Results of non-selective adrenocorticolysis by o,p'-DDD in 129 dogs with pituitary-dependent hyperadrenocorticism

One hundred and twenty-nine dogs with pituitary-dependent hyperadrenocorticism were treated according to a protocol aimed at the complete destruction of the adrenal cortices by the administration of o,p'-DDD (mitotane) at a daily dose of 50 to 75 mg/kg bodyweight for 25 days. On the third day, glucocorticoid and mineralocorticoid supplementation was begun for the induced adrenocortical insufficiency. The first followup examination after completion of the 25-day course and the subsequent twice-yearly follow-up examinations included physical examination and measurements of plasma concentrations of sodium and potassium to optimise substitution therapy. In 19 dogs the full course of 25 days treatment could not be completed. Of the 110 dogs which received the full course of treatment, the administration had to be stopped temporarily in 32 because of side-effects, such as anorexia and vomiting. The actual dose of o,p'-DDD administered was not significantly different in the dogs with and without these side-effects. Clinical remission occurred in 111 dogs (86 per cent), of which 43 (39 per cent) had a relapse. The estimated one-year disease-free fraction was 77 per cent (95 per cent confidence interval [CI]: 67 to 85 per cent). The estimated one-year survival fraction was 80 per cent (95 per cent CI: 71 to 87 per cent), the two-year survival was 69 per cent (95 per cent CI: 59 to 78 per cent), and the three-year survival was 61 per cent (95 per cent CI: 49 to 71 per cent). The bodyweight and age of the dog, and vomiting occurring during the period of treatment, were positively correlated with the length of the disease-free period, whereas weakness during the treatment and resistance to dexamethasone suppression of the urinary corticoid/creatinine ratios at the start of the treatment were associated with a relatively short survival time.     

Inefficacy of selegiline in treatment of canine pituitary-dependent hyperadrenocorticism

OBJECTIVE: To evaluate selegiline, a monoamine oxidase-B inhibitor, for treating dogs with pituitary-dependent hyperadrenocorticism. DESIGN: Prospective clinical trial using client-owned dogs with pituitary-dependent hyperadrenocorticism treated at The University Veterinary Centre, Sydney, from September 1999 to July 2001. PROCEDURE: Eleven dogs with pituitary-dependent hyperadrenocorticism treated with selegiline were monitored at days 10, 30 and 90 by clinical examination, tetracosactrin stimulation testing, urinary corticoid:creatinine ratio measurement and client questionnaire. Endogenous adrenocorticotropic hormone measurements were also performed on most dogs on days 0 and 90. No dog treated with selegiline had satisfactory control of disease. CONCLUSION: Selegiline administration was safe and free of side-effects at the doses used, but did not satisfactorily control disease in pituitary-dependent hyperadrenocorticism affected dogs.     

Trilostane treatment in dogs with pituitary-dependent hyperadrenocorticism

OBJECTIVE: To evaluate the efficacy of trilostane in treating dogs with pituitary-dependent hyperadrenocorticism. DESIGN: Prospective clinical trial using client-owned dogs with pituitary-dependent hyperadrenocorticism treated at University Veterinary Centre, Sydney from September 1999 to July 2001. PROCEDURE: Thirty dogs with pituitary-dependent hyperadrenocorticism treated with trilostane, a competitive inhibitor of 3beta-HSD, were monitored at days 10, 30 and 90 then 3-monthly by clinical examination, tetracosactrin stimulation testing, urinary corticoid:creatinine ratio measurement and by client questionnaire. RESULTS: Twenty-nine of 30 dogs were successfully treated with trilostane (median dose 16.7 mg/kg; range 5.3 to 50 mg/kg, administered once daily); one responded favourably but died of unrelated disease before full control was achieved. CONCLUSION: Trilostane administration controlled pituitary-dependent hyperadrenocorticism in these dogs. It was safe, effective and free of side-effects at the doses used. Most dogs were initially quite sensitive to the drug for 10 to 30 days, then required higher doses until a prolonged phase of stable dose requirements occurred. Urinary corticoid:creatinine ratio was useful in assessing duration of drug effect. Some dogs treated for more than 2 years required reduction or temporary cessation of drug because of iatrogenic hypoadrenocorticism.     

Hyperthyroidism due to an intrathoracic tumour in a dog with test results suggesting hyperadrenocorticism

The elevated urinary corticoid/creatinine ratios of an 11-year-old Jack Russell terrier with polyuria were suppressible in a high-dose dexamethasone suppression test, which was suggestive of pituitary-dependent hyperadrenocorticism. The absence of physical and routine-laboratory changes compatible with hyperadrenocorticism and the relatively high plasma thyroxine concentration were the impetus for additional studies of thyroid and adrenocortical functions. A high plasma thyroxine concentration (62 nmol/l; 5.0 microg/100 ml) suggested the presence of hyperthyroidism. Radiography, (99m)TcO(4) (-) scintigraphy, ultrasonography, computed tomography and cytology revealed a hyperfunctioning intrathoracic thyroid tumour. In the low-dose dexamethasone suppression test, the plasma cortisol concentration exceeded the reference value of 40 nmol/l (1.4 microg/100 ml) at eight hours after dexamethasone administration (0.01 mg/kg intravenously), a test result compatible with hyperadrenocorticism. In conclusion, this report represents the first case of a dog with an autonomously hyperfunctioning thyroid tumour in the thorax. The elevated urinary corticoid excretion and the positive low-dose dexamethasone suppression test may be explained by alterations in cortisol metabolism, the stress of the hyperthyroid state or both.     

Absence of urinary tract infection in dogs with experimentally induced hyperadrenocorticism

Objectives of this study were to determine occurrence of urinary tract infection and describe results of urine analysis and urine culture in dogs with experimentally induced hyperadrenocorticism. Dogs were randomly assigned to receive either hydrocortisone (nine dogs) or placebo (eight dogs) for 49 consecutive days. Before and on day 49 of treatment, evaluation of dogs included physical examination, abdominal ultrasound, urine culture, urinalysis, adrenal function testing, and measurement of urine protein and creatinine and activity of serum alkaline phosphatase. All dogs in the experimental group had clinical and laboratory findings of hyperadrenocorticism. Urine specific gravity was significantly decreased and urine protein-to-creatinine ratio was significantly increased in dogs with hyperadrenocorticism. Urinary tract infection did not occur in any dogs. We conclude that administration of hydrocortisone created a model of hyperadrenocorticism; however, urinary tract infection did not occur. Additional evaluation is needed to determine association between urinary tract infection and hyperadrenocorticism.     

A Retrospective Study of Aldosterone Secretion in Normal and Adrenopathic Dogs

A retrospective study on stored plasma from normal dogs and dogs with pituitary dependent hyperadrenocorticism (PDH), pituitary dependent hyperadrenocorticism controlled by mitotane (o,p'-DDD),* iatrogenic hyperadrenocorticism, and hypoadrenocorticism was conducted to determine if alterations in aldosterone production exist in these disorders. The plasma aldosterone concentration (PAC) was measured by radioimmunoassay immediately before and 1 hour after adrenocorticotropic hormone (ACTH) administration (0.5 IU/kg, intravenously [IV]). PACs increased significantly when ACTH was administered to normal dogs. Dogs with PDH had a lower baseline PAC, but their PAC increased to levels similar to that of normal dogs after ACTH administration. In dogs with PDH controlled by o,p'-DDD therapy, the response to ACTH was significantly less than that of normal dogs or dogs with untreated PDH. Dogs with iatrogenic hyperadrenocorticism had a lower baseline and post-ACTH PAC than normal dogs. Dogs with hypoadrenocorticism had a normal basal PAC, but showed no significant increase in PAC following ACTH administration. These findings suggest that PACs are significantly altered in a variety of adrenal diseases, and that the ACTH stimulation test may be useful when evaluating aldosterone secretion in adrenopathic disorders. In addition, at therapeutic dosages, o,p'-DDD treatment was associated with a decrease in basal and post-ACTH PACs in dogs with PDH.     

Systemic availability of o,p'-DDD in normal dogs, fasted and fed, and in dogs with hyperadrenocorticism

The systemic availability of o,p'-DDD was studied in 12 normal dogs and seven dogs with pituitary-dependent hyperadrenocorticism (PDH). The drug was given by mouth at 50 mg kg-1 and plasma o,p'-DDD concentrations were determined by gas-liquid chromatography. First, six normal dogs were given the drug three times at intervals of one week in a Latin square pattern. Systemic drug availability was found to be very poor from intact tablets in fasted dogs, better with pure drug dissolved in maize oil given by stomach tube, and best with ground tablets mixed in oil poured on dog food. Then six normal dogs and five with PDH were given one dose of o,p'-DDD as intact tablets in dog food. Systemic drug availability was good in the normal animals and, for unknown reasons, better in dogs with PDH. The half-time of elimination was shorter in dogs with PDH than in normal ones. There was evidence of a gradual rise in plasma o,p'-DDD concentrations in seven dogs with PDH treated with 25 mg kg-1 every 12 hours for 14 or 20 days. The interaction between food and o,p'-DDD probably contributes to the variation in clinical response of dogs treated with the drug. The efficiency of therapy with o,p'-DDD should be improved considerably by administering the drug with food.     

Assessment of two tests for the diagnosis of canine hyperadrenocorticism

The low-dose dexamethasone suppression test and the urinary corticoid/creatinine ratio were assessed in 166 and 150 dogs, respectively, for their value in the diagnosis of hyperadrenocorticism. The diagnostic accuracy of the low-dose dexamethasone suppression test was 0.83, with a 95 per cent confidence interval from 0.76 to 0.88. The urinary corticoid/creatinine ratio had a diagnostic accuracy of 0.91 with a 95 per cent confidence interval from 0.85 to 0.95. The high predictive value of a negative corticoid/creatinine ratio (0.98; confidence interval 0.80 to 1.00) and the low cost of this test makes it preferable for screening purposes to the low-dose dexamethasone suppression test for which the predictive value of a negative test was calculated as 0.5g (confidence interval 0.43 to 0.73).     

Urinary corticoids in the diagnosis of canine hyperadrenocorticism

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

Urinary excretion of glucocorticoids in the diagnosis of hyperadrenocorticism in cats

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

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.     

Influence of Veterinary Care on the Urinary Corticoid: Creatinine Ratio in Dogs

Physical and emotional stresses are known to increase the production and secretion of glucocorticoids by the adrenal cortex in both humans and experimental animals. The urinary corticoid: creatinine (C:C) ratio is increasingly used as a measure of adrenocortical function. In this study we investigated whether a visit to a veterinary practice for vaccination, a visit to a referral clinic for orthopedic examination, or hospitalization in a referral clinic for 1.5 days resulted in increases of the urinary C: C ratio in pet dogs. In experiment 1, owners collected voided urine samples from 19 healthy pet dogs at specified times before and after taking the dogs to a veterinary practice for yearly vaccination. In experiment 2, 12 pet dogs were evaluated in a similar way before and after an orthopedic examination at a referral clinic. In experiment 3, 9 healthy pet dogs were hospitalized for 1.5 days and urine samples were collected before, during, and after this stay. Basal urinary C:C ratios in all experiments ranged from 0.8 to 8.3 × 10^-6. In experiment 1, the urinary C:C ratio after the visit to the veterinary practice ranged from 0.9 to 22.0 × 10^-6. Six dogs had a significantly increased urinary C:C ratio (responders), but in 5 of these dogs the ratio was ≤10 × 10^-6 In experiment 2. 8 of 12 dogs responded significantly with urinary C:C ratios ranging from 3.1 to 27.0 × 10^-6. In experiment 3, 8 of 9 dogs had significantly increased urinary C:C ratios, ranging from 2.4 to 24.0 × 10^-6, in some or all urine samples collected during hospitalization. In 4 dogs urinary C:C ratios 12 hours after hospitalization were still significantly higher than the initial values. Thus, a visit to a veterinary practice, an orthopedic examination in a referral clinic, and hospitalization can be considered stressful conditions for dogs. A large variation occurs in response, and in individual dogs the increases in urinary C:C ratios can exceed the cutoff level for the diagnosis of hyperadrenocorticism. Therefore, urine samples for measurement of the C: C ratio in the diagnosis of hyperadrenocorticism should be collected in the dog's home environment, to avoid the influence of stress on glucocorticoid secretion.     

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.     

Urinary corticoid:creatinine ratios in healthy pet dogs after oral low-dose dexamethasone suppression tests

Eleven dogs were used in a trial to find a suitable dose of dexamethasone for an oral dexamethasone suppression test for the diagnosis of hyperadrenocorticism. Basal urinary corticoid:creatinine ratios were established in all 11 and then groups of seven were given oral doses of 0.02, 0.01 or 0.0075 mg dexamethasone/kg bodyweight and urine samples were collected at two-hour intervals from 08.00 to 22.00. The doses of 0.02 and 0.01 mg/kg consistently suppressed their urinary corticoid:creatinine ratios measured at 16.00 by a mean of more than 50 per cent and those of individual dogs to less than 1.0 x 10(-6), whereas the dose of 0.0075 mg/kg did not.     

Use of aminoglutethimide in the treatment of pituitary-dependent hyperadrenocorticism in the dog

The aim of this study was to evaluate the efficacy and safety of aminoglutethimide in the treatment of dogs with pituitary-dependent hyperadrenocorticism (PDH). Ten dogs were diagnosed with PDH based on clinical and laboratory data, adrenal function tests (adrenocorticotropic hormone [ACTH] stimulation test and urinary cortisol/creatinine ratio [UCCR] combined with a high dose oral dexamethasone suppression test) and ultrasonographic evaluation of the adrenal glands. Aminoglutethimide was administered daily at a dose of 15 mg/kg bodyweight for one month. Median basal cortisol concentration and post-ACTH cortisol concentration one month after treatment were significantly lower than pretreatment values. Complete response was achieved in one dog, and partial response was obtained in three dogs. Severe side effects of anorexia, vomiting and weakness occurred in one dog and medication was withdrawn. Two further dogs developed decompensations of concurrent diseases and medication was stopped in these animals as well. Mild toxicity occurred in four dogs. Moderate to severe elevations in liver enzymes occurred in all dogs. The efficacy of this drug is lower than that observed using mitotane and ketoconazole, and adverse effects limit its use. Aminoglutethimide, using the protocol described, cannot be recommended for long-term management of PDH in the dog.     

Response of dogs with functional pituitary macroadenomas and macrocarcinomas to radiation

A prospective study was conducted to assess the use of radiation therapy for treatment of dogs with large, functional pituitary tumours and pituitary-dependent hyperadrenocorticism. Four dogs received only pituitary irradiation, whereas two dogs received irradiation and concurrent mitotane treatment. Effects of radiation therapy on tumour size and function were assessed by sequential CT scans, ACTH assays and ACTH stimulation tests. Reduction in tumour size and resolution of neurological abnormalities occurred in all dogs. The mean and median survival time following irradiation for dogs in this report was 740 days and 743 days, respectively. Atnecropsy, a pituitary chromophobe adenoma was detected in three dogs, and a pituitary carcinoma in one dog; necropsy was not carried out on two dogs. Pituitary hypersecretion of ACTH persisted for at     

Hyperadrenocorticism in a dog due to ectopic secretion of adrenocorticotropic hormone

Spontaneous hyperadrenocorticism in dogs is known to be the result of excessive secretion of adrenocorticotropic hormone (ACTH) by the pituitary gland or excessive autonomous glucocorticoid secretion by an adrenocortical tumor. Here, we report on an 8-year-old German shepherd dog in which ACTH-dependent hyperadrenocorticism was a result of ectopic ACTH secretion and could be related to an abdominal neuroendocrine tumor. Hyperadrenocorticism was diagnosed on the basis of the history, clinical signs, and elevated urinary corticoid/creatinine ratios (UCCRs; 236 and 350 x 10(-6); reference range < 10 x 10(-6)). The UCCR remained elevated (226 x 10(-6)) after three oral doses of dexamethasone (0.1 mg/kg body weight) at 8-h intervals. Ultrasonography revealed two equivalently enlarged adrenal glands, consistent with adrenocortical hyperplasia. Plasma ACTH concentration was clearly elevated (159 and 188 ng/l; reference range 5-85 ng/l). Computed tomography (CT) revealed that the pituitary was not enlarged. These findings were interpreted as indicating dexamethasone-resistant pituitary-dependent hyperadrenocorticism. Transsphenoidal hypophysectomy was performed but within 2 weeks after surgery, there was exacerbation of the clinical signs of hyperadrenocorticism. Plasma ACTH concentration (281 ng/l) and UCCRs (1518 and 2176 x 10(-6)) were even higher than before surgery. Histological examination of the pituitary gland revealed no neoplasia. Stimulation of the pituitary with corticotropin-releasing hormone did not affect plasma ACTH and cortisol concentrations. Treatment with trilostane was started and restored normocorticism. CT of the pituitary fossa, 10 months after hypophysectomy, revealed an empty sella. Hence, it was presumed that there was ectopic secretion of ACTH. CT of the abdomen revealed a mass in the region of the pancreas and a few nodules in the liver. Partial pancreatectomy with adjacent lymph node extirpation was performed and the liver nodules were biopsied. Histological examination revealed a metastasized neuroendocrine tumor. Abdominal surgery was not curative and medical treatment with trilostane was continued. At 18 months after the abdominal surgery, the dog is still in good condition. In conclusion, the combination of (1) severe dexamethasone-resistant hyperadrenocorticism with elevated circulating ACTH levels, (2) definitive demonstration of the absence of pituitary neoplasia, and (3) an abdominal neuroendocrine tumor allowed the diagnosis of ectopic ACTH secretion.     

Effect of phenobarbitone on the low-dose dexamethasone suppression test and the urinary corticoid: creatinine ratio in dogs

OBJECTIVES: To investigate potential effects of phenobarbitone on the low-dose dexamethasone suppression (LDDS) test and urinary corticoid to creatinine ratio in dogs in a controlled prospective study and in a clinical setting. ANIMALS: Ten crossbreed experimental dogs and 10 client-owned dogs of mixed breeds treated chronically with phenobarbitone to control seizures. PROCEDURES: Experimental dogs were allocated to treatment (6 mg/kg oral phenobarbitone, n = 6) and control (n = 4) groups. LDDS tests (dexamethasone 0.01 mg/kg intravenously, cortisol concentration determined at 0, 2, 4, 6 and 8 h) were conducted repeatedly over a 3-month period. Urinary corticoid to creatinine ratios were measured before LDDS tests. A single LDDS test was performed on 10 epileptic dogs. RESULTS: LDDS and urinary corticoid to creatinine ratios in dogs were not affected by treatment with phenobarbitone. CONCLUSIONS: Phenobarbitone does not interfere with LDDS testing regardless of dosage or treatment time. Urinary corticoid to creatinine ratios are also unaffected.     

Evaluation of a Urine Cortisol:Creatinine Ratio as a Screening Test for Hyperadrenocorticism in Dogs

The authors collected urine specimens in 31 normal dogs, 25 dogs with hyperadrenocorticism, 21 dogs in which hyperadrenocorticism was suspected but was not present, and 28 dogs with a variety of severe, nonadrenal diseases. Cortisol and creatinine were measured in unextracted urine by radioimmunoassay and spectrophotometry, respectively, and the cortisol:creatinine ratio was calculated for each specimen. The mean ± SD urine cortisol:creatinine concentration ratio in the dogs with hyperadrenocorticism (103.1 ± 100.7) was significantly (P < 0.001) higher than that in the normal dogs (13.1 ± 7.0). The mean urine cortisohcreatinine ratio in dogs initially suspected of having hyperadrenocorticism (16.3 ± 7.0) was significantly (P < 0.001) lower than the ratio in dogs with hyperadrenocorticism, but was not significantly different than that in the normal dogs. The mean urinary cortisohcreatinine ratio in the dogs with nonadrenal disease (82.8 ± 97.7) was significantly (P < 0.001) higher than that in both the normal dogs and dogs in which hyperadrenocorticism was initially suspected, but was not different than the ratio in the dogs with hyperadrenocorticism. The sensitivity of the urine cortisohcreatinine ratio as a diagnostic test for hyperadrenocorticism was 0.92. The specificity was high in the normal dogs (0.97) and the dogs initially suspected of having hyperadrenocorticism (0.95), with ≤ 5% having false-positive results. However, the specificity was very low (0.21) in the dogs with moderate to severe nonadrenal disease, with 79% having false-positive results. Similarly, both positive and negative predictive values and diagnostic efficiency were high in the normal dogs and dogs suspected of having hyperadrenocorticism but were low in the dogs with nonadrenal illness. When the results of the cortisol assay used in the study were compared to results obtained by two other commercially available cortisol radioimmunoassays, a high correlation between results was found. The urine cortisohcreatinine ratio is a sensitive screening test for the detection of hyperadrenocorticism in dogs. As with other pituitary-adrenal function tests, however, the urine cortisohcreatinine ratio cannot be used to diagnose hyperadrenocorticism in dogs that have moderate to severe nonadrenal disease.     

Comparison of mitotane treatment for adrenal tumor versus pituitary-dependent hyperadrenocorticism in dogs.

The purpose of this study was to determine the sensitivity of dogs with hyperadrenocorticism to treatment with the adrenocorticolytic agent mitotane. Specifically, we looked for differences in response to treatment using this drug in dogs with adrenocortical tumors (adrenal tumor hyperadrenocorticism, ATH) vs those with pituitary-dependent hyperadrenocorticism (PDH). For inclusion in this study, each dog must have had clinical signs, data base laboratory abnormalities, and endocrine screening test results consistent with the diagnosis of hyperadrenocorticism. Further, each dog had to have been treated for at least 6 months with mitotane and have histologic evidence for adrenocortical or pituitary neoplasia (all dogs were necropsied). Thirteen dogs with ATH (8 carcinomas, 5 adenomas) were identified. The ages and body weights of these 13 dogs were computer-matched to 13 dogs with PDH. All dogs were initially treated with approximately 50 mg of mitotane/kg/d of body weight. Reexaminations were performed after 7, 30, 90, and 180 days of treatment. Individual dosages varied widely after the initial 5 to 12 days of treatment. The mean (+/- SD) dose of mitotane (mg/kg/d) for the first 7 days of treatment was 47.5 +/- 9.4 for dogs with ATH vs 45.7 +/- 11.9 for dogs with PDH. The mean plasma cortisol concentrations 1 hour after ACTH administration at the 7-day recheck were significantly higher in dogs with ATH (502 +/- 386 nmol/L) than in dogs with PDH (88 +/- 94 nmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)