A prospective study of basal insulin concentrations in dogs with congenital portosystemic shunts

Objectives : Hypoglycaemia is a common cause of morbidity in dogs with congenital portosystemic shunts but the aetiology is unknown. The hypothesis of this study was that dogs with congenital portosystemic shunts would have significantly higher insulin concentrations than dogs without congenital portosystemic shunts. The main objective of the study was to compare peripheral glucose and insulin concentrations between dogs with congenital portosystemic shunts and dogs without congenital portosystemic shunts. Methods : Peripheral serum insulin and plasma glucose concentrations were measured in dogs with congenital portosystemic shunts and without congenital portosystemic shunts and compared both between groups as well as to reference intervals derived from healthy dogs. Results : Congenital portosystemic shunts were diagnosed in 41 dogs. Forty‐eight dogs hospitalised with other conditions acted as controls. Serum insulin concentrations were mildly elevated (Ä40 μU/mL) in seven dogs and were markedly elevated in two dogs with congenital portosystemic shunts, yet mild hypoglycaemia (3·3 mmol/L) was detected in only one of these dogs. Four dogs with congenital portosystemic shunts showed fasting hypoglycaemia, yet insulin concentrations were within or below the reference interval in three. There was no difference between the median insulin concentration of dogs with congenital portosystemic shunts and without congenital portosystemic shunts. Clinical Significance : Hyperinsulinaemia is infrequently observed in dogs with congenital portosystemic shunts. The aetiology of hypoglycaemia in dogs with congenital portosystemic shunts merits further investigation.     

Congenital portosystemic shunts in Maltese and Australian Cattle Dogs

SUMMARY Congenital portosystemic shunts were definitively diagnosed in 62 dogs over a period of 15 years. Maltese and Australian Cattle Dogs were significantly over-represented, accounting for 14 and 13 cases, respectively. Maltese invariably had a single extrahepatic shunt derived from the left gastric or gastrosplenic vein, whereas Cattle Dogs usually had large intrahepatic shunts involving the right liver lobes. The clinical syndromes resulting from anomalous portosystemic communications were indistinguishable in the 2 breeds. Fasting blood ammonia concentration was elevated in 20 of 22 dogs tested, providing a minimally invasive and effective means of diagnosis. Complete or partial shunt attenuation was performed successfully in all 9 Maltese and in 2 of 6 Cattle Dogs in which it was attempted.     

USE OF TRANSCOLONIC 123I-IODOAMPHETAMINE TO DIAGNOSE SPONTANEOUS PORTOSYSTEMIC SHUNTS IN 18 DOGS

Transcolonic ¹²³I-Iodoamphetamine is rapidly absorbed across the colonic mucosa and binds to amine receptors in the liver and lungs. During the first ten minutes following colonic administration, a simple ratio of lung counts to lung counts plus liver counts provides an accurate estimate of the fraction of portal blood that bypasses hepatic sinusoids in dogs with portosystemic shunts. Studies were performed on 24 dogs with suspect portosystemic shunt. Shunt fraction values for 18 dogs with surgically confirmed portosystemic shunt were obviously higher than published values for normal dogs, and also significantly higher than values for the other six dogs, later confirmed to lack shunts. Postoperative studies were repeated on ten dogs with single shunt vessels 1–2 days after shunt closure. Total shunt ligation resulted in normal postoperative shunt fraction, whereas partial shunt ligation resulted in persistant elevation of shunt fraction. Transcolonic iodoamphetamine scintigraphy is noninvasive, easy to perform, and provides an accurate method to diagnose dogs with portosystemic shunt.     

Mass screening of Irish wolfhound puppies for portosystemic shunts by the dynamic bile acid test.

Five hundred and sixty-six Irish wolfhound puppies aged six to 15 weeks were tested for congenital portosystemic shunts by the dynamic bile acid method. Plasma ammonia concentration was also measured in 165 of the puppies both fasting and postprandially. Nineteen puppies (3.4 per cent), nine males and 10 females, had portosystemic shunts. Smaller litters appeared to be more likely to contain affected puppies. The postprandial bile acid concentration was a reliable predictor of the presence of a shunt, with the highest concentration in a normal puppy being 38 mumol/litre and the lowest in an affected puppy being 43 mumol/litre. In contrast, fasting bile acid concentrations were normal in the majority of the affected puppies. There was considerable overlap in fasting plasma ammonia concentrations between normal and affected puppies (26 puppies, 15.8 per cent of those tested). Postprandial ammonia concentration appeared to give better separation between the two groups, apart from two individuals which produced bizarre results. It was concluded that the postprandial or dynamic bile acid test is an appropriate test for the mass screening of Irish wolfhound puppies for portosystemic shunts, and guidelines are proposed for the interpretation and follow-up of the test.     

Cellophane banding for the gradual attenuation of single extrahepatic portosystemic shunts in eleven dogs

Objective To evaluate the efficacy and short term effects of a cellophane banding technique for progressive attenuation of canine single extrahepatic portosystemic shunts.
Design A prospective trial of 11 dogs with single congenital extrahepatic shunts.
Procedure Rectal ammonia tolerance testing and routine biochemical tests were performed preoperatively on all dogs. In seven dogs, preoperative abdominal Doppler ultrasonography was also performed. Exploratory laparotomy revealed a single extrahepatic portocaval shunt in each animal, which was attenuated using a cellophane band with an internal diameter of 2 to 3 mm. The abdomen was closed routinely. Follow-up biochemical analysis and abdominal Doppler ultrasonography or splenoportography were performed postoperatively.
Results The shunt was not amenable to total ligation in 11 dogs, based upon reported criteria. All dogs recovered uneventfully from surgery without evidence of portal hypertension, and showed clinical improvement thereafter. Shunt occlusion was deemed to have occurred in 10 dogs based on resolution of biochemical and/or sonographic abnormalities. One dog continued to have sonographic evidence of portosystemic shunting when evaluated 3 weeks after surgery, despite normal ammonia tolerance, but was lost to subsequent follow-up. Two dogs, in which 3 mm cellophane bands were placed, experienced delayed shunt occlusion.
Conclusion Cellophane banding is simple to perform, and causes progressive attenuation of single extrahepatic shunts in dogs. Further work is needed to determine the maximum diameter of a cellophane band which will produce total attenuation, and the long-term safety and reliability of the treatment.     

Medical management of congenital portosystemic shunts in 27 dogs—a retrospective study

Case records of 27 dogs with medically managed congenital portosystemic shunts were reviewed. Fourteen were followed up by telephone questionnaires to the owners. Age, breed, sex, clinical signs and blood results were similar to previous studies. Weight and quality of life were stable or improved on treatment in all cases. Total serum protein concentration and alanine aminotransferase and alkaline phosphatase activities fell significantly during treatment. Fourteen dogs were euthanased, four were lost to follow-up and nine remained alive. Mean survival time for the dogs euthanased was 9.9 months. Mean follow-up period for the dogs still alive was 56.9 months and all had survived more than 36 months from diagnosis. Surviving dogs with intrahepatic shunts had a significantly shorter follow-up period than dogs with extrahepatic shunts. Two prognostic indicators were identified, age at initial signs and blood urea concentration on presentation, both correlating with survival time. It was demonstrated that a significant proportion of dogs with portosystemic shunts managed medically have a good prognosis.     

ULTRASONOGRAPHIC DIAGNOSIS OF CONGENITAL PORTOSYSTEMIC SHUNTS IN DOGS: RESULTS OF A PROSPECTIVE STUDY

The aims of this study were to determine if accurate diagnosis of congenital portosystemic shunt was possible using two dimensional, grey-scale ultrasonography, duplex-Doppler, and color-flow Doppler ultrasonography in combination, and to determine if dogs with congenital portosystemic shunts have increased or variable mean portal blood flow velocity. Eighty-two dogs with clinical and/or clinicopathologic signs compatible with portosystemic shunting were examined prospectively. Diagnosis of congenital portosystemic shunt was subsequently confirmed in 38 of these dogs using operative mesenteric portography: 14(37%) dogs had an intrahepatic shunt and 24(63%) had an extrahepatic shunt. Ultrasonography had a sensitivity of 95%, specificity of 98%, and accuracy of 94%. Ultrasonographic signs in dogs with congenital portosystemic shunts included small liver, reduced visibility of intrahepatic portal vessels, and anomalous blood vessel draining into the caudal vena cava. Correct determination of intra - versus extrahepatic shunt was made ultrasonographically in 35/38 (92%) dogs. Increased and/or variable portal blood flow velocity was present in 21/30 (70%) dogs with congenital portosystemic shunts. In one dog with an intrahepatic shunt the ultrasonographic diagnosis was based partly on finding increased mean portal blood flow velocity because the shunting vessel was not visible. Detection of the shunting vessel and placement of duplex-Doppler sample volumes were facilitated by use of color-flow Doppler. Two-dimensional, grey-scale ultrasonography alone is sufficient to detect most intrahepatic and extrahepatic shunts; sensitivity is increased by additional use of duplex-Doppler and color-flow Doppler. Increased and/or variable portal blood flow velocity occurs in the majority of dogs with congenital portosystemic shunts.     

Progressive remission of portosystemic shunting in 23 dogs after partial closure of congenital portosystemic shunts

The congenital portosystemic shunts in 23 dogs were closed partially in 18 and completely in five with a single silk ligature. The clinical results were studied and the degree of portosystemic shunting was measured by a scintigraphic method, the results being expressed as the shunt index (SI). In 17 of the dogs, the mean (sd) SI decreased from 0.92 (0.16) before surgery to 0.34 (0.25) during surgery after the attenuation of the shunt, and then to 0.10 (0.12) one month later. The dogs' venous ammonia concentration decreased from 203 (122) microM before surgery to 36 (18) one month after surgery. At the same time the clinical scores improved significantly. There were positive correlations between the SI and the general evaluation of the dogs' well-being by their owners (rs = 0.60), the ammonia concentration (rs = 0.86), and the diameter of the shunt (rs = 0.86). In the other six dogs, the intraoperative and/or postoperative SI was high. In two of them the shunt was further attenuated during a second operation, which resulted in lower SI values; in two a second small shunt was responsible for the high SI; in one multiple portosystemic shunts were found postmortem; and one dog was lost to follow-up.     

Canine congenital portosystemic encephalopathy

The case records of 21 dogs with congenital portosystemic encephalopathy are reviewed. The disorder was most common in Australian cattledogs (blue heelers; 8 cases), Old English sheepdogs (3 cases) and Maltese terriers (3 cases). Extra-hepatic shunts occurred in small breeds, with the exception of 1 cattledog, while intra-hepatic shunts occurred in the medium to large breeds. The most common clinical pathology abnormalities were abnormal ammonia tolerance, mild to moderate increases in plasma alanine aminotransferase or alkaline phosphatase concentrations, decreased total serum protein concentrations, increased fasting ammonia concentrations and ammonium biurate crystalluria. Radiological examination revealed that all the dogs had a small liver. The kidneys were enlarged in 5 of 10 dogs in which kidney size could be estimated. Surgical ligation of an extra-hepatic shunt was successful in 2 of 4 dogs in which it was attempted. Medical management resulted in alleviation of clinical signs in 5 of 8 dogs. The period of successful treatment ranged from a few months to over a year.     

Ultrasonographic findings in dogs with hyperammonemia: 90 cases (2000-2002)

OBJECTIVE: To determine ultrasonographic abnormalities in dogs with hyperammonemia. DESIGN: Retrospective study. ANIMALS: 90 client-owned dogs with hyperammonemia. PROCEDURE: Ultrasonography of the abdominal vessels and organs was performed in a systematic way. Dogs in which the ultrasonographic diagnosis was a congenital portosystemic shunt were included only if they underwent laparotomy or necropsy. Dogs in which the abdominal vasculature appeared normal and dogs in which the ultrasonographic diagnosis was acquired portosystemic shunts and portal hypertension were included only if liver biopsy specimens were submitted for histologic examination. RESULTS: Ultrasonography excluded portosystemic shunting in 11 dogs. Acquired portosystemic shunts were found in 17 dogs, of which 3 had arterioportal fistulae and 14 had other hepatic abnormalities. Congenital portosystemic shunts were found in 61 dogs, of which 19 had intrahepatic shunts and 42 had extrahepatic shunts. Intrahepatic shunts originated from the left portal branch in 14 dogs and the right portal branch in 5. Extrahepatic shunts originated from the splenic vein, the right gastric vein, or both and entered the caudal vena cava or the thorax. Ultrasonography revealed splenic-caval shunts in 24 dogs, right gastric-caval shunts in 9 dogs, splenic-azygos shunts in 8 dogs, and a right gastric-azygos shunt in 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that ultrasonography is a reliable diagnostic method to noninvasively characterize the underlying disease in dogs with hyperammonemia. A dilated left testicular or ovarian vein was a reliable indicator of acquired portosystemic shunts.     

USE OF QUANTITATIVE HEPATIC SCINTIGRAPHY TO EVALUATE SPONTANEOUS PORTOSYSTEMIC SHUNTS IN 12 DOGS

Quantitative hepatic scintigraphy is a valid means for estimating total liver blood flow and relative portal hepatic perfusion. The Hepatic perfusion index (HPI) was determined for a group of 12 dogs with portosystemic shunts prior to and two days after corrective surgery. HPI values for the dogs prior to operation were significantly elevated (p<0.001) as compared with those for a group of normal dogs, indicating reduced effective portal hepatic perfusion in dogs with shunts. Dogs showing a favorable clinical response after surgery had a significant decrease (p<0.02) in HPI values after operation. One dog showing a poor clinical response after operation had an increase in HPI score after operation. Quantitative hepatic scintigraphy is a valuable diagnostic test for screening presumptive cases of portosystemic shunts and monitoring the response to surgical intervention.     

Outcomes after extrahepatic portosystemic shunt ligation in 49 dogs

OBJECTIVE: To evaluate outcomes after attenuation of extrahepatic portosystemic shunts in dogs using surgical silk. DESIGN: Retrospective study. PROCEDURE: Case records were reviewed for degree of surgical attenuation, experience of the primary surgeon, perioperative mortality and problems related to persistent portosystemic shunting or shunt ligation. Presence of portosystemic shunting after surgery was evaluated by ammonia tolerance testing, measurement of postprandial serum bile acid, plasma urea and cholesterol concentrations and liver enzyme activity. The influence of age, postocclusion portal pressure, primary surgeon, degree of attenuation and postoperative biochemical findings on the occurrence of postoperative problems was assessed. RESULTS: The mortality rate was 2.1%. Shunt attenuation was complete in 34% and partial in 66% of dogs. Portal hypertension necessitating ligature removal was encountered in only one dog. Five dogs experienced neurological abnormalities (seizures or ataxia), possibly as a manifestation of 'postligation seizure syndrome'. Postoperative liver function was normal in 78% of dogs, including 70% with partial shunt attenuation. Experience of the surgeon was related positively to outcome after partial attenuation (P = 0.002). Postoperative biochemical evidence of abnormal liver function was the most sensitive predictor of recurrence of clinical signs referable to persistent portosystemic shunting. CONCLUSIONS: In the hands of an experienced surgeon, surgical attenuation of single extrahepatic shunts was safe and effective, even in animals with partial attenuation. Most dogs with biochemical evidence of persistent shunting suffer relapse of clinical signs within 18 months of surgery. Postligation neurological syndromes of variable intensity may be more common than previously thought.     

Post-prandial serum bile acid concentrations and ammonia tolerance in Maltese dogs with and without hepatic vascular anomalies

SUMMARY: Post-prandial serum bile acid concentrations were measured in 200 Maltese dogs in an attempt to identify those with subclinical portosystemic shunts. Five of these were later shown to have hepatic pathology or abnormal liver function. In the other 195 Maltese bile acid concentrations ranged from 1 to 362 μmol.L^-1 (mean ± SD, 70 ±50 μmol.L^-1; median, 65.0 μmol.L^-1). Of these, 79% were above the reference range (0 to 31 μmol.L^-1) established from 23 mixed-breed control dogs. It was therefore not possible to determine the prevalence of subclinical portosystemic shunts on the basis of bile acid determinations.
Further investigation of liver function was performed to investigate why bile acid concentrations were increased in these dogs. Rectal ammonia tolerance tests were normal in 102 of 106 Maltese tested and liver samples (11 dogs) and plasma biochemistry profiles (9 dogs) demonstrated no significant hepatic disease or dysfunction.
Of 2 Maltese with hyperammonaemia after administration of ammonium chloride, one had a large congenital portosystemic shunt that was confirmed at surgery. In the other there were no macroscopic portosystemic communications, but a liver biopsy showed histological changes consistent with microscopic portovascular dysplasia.
Total serum bile acid concentrations were consistently lower when assessed by highperformance liquid chromatography than by an enzymatic spectrophotometric method. This discrepancy was substantially larger in Maltese than in control dogs, suggesting the presence of an additional reacting substance in the serum of Maltese dogs.     

Outcomes of cellophane banding for congenital portosystemic shunts in 106 dogs and 5 cats

OBJECTIVE : To report outcomes after cellophane banding of single congenital portosystemic shunts in dogs and cats. STUDY DESIGN : Retrospective study of sequential cases. ANIMALS : One hundred and six dogs and five cats. METHODS : Medical records were reviewed for breed, sex, age at surgery, shunt anatomy, results of pre- and postoperative biochemical analysis, development of postligation neurologic dysfunction, portal hypertension or other serious complications, and the owners' perception of their animal's response to surgery. RESULTS : Ninety-five dogs and all 5 cats had extrahepatic shunts. Eleven dogs had intrahepatic shunts. Six dogs (5.5%) died as a result of surgery from portal hypertension (2 dogs), postligation neurologic dysfunction (2), splenic hemorrhage (1) and suspected narcotic overdose (1). Serious complications were more common in dogs with intrahepatic shunts than those with extrahepatic shunts (P=.002). Postligation neurologic dysfunction necessitated treatment in 10 dogs and 1 cat; 8 dogs and the cat survived. Clinical signs attributed to portosystemic shunting resolved or were substantially attenuated in all survivors. Postoperative serum bile acid concentrations or results of ammonia tolerance testing were available for 88 animals; 74 (84%) were normal and 14 (16%) were abnormal. Multiple acquired shunts were documented in two animals. CONCLUSIONS : Cellophane banding is a safe and effective alternative to other methods of attenuation. CLINICAL RELEVANCE : Slow occlusion of portosystemic shunts using a variety of methods is being evaluated world wide. Cellophane banding is a relatively simple procedure with comparable safety and efficacy to previously reported techniques.     

Liver function tests in dogs with portosystemic shunts: measurement of serum bile acid concentration

Sulfobromophthalein excretion and plasma ammonia and serum bile acid concentrations were measured in 11 dogs with portal vascular anomalies. The fasting serum bile acid concentration was increased in all 11 dogs (78.9 +/- 16.1 mumol/L; normal, 2.6 +/- 0.4 mumol/L). For values measured in 8 dogs, the 2-hour postprandial serum bile acid concentration was increased further (177.0 +/- 26.4 mumol/L; normal, 7.6 +/- 2.3 mumol/L). The fasting plasma ammonia concentration was markedly increased in all 11 dogs (246.9 +/- 40.3 micrograms/dl; normal, 27 to 15 micrograms/dl). Thirty minutes after the oral administration of ammonium chloride, the plasma ammonia concentration was increased further in the 7 dogs (510.7 +/- 45.5 micrograms/dl; normal, 57.5 to 20.5 micrograms/dl). Results of the sulfobromophthalein excretion test were abnormal in 10 of 11 dogs (12.3 +/- 1.4%; normal, less than 5% retention after 30 minutes).     

Per Rectal Portal Scintigraphy Using 99mTechnetium Pertechnetate to Diagnose Portosystemic Shunts in Dogs and Cats

Per rectal portal scintigraphy using 99mTechnetium pertechnetate (99mTcO4-) was used to diagnose portosystemic shunts (PSS) before surgical confirmation in seven dogs and two cats. Shunt fractions, representing the percent of portal blood that bypasses the liver, were determined by computer analysis of the scintigraphic images. Animals with portosystemic shunts had a mean preoperative shunt fraction of 84.02% (n = 9). The mean postoperative shunt fraction in four animals was 58.22%. The mean shunt fraction in ten control dogs was 5.00%. Per rectal portal scintigraphy is an innovative, easily performed, inexpensive method to diagnose congenital portosystemic shunts in dogs and cats.     

Use of transcolonic portal scintigraphy to evaluate efficacy of cellophane banding of congenital extrahepatic portosystemic shunts in 16 dogs

OBJECTIVE: To evaluate the efficacy of cellophane banding of single congenital extrahepatic portosystemic shunts in dogs using transcolonic portal scintigraphy. To investigate the portal circulation of those dogs with elevated postoperative shunt fractions to determine the cause of the persistent shunting. Further, to evaluate whether presenting signs, clinical pathology findings and liver histopathology are predictive of outcome. DESIGN: Prospective study of 16 dogs presenting with single congenital extrahepatic portosystemic shunts. PROCEDURE: Dogs with single extrahepatic portosystemic shunts attenuated by cellophane banding underwent portal scintigraphy and bile acids tolerance testing pre- and post-operatively. Dogs identified with elevated shunt fractions at 10 weeks post-operatively underwent mesenteric portovenography. Qualitative hepatic histopathology from all dogs was reviewed by a veterinary pathologist and assigned a semi-quantitative score to identify any abnormalities that may predict surgical outcome. RESULTS: At 10 weeks post cellophane banding, 10 of 16 cases (63%) had normal shunt fractions, whilst six dogs (37%) had increased shunt fractions and seven dogs (44%) had increased serum bile acids. Of these dogs, mesenteric portovenography revealed incomplete closure of the shunt in three dogs (18.6%) and multiple acquired shunts in three dogs (18.6%). Liver histopathology findings were similar for all dogs, regardless of outcome. CONCLUSIONS: Cellophane banding is an efficacious method for complete gradual occlusion of single extrahepatic shunts when the shunt vessel is attenuated to < or = 3 mm. Transcolonic portal scintigraphy is a reliable method for assessment of shunt attenuation and, unlike serum bile acids, is not influenced by other causes of liver dysfunction.     

Intravascular Occlusion for the Correction of Extrahepatic Portosystemic Shunts in Dogs

Background: Congential extrahepatic portosystemic shunts (EHPSS) are common in dogs. An effective minimally invasive technique for correction of EHPSS could result in reduced morbidity, reduced costs, and reduced hospitalization times. Hypothesis: Use of an intravascular occlusion device can effectively and safely result in acute complete occlusion of EHPSS in dogs. Animals: Seven dogs with naturally occurring EHPSS that presented to the Purdue University Veterinary Teaching Hospital. Methods: Prospective, clinical trial. The 7 dogs were consecutively enrolled over a 2‐year period. Results of serum biochemistry, total serum bile acids, fasting plasma ammonia, abdominal radiography, and ultrasonography suggested the diagnosis of portosystemic shunts in all dogs. Definitive diagnosis of EHPSS was achieved with cranial mesenteric arterial portography and acute occlusion was attempted by the deployment of the Amplatzer vascular plug (AVP). Results: EHPSS were identified in all dogs consisting of 5 portocaval and 2 portoazygous variants; 1/7 dogs (14%) were intolerant to temporary complete occlusion of the EHPSS. Of the remaining 6 dogs, 5 (83%) had complete occlusion of the EHPSS by the AVP. There were no complications and resolution of abnormal clinical signs and laboratory values was achieved in 4/5 (80%) dogs with complete occlusion. Conclusions and Clinical Importance: Intravascular correction of EHPSS by the AVP is a viable option to surgical correction while larger studies will be required to determine the clinical applicability of this procedure in the broader portosystemic shunt population.     

HELICAL COMPUTED TOMOGRAPHIC ANGIOGRAPHY OF CANINE PORTOSYSTEMIC SHUNTS

Helical computed tomographic (CT) angiography was performed in 16 dogs with known or suspected portosystemic shunts. Fifteen portosystemic shunts were detected including five single intrahepatic shunts, five single extrahepatic shunts, and five multiple extrahepatic shunts. One dog had a normal CT examination. All diagnoses were confirmed by one or several alternate methods including ultrasound, surgery, necropsy, angiography, and liver biopsy. CT detected the origin of 13 of 15 portosystemic shunts and insertion of 13 of 15 shunts. Limitations included inability to resolve two vessels originating very close to each other, and identification of vessels that traveled parallel to the axial image plane. CT angiography is a promising, minimally invasive method of diagnosing a variety of portosystemic shunts in dogs.     

Plasma cortisol response to ketoconazole administration in dogs with hyperadrenocorticism

The effect of orally administered ketoconazole on plasma cortisol concentration in dogs with hyperadrenocorticism was evaluated. Every 30 minutes from 0800 hours through 1600 hours and again at 1800 hours, 2000 hours, and 0800 hours the following morning, 15 clinically normal dogs and 49 dogs with hyperadrenocorticism had plasma samples obtained and analyzed for cortisol concentration. The mean (+/- SD) plasma cortisol concentration for the initial 8-hour testing period was highest in 18 dogs with adrenocortical tumor (5.3 +/- 1.6 micrograms/dl), lowest in 15 control dogs (1.3 +/- 0.5 micrograms/dl), and intermediate in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH; 3.4 +/- 1.2 micrograms/dl). Results in each of the 2 groups of dogs with hyperadrenocorticism were significantly (P less than 0.05) different from results in control dogs, but not from each other. The same cortisol secretory experiment was performed, using 8 dogs with hyperadrenocorticism (5 with PDH; 3 with adrenocortical tumor) before and after administration at 0800 hours of 15 mg of ketoconazole/kg of body weight. Significant (P less than 0.05) decrease in the 8-hour mean plasma cortisol concentration (0.9 +/- 0.2 microgram/dl) was observed, with return to baseline plasma cortisol concentration 24 hours later. Twenty dogs with hyperadrenocorticism (11 with PDH, 9 with adrenocortical tumor) were treated with ketoconazole at a dosage of 15 mg/kg given every 12 hours for a half month to 12 months. The disease in 2 dogs with PDH failed to respond to treatment, but 18 dogs had complete resolution of clinical signs of hyperadrenocorticism and significant (P less than 0.05) reduction in plasma cortisol responsiveness to exogenous adrenocorticotropin (ACTH).(ABSTRACT TRUNCATED AT 250 WORDS)