Accuracy of Ultrasonographic Measurements of Adrenal Glands in Dogs: Comparison with Necroscopic Findings

Ultrasonographic evaluation of the adrenal glands was performed in 85 dogs, followed by macroscopic and histopathological examination either post‐mortem or after adrenalectomy. This retrospective cross‐sectional study evaluated the difference between gross and ultrasonographic measurements to determine the diagnostic accuracy of ultrasonography in the evaluation of canine adrenal gland size. The differences were assessed for gland length, thickness at cranial, middle and caudal regions, and surface area. In our sample, ultrasound error accuracy ranged between 0% in measurement of the right adrenal gland surface area and 25.21% for left cranial pole thickness. The parameters with minor errors were caudal pole thickness (3.64% right side and 3.49% left side) and length (5.75% right side and 2.19% left side). The ultrasonographic measurements generally underestimated the actual size of the adrenal glands. No statistically significant differences were observed for measurement errors between normal and pathological adrenal glands. This study confirmed that the caudal pole of both glands is the best parameter for ultrasonographic evaluation of normal and pathological adrenal glands size in dog. Furthermore, the surface area could be considered as a dimensional parameter for better assessment of the complex shape and the global aspect of the adrenal glands, while standardize ultrasonographic projections are needed to measure the cranial pole of both adrenal glands.     

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.     

Ultrasonographic Adrenal Gland Measurements in Healthy Yorkshire Terriers and Labrador Retrievers

An upper threshold of 7.4 mm for maximal adrenal gland diameter is commonly used to detect pituitary‐dependent hyperadrenocorticism ultrasonographically in dogs. There is a substantial overlap between adrenal gland diameter of healthy dogs and of those with pituitary‐dependent hyperadrenocorticism. The aim of this study is to determine the measurements of both adrenal glands, in particular, of the height at the caudal glandular pole in a longitudinal plane, in the Labrador retriever and Yorkshire terrier, two breeds widely represented in the population suspected of hyperadrenocorticism. Seventeen Labrador retrievers and 24 Yorkshire terriers considered healthy were included in the study. Adrenal gland measurements were taken on static images and comprised in measurements of the length in a longitudinal plane (L), of the height at the cranial (CrHLG) and caudal pole (CdHLG) in a longitudinal plane and in a transverse plane (CrHTR and CdHTR, respectively), and of the width at the cranial and caudal poles in a transverse plane (CrWTR and CdWTR, respectively). This study established new upper thresholds for the left and right height at the caudal pole measured in a longitudinal plane: 7.9 mm (left) and 9.5 mm (right) for the Labrador retrievers and 5.4 mm (left) and 6.7 mm (right) for the Yorkshire terriers. All the measurements were significantly different between the two breeds. There was a significant relationship between CdHTR and CdHLG, and the age of the dogs for both breeds.     

Histological evaluation of the adrenal glands of seven dogs with hyperadrenocorticism treated with trilostane

The lesions in the adrenal glands of seven dogs with hyperadrenocorticism that had been treated with trilostane were studied histologically. The glands of the six dogs with pituitary-dependent hyperadrenocorticism had moderate to severe cortical hyperplasia that was either diffuse or nodular. The lesions were more pronounced in the zona fasciculata than in the zona reticularis, and the zona glomerulosa was normal. In the dog with a functional adrenal tumour the non-tumour bearing adrenal gland showed mild nodular hyperplasia. Five of the seven dogs had variable degrees of adrenal necrosis, which was severe in two of them. The terminal deoxynucleotidyl transferase-mediated DUTP nick-end labelling (TUNEL) reaction specified areas of cell death as apoptosis in three of the dogs, and was positive in one of the dogs without visible areas of cell death. There were variable degrees of cortical haemorrhage in three of the dogs. In some of the dogs the lesions were severe enough to lead to hypoadrenocorticism.     

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.     

ULTRASONOGRAPHIC EVALUATION OF ADRENAL GLAND SIZE COMPARED TO BODY WEIGHT IN NORMAL DOGS

The accepted cut‐off value for adrenal gland maximum diameter of 0.74 cm to distinguish adrenal gland enlargement in dogs regardless of body weight may not be appropriate for small to medium breed dogs. The purpose of the current retrospective study was to examine adrenal gland dimensions as a function of body weight in healthy dogs in three weight categories (< 10 kg, 10–30 kg, and > 30 kg) representing small, medium, and large breeds, respectively, to establish greater confidence in determining if adrenal gland size is abnormal. The measurements of length (sagittal plane), cranial and caudal pole thickness (sagittal and transverse planes), and caudal pole width (transverse plane) of both adrenal glands were obtained ultrasonographically in clinically healthy dogs (n = 45) with 15 dogs in each weight group. Findings support our hypothesis that adrenal gland size correlates with body weight in normal dogs, and more precise reference intervals should be created for adrenal gland size by categorizing dogs as small, medium, or large breed. The caudal pole thickness of either adrenal gland in a sagittal plane was the best dimension for evaluating adrenal gland size based on low variability, ease, and reliability in measurement.     

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.     

Adrenal necrosis in a dog receiving trilostane for the treatment of hyperadrenocorticism

Clinical and biochemical changes suggestive of hypoadrenocorticism were observed in a 10-year-old male neutered Staffordshire bull terrier shortly after beginning therapy with trilostane for the treatment of hyperadrenocorticism. The dog's condition was stabilised with intravenous fluids, fludrocortisone and prednisolone. An exploratory laparotomy and excisional biopsy of the left adrenal gland were performed. Histopathological analysis showed adrenal cortical necrosis with reactive inflammation and fibrosis. Trilostane is a reversible inhibitor of steroid synthesis and this complication has not been reported previously. Clinicians should be aware that trilostane therapy may result in adrenal necrosis but that prompt treatment might correct a life-threatening situation.     

Adrenocorticotropic hormone, but not trilostane, causes severe adrenal hemorrhage, vacuolization, and apoptosis in rats

Adrenal necrosis has been reported as a complication of trilostane application in dogs with hyperadrenocorticism. One suspicion was that necrosis results from the increase of adrenocorticotropic hormone (ACTH) during trilostane therapy. The aim of the current study was to assess the effects of ACTH and trilostane on adrenal glands of rats. For experiment 1, 36 rats were divided into 6 groups. Groups 1.1 to 1.4 received ACTH in different doses (60, 40, 20, and 10 μg/d) infused subcutaneously with osmotic minipumps for 16 wk. Group 1.5 received saline, and group 1.6 received no therapy. For experiment 2, 24 rats were divided into 3 groups. Group 2.1 and 2.2 received 5 and 50 mg/kg trilostane/d orally mixed into chocolate pudding for 16 wk. Eight control rats received pudding alone. At the end of the experiments, adrenal glands were assessed for necrosis by histology and immunohistochemistry; levels of endogenous ACTH and nucleosomes were assessed in the blood. Rats treated with 60 μg ACTH/d showed more hemorrhage and vacuolization and increased numbers of apoptotic cells in the adrenal glands than rats treated with 20 or 10 μg ACTH/d, trilostane, or control rats. Rats treated with 60 μg ACTH/d had a higher amount of nucleosomes in the blood compared with rats treated with 10 μg ACTH/d, trilostane, or saline. We conclude that in healthy rats ACTH, but not trilostane, causes adrenal degeneration in a dose-dependent manner. Results of this study support the hypothesis that adrenal gland lesions seen in trilostane-treated dogs are caused by ACTH and not by trilostane.     

TRANSRECTAL ULTRASONOGRAPHY OF THE LEFT ADRENAL GLAND IN HEALTHY HORSES

Little information is available on medical imaging of the adrenal glands in horses. We investigated the feasibility of transrectal ultrasonography to characterize the normal equine adrenal gland. Transrectal ultrasonography was performed in 25 healthy horses using a 7.5 MHz linear array probe at a displayed depth of 8 cm. Transrectal ultrasonography of the right adrenal gland was not feasible. For the left adrenal gland, the left kidney, the abdominal aorta, the left renal artery, the left renal vein, and the cranial mesenteric artery were used as landmarks. The size of the left adrenal gland was variable, but it generally appeared as a long, flat structure with a hyperechoic medulla surrounded by a hypoechoic cortex. The most cranial part of the gland could not be delineated appropriately in 11 horses (44%). The mean (±SD) thickness of the gland and medulla was 0.66±0.15 cm (n=25) and 0.28±0.09 cm (n=25) near the caudal pole, 0.87±0.25 cm (n=14) and 0.40±0.18 cm (n=12) near the cranial pole, and 0.89±0.18 cm (n=25) and 0.36±0.13 cm (n=25) in the middle of the gland, respectively. The mean (±SD) length of the entire adrenal gland and of the medulla was 6.22±0.77 cm (n=14) and 5.45±0.71 cm (n=6), respectively. Transrectal ultrasonography allowed adequate visualization of the left adrenal gland in horses.     

Medical management of pituitary-dependent hyperadrenocorticism: mitotane versus trilostane

Pituitary-dependent hyperadrenocorticism is a common endocrine disorder in dogs in the United States. Once a diagnosis is established, a decision must be made whether or not to pursue treatment, and if so, which medication to use. Historically, mitotane (Lysodren, o,p'-DDD, Bristol-Myers Squibb, New York) has been the most commonly used treatment for medical management. Its use is complicated and comes with many potential side effects, making many practitioners wary of its use. Recently, trilostane has been proven to be an effective treatment of pituitary-dependent hyperadrenocorticism and is approved for use in other countries. Treatment with trilostane is somewhat simpler and the incidence of side effects seems to be less when compared with mitotane therapy. Either treatment can be a safe and effective method of treatment for pituitary-dependent hyperadrenocorticism when the practitioner and client are well educated regarding their use and an appropriate monitoring protocol is used.     

Ultrasonographic evaluation of the adrenal glands in six dogs with hypoadrenocorticism.

The purpose of this study was to determine the value of ultrasonographic characterization of the adrenal glands in dogs with hypoadrenocorticism. Measurements of adrenal glands were obtained in six dogs with hypoadrenocorticism. The adrenal glands on both sides were shorter (range: left adrenal gland length, 10.0 to 19.7 mm; right adrenal gland length, 9.5 to 18.8 mm) and thinner (range: left adrenal gland thickness, 2.2 to 3.0 mm; right adrenal gland thickness, 2.2 to 3.4 mm) than in normal dogs (range: left adrenal gland length, 13.2 to 26.3 mm; right adrenal gland length, 12.4 to 22.6 mm; left adrenal gland thickness, 3.0 to 5.2 mm; right adrenal gland thickness, 3.1 to 6.0 mm). Statistical analysis revealed a significant reduction in size of the left adrenal gland (p less than 0.05) in dogs with hypoadrenocorticism compared to the left adrenal gland in normal dogs. The results of this study show that atrophy of the adrenal glands in dogs with hypoadrenocorticism seems to lead to an ultrasonographic-measurable reduction in size of the adrenal glands.     

Long-term outcome of domestic ferrets treated surgically for hyperadrenocorticism: 130 cases (1995-2004)

OBJECTIVE: To determine the long-term survival rate and factors that affect survival time of domestic ferrets treated surgically for hyperadrenocorticism. STUDY DESIGN: Retrospective case series. ANIMALS: 130 ferrets with hyperadrenocorticism that were treated surgically. PROCEDURES: Medical records of ferrets surgically treated for hyperadrenocorticism were reviewed. Data recorded included signalment, duration of clinical signs prior to hospital admission, CBC values, serum biochemical analysis results, anesthetic time, surgical time, concurrent diseases, adrenal gland affected (right, left, or both [bilateral]), histopathologic diagnosis, surgical procedure, caudal vena caval involvement (yes or no), postoperative melena (yes or no), days in hospital after surgery, and whether clinical signs of hyperadrenocorticism developed after surgery. RESULTS: 130 ferrets were entered in the study (11 of 130 ferrets were admitted and underwent surgery twice). The 1- and 2-year survival rates were 98% and 88%, respectively. A 50% survival rate was never reached. Combined partial adrenal gland resection with cryosurgery had a significantly negative effect on survival time. No other risk factors were identified. Survival time was not significantly affected by either histopathologic diagnosis or specific affected adrenal gland (right, left, or bilateral). CONCLUSIONS AND CLINICAL RELEVANCE: Ferrets with adrenal gland masses that were treated surgically had a good prognosis. Survival time of ferrets with hyperadrenocorticism undergoing surgery was not affected by the histologic characteristic of the tumor, the adrenal glands affected (right, left, or bilateral), or complete versus partial adrenal gland resection. Debulking was a sufficient surgical technique to allow a favorable long-term outcome when complete excision was not possible.     

Medical Management of Pituitary-Dependent Hyperadrenocorticism: Mitotane versus Trilostane

Pituitary-dependent hyperadrenocorticism is a common endocrine disorder in dogs in the United States. Once a diagnosis is established, a decision must be made whether or not to pursue treatment, and if so, which medication to use. Historically, mitotane (Lysodren, o,p'-DDD, Bristol-Myers Squibb, New York) has been the most commonly used treatment for medical management. Its use is complicated and comes with many potential side effects, making many practitioners wary of its use. Recently, trilostane has been proven to be an effective treatment of pituitary-dependent hyperadrenocorticism and is approved for use in other countries. Treatment with trilostane is somewhat simpler and the incidence of side effects seems to be less when compared with mitotane therapy. Either treatment can be a safe and effective method of treatment for pituitary-dependent hyperadrenocorticism when the practitioner and client are well educated regarding their use and an appropriate monitoring protocol is used.     

Persistent isolated hypocortisolism following brief treatment with trilostane

A 12‐year‐old male neutered Miniature Poodle with confirmed pituitary‐dependent hyperadrenocorticism was treated with trilostane. After three doses, it developed clinical and laboratory changes suggestive of isolated hypocortisolism (‘atypical hypoadrenocorticism’), which persisted and progressed for more than 3 months despite immediate withdrawal of the trilostane. The clinical signs of hyperadrenocorticism resolved without further trilostane. After 3 months, prednisolone treatment was started and the clinical signs of hypocortisolism resolved. Prednisolone therapy was required for more than 1 year. Ultrasonography initially demonstrated large hypoechoic adrenal cortices, typical of dogs with hyperadrenocorticism, which then became small and heteroechoic, consistent with the development of adrenal necrosis. Persistent isolated hypocortisolism has not been reported previously as a complication of trilostane therapy. The case is also remarkable for the very short duration of trilostane therapy that elicited this complication. Clinicians should be aware that trilostane therapy may result in adrenal necrosis, even in the very earliest stages of therapy, but prompt action can prevent a life‐threatening situation.     

Trilostane treatment in dogs with pituitary-dependent hyperadrenocorticism

OBJECTIVE: To evaluate the efficacy of trilostane in treating dogs with pituitary-dependent hyperadrenocorticism. DESIGN: Prospective clinical trial using client-owned dogs with pituitary-dependent hyperadrenocorticism treated at University Veterinary Centre, Sydney from September 1999 to July 2001. PROCEDURE: Thirty dogs with pituitary-dependent hyperadrenocorticism treated with trilostane, a competitive inhibitor of 3beta-HSD, were monitored at days 10, 30 and 90 then 3-monthly by clinical examination, tetracosactrin stimulation testing, urinary corticoid:creatinine ratio measurement and by client questionnaire. RESULTS: Twenty-nine of 30 dogs were successfully treated with trilostane (median dose 16.7 mg/kg; range 5.3 to 50 mg/kg, administered once daily); one responded favourably but died of unrelated disease before full control was achieved. CONCLUSION: Trilostane administration controlled pituitary-dependent hyperadrenocorticism in these dogs. It was safe, effective and free of side-effects at the doses used. Most dogs were initially quite sensitive to the drug for 10 to 30 days, then required higher doses until a prolonged phase of stable dose requirements occurred. Urinary corticoid:creatinine ratio was useful in assessing duration of drug effect. Some dogs treated for more than 2 years required reduction or temporary cessation of drug because of iatrogenic hypoadrenocorticism.     

Ultrasonographic measurements of adrenal glands in cats with hyperthyroidism

Feline hyperthyroidism is potentially associated with exaggerated responsiveness of the adrenal gland cortex. The adrenal glands of 23 hyperthyroid cats were examined ultrasonographically and compared to the adrenal glands of 30 control cats. Ten hyperthyroid cats had received antithyroid drugs until 2 weeks before sonography, the other 13 were untreated. There was no difference in adrenal gland shape between healthy and hyperthyroid cats: bean-shaped, well-defined, hypoechoic structures surrounded by a hyperechoic halo in 43/60 (71.6%) healthy cats and 34/46 (73.9%) hyperthyroid cats; more ovoid in 13/60 (21.6%) healthy cats and 9/46 (19.6%) hyperthyroid cats while more elongated in 4/60 (6.7%) healthy cats, 3/46 (6.5%) hyperthyroid cats. Hyperechoic foci were present in 9/23 (39.1%) hyperthyroid cats and 2/30 (6.7%) healthy cats. The adrenal glands were significantly larger in hyperthyroid cats, although there was overlap in size range. The mean difference between hyperthyroid cats and healthy cats was 1.6 and 1.7 mm in left and right adrenal gland length, 0.8 and 0.9 mm in left and right cranial adrenal gland height, and 0.4 and 0.9 mm in left and right caudal adrenal gland height. There was no significant difference between the adrenal gland measurements in treated and untreated hyperthyroid cats. The adrenomegaly was most likely associated with the hypersecretion of the adrenal cortex documented in hyperthyroid cats. Hyperthyroidism should be an alternative to hyperadrenocorticism, hyperaldosteronism, and acromegaly in cats with bilateral moderate adrenomegaly.     

Effects of mitotane therapy in dogs with pituitary dependent Cushing syndrome on the adrenal gland size--an ultrasonographic study]

The effect of mitotane therapy on adrenal gland size was evaluated in 13 dogs with pituitary dependent hyperadrenocorticism. Ultrasonographic measurements were obtained before and during mitotane therapy. During therapy both adrenal glands were shorter and thinner (median during therapy: left adrenal gland 19.4 mm long, 5.4 mm thick, right adrenal gland 18.1 mm long, 6.1 mm thick) than before mitotane therapy (median before therapy: left adrenal gland 23.6 mm long, 8.3 mm thick, right adrenal gland 21.6 mm long, 8.1 mm thick). Statistical evaluation showed a significant reduction in size. But ultrasonographic measurement of adrenal gland size is not useful in the evaluation of adrenal reserve during mitotane therapy. Inadequate adrenal reserve was not identified and adrenal size measurement by ultrasonography was not helpful to differentiate adequate and inadequate control of adrenal cortisol secretion during mitotane therapy.     

ADRENAL ULTRASONOGRAPHY CORRELATED WITH HISTOPATHOLOGY IN FERRETS

The adrenal glands of twenty-six, 12-to 53-month-old, ferrets without clinical signs of adrenal disease were examined and measured by ultrasonography and the findings compared with those from gross examination and histopathology. Of 51 adrenal glands examined, 27 were normal, 23 had either nodular or diffuse cortical hyperplasia and 1 had an adenocarcinoma. There was no statistically significant difference between the sonographic nor gross size of normal adrenal glands and those with hyperplasia. Moderate correlation was found between gross and sonographic measurements of length for both right (r=0.783; p<0.0001) and left (r=0.609; p<0.001) adrenal glands; however, the sonographic measurements were less than the gross measurements. Correlation was found between the sex and weight of the ferret and adrenal gland length (p<0.01) and width (p<0.02). In female ferrets, the length, width, and depth of the right adrenal gland sonographically measured (mean±sd) 7.5±1.2 mm, 3.7±0.6 mm, 2.8±0.4 mm, respectively, and the left measured 7.4±1.0 mm, 3.7±0.4 mm, 2.8±0.4 mm; in males, the right adrenal measured 8.9±1.6 mm, 3.8±0.6 mm, 3.0±0.8 mm and the left measured 8.6±1.2 mm, 4.2±0.6 mm, 3.0±0.6 mm. Accessory adrenal tissue was not identified during the sonographic examination but was grossly found in 10 of the ferrets. It was associated with either the right, left or both adrenal glands.     

ULTRASONOGRAPHY OF ADRENAL GLANDS IN NORMAL FERRETS

The adrenal glands of 20 normal ferrets were imaged with ultrasound. Of the forty glands, only 4 (three right and one left) could not be clearly identified. Mean (±standard deviation) dimensions of the right (7.6 ± 1.8 mm length by 2.6 ± 0.4 mm width) and left (7.2 ± 1.8 mm length by 2.8 ± 0.5 mm width) glands were similar. Both adrenal glands were wider (p<0.05) sonographically in males than females. Measured length and width of the right gland positively correlated (p<0.05) with body weight. The glands had a hypoechoic outer zone and hyperechoic central region, were elongate to avoid in shape and located medial and, variably, at the level of the cranial pole of the ipsilateral kidney. This study demonstrates that normal adrenal glands can be imaged in ferrets.