Serum Inhibin Concentration in Dogs with Adrenal Gland Disease and in Healthy Dogs

Background

Studies in humans identified the synthesis and secretion of inhibin from adrenocortical tumors, but not pheochromocytoma (PHEO). Inhibin has not been examined in dogs as a serum biomarker for adrenal gland tumors.

Objective

To determine serum inhibin concentration in dogs with adrenal gland disease and in healthy dogs.

Animals

Forty‐eight neutered dogs with adrenal disease including pituitary‐dependent hyperadrenocorticism (PDH, 17), adrenocortical tumor (18), and PHEO (13), and 41 healthy intact or neutered dogs.

Methods

Prospective observational study. Dogs were diagnosed with PDH, adrenocortical tumor (hyperadrenocorticism or noncortisol secreting), or PHEO based on clinical signs, endocrine function tests, abdominal ultrasound examination, and histopathology. Inhibin concentration was measured by radioimmunoassay in serum before and after ACTH stimulation, and before and after treatment.

Results

In neutered dogs, median inhibin concentration was significantly higher in dogs with adrenocortical tumors (0.82 ng/mL) and PDH (0.16 ng/mL) than in dogs with PHEO and healthy dogs (both undetectable). Median inhibin concentration was significantly higher in dogs with adrenocortical tumors than in those with PDH and decreased after adrenalectomy. Median inhibin concentration was significantly higher in intact than in neutered healthy dogs and was similar in pre‐ and post‐ACTH stimulation. Sensitivity, specificity, and accuracy of serum inhibin concentration for identifying an adrenal tumor as a PHEO were 100, 88.9, and 93.6%, respectively.

Conclusions and Clinical Importance

Adrenocortical tumors and PDH but not PHEOs are associated with increased serum inhibin concentration; undetectable inhibin is highly supportive of PHEO in neutered dogs with adrenal tumors.     

Ultrasonography Criteria for Differentiating ACTH Dependency from ACTH Independency in 47 Dogs with Hyperadrenocorticism and Equivocal Adrenal Asymmetry

Background: Adrenal ultrasonography (US) in dogs with hyperadrenocorticism (HAC) is commonly used to distinguish adrenocorticotropic hormone (ACTH)‐independent (AIHAC) and ACTH‐dependent hyperadrenocorticism (ADHAC). To date, no cut‐off values for defining adrenal atrophy in cases of adrenal asymmetry have been determined. Given that asymmetrical hyperplasia is sometimes observed in ADHAC, adrenal asymmetry without ultrasonographic proof of adrenocortical tumor such as vascular invasion or metastasis can be equivocal. Objective: The purpose of this study was to compare adrenal US findings between cases of ADHAC and AIHAC in dogs with equivocal adrenal asymmetry (EAA), and to identify useful criteria for their distinction. Animals: Forty dogs with EAA were included. Methods: Ultrasound reports of HAC dogs with adrenal asymmetry without obvious vascular invasion or metastases were reviewed. Dogs were classified as cases of ADHAC (n = 28) or AIHAC (n = 19), determined by plasma ACTH concentration. The thickness, shape, and echogenicity of both adrenal glands and presence of adjacent vascular compression were compared between AIHAC and ADHAC groups. Results: The maximal dorsoventral thickness of the smaller gland (SDV) ranged from 2.0 to 5.0 mm in AIHAC and from 5.0 to 15.0 mm in ADHAC. The 95% confidence intervals for estimated sensitivity and specificity of a SDV cut‐off set at 5.0 mm in the diagnosis of AIHAC were 82–100 and 82–99%, respectively. Other tested US criteria were found to overlap extensively between the 2 groups, precluding their usefulness for distinction. Conclusion and Clinical Importance: In EAA cases, an SDV ≤5.0 mm is an appropriate cut‐off for AIHAC ultrasonographic diagnosis.     

Ultrasonographic adrenal gland measurements in clinically normal small breed dogs and comparison with pituitary-dependent hyperadrenocorticism

Ultrasonography is a sensitive and specific screening method for assessing the adrenal glands. The upper limit of the normal adrenal gland width is used as 7.5 mm. It is not known if adrenal gland width remains consistent with body weight. A reliable criterion of adrenal gland width in small breed dogs should be established. Small breed dogs with body weights of less than 10 kg were divided into two groups: 189 normal dogs and 22 dogs with pituitary-dependent hyperadrenocorticism (PDH). A retrospective study was conducted on dogs seen between January 1, 2006, and February 10, 2008. One hundred eighty-nine dogs of 14 different small breeds were enrolled in the normal adrenal gland group; the median gland width was 4.20 mm. Twenty-two dogs were in the PDH group; the median gland width was 6.30 mm. The cut-off value between normal adrenal glands and PDH was 6.0 mm. This figure gave a sensitivity and specificity of 75 and 94%, respectively, for detecting PDH. The adrenal gland appeared as a peanut shape with homogeneous hypoechoic parenchyma in normal dogs and in most dogs with PDH as well. This study was performed in a large population of small breed dogs and suggests that the normal adrenal gland size in small breed dogs is smaller than previously reported. We believe that a cut-off of 6.0 mm may be used as the criterion for differentiating a normal adrenal gland from adrenal hyperplasia.     

RETROSPECTIVE REVIEW OF THE ULTRASONOGRAPHIC FEATURES OF ADRENAL LESIONS IN 21 FERRETS

Clinical signs and follow-up information were recorded. Histopathologic diagnoses were obtained for 25 adrenal glands in 21 ferrets. Adrenal lesions included ten adenocarcinomas, nine adenomas, one hyperplasia and one cortical cyst. Four adrenal glands (all right-sided) were diagnosed as unspecified adrenal tumors but lacked a definite histopathologic diagnosis (adenoma vs. adenocarcinoma) due to incomplete surgical resection and consequent small sample sizes. Bilateral adrenal lesions were identified in 4 ferrets (19%). Adrenal shape, size, echogenicity, laterality, and the presence of vascular invasion were evaluated with ultrasound. Size and shape were variable and not specific to lesion type. Both benign and malignant adrenal tumors (adenomas, adenocarcinomas) appeared most often as masses with increased thickness and a normal length (11/23), less frequently as larger masses with increased thickness and length (4/23) or as nodules focally deforming the normal adrenal shape (6/23). The only cortical cyst appeared as a nodule. Three adrenal glands had a normal size and shape and were diagnosed as adenomas (2) or hyperplasia (1). Therefore treatment may be warranted based solely on clinical signs if adrenal glands are ultrasonographically normal. Vascular invasion was not identified ultrasonographically. However, focal absence of periglandular fat resulting in contact of 8 adrenal glands with either caudal vena cava (6), aorta (1) or liver (1) identified ultrasonographically, correlated with incomplete surgical resectability (6/8) and histopathologic diagnoses of carcinoma (4/8) or unspecified tumors (4/8). Therefore, a focal absence of periglandular fat between the adrenal gland and the large vessels or liver, deviation or compression of the large vessels by the adrenal lesion may indicate malignancy. Adrenal tumors (benign and malignant) were often associated with a prominent uterus, uterine stump or prostate with or without prostatic cysts.     

RETROSPECTIVE ULTRASONOGRAPHIC EVALUATION OF ADRENAL LESIONS IN 26 DOGS

A review was performed of ultrasonographic findings in 26 dogs with confirmed adrenal lesions. Adrenal shape, size, echogenicity, laterality, and the presence of vascular invasion were evaluated. Histopathologic diagnoses were obtained in all dogs. Adrenal lesions were confirmed as pheochromocytomas (9), adenocarcinomas (6), a poorly differentiated blastoma (l), bilateral adrenal metastases of a carcinoma (l), adenomas-one of which was bilateral-(4) and hyperplasia (6). Size and shape were extremely variable and not specific to lesion type. There was a tendency for pheochromocytomas (7), adenocarcinomas (5) and poorly differentiated blastoma (1) to be rounded masses. Adenomas (4), hyperplasia (7) and adrenal metastases (2) presented predominantly as nodules. No specificity in echogenicity was noted. Mineralization and bilaterality were present in both benign and malignant lesions. Vascular extension or the presence of a thrombus were suggestive but not specific signs of malignancy. Based on our prelimiary study, ultrasonography is an effective method for localizing adrenal lesions and is helpful in assessing their extension. However, no definitive differentiation between benign and malignant lesions was possible using ultrasonographic criteria alone.     

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.     

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.     

Results of Transsphenoidal Hypophysectomy in 52 Dogs With Pituitary-Dependent Hyperadrenocorticism

Objective —To evaluate microsurgical transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism (PDH). Study Design —Prospective study to evaluate the results (survival and disease-free interval, remission, recurrence) and complications of microsurgical transsphenoidal hypophysectomy by clinical follow-up, computed tomography (CT), and urinary corticoid-to-creatinine (C/C) ratios in dogs with PDH. The effect of surgical experience was investigated by comparing results of hypophysectomy cases 1 through 26 and 27 through 52. Animals or Sample Population—52 dogs with PDH. Results —Preoperative CT enabled accurate assessment of pituitary size (24 nonenlarged and 28 enlarged) and localization relative to intraoperative anatomic landmarks. Treatment failures included procedure-related mortalities (five dogs) and incomplete hypophysectomies (four dogs). The 1-year estimated survival rate was 84% (95% confidence interval [CI], 71% to 92%). The 2-year estimated survival rate was 80% (95% CI, 65% to 90%). In 43 dogs, the hyperadrenocorticism went into remission. Hyperadrenocorticism recurred in five dogs. The 1-year estimated relapse-free fraction was 92% (95% CI, 76% to 97%). The main complications were transient, mild, postoperative hypernatremia; transient reduction or cessation of tear production (25 eyes in 18 dogs); permanent (five dogs) or prolonged (nine dogs) diabetes insipidus; and secondary hypothyroidism. Normal tear production had resumed in all but one case after a median period of 10 weeks. In the second case series (27 through 52), the hospitalization period was shorter, the number of dry eyes fewer, the survival fraction greater, and the postoperative mortality lower than in the first series. In 15 dogs in which remission was obtained, postoperative CT images suggested the presence of small pituitary remnants; in 1 of these, hyperadrenocorticism recurred. In 46 dogs, the histological diagnosis was pituitary adenoma. Conclusions —Microsurgical transsphenoidal hypophysectomy in dogs with PDH is an effective method of treatment in specialized veterinary institutions having access to advanced pituitary imaging techniques. Postoperative CT findings do not correlate well with remission or subsequent recurrence of hyperadrenocorticism. Clinical Relevance —The neurosurgeon performing hypophysectomies must master a learning curve and must be familiar with the most frequent complications of the operation to recognize them as early as possible and to treat them immediately and effectively. Urinary C/C ratios are sensitive indicators for the assessment of remission and recurrence of hyperadrenocorticism.     

Plasma Taurine Concentrations in Normal Dogs and in Dogs With Heart Disease

Plasma taurine concentrations were determined in 76 dogs with dilated cardiomyopathy (DCM), 28 dogs with acquired valvular disease (AVD), and 47 normal (control) dogs. The data were collected at 2 referral centers. The Animal Medical Center, New York, NY (AMC), and the University of California, Davis (UCD), and the studies were conducted independently. Different anticoagulants (sodium citrate at AMC and lithium heparin at UCD) were used to collect the plasma samples. Paired analysis of samples showed a significant difference in plasma taurine concentrations, depending on the anticoagulant used. Consequently, results from each clinic were analyzed separately. Plasma taurine concentrations were significantly higher in dogs with AVD (median, 133 nmol/mL; range, 25 to 229 nmol/mL) than in control dogs (median, 63 nmol/mL; range 44 to 224 nmol/mL) and dogs with DCM (median, 72 nmol/mL; range, 1 to 247 nmol/mL) at AMC (P= .001). The number of dogs with AVD at UCD was too small to draw meaningful conclusions. At UCD, the median plasma taurine concentration was 98 nmol/mL (range, 28–169 nmol/mL) in dogs with AVD, 75 nmol/mL (range, 0.1–184 nmol/mL) in dogs with DCM, and 88 nmol/mL (range 52–180 nmol/mL) in control dogs. There were no significant differences in plasma taurine concentrations between dogs with DCM and the control dogs at either hospital. Congestive heart failure and administration of cardiac medication had no significant effect on plasma taurine concentrations. Plasma taurine concentration was low (<25 nmol/mL) in 17% (13/76) of the dogs with DCM. Seven of the 13 dogs with low plasma taurine concentrations were Cocker Spaniels or Golden Retrievers. It was concluded that most dogs with DCM do not have low plasma taurine concentrations. However, certain breeds or individual dogs may have low plasma taurine concentrations in association with DCM. Whether this association is causal or not is unknown. The significance of the high plasma taurine concentrations in dogs with AVD is also unknown.     

Ultrasonographic visualization of the adrenal glands of healthy ferrets and ferrets with hyperadrenocorticism

A protocol was developed to compare the ultrasonographic characteristics of the adrenal glands of 21 healthy ferrets and 37 ferrets with hyperadrenocorticism. By using specific landmarks, the adrenal glands were imaged in 97% of the cases. The adrenal glands of ferrets with hyperadrenocorticism had a significantly increased thickness, with changes in shape, structure, and echogenicity compared to the adrenal glands of healthy ferrets. Based on the findings of the study, adrenal glands may be classified as abnormal when they have a rounded appearance, increased size of the cranial/caudal pole (thickness >3.9 mm), a heterogeneous structure, increased echogenicity, and/or signs of mineralization.     

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.     

Pulsatile secretion pattern of growth hormone in dogs with pituitary-dependent hyperadrenocorticism

The amplitude and frequency of growth hormone (GH) secretory pulses are influenced by a variety of hormonal signals, among which glucocorticoids play an important role. The aim of this study was to investigate the pulsatile secretion pattern of GH in dogs in which the endogenous secretion of glucocorticoids is persistently elevated, i.e. in dogs with pituitary-dependent hyperadrenocorticism (PDH). Blood samples for the determination of the pulsatile secretion pattern of GH were collected at 10-min interval between 08:00 and 14:00 h in 16 dogs with PDH and in 6 healthy control dogs of comparable age. The pulsatile secretion patterns of GH were analyzed using the Pulsar program. GH was secreted in a pulsatile fashion in both dogs with PDH and control dogs. There was no statistical difference between the mean (+/-S.E.M.) basal GH level in dogs with PDH (0.7+/-0.1 microg/l) and the control dogs (0.6+/-0.1 microg/l). The mean area under the curve (AUC) for GH above the zero-level in dogs with PDH (4.6+/-0.6 microg/l per 6 h) was significantly lower than that in the control dogs (7.3+/-1.0 microg/l per 6 h). Likewise, the mean AUC for GH above the base-level in dogs with PDH (0.6+/-0.1 microg/l per 6 h) was significantly lower than that in the control dogs (3.7+/-1.0 microg/l per 6 h). The median GH pulse frequency in the dogs with PDH (2 pulses/6 h, range 0-7 pulses/6 h) was significantly lower (P = 0.04) than that (5 pulses/6 h, range 3-9 pulses/6 h) in the control group. The results of this study demonstrate that PDH in dogs is associated with less GH secreted in pulses than in control dogs, whereas the basal plasma GH concentrations were similarly low in both groups. It is discussed that the impaired pulsatile GH secretion in dogs with PDH is the result of alterations in function of pituitary somatotrophs and changes in supra-pituitary regulation.     

High Urine Concentrations of Basic Fibroblast Growth Factor in Dogs With Bladder Cancer

Because dogs with bladder cancer often have advanced disease at the time of diagnosis, the identification and use of a tumor marker that could facilitate earlier diagnosis is a valid approach to improve prognosis. The objective of this study was to determine if urine concentrations of the proan-giogenic peptide, basic fibroblast growth factor (bFGF), are high in dogs with bladder cancer compared with normal dogs and dogs with urinary tract infection. We used a commercially available enzyme-linked immunosorbent assay test kit to quantitate bFGF in the urine of 17 normal dogs, 10 dogs with urinary tract infection, and 7 dogs with locally active transitional cell carcinoma of the urinary bladder. In normal dogs, the median urine bFGF concentration was 2.23 ng/g creatinine (quartile range, 1.53 to 5.12 ng/g creatinine). The median urine bFGF concentration in dogs with urinary tract infection did not differ significantly from normal dogs. Dogs with bladder cancer had significantly higher urine bFGF concentrations than normal dogs ( P < .002) and dogs with infection ( P < .02). The median urine bFGF concentration in dogs with transitional cell carcinoma was 9.86 ng/g creatinine (quartile range, 7.40 to 21.63 ng/g creatinine). Six of 7 dogs with bladder cancer had urine bFGF concentrations that were up to 7.4 times the 90th percentile value for normal dogs. Only 1 of 10 dogs with infection had a urine bFGF concentration that exceeded the 90th percentile of normal. These data suggest that canine bladder cancers export bFGF, and that urine bFGF may be useful as a diagnostic tumor marker or noninvasive indicator of treatment response. J Vet Intern Med 1996;10:231–234. Copyright © 1996 by the American College of Veterinary Internal Medicine .     

CONTRAST‐ENHANCED ULTRASONOGRAPHIC CHARACTERISTICS OF ADRENAL GLANDS IN DOGS WITH PITUITARY‐DEPENDENT HYPERADRENOCORTICISM

A noninvasive method for quantifying adrenal gland vascular patterns could be helpful for improving detection of adrenal gland disease in dogs. The purpose of this retrospective study was to compare the contrast‐enhanced ultrasound (CEUS) characteristics of adrenal glands in 18 dogs with pituitary‐dependent hyperadrenocorticism (PDH) vs. four clinically healthy dogs. Each dog received a bolus of the contrast agent (SonoVue®, 0.03 ml/kg of body weight) into the cephalic vein, immediately followed by a 5 ml saline flush. Dynamic contrast enhancement was analyzed using time–intensity curves in two regions of interest drawn manually in the caudal part of the adrenal cortex and medulla, respectively. In healthy dogs, contrast enhancement distribution was homogeneous and exhibited increased intensity from the medulla to the cortex. In the washout phase, there was a gradual and homogeneous decrease of enhancement of the adrenal gland. For all dogs with PDH, there was rapid, chaotic, and simultaneous contrast enhancement in both the medulla and cortex. Three distinct perfusion patterns were observed. Peak perfusion intensity was approximately twice as high (P < 0.05) in dogs with PDH compared with that of healthy dogs (28.90 ± 10.36 vs. 48.47 ± 15.28, respectively). In dogs with PDH, adrenal blood flow and blood volume values were approximately two‐ to fourfold (P < 0.05) greater than those of controls. Findings from the present study support the use of CEUS as a clinical tool for characterizing canine adrenal gland disease based on changes in vascular patterns.     

CONTRAST‐ENHANCED ULTRASONOGRAPHY OF THE NORMAL CANINE ADRENAL GLAND

Contrast‐enhanced ultrasonography is useful in differentiating adrenal gland adenomas from nonadenomatous lesions in human patients. The purposes of this study were to evaluate the feasibility and to describe contrast‐enhanced ultrasonography of the normal canine adrenal gland. Six healthy female Beagles were injected with an intravenous bolus of a lipid‐shelled contrast agent (SonoVue^®). The aorta enhanced immediately followed by the renal artery and then the adrenal gland. Adrenal gland enhancement was uniform, centrifugal, and rapid from the medulla to the cortex. When maximum enhancement was reached, a gradual homogeneous decrease in echogenicity of the adrenal gland began and simultaneously enhancement of the phrenicoabdominal vessels was observed. While enhancement kept decreasing in the adrenal parenchyma, the renal vein, caudal vena cava, and phrenicoabdominal vein were characterized by persistent enhancement until the end of the study. A second contrast enhancement was observed, corresponding to the refilling time. Objective measurements were performed storing the images for off‐line image analysis using Image J (ImageJ^©). The shape of the time–intensity curve reflecting adrenal perfusion was similar in all dogs. Ratios of the values of the cortex and the medulla to the values of the renal artery were characterized by significant differences from initial upslope to the peak allowing differentiation between the cortex and the medulla for both adrenal glands only in this time period. Contrast‐enhanced ultrasonography of the adrenal glands is feasible in dogs and the optimal time for adrenal imaging is between 5 and 90 s after injection.     

Investigation of the role of aldosterone in hypertension associated with spontaneous pituitary-dependent hyperadrenocorticism in dogs

The aim of this study was to evaluate the role of aldosterone as an initiating and/or perpetuating factor in hypertension associated with pituitary-dependent hyperadrenocorticism (PDH) in dogs. Thirteen dogs with PDH and 11 healthy control dogs were used. In all dogs, arterial blood pressure and plasma sodium, potassium, basal aldosterone, post-ACTH aldosterone, basal cortisol and post-ACTH cortisol concentrations were measured. The tests were repeated 10 days and three months after the beginning of o,p'-DDD treatment in PDH dogs. In untreated PDH dogs, plasma aldosterone was significantly decreased, whereas cortisol, sodium and arterial blood pressure were significantly increased compared to healthy dogs. Hypertension remained in most treated PDH dogs despite normalisation of cortisol and persistently low aldosterone levels. These results did not demonstrate that aldosterone is involved in the development and perpetuation of hypertension in PDH. However, glucocorticoids seemed to play a major role as an initiating and perpetuating factor in PDH in dogs.     

Serum Levels of 25-Hydroxycholecalciferol and 1,25-Dihydroxycholecalciferol in Dogs with Hypercalcaemia

1,25-Dihydroxycholecalciferol (1,25-(OH)2-D3) and 25-hydroxycholecalciferol (25-OH-D3) were measured among dogs with hypercalcaemia (total serum calcium > 3.01 mmol/L) due to various causes. All values were compared to those of healthy control dogs. Serum 1,25-(OH)]2-D3 was measured by a radioimmunoassay test and serum 25-OH-D3 was measured by a protein binding assay. 1,25-(OH)2-D3 ranged from 26 to 332 pmol/L (median 110.0) in dogs with lymphoma (n = 12); from 61 to 398 pmol/L (median 248.0) in dogs with primary hyperparathyreoidism (n = 5); from 28 to 310 pmol/L (median 88.5) in dogs with chronic renal failure (n = 10); and from 60 to 239 pmol/L (median 157.5) in control dogs (n = 24). There was no significant difference in 1,25-(OH)2-D3 among dogs with different causes of hypercalcaemia. 25-OH-D3 ranged from 64 to 291 nmol/L (median 101.5) in dogs with lymphoma; from 66 to 298 nmol/L (median 91.0) in dogs with primary hyperparathyreoidism; from 35 to 184 nmol/L (median 67.0) in dogs with chronic renal failure; and from 48 to 350 nmol/L (median 306.5) in control dogs. 25-OH-D3 was significantly lower in dogs with lymphoma, primary hyperparathyroidism and chronic renal failure than in control dogs. 1,25-(OH)2-D3 and 25-OH-D3 are not predictable in dogs with hypercalcaemia.     

Early renal ultrasonographic findings in dogs with experimentally induced ethylene glycol nephrosis

Renal ultrasonographic changes were evaluated in 5 dogs administered 10 ml of commercial antifreeze (95% ethylene glycol)/kg of body weight, PO, and in 2 dogs given placebos. Studies were made prior to and after ingestion on an hourly basis over a period of 8 to 10 hours. All dogs were anesthetized immediately after toxin or placebo ingestion for the duration of the study. Renal cortical echogenicity was evaluated in comparison with that of the adjacent liver and spleen. Echogenicity of the renal medulla and definition of the corticomedullary junction were assessed. Within 4 hours after ethylene glycol administration, renal cortical echogenicity of all intoxicated dogs increased from normal to surpass that of liver and approach or equal that of the spleen. Medullary echogenicity in all intoxicated dogs progressively increased over the course of the study, with changes recognized within 5 hours after ethylene glycol administration. An ultrasonographic pattern consisting of nearly equal, marked increase in cortical and medullary echogenicity and relatively hypoechoic corticomedullary junction and central medullary regions was recognized concurrent with the development of anuria in 3 of the 5 intoxicated dogs. Mild, transient increases in cortical and medullary echogenicity were observed in anesthetized control dogs. However, no statistical difference (P less than 0.05) was detected between baseline, peak, and terminal echogenicity values in these dogs. Blood and urine samples were collected hourly from intoxicated dogs to coincide with ultrasonographic studies. Most clinicopathologic values derived from these samples were not statistically different (P less than 0.05) from those reported in a study that used a similar intoxication protocol in nonanesthetized dogs.     

Effect of glucocorticoid administration on adrenal gland size and sonographic appearance in beagle dogs

Our aim was to evaluate the influence of glucocorticoids on the adrenal gland using ultrasonography. Eleven healthy beagles were used in a prospective placebo-controlled study. All dogs received hydrocortisone at 10 mg/kg twice a day per os for 4 months or a gelatin capsule twice a day per os as a placebo. Clinical and endocrinologic examination of the dogs and ultrasonographic evaluation of adrenal echogenicity, shape, and measurement of the length and height of the cranial and caudal pole were performed at baseline (TO), at 1 (T1) and 4 months (T4) after the beginning of treatment, and 2 months after the end of the treatment including 1 month of tapering and 1 month without treatment (T6). The dogs were assigned randomly to the glucocorticoid (n = 6) and placebo groups (n = 5). At T1, the difference between the two groups for the height of the cranial and caudal pole was not ultrasonographically remarkable despite a statistically significant difference (P = 0.0165 and P = 0.0206). Decreased height and length of entire gland were observed at T4 (P < 0.0001, P = 0.0015, and P = 0.0035, respectively). Percentages of atrophy were variable between dogs. Both adrenal glands regained normal size and shape 1 month after cessation of glucocorticoid administration. As not all dogs developed marked adrenal gland atrophy and the degree of atrophy varied widely between individuals, ultrasonography cannot be the technique of choice to detect iatrogenic hypercortisolism. Ultrasonographic changes are reversible within 1 month after the end of glucocorticoid administration.     

ULTRASONOGRAPHIC PARAMETERS OF NORMAL CANINE ADRENAL GLANDS: COMPARISON TO NECROPSY FINDINGS

Ultrasonographic evaluation of the adrenal glands was performed in 14 fasted healthy adult dogs. Frequency of visualization was 100% for both the left and right adrenal glands. Moderate correlation was present between Ultrasonographic and gross measurements of thickness for both left (r_s= 0.727; p < .005) and right (r_s= 0.537; p < .05) adrenal glands. However, no correlation was found between Ultrasonographic and gross measurements for length or width of either adrenal gland. Differentiation of adrenal cortex and medulla was possible in 79% of left adrenal glands and 64% of right adrenal glands. The echogenicity of the adrenal glands was less than that of the renal cortex in all dogs. Factors which made evaluation of the adrenal glands more difficult included pyloric gas, intestinal gas, and deep-chested body conformation.