Phosphocalcic metabolism and its potential association with biomarkers of kidney disease in dogs with spontaneous hyperadrenocorticism.

The pathogenesis of increased serum phosphate concentration and proteinuria in dogs with spontaneous hyperadrenocorticism (HAC) is unclear. A potential link between proteinuria and calcium/phosphate metabolism has never been studied in dogs with HAC. The aims of the study were: (1) To evaluate calcium/phosphate metabolism in dogs with spontaneous HAC and compare to healthy dogs as well as to dogs with non-HAC illness; (2) to look for associations between markers of calcium/phosphate metabolism and biomarkers of kidney disease in dogs with HAC. Fifty-four dogs were included in the study, classified as HAC (n=27), non-HAC disease (n=17), and healthy (n=10). Serum calcium, phosphate, 25(OH)Vitamin D, 1,25(OH)2Vitamin D, plasma intact parathyroid hormone concentration (iPTH), FGF23, and urinary fractional excretion of calcium and phosphate were evaluated in all dogs at diagnosis and compared between each group. The correlation between these variables and urine protein-to-creatinine ratio (UPC) and urinary N-acetylglucosaminidase-to-creatinine ratio (uNAG/C) was evaluated in the HAC group. Medians [range] of serum phosphate concentration, urinary fractional excretion of calcium (FE(Ca)), and iPTH were significantly higher in dogs with HAC than in dogs with non-HAC illness (P<0.01) and healthy dogs (P<0.01). Increased 1,25(OH)2Vitamin D/25(OH)Vitamin D was also observed (P<0.001). In HAC group, UPC was significantly negatively correlated with 25(OH)Vitamin D (r(s): -0.54; P<0.01). Urinary NAG/C was significantly positively correlated with serum phosphate (r(s): 0.46; P=0.019). Increased serum phosphate, urinary excretion of calcium, and hyperparathyroidism were observed in dogs with HAC. Vitamin D metabolism may be shifted towards increased 1-alpha hydroxylation.

Description of serum symmetric dimethylarginine concentration and of urinary SDS-AGE pattern in dogs with ACTH dependent hyperadrenocorticism.

Serum symmetric dimethylarginine (SDMA) and patterns of urinary protein separated by sodium dodecyl sulfate agarose gel electrophoresis (SDS-AGE) have not been investigated as biomarkers in dogs with ACTH-dependent hyperadrenocorticism (ADHAC). This exploratory prospective study aimed to evaluate SDMA, serum creatinine (sCR), and SDS-AGE in dogs with ADHAC with and without proteinuria (ADHAC-P and ADHAC-nP, respectively). Thirty-five pet dogs classified as ADHAC-P (n=16), ADHAC-nP (n=6) and healthy (n=13) were included. Renal biomarkers were evaluated in all dogs at diagnosis. Baseline concentration of SDMA was not significantly different between the three groups (P = 0.15) whereas sCr was significantly lower in dogs in ADHAC dogs compared to healthy dogs (88.0 µmol/L [70.4-132.6; 79.2-114.4]) whether they had proteinuria or not (P = 0.014 and 0.002, respectively). However, baseline concentrations of sCr and SDMA were not significantly different between dogs with ADHAC-P dogs (SDMA, 8 µg/dL [5-12; 7-9]; sCr, 57.2 µmol/L [35.2-212.2; 52.8-92.4]) and ADHAC-nP dogs (SDMA, 8.5 µg/dL [7-13; 8-10]; sCr, 70.4 µmol/L [61.6-79.2; 61.6-70.4]) (P = 0.35 and P = 0.41, respectively). Proteinuria in dogs with ADHAC-P was mainly of glomerular origin (SDS-AGE pattern: glomerular in 10/16 dogs; mixed glomerular/tubular in four dogs). In our study, SDMA was neither significantly different in dogs with ADHAC whether they were proteinuric or not, nor between ADHAC and healthy dogs. Urinary electrophoresis provides additional information to the UPC and further investigations are needed to determine whether it may help identify dogs with ADHAC-P requiring specific antiproteinuric treatment.

Plasma ACTH precursors in cats with pituitary-dependent hyperadrenocorticism.

BACKGROUND: Diagnosis of pituitary-dependent hyperadrenocorticism (PDH) in cats is challenging because there is no specific diagnostic test. HYPOTHESIS/OBJECTIVE: The determination of plasma ACTH precursor (POMC and pro-ACTH) concentration might facilitate the diagnosis of PDH in cats. The aim of the study was to evaluate prospectively the plasma concentrations of ACTH precursors in a small cohort of cats with PDH and to estimate the value of this approach for diagnosis. ANIMALS: Four groups of cats were included: group 1 (cats with PDH), group 2 (cats with diabetes mellitus but not hyperadrenocorticism (HAC)), group 3 (cats with diabetes mellitus and confirmed acromegaly but not HAC), and group 4 (healthy cats). METHODS: PDH diagnosis was based on clinical data, low-dose dexamethasone suppression test (LDDST), and adrenal and pituitary gland computed tomography (CT) scan. For groups 2, 3, and 4, hyperadrenocorticism was excluded by LDDST or urine cortisol:creatinine ratio (UCCR). An immunoluminometric assay was used to determine plasma concentrations of ACTH precursors in the 4 groups of cats. RESULTS: Group 1 contained 9 cats (enlarged pituitary gland in 7/9). Plasma ACTH precursor concentrations ranged from <53 to >1010 pmol/L with 8/9 concentrations ≥ 229 pmol/L. Groups 2, 3, and 4 included 13, 7, and 13 cats, respectively. Plasma ACTH precursor concentrations ranged from <53 to 96 pmol/L in group 2, <53 to 72 pmol/L in group 3, and <53 to 99 pmol/L in group 4. CONCLUSION AND CLINICAL IMPORTANCE: High plasma concentration of ACTH precursors in cats (>100 pmol/L) is highly suggestive of PDH.

Associations among systemic blood pressure, microalbuminuria and albuminuria in dogs affected with pituitary- and adrenal-dependent hyperadrenocorticism.

BACKGROUND: Hypertension and proteinuria are medical complications associated with the multisystemic effects of long-term hypercortisolism in dogs with hyperadrenocorticism (HAC). METHODS: This study investigated the relationships among adrenocorticotropic hormone (ACTH)-stimulation test results, systemic blood pressure, and microalbuminuria in clinically-healthy dogs (n = 100), in dogs affected with naturally occurring pituitary-dependent (PDH; n = 40), or adrenal-dependent hyperadrenocorticism (ADH; n = 30). RESULTS: Mean systemic blood pressure was similar between clinically healthy dogs and dogs with HAC (p = 0.803). However the incidence of hypertension was highest in dogs with ADH (p = 0.017), followed by dogs with PDH, with the lowest levels in clinically healthy dogs (p = 0.019). Presence of microalbuminuria and albuminuria in clinically healthy dogs and dogs affected with HAC was significantly different (p < 0.001); incidences of albuminuria followed the same pattern of hypertension; highest incidence in dogs with ADH, and lowest level in clinically healthy dogs; but microalbuminuria showed a different pattern: clinically healthy dogs had highest incidences and dogs with ADH had lowest incidence. The presence of albuminuria was not associated with blood pressure values, regardless of whether dogs were clinically healthy or affected with ADH or PDH (p = 0.306). CONCLUSIONS: Higher incidence of hypertension and albuminuria, not microalbuminuria was seen in dogs affected with HAC compared to clinically healthy dogs; incidence of hypertension and albuminuria was significantly higher in dogs affected with ADH compared to PDH. However, presence of albuminuria was not correlated with systemic blood pressure.

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.

Tailored reference limits for urine corticoid:creatinine ratio in dogs to answer distinct clinical questions.

To establish reference intervals for the urinary corticoid:creatinine ratio (UCCR) determined by chemiluminometric immunoassay, UCCR was measured by this method in 50 healthy dogs. To assess the diagnostic performance of different cut-off levels, the UCCR of 66 dogs with hyperadrenocorticism and 87 dogs with diseases mimicking hyperadrenocorticism were used to construct a receiver operating characteristic (ROC) curve. The upper reference limit derived from morning samples in healthy dogs was 30.81 × 10(-6). The area under the ROC curve was 0.94. The diagnostic cut-off with the highest negative likelihood ratio was 26.5 × 10(-6) (sensitivity 1, specificity 0.54), whereas the cut-off with the highest positive likelihood ratio was 161.2 × 10(-6) (specificity 0.988, sensitivity 0.515). The application of these two different diagnostic cut-offs eliminated the necessity to perform additional tests in 53 per cent of the patient population.

ACTH-independent hyperadrenocorticism due to food-dependent hypercortisolemia in a dog: a case report.

In addition to adrenocortical tumours, aberrant expression of functional hormone receptors in the adrenal cortex may cause adrenocorticotrophic hormone (ACTH)-independent hyperadrenocorticism. Here we report on a 6 year old Vizsla dog in which ACTH-independent hyperadrenocorticism was associated with meal-induced hypercortisolemia. Diagnosis was based on history, physical findings, biochemical changes, and elevation of the urinary corticoid/creatinine ratio (UCCR) on two consecutive days (11 and 8.3 x 10(-6), reference range <8.3 x 10(-6)). Basal plasma ACTH concentration was found by repeated measurements to be suppressed (<1 ng/L, reference range 5-85 ng/L) and administration of corticotrophin releasing hormone (CRH) resulted in a minor increase (to 6 ng/L), consistent with ACTH-independent hyperadrenocorticism. Ultrasonography and computed tomography revealed two uniformly enlarged adrenal glands. Magnetic resonance imaging of the pituitary area showed a non-enlarged, normally enhancing pituitary gland. Based on these results, expression of functional aberrant adrenocortical receptors was suspected and the possibility of food-dependent hyperadrenocorticism was explored. The UCCR on two separate occasions rose from 11 and 8 x 10(-6) before a meal to 25 and 23 x 10(-6) at 3 h after ingestion of a meal, respectively. There was a corresponding increase in plasma cortisol concentration (from 90 to 150 nmol/L), while plasma ACTH concentration remained low or undetectable. Consistent with the diagnostic criteria for food-dependent hyperadrenocorticism in humans, administration of octreotide completely prevented meal-induced hypercortisolemia. The dog was treated successfully with the cortisol-synthesis-inhibitor trilostane (2h before meal), and at 26 months after the final diagnosis the dog is still in good condition. The combination of (1) low plasma ACTH concentration in the absence of an adrenocortical tumour, (2) an increase of >100% in UCCR after ingestion of a meal, (3) prevention of the meal-induced increase in plasma cortisol concentration by octreotide, and (4) reversal of signs of hypercortisolism by administration of trilostane a few hours before the meal led to the diagnosis of food-dependent hyperadrenocorticism in this dog.

Diagnosis of hyperadrenocorticism in dogs.

A presumptive diagnosis of hyperadrenocorticism in dogs can be made from clinical signs, physical examination, routine laboratory tests, and diagnostic imaging findings, but the diagnosis must be confirmed by use of pituitary-adrenal function tests. Screening tests designed to diagnose hyperadrenocorticism include the corticotropin (adrenocorticotropic hormone; ACTH) stimulation test, low-dose dexamethasone suppression test, and the urinary cortisol:creatinine ratio. None of these screening tests are perfect, and all are capable of giving false-negative and false-positive test results. Because of the limitation of these diagnostic tests, screening for hyperadrenocorticism must be reserved for dogs in which the disease is strongly suspected on the basis of historical and clinical findings. Once a diagnosis has been confirmed, the next step in the workup is to use one or more tests and procedures to distinguish pituitary-dependent from adrenal-dependent hyperadrenocorticism. Endocrine tests in this category include the high-dose dexamethasone suppression test and endogenous plasma ACTH measurements. Imaging techniques such as abdominal radiography, ultrasonography, computed tomography, and magnetic resonance imaging can also be extremely helpful in determining the cause.

Alopecia in pomeranians and miniature poodles in association with high urinary corticoid:creatinine ratios and resistance to glucocorticoid feedback.

The adrenocortical function of pomeranians and miniature poodles with alopecia was tested by serial measurements of the urinary corticoid:creatinine ratio (uccr) and by an oral low-dose dexamethasone suppression test (lddst) and uccr measurements. In most of the dogs there was day-to-day variation in the uccrs of the 10 sequential urine samples, often with values above or below the upper limit of the range of healthy control dogs. In 22 alopecic pomeranians the basal uccrs were significantly higher than in 18 non-alopecic pomeranians, and the values of both groups were significantly higher than those of 88 healthy pet dogs. The uccrs of 12 alopecic miniature poodles were significantly higher than those of healthy dogs. In 12 alopecic pomeranians and eight alopecic miniature poodles the oral lddst revealed increased resistance to dexamethasone. In six non-alopecic pomeranians the uccrs after the administration of dexamethasone were not significantly different from those in seven healthy dogs at the same time. In an oral high-dose dexamethasone suppression test, using 0.1 mg dexamethasone/kg bodyweight, the uccrs of seven alopecic pomeranians and five alopecic miniature poodles decreased to low levels.

Suspected case of hyperadrenocorticism in a golden hamster (Mesocricetus auratus).

Dermatologic disease is a common problem in pet rodents. This article describes the case of a pet golden hamster (Mesocricetus auratus) with dermatologic and other clinical signs (polyuria, polydypsia) similar to those found in other mammalian species with hyperadrenocorticism. Among other diagnostic tests, the urine cortisol/creatinine ratio was measured and was found to be increased, which appeared to support the diagnosis. Treatment with ketoconazole was initiated, without apparent success.

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 6-sulfatoxymelatonin excretion in hyperandrogenic women with polycystic ovary syndrome: the effect of ethinyl estradiol-cyproterone acetate treatment.

The role of melatonin in human reproduction is still unknown. Data obtained in patients with hypogonadism and precocious puberty suggest that melatonin and the reproductive hormones are interrelated. The aim of this study was to determine melatonin production in hyperandrogenic women. We studied 12 women with polycystic ovary syndrome (PCOS) and 10 women with idiopathic hirsutism (IH). Patients were treated with cyproterone acetate-ethinyl estradiol (Diane 35) for 4 months. Fasting blood samples for the determination of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and dehydroepiandrosterone sulfate (DHEAS) and 24-h urine collections for the determination of 6-sulfatoxymelatonin (alpha MT6s) excretion were obtained from all patients at baseline and after 4 months of treatment. The results were compared with those obtained in 15 control women. At baseline, women with PCOS had significantly higher LH and testosterone levels than those with IH and controls. Their alpha MT6s values (52.6 +/- 20.3 micrograms/24 h) were significantly higher than the values in women with IH (34.3 +/- 7.1) and controls (30.5 +/- 6.5) (p < 0.001). Diane 35 treatment significantly decreased LH, FSH, testosterone and alpha MT6a values in PCOS (28.0 +/- 13.9 micrograms/24 h) (p < 0.0001). These results indicate that women with PCOS have increased melatonin production. The normalization of alpha MT6s and testosterone values during Diane 35 treatment suggests that sex steroids modulate melatonin secretion in these patients either directly or through the suppression of gonadotropin.

Cyproterone acetate-ethinyl estradiol treatment alters urinary 6-sulfatoxymelatonin excretion in hyperandrogenic women.

OBJECTIVES: To investigate melatonin production in hyperandrogenic women before and during treatment with cyproterone acetate and ethinyl estradiol (Diane 35). MATERIAL AND METHODS: We studied 10 women with late onset adrenal hyperplasia due to 21-hydroxylase deficiency (LOCAH) and 10 women with idiopathic hirsutism (IH). Patients were treated with Diane 35 for four months. Fasting blood samples for the determination of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and dihydroepiandrosterone sulfate (DHEAS) and 24-hour urine collections for the determination of 6-sulfatoxymelatonin (aMT6s) excretion were obtained from all patients at baseline and after 4 months of treatment. Results were compared with those obtained in 15 control women. RESULTS: At baseline, women with LOCAH had significantly higher serum testosterone, 17-hydroxyprogesterone (17OHP) and ACTH stimulated 17OHP values than IH and control women. Their aMT6s values (51.0+/-20.5 mg/24h) were significantly higher than the values in IH (34.3+/-7.1) and control women (30.5+/-6.5) (p< 0.001). Diane 35 treatment significantly decreased serum LH, FSH and testosterone levels and aMT6s values in LOCAH patients (29.8+/-16.6 mg/24h) (p<0.0001) in LOCAH patients. CONCLUSIONS: These results indicate that hyperandrogenic women with LOCAH have increased melatonin production. The normalization of aMT6s and testosterone values during cyproterone acetate-ethinyl estradiol treatment, suggest that sex steroids either directly or through the suppression of gonadotropin, modulate melatonin secretion in these patients.

Use of the urine cortisol-to-creatinine ratio for monitoring dogs with pituitary-dependent hyperadrenocorticism during induction treatment with mitotane (o,p'-DDD).

OBJECTIVE: To determine whether the urine cortisol-to-creatinine ratio (UCCR) could replace the ACTH stimulation test in monitoring effectiveness of mitotane induction treatment in dogs with pituitary-dependent hyperadrenocorticism (PDH). ANIMALS: 15 dogs with PDH. PROCEDURE: All 15 dogs were given an induction dose of mitotane (o,p'-DDD: 35 to 50 mg/kg of body weight/d) for 3 to 14 days. During the induction period, free-catch morning urine samples were collected for determination of UCCR, followed by ACTH stimulation testing, every other day. Treatment response was divided into 3 categories: well-controlled PDH (post-ACTH serum cortisol concentration > or = 28 nmol/L but < or = 138 nmol/L), deficient cortisol secretion (post-ACTH serum cortisol concentration < 28 nmol/L), and excess cortisol secretion (post-ACTH serum cortisol concentration > 138 nmol/L). RESULTS: The linear relation between UCCR and post-ACTH serum cortisol concentration was significant (P < 0.001); however, the prediction intervals surrounding the line were too broad to be clinically useful. The UCCR overlapped among the 3 categories of treatment response. Nevertheless, dogs with PDH receiving mitotane induction treatment and with UCCR > 79 x 10(-6) were always classified as having excess cortisol secretion. CONCLUSION AND CLINICAL RELEVANCE: The UCCR failed to predict post-ACTH cortisol concentration during mitotane induction treatment sufficiently close to be a clinically reliable indicator of treatment control. Seemingly, however, UCCR > 79 x 10(-6) obtained from a dog with PDH during mitotane induction would indicate inadequate adrenal cortex destruction and the need for continued mitotane induction; UCCR < or = 79 x 10(-6) would be inconclusive.

Evaluation of urine protein content in dogs with pituitary-dependent hyperadrenocorticism.

OBJECTIVE: To evaluate urine protein content in dogs with pituitary-dependent hyperadrenocorticism (PDHAC) and to determine the effect of mitotane administration on proteinuria in these dogs. DESIGN: Prospective case series. ANIMALS: 16 dogs with PDHAC were evaluated (age range, 7 to 14 years; mean age, 10 years; female-to-male ratio, 2.2:1). PROCEDURE: Urine protein-to-creatinine (UPC) ratios and 24-hour urine protein excretion (24-hour UPE) values were measured before beginning treatment with mitotane and after establishing appropriate maintenance treatment. RESULTS: Before treatment, UPC ratios ranged from 0.03 to 4.16 (16 dogs, median, 0.695; reference range value, UPC ratio < 0.5; questionable value, UPC ratio > 0.5 but < 1.0; high value, UPC ratio > 1.0). Seven dogs had proteinuria with UPC ratios > 1.0. Twenty-four-hour UPE values ranged from 0.67 to 61.7 mg/kg of body weight/d (0.30 to 28.0 mg/lb/d; 13 dogs, median, 9.7 mg/kg/d [4.4 mg/lb/d]; reference value, 24-hour UPE value, < 20 mg/kg/d [9.1 mg/lb/d]). Five dogs with high UPC ratios also had high values for 24-hour UPE. After establishment of maintenance treatment with mitotane (median, 7 weeks; mean, 7.3 weeks), UPC ratios ranged from 0.02 to 6.5 (16 dogs, median, 0.36). Five dogs continued to have high UPC ratios. Values of 24-hour UPE ranged from 0.47 to 122 mg/kg/d (0.21 to 55.5 mg/lb/d; 13 dogs, median, 5.1 mg/kg/d [2.3 mg/lb/d]). Three dogs continued to have high 24-hour UPE values. Significant differences were not found between dogs before and after treatment with mitotane in terms of UPC ratios or 24-hour UPE values. CLINICAL IMPLICATIONS: In dogs with PDHAC and proteinuria, UPC ratios should be monitored closely. Some dogs with PDHAC may have a decrease in urine protein content following treatment with mitotane. We suggest that renal biopsies be considered in those dogs with progressive increases in UPC ratios.

Use of the urine cortisol: creatinine ratio to monitor treatment response in dogs with pituitary-dependent hyperadrenocorticism.

OBJECTIVE: To determine the usefulness of measuring urine cortisol:creatinine ratio (UCCR) as a means of monitoring response to mitotane treatment in dogs with pituitary-dependent hyperadrenocorticism (PDH). DESIGN: Case series. ANIMALS: 51 clinically normal dogs and 21 dogs with PDH. PROCEDURE: The reference range for the UCCR was determined by measuring the ratio in 51 clinically normal dogs. The usefulness of measuring UCCR in evaluating response of 21 dogs with PDH to treatment with mitotane was evaluated by comparing ACTH-stimulated blood cortisol concentrations with UCCR at the end of the induction phase of treatment (13 dogs) and during the maintenance phase of treatment (21). RESULTS: UCCR was not useful for identifying dogs with inadequate adrenal reserves at the end of the induction phase of treatment or during the maintenance phase. The UCCR was useful for identifying dogs in which control of cortisol secretion was not adequate. CLINICAL IMPLICATIONS: UCCR should not be used for evaluation of dogs during the induction phase of treatment, because the potential consequences of not identifying dogs with inadequate adrenal reserves are great. The UCCR may be useful as an adjunct means of monitoring treatment response during the maintenance phase of treatment. However, the ACTH stimulation test remains a necessary component when monitoring response to treatment in dogs with PDH receiving mitotane.

Urinary corticoid/creatinine ratios in the differentiation between pituitary-dependent hyperadrenocorticism and hyperadrenocorticism due to adrenocortical tumour in the dog.

In a study on the differentiation between pituitary-dependent hyperadrenocorticism (PDH) and hyperadrenocorticism due to adrenocortical tumour (AT), two questions were addressed: 1. Do basal urinary corticoid/creatinine (c/c) ratios have any value in this respect, and 2. what is the reference percentage suppression of the urinary c/c ratios in the high-dose dexamethasone suppression test? Data obtained from 160 dogs with hyperadrenocorticism were analysed. In 49 dogs the diagnosis AT was confirmed by the finding of plasma ACTH concentrations < 40 ng/l, by visualisation of the tumour by ultrasonography and/or computed tomography, and by histological examination of the adrenal tissue obtained at surgery or autopsy. Among the 111 dogs with PDH, there were 31 animals with resistance to dexamethasone suppression, i.e., suppression < 50%. The basal urinary c/c ratios of dogs with PDH and AT did not differ significantly, although urinary c/c ratios > 100 x 10(-6) almost exclusively occurred in association with PDH. Among the dogs with hyperadrenocorticism, the positive predictive value of a basal urinary c/c ratio > 100 x 10(-6) for the diagnosis of PDH was 0.90 (95% CI: 0.74-0.98). Of the 49 dogs with AT, 34 had a urinary c/c ratio after dexamethasone administration higher than the basal urinary c/c ratio. The maximum suppression of the basal urinary c/c ratio in dogs with AT was 43.7%. It is concluded that in dogs with hyperadrenocorticism basal urinary c/c ratios only have predictive value in the differentiation between AT and PDH when the ratio exceeds 100 x 10(-6). The generally accepted criterion of 50% suppression by dexamethasone in the differentiation between PDH and AT is also applicable to the urinary c/c ratio.

Evaluation of the urinary cortisol: creatinine ratio in the diagnosis of hyperadrenocorticism in dogs.

The diagnostic accuracy of the urinary cortisol:creatinine ratio (CCR), with the cortisol being measured by ELISA, was evaluated by subjecting data from 18 dogs with and 20 dogs without hyperadrenocorticism to receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (W 0.93, SE(w) 0.044) was much higher than 0.5, indicating that the CCR did distinguish between dogs with and without hyperadrenocorticism. A cutoff value of about 60 x 10(-6) was associated with the highest sensitivity (1.0) and specificity (0.85). At the disease prevalence rate of the present study (0.47), the positive and negative predictive values were 0.87 and 1.0, respectively. These numbers indicate that canine hyperadrenocorticism may be safely excluded when the CCR is below 60 x 10(-6) but that a test of higher specificity (eg, the ACTH stimulation test) should be used to confirm the diagnosis of canine hyperadrenocorticism when the CCR is above 60 x 10(-6).

Systemic arterial blood pressure and urine protein/creatinine ratio in dogs with hyperadrenocorticism.

OBJECTIVE: To determine prevalence and severity of systemic arterial hypertension and proteinuria in dogs with naturally developing hyperadrenocorticism and to determine whether these abnormalities resolve with adequate management of the disease. DESIGN: Case series and cohort study. ANIMALS: 77 dogs with naturally developing hyper-adrenocorticism examined once; 15 dogs examined before and after treatment. RESULTS: Among dogs examined only once, hypertension was diagnosed in 21 of 26 dogs with untreated pituitary-dependent hyperadrenocorticism (PDH), 17 of 21 with inadequately controlled PDH, 8 of 16 with well-controlled PDH, 10 of 10 with an untreated adrenocortical tumor, and 0 of 4 that had undergone adrenalectomy because of an adrenocortical tumor. Untreated dogs and dogs with inadequately controlled PDH had significantly higher blood pressures than did other dogs. Proteinuria was documented in 12 of 26 dogs with untreated PDH, 5 of 16 with inadequately controlled PDH, 3 of 14 with well-controlled PDH, 5 of 8 with an untreated adrenocortical tumor, and 1 of 3 that had undergone adrenalectomy. Dogs with untreated PDH and dogs with an untreated adrenocortical tumor had higher urine protein/creatinine ratios than did dogs with well-controlled PDH. Among dogs evaluated before and after treatment, blood pressure and urine protein/creatinine ratio did not change in 8 dogs with inadequately controlled hyperadrenocorticism, but decreased in 7 dogs with well-controlled disease. CLINICAL IMPLICATIONS: Results suggest that systemic hypertension and proteinuria are common in dogs with untreated hyperadrenocorticism and that successful treatment of hyperadrenocorticism will result in resolution of these abnormalities in many, but not all, dogs.