisol concentration was detected in 95.5% (ci95%, 76.1-100) of dogs with PDH, 62.5% (ci95%, 46.1-78.9) of dogs with ADH and 88.2% (ci95%, 69.1-100) of dogs with EAA. The sensitivity of the ACTH stimulation test using a low-dose of depot ACTH in high in dogs with CS.
Subject(s)
Cushing Syndrome , Dog Diseases , Pituitary ACTH Hypersecretion , Male , Female , Dogs , Animals , Cushing Syndrome/diagnosis , Cushing Syndrome/veterinary , Adrenocorticotropic Hormone/pharmacology , Hydrocortisone , Retrospective Studies , Pituitary ACTH Hypersecretion/veterinary , Dog Diseases/diagnostic imagingABSTRACT
Canine pituitary-dependent hypercortisolism (PDH) management with trilostane usually demands lifelong therapy. The greater the dose needed, the greater the risk of side effects. Selegiline therapy has been previously described but not commonly used for PDH treatment. The present work aimed to assess the efficacy of selegiline and trilostane combined therapy for canine PDH treatment. Fifteen client-owned dogs diagnosed with spontaneous PDH were enrolled. The patients were treated with trilostane (Tri group, n = 8, initial dose of 0.5 mg/kg, PO, q12h), or with trilostane and selegiline (Tri + Sel group, n = 7, initial trilostane dose of 0.5 mg/kg, PO, q12h and selegiline 1 mg/kg, PO, q24h). Dogs underwent clinical examination, serum biochemical analysis, urinalysis, abdominal ultrasound, and eACTH and post-ACTH cortisol measurements on treatment days zero (D0), 30 (D30), 90 (D90), and 180 (D180). There was a lack of adverse effects due to the combined therapy. Both groups showed a similar clinical response and lower post-ACTH cortisol levels at the study's end. There was no significant difference in trilostane dosage at D180 between groups. There was no documented increase in either right or left adrenal gland thickness in the Tri + Sel group in contrast with patients in the Tri group. However, there was no statistical difference between the groups regarding eACTH at D0 and D180. Patients in the Tri + Sel group achieved better serum triglycerides control at the end of the study. The association of selegiline with trilostane might be a feasible therapy for canine PDH; however, its eventual advantages need larger studies.