Trabecular bone morphometry in beagles with hyperadrenocorticism and adrenal adenomas

Trabecular bone morphometry was done on rib samples of beagles with hyperadrenocorticism and adrenal adenomas to evaluate bone loss and the remodeling changes responsible. Beagles diagnosed as having clinical hyperadrenocorticism and those with milder or subclinical hyperadrenocorticism diagnosed on the basis of adrenal and pituitary lesions at necropsy had increased adrenal and pituitary gland weights. In a group of dogs with adrenal cortical adenomas there was atrophy of remaining cortex, and the combined weight of adrenal glands or pituitary weights were not increased. In dogs with clinical hyperadrenocorticism, mean trabecular bone volume was 25% less than controls (P = 0.10). In both clinical and subclinical hyperadrenocorticism groups, the extent of trabecular surface with unmineralized osteoid matrix and osteoblasts was significantly reduced. There were no changes in resorption surfaces or number of osteoclasts present. No bone changes were seen in dogs with adrenal adenomas. In dogs with hyperadrenocorticism it appeared that decreased bone formation was primarily responsible for the relative osteopenia that developed. Although parathyroid glands were moderately enlarged in those dogs for which weights were available, the bone changes were not those of increased remodeling expected in hyperparathyroidism.     

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.     

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 .     

Results of adrenalectomy in 36 dogs with hyperadrenocorticism caused by adrenocortical tumour

Summary

A total of 38 adrenocortical tumours were removed from 36 dogs with hyperadrenocorticism. The surgical approach was by way of a unilateral flank laparotomy (32 dogs; 14 left and 18 right), a bilateral flank laparotomy (3 dogs) or a midline celiotomy (1 dog).

Two dogs were euthanized during surgery because their tumours could not be resected. Eight dogs died from post‐operative complications. Pancreatic necrosis with peritonitis was the most common cause of death. Eight of the 26 dogs that survived had signs of recurrence of hyperadrenocorticism. Unsuppressible hyperadrenocorticism was found in four dogs; one dog had probably pre‐existent pituitary‐dependent hyperadrenocorticism, and adrenocortical function could not be re‐examined in the remaining three dogs.

Among the 37 tumours examined microscopically expansion of neoplastic tissue into blood vessels was found in 22 of them. Four adrenal glands with adrenocortical tumours also contained phaeochromocytomas. Necropsy was performed in eight dogs. Metastases were found in the lungs of two dogs and in the lungs and liver in one dog.

In combination with the data of previous reports, it is suggested that histological findings in surgery specimens are not good predictors for the clinical outcome.     

Adrenal Cortex of the Dog (Canis familiaris): I. Histomorphologic Changes during Growth,Maturity, and Aging1

The adrenal glands of 56 dogs ranging in age from birth to 13.6 years were examined for a determination of normal zonal and cellular morphology patterns throughout development, maturity and aging. Routine light microscopic techniques as well as lipid and cholesterol staining were used. The zona arcuata is described as developing between the fibrous and cellular layers of the capsule forming the cortical blastema layer, a zona biproliferativa. It is proposed that both centrifugal and centripetal migration of cortical parenchyma can result. The formation of accessory nodules is described as compensatory hyperplasia. Histomorphometric analysis revealed growth in the zona fasciculata to be by hyperplasia and the zonal volume percentages to be arcuata, 27%; fasciculata, 50%; reticularis, 23%.     

Quantitative CT assessment of bone mineral density in dogs with hyperadrenocorticism

Canine hyperadrenocorticism (HAC) is one of the most common causes of general osteopenia. In this study, quantitative computed tomography (QCT) was used to compare the bone mineral densities (BMD) between 39 normal dogs and 8 dogs with HAC (6 pituitary-dependent hyperadrenocorticism [PDH]; pituitary dependent hyperadrenocorticism, 2 adrenal hyperadrenocorticism [ADH]; adrenal dependent hyperadrenocorticism) diagnosed through hormonal assay. A computed tomogaraphy scan of the 12th thoracic to 7th lumbar vertebra was performed and the region of interest was drawn in each trabecular and cortical bone. Mean Hounsfield unit values were converted to equivalent BMD with bone-density phantom by linear regression analysis. The converted mean trabecular BMDs were significantly lower than those of normal dogs. ADH dogs showed significantly lower BMDs at cortical bone than normal dogs. Mean trabecular BMDs of dogs with PDH using QCT were significantly lower than those of normal dogs, and both mean trabecular and cortical BMDs in dogs with ADH were significantly lower than those of normal dogs. Taken together, these findings indicate that QCT is useful to assess BMD in dogs with HAC.     

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.     

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)     

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.     

Bald thigh syndrome of Greyhound dogs: gross and microscopic findings

Bald thigh syndrome (BTS) is a disease limited to Greyhound dogs. It is characterized clinically and grossly by bilateral hair loss on the lateral and caudal thighs. The cause of BTS is unknown but may be associated with hypothyroidism or hyperadrenocorticism. Samples of skin, thyroid glands, and adrenal glands from 43 Greyhound dogs with BTS were examined microscopically. Microscopic changes were characterized by dilatation of follicular infundibula, presence of catagen follicles and epidermal hyperplasia. Changes in the skin from these Greyhound dogs suggest an endocrinopathy as the cause; however, we were unable to confirm which one.     

INTRA‐ AND INTEROBSERVER VARIABILITY OF ULTRASONOGRAPHIC MEASUREMENTS OF THE ADRENAL GLANDS IN HEALTHY BEAGLES

The aim of the present study was to establish which adrenal gland measurement was characterized by the least variations. To do this, we quantified the variability of seven different size measurements of the canine adrenal gland (maximal length, maximal height at the cranial and caudal poles on longitudinal and transverse images, and maximal width of the cranial and caudal poles) within observer, between observer, and between dogs based on three different measurements made by each of the three observers in six healthy Beagle dogs. The height of the caudal pole of both adrenal glands measured on longitudinal images had the lowest intra‐ and interobserver variability, while measurements of the length had the highest intra‐ and interobserver variability. Other measurements that were characterized by low intra‐ and interobserver variability were: height and width of the caudal pole on transverse images and height of the cranial pole on longitudinal images only. These results provide a basis for further study of the changes in adrenal gland size in dogs with pituitary‐dependent hyperadrenocorticism.     

Adrenal and thyroid dysfunctions in experimental Trypanosoma congolense infection in cattle.

Severe pathological changes were observed in the adrenal and thyroid glands of Zebu (Bos indicus) heifers infected with Trypanosoma congolense. In the adrenal glands, severe inflammatory changes characterised by mononuclear cellular infiltration in the subcapsular areas, zona glomerulosa, zona fasciculata and zona reticularis were observed. In addition, there were hyperaemia, haemorrhage and hyperplasia resulting in increased adrenal weight in the two heifers slaughtered on Days 50 and 70 post-infection (p.i.). In the medullary areas of these two heifers, there was only mononuclear cellular infiltration. In the two heifers slaughtered on Day 113, localised mononuclear cellular infiltration was observed in addition to cortical cell depletion and fibrosis, resulting in reduced adrenal weight when compared with the controls. In the thyroid glands of the infected heifers, gross enlargement of the follicles filled with pale staining colloids were observed in association with squamous metaplasia of the follicular epithelium and fibroplasia. Serum cortisol concentrations showed an appreciable but non-significant increase (P less than 0.05) between Weeks 2 and 6 p.i. in the infected heifers (5.6 +/- 0.86 ng ml-1 vs. 4.4 +/- 0.34 ng ml-1) when compared with the uninfected controls or the pre-infection level. Thereafter, cortisol levels declined though non-significantly throughout the rest of the study. However, there was a steady increase towards normal levels from Week 12 p.i. until the end of the experiment. Changes in the basal serum concentrations of thyroxine (T4) were also measured weekly. There was a progressive decrease in the levels of T4 from the third until the 11th week p.i., when the decrease became significant (P less than 0.05) and remained so until the 16th week when the experiment ended.     

Hyperadrenocorticism in six cats

The case records of six cats with hyperadrenocorticism presented to the Department of Clinical Veterinary Medicine, University of Cambridge, over an 11-year period were reviewed. Signalment and clinical signs were similar to previous reports but, in contrast to other reports, only three cats had diabetes mellitus on presentation. Abdominal radiographs revealed an adrenal mass in one case, obesity in all cases but no hepatomegaly. The adrenal glands were identified ultrasonographically in three out of six cases. Clinicopathological findings were non-specific. The diabetic cats had a significantly lower serum potassium concentration than the non-diabetic cats (P<0·05). Results of adrenocorticotrophic hormone (ACTH) stimulation tests were supportive of a diagnosis of hyperadrenocorticism in the five cats in which they were performed. Five cats had pituitary-dependent hyperadrenocorticism (PDH) and one had an adrenal tumour. Differentiation between the two forms of hyperadrenocorticism was possible preoperatively in five out of six cats. Adrenal histopathology confirmed hyperplasia in four cats and adenocarcinoma in one cat. Three cats with PDH underwent bilateral adrenalectomy and two of these cats had low, flat ACTH stimulation tests postoperatively and survived for significant periods. The cat with an adrenal tumour underwent partial unilateral adrenalectomy, maintained a positive ACTH stimulation test postoperatively and was euthanased one week after surgery.     

Use of computed tomography adrenal gland measurement for differentiating ACTH dependence from ACTH independence in 64 dogs with hyperadenocorticism

Background: The measurement of adrenal gland size on computed tomography (CT) scan has been proposed for the etiological diagnosis of hyperadrenocorticism (HAC) in dogs. Symmetric adrenal glands are considered to provide evidence for ACTH‐dependent hyperadrenocorticism (ADHAC), whereas asymmetry suggests ACTH‐independent hyperadrenocorticism (AIHAC). However, there are currently no validated criteria for such differentiation. Objective: The aim of this retrospective study was to compare various adrenal CT scan measurements and the derived ratios in ADHAC and AIHAC cases, and to validate criteria for distinguishing between these conditions in a large cohort of dogs. Animals: Sixty‐four dogs with HAC (46 ADHAC, 18 AIHAC). Methods: Dogs with confirmed HAC and unequivocal characterization of its origin were included. Linear measurements of adrenal glands were made on both cross‐sectional and reformatted images. Results: An overlap was systematically observed between the AIHAC and ADHAC groups for all measurements tested. Overlaps also were observed for ratios tested. For the maximum adrenal diameter ratio derived from reformatted images (rADR), only 1/18 AIHAC dogs had a rADR within the range for ADHAC. For a threshold of 2.08, the 95% confidence intervals for estimated sensitivity and specificity extended from 0.815 to 1.000 and from 0.885 to 0.999, respectively, for AIHAC diagnosis. Conclusion and Clinical Importance: Measurements from cross‐sectional or reformatted CT scans are of little use for determining the origin of HAC. However, rADR appears to distinguish accurately between ADHAC and AIHAC, with a rADR > 2.08 highly suggestive of AIHAC.     

Computed tomographic adrenal gland quantification in canine adrenocorticotroph hormone-dependent hyperadrenocorticism

We conducted a retrospective study to determine whether multidetector computed tomography (CT) could be of value for adrenal gland assessment in dogs with pituitary-dependent hyperadrenocorticism. Adrenal gland attenuation and volume values of 49 dogs with hyperadrenocorticism were recorded and age, body weight, and gender were examined to determine if a relationship existed between these variables and adrenal gland morphology. There was not a statistically significant difference in mean X-ray attenuation of the left vs. right adrenal gland in normal dogs (35.3 +/- 6.1 HU), or in dogs with hyperadrenocorticism. The mean adrenal X-ray attenuation (+/- standard deviation [SD]) in dogs with microadenoma was 33.1 +/- 6.8 vs. 31.8 +/- 12.7 HU for dogs with macroadenoma, and these values were not statistically different. The mean volume of the left adrenal gland in normal dogs (0.59 +/- 0.17 cm3) was greater than that of the right adrenal gland (0.54 +/- 0.19 cm3) (P < 0.05). The mean CT volume (+/- SD) of the adrenal glands in dogs with microadenoma vs. macroadenoma were 1.60 +/- 1.25 vs. 2.88 +/- 1.60 cm3, respectively. There was no effect of age or gender on adrenal gland morphology or X-ray attenuation. The weight effect was the most important source of variation for the volume measurement in dogs with hyperadrenocorticism.     

Results of surgical treatment for hyperadrenocorticism caused by adrenocortical neoplasia in the dog: 25 cases (1980-1984)

Results of surgical treatment for neoplasia of the adrenal cortex that caused hyperadrenocorticism were evaluated in 25 dogs. Surgical examination of the adrenal glands was performed by use of a ventral midline approach in 24 dogs and a retroperitoneal approach in 1 dog. All 25 dogs had a unilateral, adrenocortical tumor. Histologic examination identified 14 adrenocortical carcinomas and 11 adenomas. Seven dogs with carcinoma had visible metastasis to the liver, 3 had local invasion into the caudal vena cava, and 1 had extension into the adjacent renal vein. Seven of the 9 dogs with metastasis were euthanatized at time of surgery. Of the remaining 18 dogs that survived surgery, 9 (4 with carcinoma and 5 with adenoma) developed serious postoperative complications including acute renal failure, pneumonia, and pulmonary artery thromboembolism; 8 of these dogs died or were euthanatized. Of the remaining 10 dogs, clinical signs associated with hyperadrenocorticism resolved in the 7 dogs that had adrenocortical adenoma and in 1 of the 3 dogs that had carcinoma. The remaining 2 dogs with carcinoma had persistent hyperadrenocorticism and were treated with high doses of mitotane. Although no response was observed in 1 dog with visible hepatic metastasis, a decrease in serum cortisol concentrations and resolution of clinical signs were detected in the other dog during prolonged daily administration of mitotane.     

Type 1 diabetes mellitus and hyperadrenocorticism in a ferret

Diabetes mellitus (DM) was diagnosed in a 6-year-old neutered male ferret with polyuria/polydipsia, symmetrical alopecia, and weight loss. Laboratory tests revealed severe hyperglycemia, glucosuria, and increased steroid hormone profile. Abdominal ultrasound revealed a bilateral enlargement of the adrenal glands. Significant clinical improvement was achieved with insulin- and leuprolide acetate-based therapy. After 2 months of therapy, the ferret showed a severe ketoacidosis, and the owner decided to euthanize the animal. Histological findings revealed carcinoma of the left adrenal cortex and cortical hyperplasia of the right adrenal gland. Moderate, chronic, and active pancreatitis with a marked decrease in the number of β-cells was also present. This is the first reported case of type 1 DM associated with hyperadrenocorticism and chronic pancreatitis in a ferret.

     

Evaluation of canine hyperadrenocorticism, using computed tomography

Abdominal computed tomography was performed in 9 dogs with hyperadrenocorticism and in 2 healthy dogs. Both adrenal glands were identified in all dogs. Computed tomography allowed accurate identification of the sites of adrenal gland dysfunction, when interpreted in combination with a biochemical diagnosis of canine hyperadrenocorticism. This accuracy permitted the retroperitoneal approach to be used for all adrenalectomies. Use of contrast medium (although not essential) was helpful in the computed tomographic identification of blood vessels, kidneys, and other abdominal organs.     

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.     

CHANGES IN ULTRASONOGRAPHIC APPEARANCE OF ADRENAL GLANDS IN DOGS WITH PITUITARY-DEPENDENT HYPERADRENOCORTICISM TREATED WITH TRILOSTANE

Trilostane, a 3beta-hydroxysteroid dehydrogenase inhibitor, has been used successfully over the last few years for the treatment of canine pituitary-dependent hyperadrenocorticism. In a prospective study of 19 dogs with pituitary-dependent hyperadrenocorticism, the adrenal glands were measured before and at least 6 months after initiation of trilostane therapy. Right adrenal gland length and caudal pole thickness and left adrenal gland caudal pole thickness increased significantly (p < or = 0.05); there was no significant change in left adrenal gland length. Enlargement of adrenal glands during trilostane therapy may occur as a result of suppression of the negative feedback mechanism affecting cortisol production.