Evaluation of a combined dexamethasone suppression/ACTH stimulation test in dogs with hyperadrenocorticism

Twenty-one dogs with hyperadrenocorticism were studied. Six dogs had functioning adrenocortical tumors and 15 had pituitary-dependent hyperadrenocorticism. Each dog was evaluated, using endogenous plasma ACTH, ACTH stimulation, dexamethasone screening, dexamethasone suppression, and combined dexamethasone suppression/ACTH stimulation tests. The ACTH stimulation portion of the combined test was less reliable as a screening test in diagnosing hyperadrenocorticism than was the isolated ACTH stimulation test or the dexamethasone screening test. The dexamethasone suppression portion of the combined test was less reliable in distinguishing dogs with adrenocortical tumors from those with pituitary-dependent hyperadrenocorticism than was the endogenous ACTH or isolated dexamethasone suppression test. The combined test is not recommended for use. The ACTH stimulation test is the recommended screening test because of its diagnostic reliability and its subsequent importance as a base line in determining success of mitotane therapy.     

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.     

Evaluation of a six-hour combined dexamethasone suppression/ACTH stimulation test in dogs with hyperadrenocorticism

Seventeen dogs with hyperadrenocorticism were studied. Three dogs had functioning adrenocortical tumors and 14 had pituitary-dependent hyperadrenocorticism. Each dog was evaluated by determining the endogenous plasma ACTH concentration and by performing 4 tests: ACTH stimulation, dexamethasone screening, dexamethasone suppression, and a 6-hour combined dexamethasone suppression/ACTH stimulation test. The combined test was less reliable as a screening test in diagnosing hyperadrenocorticism than was the dexamethasone screening test or the ACTH stimulation test. Compared with the endogenous plasma ACTH concentration, results of the dexamethasone suppression portion of the combined test were less reliable in distinguishing dogs with adrenocortical tumors from those with pituitary-dependent hyperadrenocorticism. It was concluded that the combined test cannot be recommended for use.     

Stages of hyperadrenocorticism: response of hyperadrenocorticoid dogs to the combined dexamethasone suppression/ACTH stimulation test

A study was designed to evaluate the response of blood cortisol content in dogs tentatively diagnosed as having hyperadrenocorticism by using the combined dexamethasone suppression/ACTH stimulation test procedure. Four groups of abnormal responses were identified in 54 dogs. In group I (14.8% of the dogs with abnormal responses), the only abnormality was partial suppression with dexamethasone (clinically normal dogs suppressed to less than 10 ng/ml). In group II (29.6%), 2 abnormalities were found: partial suppression with dexamethasone and hyperreactivity to the ACTH stimulation test. In group III (typical pituitary-dependent hypercortisolism, 48.1%), 3 abnormalities were found: base-line hypercortisolemia, partial suppression with dexamethasone, and hyperreactivity to the ACTH stimulation test. In group IV (7.4%), 2 abnormalities were found: base-line hypercortisolemia and partial suppression with dexamethasone. Base-line blood cortisol content was normal in 44.4% of the adrenopathic dogs. A normal response to ACTH stimulation was seen in 25.9% of the dogs, and 74.1% of the dogs hyperreacted to the ACTH stimulation test. All of the adrenopathic dogs were found to suppress partially with dexamethasone. Failure to suppress the adrenal gland completely (less than 10 ng/ml) with dexamethasone was the most consistent finding in adrenopathic dogs when using the combined dexamethasone suppression/ACTH stimulation test procedure. It was concluded that the test procedure is feasible, flexible, and convenient for clinical situations. Also, these results suggested that there may be several stages in the negative feedback failure associated with hyperadrenocorticism in dogs.     

Hyperparathyroidism in dogs with hyperadrenocorticism

OBJECTIVES: To assess the effect of canine hyperadrenocorticism (HAC) on parathyroid hormone (PTH), phosphate and calcium concentrations. METHODS: PTH concentrations and routine biochemical parameters were measured in 68 dogs with HAC. Ionised calcium was measured in 28 of these dogs. The results obtained were compared with an age- and weight-matched group of 20 hospital patients that did not show signs of HAC. RESULTS: There were significant differences between the PTH, phosphate, alkaline phosphatase, creatinine and albumin concentrations between the two groups. Total and ionised calcium concentrations were not significantly different. Most of the dogs (92 per cent) with HAC had PTH concentrations that were greater than the reference range (10 to 60 pg/ml), and in 23 dogs they were greater than 180 pg/ml. There were significant positive correlations between the PTH and basal cortisol, post-adrenocorticotropic hormone (ACTH) cortisol and alkaline phosphatase concentrations, and also the phosphate and post-ACTH cortisol concentrations. CLINICAL SIGNIFICANCE: Adrenal secondary hyperparathyroidism is a cause of increased PTH concentrations and may be associated with abnormalities in calcium and phosphate metabolism in dogs with HAC. The findings of this study could explain why canine HAC may cause clinical signs such as calcinosis cutis that are associated with altered calcium metabolism.     

Urine cortisol:creatinine ratio as a screening test for hyperadrenocorticism in dogs.

A urine cortisol:creatinine (c:c) ratio, determined from a free-catch morning sample, was evaluated in each of 83 dogs as a screening test for hyper-adrenocorticism. The dogs evaluated were allotted to 3 groups, including 20 healthy dogs, 40 dogs with confirmed hyperadrenocorticism (HAC), and 23 dogs with polyuria and polydipsia not attributable to HAC (polyuria/polydipsia group; PU/PD). Overlap in the urine c:c ratios (mean +/- SEM), comparing results from the healthy dogs (5.7 x 10(-6) +/- 0.9) with those from the HAC dogs (337.7 x 10(-6) +/- 72.0) was not found. However, 11 (64%) of the 18 values from the PU/PD dogs (42.6 x 10(-6) +/- 9.4) were above the lowest ratio in the HAC group and 50% of the HAC group had a urine c:c ratio below the highest value in the PU/PD group. When the mean urine c:c ratio (+/- 2 SD) for the group of healthy dogs was used as a reference range, 100% of the HAC dogs and 18 (77%) of 23 dogs in the PU/PD group had abnormal urine c:c ratios. The sensitivity of the urine c:c ratio to discriminate dogs with HAC was 100%. The specificity of the urine c:c ratio was 22% and its diagnostic accuracy was 76%. On the basis of our findings, a urine c:c ratio within the reference range provides strong evidence to rule out HAC. However, abnormal urine c:c ratios are obtained from dogs with clinical diseases other than HAC. Therefore, measurement of a urine c:c ratio should not be used as the sole screening test to confirm a diagnosis of HAC.     

Evaluation of twice-daily, low-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism

OBJECTIVE: To evaluate the effects of twice-daily oral administration of a low-dose of trilostane treatment and assess the duration of effects after once-daily trilostane administration in dogs with naturally occurring hyperadrenocorticism (NOH). DESIGN: Prospective study. ANIMALS: 28 dogs with NOH. PROCEDURES: 22 dogs received 0.5 to 2.5 mg of trilostane/kg (0.23 to 1.14 mg/lb) orally every 12 hours initially. At intervals, dogs were reevaluated; owner assessment of treatment response was recorded. To assess drug effect duration, 16 of the 22 dogs and 6 additional dogs underwent 2 ACTH stimulation tests 3 to 4 hours and 8 to 9 hours after once-daily trilostane administration. RESULTS: After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [3]). At 3 to 4 hours and 8 to 9 hours after once-daily dosing, mean post-ACTH stimulation serum cortisol concentrations were 2.60 and 8.09 Pg/dL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with NOH, administration of trilostane at low doses every 12 hours was effective, although 2 dogs became ill during treatment. Drug effects diminished within 8 to 9 hours. Because of potential adverse effects, lower doses should be evaluated.     

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 low-dose synthetic adrenocorticotropic hormone stimulation test in clinically normal dogs and dogs with naturally developing hyperadrenocorticism.

OBJECTIVE: To determine whether low doses of synthetic ACTH could induce a maximal cortisol response in clinically normal dogs and to compare a low-dose ACTH stimulation protocol to a standard high-dose ACTH stimulation protocol in dogs with hyperadrenocorticism. DESIGN: Cohort study. ANIMALS: 6 clinically normal dogs and 7 dogs with hyperadrenocorticism. PROCEDURE: Each clinically normal dog was given 1 of 3 doses of cosyntropin (1, 5, or 10 micrograms/kg [0.45, 2.3, or 4.5 micrograms/lb] of body weight, i.v.) in random order at 2-week intervals. Samples for determination of plasma cortisol and ACTH concentrations were obtained before and 30, 60, 90, and 120 minutes after ACTH administration. Each dog with hyperadrenocorticism was given 2 doses of cosyntropin (5 micrograms/kg or 250 micrograms/dog) in random order at 2-week intervals. In these dogs, samples for determination of plasma cortisol concentrations were obtained before and 60 minutes after ACTH administration. RESULTS: In the clinically normal dogs, peak cortisol concentration and area under the plasma cortisol response curve did not differ significantly among the 3 doses. However, mean plasma cortisol concentration in dogs given 1 microgram/kg peaked at 60 minutes, whereas dogs given doses of 5 or 10 micrograms/kg had peak cortisol values at 90 minutes. In dogs with hyperadrenocorticism, significant differences were not detected between cortisol concentrations after administration of the low or high dose of cosyntropin. CLINICAL IMPLICATIONS: Administration of cosyntropin at a rate of 5 micrograms/kg resulted in maximal stimulation of the adrenal cortex in clinically normal dogs and dogs with hyperadrenocorticism.     

Plasma concentrations of ACTH precursors correlate with pituitary size and resistance to dexamethasone in dogs with pituitary-dependent hyperadrenocorticism

This study was performed to determine whether in dogs with pituitary-dependent hyperadrenocorticism (PDH) excessive release of adrenocorticotrophic hormone (ACTH) is accompanied by secretion of ACTH precursor molecules. In addition, we investigated whether the plasma ACTH precursor concentrations were correlated with the size of the pituitary gland and with the degree of resistance to negative glucocorticoid feedback. In 72 dogs with PDH, the plasma ACTH precursor concentration was determined by calculating the difference between the results of a radioimmunoassay (RIA) in which besides ACTH, ACTH precursors were also measured and a highly specific immunoradiometric assay (IRMA) using a polyclonal antibody against ACTH. The degree of resistance to glucocorticoid feedback was established by determining the effect of dexamethasone administration (0.1 mg/kg) on the urinary corticoid/creatinine ratio. The pituitary height/brain area (P/B) ratio, determined by computed tomography, was used as a measure for the size of the pituitary gland. The plasma ACTH precursors concentration ranged from 18 to 2233 ng/L (median 93 ng/L). In 38 dogs, the pituitary was enlarged and plasma ACTH precursors concentrations in these dogs (median 130 ng/L, range 24–2233 ng/L) were significantly (P<0.05) higher than those in the dogs without pituitary enlargement (median 72 ng/L, range 18–481 ng/L). In concordance, P/B ratios correlated significantly with plasma ACTH precursor concentrations (r=0.35, P<0.01). In addition, the P/B ratios were significantly correlated with the degree of dexamethasone resistance (r=0.42, P<0.001). Plasma ACTH precursor concentrations in the dexamethasone-resistant dogs (median 210 ng/L, range 24–628 ng/L) were significantly higher (P<0.01) than those in the dexamethasone-sensitive dogs (median 72 ng/L, range 18–2233 ng/L). Similarly, the degree of dexamethasone resistance was also significantly correlated with the plasma ACTH precursor concentrations (r=0.33, P<0.01). Dogs with an elevated plasma -MSH concentration (n=14) had significantly (P<0.001) higher plasma ACTH precursor concentrations (median 271 ng/L, range 86–2233 ng/L) than dogs with non-elevated -MSH (median 73 ng/L, range 18–481 ng/L). In addition, the plasma concentrations of -MSH correlated significantly with both plasma ACTH precursor concentrations (r=0.53, P<0.001) and P/B ratios (r=0.26, P<0.05). In conclusion, in all dogs with PDH the ACTH concentrations determined by the RIA were higher than the concentrations measured by IRMA indicating the presence of circulating ACTH precursors. High plasma ACTH precursor concentrations were especially found in dexamethasone-resistant dogs with large corticotroph adenomas, some of them probably of PI origin. In the association of large corticotroph adenoma, dexamethasone resistance and high plasma concentrations of ACTH precursors, the decreased sensitivity of the corticotroph cells to glucocorticoid feedback may play a pivotal role.     

Comparison of two insulin protocols for diabetic dogs undergoing cataract surgery

Objective To evaluate the effectiveness of two insulin doses to maintain an acceptable range of blood glucose concentrations (70–200 mg dL^?1) in the peri‐operative period in diabetic dogs. Animals Twenty‐four diabetic dogs with a median weight of 20.6 kg and a median age of 8 years old. Methods The dogs were randomly assigned to receive either 25 or 100% of their normal insulin dose subcutaneously on the morning of surgery. The anesthetic and feeding protocols were standardized. On the day before surgery, venous blood was collected for measurement of β‐hydroxybutyrate, cholesterol, glucose, glycosylated hemoglobin, hematocrit, total plasma protein and urea nitrogen. On the day of surgery, blood glucose concentrations were measured prior to anesthesia, prior to the start of surgery, 1 and 2 hours after beginning of surgery, 1 hour after extubation, at 16 : 00 hours and at 20 : 00 hours. β‐hydroxybutyrate concentrations were measured at 20 : 00 hours that day. At 08 : 00 hours the following day, β‐hydroxybutyrate and glucose concentrations were measured. The significance of differences between groups was tested with Wilcoxon's two‐tailed rank‐sum test, Chi‐square test and Fisher's exact test. Results There were no differences in insulin treatments, clinical signs, concurrent diseases and most clinicopathological parameters between the two groups of dogs at entry to the study. The 25% dose group had blood glucose values of 296 (102–601) mg dL^?1 at 16 : 00 hours and 429 (97–595) mg dL^?1 at 20 : 00 hours on the day of surgery. The 100% insulin dose group had lower corresponding values of 130 (55–375) mg dL^?1 (p = 0.04) and 185 (51–440) mg dL^?1 (p = 0.004). No other differences (p < 0.05) were detected between the two groups. Conclusions The administration of a full dose of insulin is only marginally advantageous for reducing glucose to normal (70–120 mg dL^?1) after anesthesia but neither dose consistently induced glycemic values in an acceptable range (70–200 mg dL^?1) or normoketonemia. Clinical relevance Blood glucose should be measured immediately before anesthesia and periodically throughout the peri‐operative period in all diabetic dogs because presurgical subcutaneous administration of 25 or 100% of the normal insulin dose resulted in unpredictable blood glucose concentrations.     

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).     

Persistent polyuria in two dogs following adrenocorticolysis for pituitary-dependent hyperadrenocorticism

In two dogs with pituitary-dependent hyperadrenocorticism, adrenocorticolysis with o.p'-DDD led to the disappearance of the signs and symptoms except for the polyuria. After a modified water-deprivation test the osmoregulation of vasopressin release was studied by hypertonic saline infusion. In both dogs the hypertonicity, thus induced, resulted in very minimal responses of the vasopressin secretion.     

Facial dermatosis in four dogs with hyperadrenocorticism

In hyperadrenocorticism in the dog, cutaneous lesions may include alopecia, thin, hypotonic skin, hyperpigmentation, comedones, calcinosis cutis, secondary bacterial and fungal infections, and demodicosis. Skin lesions affecting only the face have not been reported in reviews of hyperadrenocorticism, nor has the disease been included in the differential diagnoses of facial dermatoses. This report involves 4 dogs with hyperadrenocorticism in which cutaneous signs were limited to the face.     

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.     

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.     

Effects of a mock ultrasonographic procedure on cortisol concentrations during low-dose dexamethasone suppression testing in clinically normal adult dogs

OBJECTIVE: To determine whether the stress of an ultrasonographic procedure would interfere with the suppressive effect of dexamethasone during a low-dose dexamethasone suppression test (LDDST) in healthy dogs. ANIMALS: 6 clinically normal adult dogs. PROCEDURE: In phase 1, an LDDST was performed 5 times at weekly intervals in each dog. Serum samples were obtained 0, 2, 4, 6, and 8 hours after dexamethasone injection. A mock 20-minute abdominal ultrasonographic examination was performed on all dogs at each time point during the LDDST on weeks 2 through 5. In phase 2, serum cortisol concentrations were measured before and immediately after a 20-minute mock abdominal ultrasonographic examination, as described for phase 1. RESULTS: We did not detect significant differences after dexamethasone injection when comparing median cortisol concentrations for weeks 2 to 5 (mock ultrasonographic procedure) with median concentration for week 1 (no mock ultrasonographic procedure). For 5 of the 6 dogs, cortisol concentrations after dexamethasone injection decreased to < 35.9 nmol/L after each mock ultrasonographic procedure and remained low for the duration of the LDDST. In phase 2, all dogs had significant increases in cortisol concentrations immediately after the mock ultrasonographic procedure. CONCLUSIONS AND CLINICAL RELEVANCE: A 20-minute mock abdominal ultrasonographic examination performed during LDDST did not alter results of the LDDST in most dogs. Cortisol concentrations measured immediately after a mock ultrasonographic examination were significantly increased. Ultrasonographic procedures should be performed a minimum of 2 hours before collection of samples that will be used to measure cortisol concentrations.