Serum 17-alpha-hydroxyprogesterone and corticosterone concentrations in dogs with nonadrenal neoplasia and dogs with suspected hyperadrenocorticism

OBJECTIVE: To assess serum 17-alpha-hydroxyprogesterone (17OHP) and corticosterone concentrations in dogs with nonadrenal neoplasia and dogs being screened for hyperadrenocorticism. DESIGN: Prospective study. ANIMALS: 16 clinically normal dogs, 35 dogs with nonadrenal neoplasia, and 127 dogs with suspected hyperadrenocorticism. PROCEDURE: ACTH stimulation tests were performed in all dogs. Baseline serum cortisol and corticosterone concentrations were measured in the healthy dogs; baseline serum cortisol concentration and ACTH-stimulated cortisol, corticosterone, and 17OHP concentrations were measured in all dogs. Endogenous plasma ACTH concentration was also measured before administration of ACTH in dogs with neoplasia. RESULTS: In 35 dogs with neoplasia, 31.4% had high serum 17OHP concentration and 22.9% had high serum corticosterone concentration. Of the 127 dogs with suspected hyperadrenocorticism, 59 (46.5%) had high ACTH-stimulated cortisol concentrations; of those, 42 of 59 (71.2%) and 32 of 53 (60.4%) had high serum 17OHP and corticosterone concentrations, respectively. Of dogs with serum cortisol concentration within reference range after ACTH administration, 9 of 68 (13.2%) and 7 of 67 (10.4%) had high serum 17OHP and corticosterone concentrations, respectively. In the dogs with neoplasia and dogs suspected of having hyperadrenocorticism, post-ACTH serum hormone concentrations were significantly correlated. CONCLUSIONS AND CLINICAL RELEVANCE: Serum concentrations of 17OHP or corticosterone after administration of ACTH may be high in dogs with nonadrenal neoplasia and no evidence of hyperadrenocorticism. Changes in serum 17OHP or corticosterone concentrations after administration of ACTH are proportionate with changes in cortisol concentration.     

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.     

Lymphoma as a model for chronic illness: effects on adrenocortical function testing

Many dogs with chronic illness have serum biochemical abnormalities consistent with hyperadrenocorticism (HAC). Lymphoma (LSA) is a chronic disease of dogs. The purpose of this study was to evaluate adrenocortical screening test results in dogs with LSA to evaluate their specificity. Criteria for inclusion in the study included a diagnosis of LSA, an expected survival time of 16-56 weeks, no glucocorticoid treatment beyond 4 weeks after the initiation of chemotherapy, no evidence of HAC, and owner consent. Post-ACTH stimulation plasma cortisol concentrations (PACs), urine cortisol : creatinine (UC : Cr) ratios, and maximal left adrenal width measurements were performed at the time of LSA diagnosis before the initiation of chemotherapy and at 16, 24, 32, 40, and 52 weeks or until the loss of remission or the development of another disease. Ten dogs met the criteria for inclusion. Forty-two PACs were performed; 1 abnormal, 2 borderline, and 39 normal values were detected. Thirty-five maximal left adrenal width measurements were obtained; 0 abnormal, 5 borderline, and 30 normal measurements were detected. Thirty-six UC : Cr ratios were obtained, with 26 abnormal, 4 borderline, and 6 normal values detected and 9 of 10 dogs having at least 1 abnormal value. These data suggest that in dogs with LSA, the UC : Cr ratio frequently is abnormal and may not be a specific test for HAC, or it may be the most sensitive test for increases in cortisol secretion due to chronic illness. Maximal left adrenal width measurements and PACs were almost always normal and may be more specific for HAC or less sensitive for demonstrating chronic increases in cortisol secretion.     

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.     

Canine hyperadrenocorticism

Hyperadrenocorticism is a common endocrinopathy which results from the excessive production of cortisol by the adrenal cortex. In the majority of cases, this increased secretion of cortisol results from stimulation of the adrenal cortex by adrenocorticotrophic hormone secreted from the pituitary gland. In a smaller number of cases adrenal tumours are present. Clinical signs are variable but commonly include polydipsia and polyuria, polyphagia, obesity, a pendulous abdomen, hepatomegaly, alopecia, lethargy, weakness and anoestrus. Haematology, serum chemistry analysis and urinalysis should be performed on a dog with suspected hyperadrenocorticism. Finding a significant number of changes that are consistent with hyperadrenocorticism often allows a presumptive diagnosis to be made. Other tests can then be used to confirm the diagnosis and to help localise the cause, including liver biopsy, radiology, ultrasonography, gamma camera imaging, computed tomography, and measurement of blood and urine hormone levels. The ACTH stimulation test, low dose dexamethasone suppression test and measurement of the urine cortisol:creatinine ratio are used to assess whether hyperadrenocorticism is present. The high dose dexamethasone suppression test, measurement of plasma ACTH, corticotropin-releasing hormone stimulation test, and a modification of the urinary cortisol:creatinine ratio test are then implemented to determine the aetiology. The treatment of choice for adrenal neoplasia is surgical removal of the affected adrenal. On the other hand, pituitary hyperplasia or neoplasia may be treated either surgically, by bilateral adrenalectomy or hypophysectomy, or medically. The drug which is chosen most commonly for medical management is 1,1-dichloro-2(O-chlorophenyl)-2-(P-chlorophenyl) ethane (op'-DDD), which can be used to suppress adrenal function or to completely destroy the adrenal cortex. The antifungal agent ketoconazole also suppresses adrenal steroid synthesis and provides an alternative form of medical treatment for hyperadrenocorticoid dogs.     

Changes in adrenal cortisol secretion as reflected in the urinary cortisol/creatinine ratio in dogs

In Experiment 1, voided urine samples were collected from 12 adult dogs at 0500, 1400, and 2200 hr for 4 days. Cortisol was measured in unextracted urine by radioimmunoassay, creatinine by spectrophotometry, and the cortisol/creatinine ratio (UCCR) was calculated for each sample. There was considerable variation both within and among dogs in UCCR but there was no consistent time of day fluctuation in UCCR. In Experiment 2, these dogs were randomly assigned to 1 of 4 groups. The groups received each of 4 treatments (saline, dexamethasone, ACTH gel, and aqueous ACTH) at 7 day intervals in a Latin square design. All urine was collected from 0 through 8 hr. Blood samples were collected at 20 minute intervals from 0 through 8 hr. Plasma cortisol exposure was determined by quantifying area under the curve (AUC). UCCR measurement was shown to differentiate basal from elevated, but not lowered, cortisol secretion. A positive linear relationship between UCCR and AUC was seen for all treatments except dexamethasone. These results indicate that changes in cortisol secretion are reflected in changes in UCCR, but measurement of UCCR may lack sensitivity to differentiate basal from reduced states of cortisol secretion. In Experiment 3, urine was collected daily before and during induction therapy with o,p′-DDD from dogs with pituitary-dependent hyperadrenocorticism. Successful suppression of the adrenal glands was accompanied by a progressive decrease in UCCR. There was considerable variation in the rate of adrenal suppression.     

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 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.     

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.     

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 recelver operating characteristic (ROC) curve analysis. The area under the ROC curve (W 0–93, SE_w 0–044) was much higher than 045, indicating that the CCR did distinguish between dogs with and without hyperadrenocorticism.A cutoff value of about 60 × 10^-6 was assoclated with the highest sensitivity (1.0)and speciflcity (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 × 10^-6 but that a test of higher specificlty (eg, the ACTH stimulation test) should be used to confirm the diagnosis of canine hyperadrenocorticism when the CCR Is above 60 × 10^-6.     

VARIABILITY IN THE ULTRASONOGRAPHIC APPEARANCE OF THE PANCREAS IN HEALTHY DOGS COMPARED TO DOGS WITH HYPERADRENOCORTICISM

Anecdotally, an unusually hyperechoic pancreas can be found in seemingly healthy dogs on ultrasound examination and the prevalence and clinical significance of this finding is unknown. The objective of this study was to describe the prevalence of a hyperechoic and/or heterogenous pancreas in healthy dogs and correlate these findings to weight, age, and body condition score (BCS). An additional objective was to describe the prevalence of a hyperechoic and/or heterogenous pancreas in dogs with hyperadrenocorticism and compare this to the healthy dogs. Pancreata of 74 healthy dogs were evaluated prospectively and pancreatic echogenicity and echotexture were graded. Each dog's age, BCS, and weight were recorded. Dogs were screened for health by physical examination, serum chemistry panel, urine specific gravity, and a canine pancreatic lipase immunoreactivity assay. Pancreatic images for 92 dogs having hyperadrenocorticism were also reviewed and pancreatic echogenicity and echotexture were recorded. The prevalence of pancreatic hyperechogenicity in normal dogs was 7% (5 of 74) and heterogeneity was 40% (30 of 74). No correlation existed between pancreatic echogenicity and weight, age, or BCS (P > 0.1 for all sets). A statistically significant increase in the proportion of dogs having a hyperechoic pancreas was found in the hyperadrenocorticism sample of dogs (40%, 37 of 92, P < 0.0001). The underlying cause of pancreatic variability in the few healthy dogs and in dogs with hyperadrenocorticism is unknown and the varying appearance of the pancreas in these samples confounds interpretation of diseases such as chronic pancreatitis.     

High urinary corticoid/creatinine ratios in cats with hyperthyroidism

Measurement of the urinary corticoid : creatinine (C : C) ratio provides an assessment of cortisol secretion over a period of time. Therefore, this test is a very sensitive measure of adrenocortical function. The stress of the diagnostic procedure and nonadrenal disease may increase the urinary C : C ratio. In addition, diseases such as hyperthyroidism may influence the metabolic clearance of cortisol. To evaluate the effect of thyroid hormone excess, urinary C : C ratios were measured in 32 cats with hyperthyroidism and 45 healthy household cats. In 7 cats, urinary C : C ratios were measured both before and after treatment for hyperthyroidism. With data from the healthy cats, the reference range for the urinary C : C ratio was determined to be 8.0 to 42.0 X 10(-6). The urinary C : C ratios in the cats with hyperthyroidism (median, 37.5 x 10(-6); range, 5.9-169.5 x 10(-6)) were significantly (P = .001) higher than those in the healthy cats (median, 16 x 10(-6); range, 4.8-52.5 x 10(-6)). In 15 cats with hyperthyroidism, the urinary C : C ratios exceeded the upper limit of the reference range. Treatment for hyperthyroidism led to a marked decrease in urinary C : C ratios. The results of this study demonstrate that the urinary C : C ratio may be abnormally high in cats with hyperthyroidism, probably because of increased metabolic clearance of cortisol and activation of the pituitary-adrenocortical axis by disease. Although the clinical features of hyperthyroidism and hyperadrenocorticism in cats are different, hyperthyroidism should be ruled out when cats are suspected of hyperadrenocorticism on the basis of abnormally high urinary C : C ratios.     

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)     

Urinary concentration of corticoids in ponies with hyperlipoproteinaemia or hyperadrenocorticism

Summary

The urinary corticoid:creatinine (c:c) ratio was determined in ten pony mares suffering from hyperlipoproteinaemia. The mean (± sd) urinary c:c ratio of these ten ponies (47 ± 31 x 10^‐6) was not significantly different from that of twelve pony mares with a pituitary pars intermedia adenoma (31 ± 18 x 10^‐6). The correlation between the urinary concentration of corticoids and plasma total lipids, and the correlation between the urinary c:c ratio and plasma total lipids in ponies with hyperlipoproteinaemia were not significant (P > 0.05; r=0.53 and r=‐0.008, respectively).

Preliminary results favour primary hyperadrenocorticism being associated with hyperlipoproteinaemia. In conclusion, the data presented here suggest that cortisol can contribute to insulin resistance in ponies with hyperlipoproteinaemia.     

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.     

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 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.     

Plasma free cortisol concentrations in dogs with hyperadrenocorticism.

Unbound or free cortisol constitutes a small fraction of total plasma cortisol, but is believed to represent the biologically active portion of this circulating glucocorticoid. We tested the hypothesis that the percentage free cortisol was altered in plasma from dogs with hyperadrenocorticism, which could account for a greater target tissue response to this circulating hormone. The percentage free cortisol in plasma samples from human beings, healthy dogs, and dogs with hyperadrenocorticism was estimated, using centrifugal ultrafiltration-dialysis. Total cortisol concentrations were determined by use of radioimmunoassay. Total cortisol concentrations appeared greater in plasma from human beings than in plasma from either group of dogs. However, the percentage free cortisol was lower in plasma from human beings, resulting in a calculated concentration of free cortisol that was quite similar between plasma from human beings and healthy dogs. Total plasma cortisol concentrations were greater (P less than 0.01) in samples from dogs with hyperadrenocorticism (190 +/- 113 nmol/L; mean +/- SD) than in healthy dogs (102 +/- 85 nmol/L), but the percentage free cortisol was not different between these 2 groups (dogs with hyperadrenocorticism, 16 +/- 9%; healthy dogs, 13 +/- 6%). However, plasma free cortisol concentrations (product of total and the percentage of free cortisol) were greater (P less than 0.01) in samples from dogs with hyperadrenocorticism (36 +/- 41 nmol/L) than in those from healthy dogs (16 +/- 9 nmol/L). Significant (P less than 0.001) positive linear relationships were found between total cortisol concentrations and percentage free cortisol in plasma samples from healthy dogs and dogs with hyperadrenocorticism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma cortisol response to exogenous ACTH in 22 dogs with hyperadrenocorticism caused by adrenocortical neoplasia

The plasma cortisol response to exogenous ACTH (ACTH stimulation test) was evaluated in 22 dogs with hyperadrenocorticism caused by adrenocortical neoplasia. The mean basal cortisol concentration (6.3 microgram/dl) was high, but 7 dogs had basal cortisol concentrations that were within normal range. Administration of exogenous ACTH increased the plasma cortisol concentrations in each dog. Normal post-ACTH cortisol concentrations were found in 9 (41%) of the 22 dogs; 13 (59%) had an exaggerated increase in cortisol concentrations after ACTH administration. In 9 of 13 dogs with carcinoma and in 4 of 9 with adenoma, the cortisol response was exaggerated. The mean post-ACTH cortisol concentration in the dogs with carcinoma was approximately 4 times that of the dogs with adenoma; the 7 dogs with the highest concentrations had carcinoma. Repeat studies were performed in 6 dogs 2 to 8 weeks after initial testing. In 5 of the 6 dogs, repeat testing yielded data of similar diagnostic significance. One dog, however, had an abnormally high post-ACTH cortisol concentration at initial evaluation, but had only a minimal response to ACTH administration, with a normal post-ACTH cortisol concentration, at time of resting. Although ACTH stimulation testing is useful in diagnosing hyperadrenocorticism, it can not reliably separate dogs with hyperfunction adrenocortical tumors from clinically normal dogs or from dogs with pituitary-dependent hyperadrenocorticism (bilateral adrenocortical hyperplasia).     

Non-dexamethasone-suppressible, pituitary-dependent hyperadrenocorticism in a dog

A 5-year-old female dog with hyperadrenocorticism was determined to have pituitary-dependent hyperadrenocorticism even though plasma cortisol concentrations were not suppressed after high-dosage dexamethasone administration. The diagnosis was based on a supranormal response of plasma cortisol to ACTH administration and a lack of suppression of plasma cortisol concentration after administration of 0.1 mg of dexamethasone/kg. Although a higher dosage of dexamethasone (1 mg/kg) did not cause suppression of plasma cortisol, plasma ACTH concentrations in the dog were increased above those in clinically normal dogs, supporting a diagnosis of pituitary-dependent hyperadrenocorticism. During treatment with mitotane, the dog became unconscious and died. Necropsy revealed a pituitary tumor that had compressed and displaced the hypothalamus. Although high-dosage dexamethasone suppression tests often are useful in the differential diagnosis of hyperadrenocorticism, a lack of suppression of plasma cortisol does not necessarily exclude pituitary-dependent hyperadrenocorticism.