Ultrasonographic Characteristics of the Adrenal Glands in Dogs With Pituitary-Dependent Hyperadrenocorticism: Comparison With Normal Dogs

Ultrasonographic evaluation of the adrenal glands was performed in 10 dogs with pituitary-dependent hyperadrenocorticism (PDH) and in 10 age- and weight-matched healthy control dogs. Thickness, shape, and echogenicity were determined for each adrenal gland. Adrenal thickness in dogs with PDH (median, 10 mm-left; 8.5 mm-right) was significantly greater than thickness in control dogs (median, 6 mm-left; 6 mm-right). Other ultrasonographic characteristics associated with PDH included bilaterally symmetrical adrenomegaly and maintenance of normal adrenal shape. Adrenal echogenicity was homogeneous and less than that of the adjacent renal cortex in 8 of 10 dogs with PDH and in 10 of 10 control dogs. Heterogenous echogenicity was present in 2 of 10 dogs with PDH, and was associated with nodular cortical hyperplasia in one of those dogs. Results of this study confirm the difference in sonographic appearance between PDH-induced bilateral cortical hyperplasia and functional adrenocortical neoplasia, and show a difference in so-nographically determined adrenal size between healthy dogs and dogs with PDH. J Vet Intern Med 1996; 10:110–115. Copyright © 1996 by the American College of Veterinary Internal Medicine .     

Canine Hyperadrenocorticism Due to Adrenocortical Neoplasia: Pretreatment Evaluation of 41 Dogs

This retrospective study identifies parameters that might separate dogs with hyperadrenocorticism caused by adrenocortical tumors from dogs with pituitary-dependent hyperadrenocorticism. Further, an attempt was made to identify factors that could separate dogs with adrenocortical adenomas from dogs with carcinomas. The records of 41 dogs with hyperadrenocorticism caused by adrenocortical neoplasia were reviewed. The history, physical examination, urinalysis, hemogram (CBC), chemistry profile adrenocorticotrophic hormone (ACTH) stimulation and low dose dexamethasone test results were typical of the nonspecific diagnosis of hyperadrenocorticism. The preceding information on the 41 dogs with adrenocortical tumors was compared with that from 44 previously diagnosed pituitary-dependent hyperadrenocorticoid dogs. There was no parameter which aided in separating these two groups of dogs. Thirty dogs with adrenocortical tumors were tested with a high-dose dexamethasone test and none had suppressed plasma cortisol concentrations 8 hours after IV administration of 0.1 mg/kg of dexamethasone. In 29 of the 41 adrenal tumor dogs, plasma endogenous ACTH was not detectable on at least one measurement (less than 20 pg/ml). The remaining 12 dogs from this group had nondiagnostic concentrations (20-45 pg/ml). Thirteen of 22 dogs (59%) with adrenocortical carcinomas had adrenal masses identified on abdominal radiographs and seven of 13 dogs (54%) with adrenocortical adenomas had radiographically visible adrenal masses. Thirteen of 17 adrenocortical carcinomas (76%) and five of eight adenomas (62%) were identified with ultrasonography. Radiographs of the thorax and ultrasonography of the abdomen identified most of the dogs (8 of 11) with metastatic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Secretion of sex hormones in dogs with adrenal dysfunction

OBJECTIVE: To evaluate adrenal sex hormone concentrations in response to ACTH stimulation in healthy dogs, dogs with adrenal tumors, and dogs with pituitary-dependent hyperadrenocorticism (PDH). DESIGN: Prospective study. ANIMALS: 11 healthy control dogs, 9 dogs with adrenal-dependent hyperadrenocorticism (adenocarcinoma [ACA] or other tumor); 11 dogs with PDH, and 6 dogs with noncortisol-secreting adrenal tumors (ATs). PROCEDURE: Hyperadrenocorticism was diagnosed on the basis of clinical signs; physical examination findings; and results of ACTH stimulation test, low-dose dexamethasone suppression test, or both. Dogs with noncortisol-secreting ATs did not have hyperadrenocorticism but had ultrasonographic evidence of an AT. Concentrations of cortisol, androstenedione, estradiol, progesterone, testosterone, and 17-hydroxyprogesterone were measured before and 1 hour after i.m. administration of 0.25 mg of synthetic ACTH. RESULTS: All dogs with ACA, 10 dogs with PDH, and 4 dogs with ATs had 1 or more sex hormone concentrations greater than the reference range after ACTH stimulation. The absolute difference for progesterone, 17-hydroxyprogesterone, and testosterone concentrations (value obtained after ACTH administration minus value obtained before ACTH administration) was significantly greater for dogs with ACA, compared with the other 3 groups. The absolute difference for androstenedione was significantly greater for dogs with ACA, compared with dogs with AT and healthy control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with ACA secrete increased concentrations of adrenal sex hormones, compared with dogs with PDH, noncortisol-secreting ATs, and healthy dogs. Dogs with noncortisol-secreting ATs also have increased concentrations of sex hormones. There is great interdog variability in sex hormone concentrations in dogs with ACA after stimulation with ACTH.     

Evaluation of serum 17-hydroxyprogesterone concentration after administration of ACTH in dogs with hyperadrenocorticism

OBJECTIVE: To evaluate serum 17-hydroxyprogesterone (17-OHP) concentration measurement after administration of ACTH for use in the diagnosis of hyperadrenocorticism in dogs. DESIGN: Prospective study. ANIMALS: 110 dogs. PROCEDURE: Serum 17-OHP concentrations were measured before and after ACTH stimulation in 53 healthy dogs to establish reference values for this study. Affected dogs had pituitary-dependent (n = 40) or adrenal tumor-associated (12) hyperadrenocorticism or potentially had atypical hyperadrenocorticism (5; diagnosis confirmed in 1 dog). In affected dogs, frequency interval and borderline and abnormal serum 17-OHP concentrations after ACTH stimulation were determined. Serum cortisol concentrations were assessed via low-dose dexamethasone suppression and ACTH stimulation tests. RESULTS: In healthy dogs, serum 17-OHP concentration frequency intervals were grouped by sex and reproductive status (defined as < 95th percentile). Frequency intervals of serum 17-OHP concentrations after ACTH stimulation were < 77, < 2.0, < 3.2, and < 3.4 ng/mL (< 23.3, < 6.1, < 9.7, and < 10.3 nmol/L) for sexually intact and neutered females and sexually intact and neutered males, respectively. In 53 dogs with confirmed hyperadrenocorticism, serum cortisol concentrations after ACTH stimulation and 8 hours after administration of dexamethasone and serum 17-OHP concentrations after ACTH stimulation were considered borderline or abnormal in 79%, 93%, and 69% of dogs, respectively. Two of 5 dogs considered to have atypical hyperadrenocorticism had abnormal serum 17-OHP concentrations after ACTH stimulation. CONCLUSIONS AND CLINICAL RELEVANCE: Serum 17-OHP concentration measurement after ACTH stimulation may be useful in the diagnosis of hyperadrenocorticism in dogs when other test results are equivocal.     

Dynamic adrenal function testing in eight dogs with hyperadrenocorticism associated with adrenocortical neoplasia.

The results of adrenocorticotropin (ACTH) stimulation and low-dose dexamethasone suppression tests (LDDST) were evaluated retrospectively in eight dogs with clinical signs of hyperadrenocorticism arising from functional adrenocortical tumours, and compared with the results from 12 dogs with confirmed pituitary-dependent hyperadrenocorticism (PDH). The post-ACTH cortisol concentration in the dogs with adrenocortical tumours ranged from 61 to 345-6 nmol/litre (median 251.5 nmol/litre) and they were within the reference range (150 to 450 nmol/litre) in five and unexpectedly low (< 150 nmol/litre) in three dogs. Both the basal and post-ACTH cortisol concentrations were significantly lower in the dogs with adrenocortical neoplasia than in the dogs with PDH. Eight hours after the LDDST, only two of six dogs with adrenocortical tumours had a cortisol concentration above 30 nmol/litre, and the median resting, three, and eight-hour cortisol concentrations were 31.5, 23.0, and 22.7 nmol/litre respectively. There was no significant cortisol suppression during the LDDST, although interpretation was complicated by the low cortisol concentrations, but two dogs showed a pattern of apparent suppression. Two dogs with adrenal tumours showed a diagnostically significant increase in 17-OH-progesterone concentration in response to ACTH although their cortisol concentrations did not increase greatly. These results differ from previous reports of the response of functional adrenal tumours to dynamic endocrine tests.     

Concurrent pituitary and adrenal tumors in dogs with hyperadrenocorticism: 17 cases (1978-1995).

OBJECTIVE: To describe the clinicopathologic characteristics of dogs with hyperadrenocorticism and concurrent pituitary and adrenal tumors. DESIGN: Retrospective study. ANIMALS: 17 client-owned dogs. PROCEDURE: Signalment, response to treatment, and results of CBC, serum biochemical analysis, urinalysis, endocrine testing, and histologic examinations were obtained from medical records of dogs with hyperadrenocorticism and concurrent adrenal and chromophobe pituitary tumors. RESULTS: On the basis of results of adrenal function tests and histologic examination of tissue specimens collected during surgery and necropsy, concurrent pituitary and adrenal tumors were identified in 17 of approximately 1,500 dogs with hyperadrenocorticism. Twelve were neutered females, 5 were males (3 sexually intact, 2 neutered); and median age was 12 years (range, 7 to 16 years). Hyperadrenocorticism had been diagnosed by use of low-dose dexamethasone suppression tests and ACTH stimulation tests. During high-dose dexamethasone suppression testing of 16 dogs, serum cortisol concentrations remained high in 11 dogs but decreased in 5 dogs. Plasma concentrations of endogenous ACTH were either high or within the higher limits of the reference range (12/16 dogs), within the lower limits of the reference range (2/16), or low (2/16). Adrenal lesions identified by histologic examination included unilateral cortical adenoma with contralateral hyperplasia (10/17), bilateral cortical adenomas (4/17), and unilateral carcinoma with contralateral hyperplasia (3/17). Pituitary lesions included a chromophobe microadenoma (12/17), macroadenoma (4/17), and carcinoma (1/17). CLINICAL IMPLICATIONS: Pituitary and adrenal tumors can coexist in dogs with hyperadrenocorticism, resulting in a confusing mixture of test results that may complicate diagnosis and treatment of hyperadrenocorticism.     

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

Background

Hypertension and proteinuria are medical complications associated with the multisystemic effects of long-term hypercortisolism in dogs with hyperadrenocorticism (HAC).

Methods

This study investigated the relationships among adrenocorticotropic hormone (ACTH)-stimulation test results, systemic blood pressure, and microalbuminuria in clinically-healthy dogs (n = 100), in dogs affected with naturally occurring pituitary-dependent (PDH; n = 40), or adrenal-dependent hyperadrenocorticism (ADH; n = 30).

Results

Mean systemic blood pressure was similar between clinically healthy dogs and dogs with HAC (p = 0.803). However the incidence of hypertension was highest in dogs with ADH (p = 0.017), followed by dogs with PDH, with the lowest levels in clinically healthy dogs (p = 0.019). Presence of microalbuminuria and albuminuria in clinically healthy dogs and dogs affected with HAC was significantly different (p < 0.001); incidences of albuminuria followed the same pattern of hypertension; highest incidence in dogs with ADH, and lowest level in clinically healthy dogs; but microalbuminuria showed a different pattern: clinically healthy dogs had highest incidences and dogs with ADH had lowest incidence. The presence of albuminuria was not associated with blood pressure values, regardless of whether dogs were clinically healthy or affected with ADH or PDH (p = 0.306).

Conclusions

Higher incidence of hypertension and albuminuria, not microalbuminuria was seen in dogs affected with HAC compared to clinically healthy dogs; incidence of hypertension and albuminuria was significantly higher in dogs affected with ADH compared to PDH. However, presence of albuminuria was not correlated with systemic blood pressure.     

Plasma‐Free Metanephrine and Free Normetanephrine Measurement for the Diagnosis of Pheochromocytoma in Dogs

Background

Measurement of plasma‐free metanephrines is the test of choice to identify pheochromocytoma in human patients.

Objectives

To establish the sensitivity and specificity of plasma‐free metanephrine (fMN) and free normetanephrine (fNMN) concentrations to diagnose pheochromocytoma in dogs.

Animals

Forty‐five client‐owned dogs (8 dogs with pheochromocytoma, 11 dogs with adrenocortical tumors, 15 dogs with nonadrenal disease, and 11 healthy dogs.)

Methods

A prospective study. EDTA plasma was collected from diseased and healthy dogs and submitted for fMN and fNMN measurement by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS).

Results

Free MN concentration (median [range]) was significantly higher in dogs with pheochromocytoma (8.15 [1.73–175.23] nmol/L) than in healthy dogs (0.95 [0.68–3.08] nmol/L; P < .01) and dogs with adrenocortical tumors (0.92 [0.25–2.51] nmol/L; P < .001), but was not different from dogs with nonadrenal disease (1.91 [0.41–6.57] nmol/L; P ≥ .05). Free NMN concentration was significantly higher in dogs with pheochromocytoma (63.89 [10.19–190.31] nmol/L) than in healthy dogs (2.54 [1.59–4.17] nmol/L; P < .001), dogs with nonadrenal disease (3.30 [1.30–10.10] nmol/L; P < .001), and dogs with adrenocortical tumors (2.96 [1.92–5.01] nmol/L); P < 0.01). When used to diagnose pheochromocytoma, a fMN concentration of 4.18 nmol/L had a sensitivity of 62.5% and specificity of 97.3%, and a fNMN concentration of 5.52 nmol/L had a sensitivity of 100% and specificity of 97.6%.

Conclusions and Clinical Importance

Plasma fNMN concentration has excellent sensitivity and specificity for the diagnosis of pheochromocytoma in dogs, whereas fMN concentration has moderate sensitivity and excellent specificity. Measurement of plasma‐free metanephrines provides an effective, noninvasive, means of identifying dogs with pheochromocytoma.     

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.     

Comparison of two low-dose dexamethasone suppression protocols as screening and discrimination tests in dogs with hyperadrenocorticism

Two low-dose dexamethasone suppression test protocols were evaluated in 18 dogs with hyperadrenocorticism (14 dogs with pituitary-dependent hyperadrenocorticism [PDH] and 4 dogs with adrenocortical tumor) and in 5 healthy control dogs. Blood was obtained immediately before and 2, 4, 6, and 8 hours after IV administration of either 0.01 mg of dexamethasone sodium phosphate/kg of body weight or 0.015 mg of dexamethasone polyethylene glycol/kg. At 8 hours after dexamethasone administration, 18 of 18 (100%) dogs with hyperadrenocorticism given the sodium phosphate preparation and 16 of 18 (89%) affected dogs given the polyethylene glycol preparation failed to have suppression of plasma cortisol concentration (less than 1.4 micrograms/dl). Plasma cortisol concentration was suppressed to less than 1.4 micrograms/dl at 2, 4, and/or 6 hours after administration of either dexamethasone preparation in 5 of 14 dogs with PDH and to less than 50% of baseline cortisol concentration in 10 of 14 dogs with PDH. Suppression, as identified by these 2 criteria, was not observed at 2, 4, 6, or 8 hours after administration of either dexamethasone preparation in dogs with adrenocortical tumor. For both protocols, the 8-hour plasma cortisol concentration was suppressed to less than 1.4 micrograms/dl and to less than 50% of baseline in the 5 control dogs. Both protocols were comparable for use as screening tests in establishing a diagnosis of hyperadrenocorticism. Suppression of plasma cortisol concentration to less than 50% of baseline (or less than 1.4 micrograms/dl) during the test was consistent with diagnosis of PDH. Failure to have such suppression, however, was observed in dogs with PDH as well as in those with adrenocortical tumor.     

Utility of contrast-enhanced ultrasound in differential diagnosis of adrenal tumors in dogs

This prospective case study aimed to clarify the clinical significance of contrast-enhanced ultrasound (CEUS) for the differential diagnosis of canine adrenal tumors. Forty-three client-owned dogs with adrenal tumors were included. All dogs underwent CEUS, which was evaluated qualitatively and quantitatively. The peak signal intensity (PI), time to peak signal intensity (TPI), mean transit time (MTT), upslope, and downslope were calculated for each time-intensity curve. The histopathological diagnosis of each resected mass was compared with the CEUS findings and parameters. Enhancement distribution, vascularity, tortuous nourishing vessels, enhancement pattern, and late-phase enhancement did not differ significantly between adrenal cortical adenoma (CA), adenocarcinoma (CAC), and pheochromocytoma (PHEO) in qualitative assessment. In PHEO, the TPI was significantly more rapid compared with that in CA (P=0.0287) and CAC (P=0.0404). The MTT in PHEO was significantly shorter than that in CA (P=0.0016) and CAC (P=0.0003). Upslope in PHEO was larger than that in CAC (P=0.0406). Downslope in PHEO was significantly larger than that in CA (P=0.0048) and CAC (P=0.0018). A receiver operating characteristic curve analysis demonstrated that the area under the MTT curve yielded 0.91 for distinguishing PHEO from adrenocortical tumors in dogs; an MTT cut-off value less than 6,225 msec yielded a sensitivity of 69%, specificity of 94%, and likelihood ratio of 12.46. CEUS appears to be clinically applicable for the differential diagnosis between cortical and medullary origins of primary adrenal tumors in dogs.     

Efficacy of Low‐ and High‐Dose Trilostane Treatment in Dogs (< 5 kg) with Pituitary‐Dependent Hyperadrenocorticism

Background

Trilostane is commonly used to treat pituitary‐dependent hyperadrenocorticism (PDH) in dogs. There are differing opinions regarding the dose and frequency of trilostane administration in dogs with PDH.

Objectives

To compare the efficacy of 2 trilostane protocols in the treatment of dogs with PDH.

Animals

Sixteen client‐owned dogs with PDH and a body weight <5 kg.

Methods

Prospective observational study. Group A (n=9; low‐dose treatment group) received 0.78 ± 0.26 mg of trilostane/kg PO every 12 h and group B (n = 7; high‐dose treatment group) 30 mg of trilostane/dog PO every 24 h. All of the dogs were reassessed at 2, 4, 8, 12, 16, and 24 weeks after the initiation of treatment.

Results

An improvement in both ACTH‐stimulated serum cortisol concentrations and clinical signs occurred more slowly in group A than in group B; however, after 20 weeks of treatment, 2/7 dog in group B had clinical signs and abnormal laboratory findings consistent with hypoadrenocorticism. At 24 weeks, an improvement in the clinical findings of all of the dogs in both groups was detected.

Conclusions and clinical importance

In dogs with PDH, twice‐daily administration of low‐dose trilostane is an effective approach to the management of PDH. In addition, our results suggest fewer potential adverse effects if trilostane is administered twice daily in the lower dose.     

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)     

Basal and Glucagon-Stimulated Plasma C-PeDtide Concentrations in Healthy Dogs, Dogs With Diabetes Millitus, and Dogs With Hyperadrenocorticism

Serum glucose and plasma C-peptide response to IV glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5,10,20,30, and (for healthy dogs) 60 minutes after IV administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after IV glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after IV glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sarnplkg times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .001) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .011 in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, >0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired β-cell function (ie, diabetes mellitusl, and dogs with increased β-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of β-cell loss in dogs with type-1 diabetes. J Vet Intern Med 1996;10:116–122. Copyright © 1996 by the American College of Veterinary Internal Medicine.     

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)     

Serum Cortisol Concentrations in Dogs with Pituitary‐Dependent Hyperadrenocorticism and Atypical Hyperadrenocorticism

Background

Atypical hyperadrenocorticism (AHAC) is considered when dogs have clinical signs of hypercortisolemia with normal hyperadrenocorticism screening tests.

Hypothesis/Objectives

To compare cortisol concentrations and adrenal gland size among dogs with pituitary‐dependent hyperadrenocorticism (PDH), atypical hyperadrenocorticism (AHAC), and healthy controls.

Animals

Ten healthy dogs, 7 dogs with PDH, and 8 dogs with AHAC.

Method

Dogs were prospectively enrolled between November 2011 and January 2013. Dogs were diagnosed with PDH or AHAC based on clinical signs and positive screening test results (PDH) or abnormal extended adrenal hormone panel results (AHAC). Transverse adrenal gland measurements were obtained by abdominal ultrasound. Hourly mean cortisol (9 samplings), sum of hourly cortisol measurements and adrenal gland sizes were compared among the 3 groups.

Results

Hourly (control, 1.4 ± 0.6 μg/dL; AHAC, 2.9 ± 1.3; PDH, 4.3 ± 1.5) (mean, SD) and sum (control, 11.3 ± 3.3; AHAC, 23.2 ± 7.7; PDH, 34.7 ± 9.9) cortisol concentrations differed significantly between the controls and AHAC (P < .01) and PDH (P < .01) groups. Hourly (P < .01) but not sum (P = .27) cortisol concentrations differed between AHAC and PDH dogs. Average transverse adrenal gland diameter of control dogs (5.3 ± 1.2 mm) was significantly less than dogs with PDH (6.4 ± 1.4; P = .02) and AHAC (7.2 ± 1.5; P < .01); adrenal gland diameter did not differ (P = .18) between dogs with AHAC and PDH.

Conclusions and Clinical Importance

Serum cortisol concentrations in dogs with AHAC were increased compared to controls but less than dogs with PDH, while adrenal gland diameter was similar between dogs with AHAC and PDH. These findings suggest cortisol excess could contribute to the pathophysiology of AHAC.     

Plasma aldosterone concentrations and plasma renin activity in healthy dogs and dogs with hyperadrenocorticism

The mean (se) basal plasma aldosterone concentrations were significantly lower in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH) (75 [9] pmol/litre) than in 12 healthy dogs (118 [14] pmol/litre), whereas in five dogs with hyperadrenocorticism due to an adrenocortical tumour they were significantly higher (205 [109] pmol/litre). The mean basal renin activity was not significantly different between the dogs with PDH (303 [48] fmol/litre/second), the dogs with an adrenocortical tumour (141 [63] fmol/litre/second), and the control dogs (201 [25] fmol/litre/second). At three and four hours after the intravenous administration of 0.1 mg/kg dexamethasone, the concentrations of aldosterone decreased significantly to about 60 per cent of their initial values in the control dogs but did not change in the dogs with PDH or an adrenocortical tumour. In the dogs with PDH the renin activity increased significantly after the administration of dexamethasone.     

The desmopressin stimulation test in dogs with Cushing's syndrome

Desmopressin is a synthetic analogue of the hypothalamic peptide vasopressin and binds to specific pituitary vasopressin (V3) receptors. The V3-receptor is overexpressed in pituitary corticotrope tumors and the injection of desmopressin induces a marked ACTH and cortisol release in human patients with pituitary- (PDH), but not adrenal tumor (AT) dependent hyperadrenocorticism. In this prospective study, we investigated the effects of desmopressin on serum cortisol levels in 80 dogs suspected of Cushing's syndrome. The aim was to find a sensitive and specific test to exclude AT. According to standard tests the dogs were divided into 3 groups (group 1=other disease, n=27; group 2=PDH, n=46; group 3=AT, n=7). Desmopressin was injected as an i.v. bolus of 4microg and serial blood samples were collected before and after 30, 60 and 90min. Desmopressin significantly stimulated cortisol release in dogs with PDH (median 51%, range -24 to 563%; p<0.0001), whereas no increase was seen in dogs with AT (median -12%, range -44 to 5%; p=0.063) and in controls (median +7%, range -36 to 196%; p=0.131). Using a cut off value of 10% increase over baseline, it was possible to exclude AT in 75% of patients. The results of this study suggest that the desmopressin test could be a useful tool in differentiating pituitary from adrenal dependent Cushing's syndromes. Additional dogs with adrenocortical tumor must be tested in order to recommend its use in clinical practice.     

Ultrasonographic characteristics of both adrenal glands in 15 dogs with functional adrenocortical tumors.

Ultrasonographic examination of both adrenal glands was performed in 15 dogs with functional adrenocortical tumors (FAT). Bilateral adrenal tumors were diagnosed in three of 15 dogs, and unilateral tumors were diagnosed in 12 of 15 dogs. Adrenal tumors were characterized by adrenal gland enlargement with loss of the normal shape and parenchymal structure. The contralateral adrenal gland could be imaged in all dogs with unilateral tumors. Based on size, shape, and parenchymal structure, the contralateral adrenal gland was similar to adrenal glands of normal dogs. The results of this study show that: 1) both adrenal glands should be imaged routinely in dogs with hyperadrenocorticism; 2) bilateral adrenocortical tumors seem to be more frequent than previously assumed; 3) one normal adrenal gland does not exclude the existence of a contralateral FAT; and 4) the functional atrophy of the contralateral adrenal gland in dogs with FAT may not be apparent ultrasonographically.     

Intramuscular administration of a low dose of ACTH for ACTH stimulation testing in dogs

OBJECTIVE: To compare adrenal gland stimulation achieved following administration of cosyntropin (5 microg/kg [2.3 microg/lb]) IM versus IV in healthy dogs and dogs with hyperadrenocorticism. DESIGN: Clinical trial. Animals-9 healthy dogs and 9 dogs with hyperadrenocorticism. PROCEDURES: In both groups, ACTH stimulation was performed twice. Healthy dogs were randomly assigned to receive cosyntropin IM or IV first, but all dogs with hyperadrenocorticism received cosyntropin IV first. In healthy dogs, serum cortisol concentration was measured before (baseline) and 30, 60, 90, and 120 minutes after cosyntropin administration. In dogs with hyperadrenocorticism, serum cortisol concentration was measured before and 60 minutes after cosyntropin administration. RESULTS: In the healthy dogs, serum cortisol concentration increased significantly after administration of cosyntropin, regardless of route of administration, and serum cortisol concentrations after IM administration were not significantly different from concentrations after IV administration. For both routes of administration, serum cortisol concentration peaked 60 or 90 minutes after cosyntropin administration. In dogs with hyperadrenocorticism, serum cortisol concentration was significantly increased 60 minutes after cosyntropin administration, compared with baseline concentration, and concentrations after IM administration were not significantly different from concentrations after IV administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in healthy dogs and dogs with hyperadrenocorticism, administration of cosyntropin at a dose of 5 microg/kg, IV or IM, resulted in equivalent adrenal gland stimulation.