Pathological Findings in the Adrenal Glands of 80 Dogs

Background: The adrenal glands development important endocrine functions and can be affected by primary or secondary diseases. These adrenal gland pathologies may induce clinical syndromes resulting from abnormalities in the production and secretion of hormones. Data about pathological changes in dogs are scarce. Therefore, the aim of the present study was to identify and evaluate the histopathological and epidemiological features of adrenal changes in dogs submitted to necropsy examination from 2005 to 2016 in a Veterinary Teaching Hospital, Londrina, Paraná, Brazil.Material, Methods & Results: During this period, 80 animals presented alterations of adrenal gland, representing 5.5% of all necropsied dogs. The pure breed dogs representing 58.6% and mixed breed 41.4%; 53.4% were female and 46.6% were male. The non-neoplastic adrenal lesions were more frequently (57.5%) compared to the neoplastic changes (42.5%). Most of the adrenal glands lesions occurred in older dogs (60%), following by the middle aged (31.25%) and young dogs (8.75%). The main non-neoplastic lesions observed in the adrenal glands were of hyperplastic (69.5%) and circulatory (26%) origin, among the earlier, 68.8% were diffuse hyperplasia and 31.2% nodular hyperplasia. The nodular hyperplasia was classified as micronodular multifocal in 40% of the glands with nodular hyperplasia, macronodular multifocal in 30%, micronodular diffuse in 20%, and micronodular focal in 10%. The neoplasms observed were adrenocortical adenoma (ACA) in 44.1%, pheochromocytomas in 23.5% and adrenocortical carcinomas (ACC) in 11.7% of the dogs with adrenal tumors. Metastasis from other primary tumors were observed in 20.6%.Discussion: The data in veterinary literature about the frequency of changes in adrenal gland of dogs are scarce and focus features of diagnosis by ultrasound examination. Most of the adrenal changes observed in the present study were incidental findings observed during the necropsy examination and no specific clinical signs were observed. Non-neoplastic adrenal lesions, mainly of hyperplastic origin, were more frequently observed compared to the neoplastic changes. Differing from previous studies, the diffuse hyperplasia was the most common non neoplastic finding in the adrenal glands. Considering the subclassification of nodular hyperplasia, the multifocal micronodular and macronodular multifocal pattern were the most frequent. In veterinary literature, there are no data about frequency of nodular hyperplastic subtypes. However, in humans the subclassification of nodular hyperplasia is associated to development of endocrine disorders. Previous studies reported lower incidence of neoplastic changes in adrenal gland of dogs compared to the present results. The adrenocortical adenoma was the most common primary tumor, followed by the adrenocortical carcinoma, pheochromocytoma and adrenocortical carcinoma. Congestion and hemorrhage were common findings observed in the adrenal gland primary tumors. On the other hand, necrosis and inflammatory infiltrate were observed only in the adrenocortical carcinomas. These histopathological features may be used as tool in the differential diagnosis between well differentiated adrenocortical carcinoma and adenoma. The histopathological examination was fundamental to differential and definitive diagnosis of all canine adrenal gland disorders observed.

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A case of behavioral changes in a castrated male cat due to a functional adrenocortical adenoma producing testosterone and androstenedione

Journal of Feline Medicine and Surgery Open Reports ◽

10.1177/2055116920981247 ◽

2021 ◽

Vol 7 (1) ◽

pp. 205511692098124

Author(s):

Archivaldo Reche Junior ◽

Daniela Ramos ◽

Mariana Ferreira ◽

Luís Artur GP da Silva ◽

Yumi Hirai ◽

...

Keyword(s):

Adrenal Gland ◽

Sex Hormones ◽

Adrenal Tumor ◽

Histopathological Examination ◽

Clinical Signs ◽

Behavioral Changes ◽

Adrenal Tumors ◽

Adrenocortical Adenoma ◽

Abdominal Ultrasonography ◽

Case Summary

Case summary This case report describes a 9-year-old neutered male cat with a functional adrenal tumor showing aggression toward other cats in the household, excessive meowing and urine spraying. The diagnosis was made based on the clinical signs, an enlarged right adrenal gland on ultrasound, penile spines and elevated sex hormones on an adrenocorticotropic hormone stimulation test. The cat was submitted to celiotomy and adrenalectomy. Histopathological examination confirmed the adrenocortical adenoma. Three months after surgery the penile spines disappeared and urine spraying, as well as excessive meowing, had greatly decreased; however, aggressive behavior took much longer to stop and required behavior therapy. Relevance and novel information Functional adrenal tumors producing only sex hormones and behavioral changes are uncommon. The cat reported herein started showing behavioral changes before spines appeared on the penis, and structural alterations in the adrenal gland at the abdominal ultrasonography were detected. Considering all the possible implications resulting from severe behavior problems such as cat–cat aggression, from a permanent separation of the cats to relinquishment, a detailed investigation of underlying medical mechanisms in these animals is crucial from the start. Examinations may need to be repeated later in the course.

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Properties of partially purified thymidine kinase in adrenal tissue of hyperplasia, adenomatous hyperplasia, adenoma and carcinoma of patients with Cushing's syndrome.

Acta Endocrinologica ◽

10.1530/acta.0.0930208 ◽

1980 ◽

Vol 93 (2) ◽

pp. 208-215 ◽

Cited By ~ 3

Author(s):

Hajime Nawata ◽

Ken-ichi Kato ◽

Hiroshi Ibayashi

Keyword(s):

Adrenal Gland ◽

Thymidine Kinase ◽

Cushing’S Syndrome ◽

Adrenocortical Carcinoma ◽

Catalytic Properties ◽

Deae Cellulose ◽

Cushing's Syndrome ◽

Adrenocortical Adenoma ◽

Adenomatous Hyperplasia ◽

Adrenocortical Hyperplasia

Abstract. Thymidine kinase (TK) was partially purified from adrenal tissues with adrenocortical hyperplasia, adenomatous hyperplasia, adenoma and carcinoma from patients with Cushing's syndrome and from normal adrenal glands. Adrenocortical carcinoma, adenoma, hyperplasia and nodule and hyperplastic portion of adenomatous hyperplasia contained higher concentration of TK than normal adrenal gland. By DEAE-cellulose column chromatography, adrenocortical carcinoma gave two peaks (Peak I and Peak II) of TK, while in other adrenal tissues the second peak (Peak II) was only slightly detected or hardly detected. TK in all these tissues was identical with respect to pH optimum, metal requirement and inhibition by dTTP. dCTP inhibited TK activities of normal adrenal gland and the hyperplastic portion of adenomatous hyperplasia by 55%, respectively, but hardly affected the activity of the nodule of adenomatous hyperplasia, adenoma, hyperplasia and carcinoma. TK from hyperplastic portion of adenomatous hyperplasia showed the intermediate heat stability between the heat-stable enzyme from normal adrenal gland and the heat-labile enzyme from adrenocortical carcinoma, adenoma, hyperplasia and the nodule of adenomatous hyperplasia. The apparent Km for thymidine from adenocortical carcinoma (Peak I and Peak II) was 5.0 and 11.1; adenoma, 4.8; hyperplasia, 5.5; adenomatous hyperplasia (nodule, 5.0 and hyperplastic portion, 19.8) and normal adrenal gland, 25.0 μm. These observations indicated that TK with different catalytic properties existed in various human adrenal tissues. They also demonstrated that TK isolated from the nodule of adrenocortical adenomatous hyperplasia had similar properties as adrenocortical adenoma, while TK from the hyperplastic portion had the intermediate catalytic properties between normal adrenal gland and adrenocortical hyperplasia.

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Clinical and Pathological Features of Canine Metastatic Adrenocortical Carcinoma

Acta Scientiae Veterinariae ◽

10.22456/1679-9216.84453 ◽

2016 ◽

Vol 44 (1) ◽

pp. 5

Author(s):

Elisângela Olegário Da Silva ◽

Ana Paula Frederico Rodrigues Loureiro Bracarense

Keyword(s):

Adrenal Gland ◽

Adrenocortical Carcinoma ◽

Histopathological Examination ◽

Periodic Acid ◽

Abdominal Cavity ◽

Clinical Signs ◽

Histopathological Diagnosis ◽

Adrenocortical Hormones ◽

Mixed Breed ◽

Well Differentiated

Background: Adrenocortical carcinomas (ACC) are uncommon in dogs. ACC often invade the posterior vena cava wall and the advential layer of the abdominal aorta; however, metastases to distant organs are rare. Most dogs with ACC show clinical signs of Cushing`s syndrome in a similar way with signs reported in humans. The aim of this study is to report three cases of metastatic ACC in dogs and their clinical and pathological features.Cases: This report describes three cases of metastatic adrenocortical carcinoma (ACC) in dogs diagnosed post mortem through histopathological examination. The animals presented no signs of adrenal hormones overproduction. Case 1. A 13-year-old intact, mixed breed female dog was presented with a history of progressive hepatomegaly during the last four months. The animal was submitted to an exploratory laparotomy, but due to anesthetic complications no tissue specimen was sampled and after one week, the animal died. The necropsy examination showed an increased left adrenal (3 cm in diameter), multiple yellow to whitish nodules measuring 1 to 2 cm of diameter in the lung and severe hepatomegaly. The histopathological diagnosis was established as ACC with pulmonary metastasis. A severe and diffuse accumulation of glycogen in hepatocytes was also observed in Periodic acid-Schiff (PAS) staining. Case 2. A 9-year-old female intact, mixed breed dog was presented showing ataxia, left head-tilt and dyspnoea. The clinical signs progressed and the dog died after four days. The gross examination showed a diffuse increase of the left adrenal gland (2 cm of diameter) accompanied by a yellowish colour at cut surface; diffuse bronchopneumonia and cerebral and renal discrete congestion. The microscopical diagnosis was ACC with kidney and CNS metastasis. Case 3. A 16-year-old male, intact, Poodle dog was presented with apathy, anorexia, vomiting and diarrhoea in the last two days. The animal was submitted to treatment, but the clinical signs progressed and the dog died. In the necropsy exam an increased right adrenal gland was observed (5 cm of diameter) showing multiple yellowish nodules when sectioned. The lung showed multiple whitish nodules mainly in pleural region. In the histopathological examination, the definitive diagnosis was ACC with pulmonary metastasis.Discussion: Most of adrenocortical tumours in dogs are functional and secrete excessive amounts of cortisol; therefore commonly animals show clinical signs of Cushing`s syndrome. In the present cases, the animals showed no clinical evidence of hormonal changes. Well-differentiated neoplastic cells were observed in cases 1 and 2, whereas in case 3 tumorous cells showed marked features of malignancy as cellular pleomorphism, binucleation, high mitotic index and atypical mitosis. Despite mild anaplastic features observed on cases 1 and 2, animals showed focus of metastases in lung, kidney and CNS. Apparently features of malignancy in ACC were not associated to the risk of metastasis development, indicating that even well-differentiated ACC may metastasize to distant organs. Metastases of ACC to distant sites are rare in dogs and there was no previous report of metastasis to CNS as observed in case 2. Canine ACC are considered uncommon tumours, however, they should be included in the differential diagnosis of mass in the abdominal cavity since the animals may show no clinical signs of adrenocortical hormones overproduction.Keywords: adrenal tumours, adrenocortical hormones, metastases, dog.

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

Journal of the American Animal Hospital Association ◽

10.5326/15473317-35-3-193 ◽

1999 ◽

Vol 35 (3) ◽

pp. 193-199 ◽

Cited By ~ 49

Author(s):

A Hoerauf ◽

C Reusch

Keyword(s):

Adrenal Gland ◽

Adrenal Glands ◽

Adrenal Tumors ◽

Ultrasonographic Examination ◽

Adrenocortical Tumors ◽

Normal Shape ◽

Bilateral Adrenal Tumors ◽

Gland Enlargement

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.

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Adrenal Pheochromocytoma With Contralateral Adrenocortical Adenoma in a Cat

Journal of the American Animal Hospital Association ◽

10.5326/0460036 ◽

2010 ◽

Vol 46 (1) ◽

pp. 36-42 ◽

Cited By ~ 25

Author(s):

Jon David R. Calsyn ◽

Rebecca A. Green ◽

Garrett J. Davis ◽

Christopher M. Reilly

Keyword(s):

Adrenal Gland ◽

Low Dose ◽

Clinical Signs ◽

Adrenocortical Adenoma ◽

Left Adrenal Gland ◽

Adrenal Pheochromocytoma ◽

History Of ◽

Suppression Test ◽

The Right ◽

Dexamethasone Suppression

A 7-year-old, neutered male cat was presented with a 6-month history of progressive polyuria, polydipsia, polyphagia, aggression, and weight gain. Previous blood work, urinalysis, and radiographs did not delineate a cause for the clinical signs. An ultrasound revealed bilateral adrenal gland enlargement. A low-dose dexamethasone suppression test was consistent with hyperadrenocorticism. Based on these findings, bilateral adrenalectomy was attempted and successfully performed. Histopathology was consistent with a cortical adenoma in the right adrenal gland and a pheochromocytoma in the left adrenal gland. This association has never been reported in the cat.

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Incidence of adrenal gland tumor as a second primary malignancy: SEER-based study

Endocrine Connections ◽

10.1530/ec-18-0304 ◽

2018 ◽

Vol 7 (10) ◽

pp. 1040-1048 ◽

Cited By ~ 1

Author(s):

Wafaa M Rashed ◽

Anas Saad ◽

Muneer Al-Husseini ◽

Ahmed Mahmoud Galal ◽

Assem Mohamed Ismael ◽

...

Keyword(s):

Adrenal Gland ◽

Cancer Treatment ◽

The United States ◽

Adrenal Tumors ◽

Second Primary ◽

Gland Tumor ◽

Second Primary Malignancy ◽

Primary Malignancy ◽

Primary Tumors ◽

Cancer Networks

Purpose Advances in cancer treatment achieved during the past decades have resulted in increased survival of most pediatric and adult patients that suffered from different adrenal tumor types. This article reviews the incidence and survival of adrenal gland tumors as second primary tumors, according to data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods The SEER 13 Registries Database from 1992 to 2013 was used. All primary cancer sites were selected using the multiple primary standardized incidence ratios (MP-SIR) session. Results Data for a total of 2,887,468 persons with cancer were reviewed; 117 of whom had suffered second primary adrenal tumors. The overall SIR of adrenal gland tumor as a second primary was 1.5. A high incidence ratio of the event was detected in specific primary tumor sites: hypopharynx (observed/expected (O/E) = 44.6); other endocrine tissue (including the thymus) (O/E = 38.3); small intestine (O/E = 8.9); liver (O/E = 8.7); stomach (O/E = 5); nodal NHL (O/E = 3.8); kidney and renal pelvis (O/E = 3.2) and breast (O/E = 1.8). Conclusion The underlying shared mechanisms should be investigated between adrenal tumors and hypopharyngeal, endocrine and other tumors. Racial disparity is an important challenge in cancer treatment at the United States and should be taken into consideration in the design of cancer prevention programs. This could be achieved through follow-up programs at specialized national cancer networks, especially for rare tumors like adrenal gland.

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Autogenous transplants of adrenal fragments in an animal model.

Polish Journal of Surgery ◽

10.5604/01.3001.0011.8178 ◽

2018 ◽

Vol 90 (4) ◽

pp. 23-28 ◽

Cited By ~ 1

Author(s):

Agnieszka Dworzyńska ◽

Katarzyna Paduszyńska ◽

Lech Pomorski

Keyword(s):

Adrenal Gland ◽

Adrenal Insufficiency ◽

Adrenal Glands ◽

Bilateral Adrenalectomy ◽

Adrenal Tumors ◽

Human Beings ◽

Sprague Dawley ◽

The Third ◽

Sprague Dawley Rats ◽

New Treatment

Introduction Adrenal insufficiency is a typical complication after surgical treatment of adrenal tumors, especially after the removal of both adrenal glands. Human beings are not able to survive without adrenal glands and without proper hormonal substitution. Autotransplantation of a fragment of the adrenal gland may prevent this complication. This can be done by transplanting the entire adrenal glands or its fragment, such as the adrenal cortex cells. In the case of adrenal tumors, the entire adrenal gland can not be transplanted. However, it is possible to transplant cells from the tumor-free part. Succesful adrenal autografts may result in a new treatment of adrenal insufficiency. Materials and Methods: Autograft transplantation was performed on 3 groups of Sprague Dawley rats. In the first group, physiological corticosterone concentrations were determined. These animals were not operated. In the second group, both adrenal glands were removed. Corticosterone concentrations were determined after bilateral adrenalectomy. The third group was divided into two parts. In the first subgroup, bilateral adrenalectomy was performed simultaneosly with adrenal transplant into the omentum. In the second subgroup, right adrenalectomy was performed simultaneosly with and adrenal transplant into the omentum followed a month later by left adrenalectomy. During the experiment, corticosterone concentrations were measured at 4 time points. Results. The statistical difference between corticosterone concentrations in rats after two timed adrenalectomies and rats after bilateral adrenalectomy was statistically different, but these results were far from physiological concentrations.

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Adrenal gland tumours. Different clinical presentations in three dogs: a case report

Veterinární Medicína ◽

10.17221/6919-vetmed ◽

2013 ◽

Vol 58 (No. 7) ◽

pp. 377-384

Author(s):

A. Loste ◽

M. Borobia ◽

D. Lacasta ◽

M. Carbonell ◽

...

Keyword(s):

Adrenal Gland ◽

Clinical Presentation ◽

Imaging Techniques ◽

Clinical Signs ◽

Metastatic Lesion ◽

Adrenocortical Adenoma ◽

Imaging Studies ◽

Clinical Presentations ◽

Different Types ◽

Diagnostic Imaging Techniques

Three dogs were evaluated due to the presence of unilateral adrenal gland masses with or without clinical signs. Case 1 showed a unilateral non-functional adrenocortical adenoma, discovered accidentally while Case 2 presented a unilateral cortisol-secreting adrenocortical adenoma; a pheochromocytoma was accidentally discovered in Case 3. The adrenalectomy was the treatment of choice in all cases. The development of diagnostic imaging techniques, mainly ultrasonography, and its application to routine abdominal examinations, have allowed the detection of adrenal gland masses more frequently. However, there is no pattern of echogenicity or architecture which would help in the differentiation in a functional tumour from a non-functional tumour, a pheochromocytoma, a metastatic lesion to the adrenal or a granuloma. A complete description of history, clinical signs, laboratory analysis and imaging studies is included. Moreover, a revision of the different types of adrenal gland tumours, with their clinical presentation, a standardised diagnosis protocol and options for treatment are discussed.  

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Interplay between glucocorticoids and tumor-infiltrating lymphocytes on the prognosis of adrenocortical carcinoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2019-000469 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000469 ◽

Cited By ~ 5

Author(s):

Laura-Sophie Landwehr ◽

Barbara Altieri ◽

Jochen Schreiner ◽

Iuliu Sbiera ◽

Isabel Weigand ◽

...

Keyword(s):

Overall Survival ◽

T Cells ◽

Adrenocortical Carcinoma ◽

T Helper Cells ◽

Checkpoint Inhibitors ◽

Cytotoxic T Cells ◽

Adrenal Tumors ◽

T Helper ◽

Primary Tumors ◽

Helper Cells

BackgroundAdrenocortical carcinoma (ACC) is a rare endocrine malignancy. Tumor-related glucocorticoid excess is present in ~60% of patients and associated with particularly poor prognosis. Results of first clinical trials using immune checkpoint inhibitors were heterogeneous. Here we characterize tumor-infiltrating T lymphocytes (TILs) in ACC in association with glucocorticoids as potential explanation for resistance to immunotherapy.MethodsWe performed immunofluorescence analysis to visualize tumor-infiltrating T cells (CD3+), T helper cells (CD3+CD4+), cytotoxic T cells (CD3+CD8+) and regulatory T cells (Tregs; CD3+CD4+FoxP3+) in 146 ACC tissue specimens (107 primary tumors, 16 local recurrences, 23 metastases). Quantitative data of immune cell infiltration were correlated with clinical data (including glucocorticoid excess).Results86.3% of ACC specimens showed tumor infiltrating T cells (7.7 cells/high power field (HPF)), including T helper (74.0%, 6.7 cells/HPF), cytotoxic T cells (84.3%, 5.7 cells/HPF) and Tregs (49.3%, 0.8 cells/HPF). The number of TILs was associated with better overall survival (HR for death: 0.47, 95% CI 0.25 to 0.87), which was true for CD4+− and CD8+subpopulations as well. In localized, non-metastatic ACC, the favorable impact of TILs on overall and recurrence-free survival was manifested even independently of ENSAT (European Network for the Study of Adrenal Tumors) stage, resection status and Ki67 index. T helper cells were negatively correlated with glucocorticoid excess (Phi=−0.290, p=0.009). Patients with glucocorticoid excess and low TILs had a particularly poor overall survival (27 vs. 121 months in patients with TILs without glucocorticoid excess).ConclusionGlucocorticoid excess is associated with T cell depletion and unfavorable prognosis. To reactivate the immune system in ACC by checkpoint inhibitors, an inhibition of adrenal steroidogenesis might be pivotal and should be tested in prospective studies.

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Serum inhibin pro-αC is a tumor marker for adrenocortical carcinomas

Acta Endocrinologica ◽

10.1530/eje-11-0693 ◽

2012 ◽

Vol 166 (2) ◽

pp. 281-289 ◽

Cited By ~ 6

Author(s):

Johannes Hofland ◽

Richard A Feelders ◽

Ronald van der Wal ◽

Michiel N Kerstens ◽

Harm R Haak ◽

...

Keyword(s):

Tumor Marker ◽

Adrenocortical Function ◽

Adrenal Tumors ◽

Adrenocortical Adenoma ◽

Characteristic Analysis ◽

Α Subunit ◽

Adrenocortical Hyperplasia ◽

Tumor Load ◽

Adrenocortical Carcinomas

ObjectiveThe insufficient diagnostic accuracy for differentiation between benign and malignant adrenocortical disease and lack of sensitive markers reflecting tumor load emphasize the need for novel biomarkers for diagnosis and follow-up of adrenocortical carcinoma (ACC).DesignSince the inhibin α-subunit is expressed within the adrenal cortex, the role of serum inhibin pro-αC as a tumor marker for ACC was studied in patients.MethodsRegulation of adrenal pro-αC secretion was investigated by adrenocortical function tests. Serum inhibin pro-αC levels were measured in controls (n=181) and patients with adrenocortical hyperplasia (n=45), adrenocortical adenoma (ADA,n=32), ACC (n=32), or non-cortical tumors (n=12). Steroid hormone, ACTH, and inhibin A and B levels were also estimated in patient subsets.ResultsSerum inhibin pro-αC levels increased by 16% after stimulation with ACTH (P=0.043). ACC patients had higher serum inhibin pro-αC levels than controls (medians 733 vs 307 ng/l,P<0.0001) and patients with adrenocortical hyperplasia, ADA, or non-adrenocortical adrenal tumors (148, 208, and 131 ng/l, respectively,P=0.0003). Inhibin pro-αC measurement in ACC patients had a sensitivity of 59% and specificity of 84% for differentiation from ADA patients. Receiver operating characteristic analysis displayed areas under the curve of 0.87 for ACC vs controls and 0.81 for ACC vs ADA (P<0.0001). Surgery or mitotane therapy was followed by a decrease of inhibin pro-αC levels in 10/10 ACC patients tested during follow-up (P=0.0065).ConclusionsInhibin pro-αC is produced by the adrenal gland. Differentiation between ADA and ACC by serum inhibin pro-αC is limited, but its levels may constitute a novel tumor marker for ACC.

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