POSTMORTEM FINDINGS IN CETACEANS FOUND STRANDED IN THE PELAGOS SANCTUARY, ITALY, 2007-14.

Between 2007 and 2014, 83 cetaceans were found stranded along the Ligurian coast of Italy, in the Pelagos Sanctuary, the largest marine protected area in the Mediterranean basin. Forty-nine (59%) were submitted to complete or partial necropsy, depending on the conservation status of the carcass. Based on gross and histological pathology and ancillary testing, the cause of death was determined and categorized as anthropogenic or natural (i.e., nonanthropogenic) in origin for 33 animals (67%) and of undetermined origin in the remaining 16 (33%). Natural causes of death, accompanied by either poor or good nutritional status, were attributed to 29 animals (59%), whereas four (8%) were diagnosed with an anthropogenic cause of death, consisting of interaction with fishing activities. Infectious and noninfectious disease was the most common cause of death, involving 29 cetaceans (59%). These data are valuable for understanding health and mortality trends in cetacean populations and can provide information for establishing policies for cetacean conservation and management in such an important protected area of the Mediterranean basin.

Expression of angiogenesis-related genes in canine cortisol-secreting adrenocortical tumors.

The aim of this study was to evaluate the expression of angiogenesis-related genes in canine cortisol-secreting adrenocortical tumors (ATs). Quantitative RT-PCR analysis revealed mRNA encoding for vascular endothelial growth factor, vascular endothelial growth factor receptors 1 and 2, angiopoietin 1 and 2 (ANGPT1 and ANGPT2), the splice variant ANGPT2443, the ANGPT-receptor Tie2, and basic fibroblast growth factor in 38 canine cortisol-secreting ATs (26 carcinomas and 12 adenomas) and 15 normal adrenals. The relative expression of both ANGPT2 and ANGPT2443 was higher in adenomas (P = 0.020 for ANGPT2 and P = 0.002 for ANGPT2443) and carcinomas (P = 0.003 for ANGPT2 and P < 0.001 for ANGPT2443) compared with normal adrenals, and this enhanced expression was also detected with Western blot analysis. Immunohistochemistry indicated expression of ANGPT2 protein in AT cells and in vascular endothelial cells of carcinomas, whereas Tie2 was mainly present in the tumor vascular endothelial cells. The ANGPT2-to-ANGTPT1 ratio, a marker for a proangiogenic state, was higher in both adenomas (P = 0.020) and carcinomas (P = 0.043). With the use of the human H295R cortisol-producing adrenocortical carcinoma cell line, we were able to demonstrate that the ANGPT2 expression was stimulated by cyclic adenosine monophosphate and progesterone but not by cortisol. In conclusion, canine cortisol-secreting ATs have enhanced ANGPT2 expression with a concomitant shift toward a proangiogenic state. On the basis of this information, treatment modalities may be developed that interfere with ANGPT2 expression, including inhibition of the cyclic adenosine monophosphate/protein kinase A pathway, or of the effect of ANGPT2, by using specific ANGPT2 inhibitors.

Treatment of aldosterone-secreting adrenocortical tumors in cats by unilateral adrenalectomy: 10 cases (2002-2012).

BACKGROUND: Primary hyperaldosteronism (PHA) in cats occurs as a consequence of excessive hormone production by an adrenocortical tumor. Median survival time, association between tumor type and prognosis, and the likelihood that cats require continued medical therapy after surgery have not been systematically evaluated. OBJECTIVES: To determine the median survival time of cats with PHA treated by unilateral adrenalectomy. To examine if tumor type, anesthesia time, or tumor location (left or right side) affect survival and if affected cats require continued postoperative treatment for persistent hypertension or hypokalemia. ANIMALS: Ten client-owned cats. METHODS: Retrospective study. Cats were diagnosed with PHA based on clinical signs, increased plasma aldosterone concentration, and advanced imaging. Cats underwent unilateral adrenalectomy. Survival time (days alive after surgery) was determined for each cat. Factors affecting median survival time were investigated, including histopathology, anesthesia time, and location (side) of the tumor. RESULTS: Eight of 10 cats survived to discharge from the hospital post adrenalectomy. Overall median survival was 1,297 days (range 2-1,582 days). The only significant factor affecting median survival time was anesthesia time >4 hours. Tumor type and location (side) did not significantly affect median survival time. No cats required continued medical treatment for PHA. CONCLUSIONS AND CLINICAL IMPORTANCE: Although PHA in cats is still considered an uncommon condition, it should be considered in middle to older aged cats with hypokalemic polymyopathy and systemic hypertension. Surgical correction by unilateral adrenalectomy is a viable approach to definitive treatment of PHA with no need for continued medical management.

Use of a GnRH vaccine, GonaCon, for prevention and treatment of adrenocortical disease (ACD) in domestic ferrets.

Adrenocortical disease (ACD) is a common problem in surgically sterilized, middle-aged to old ferrets (Mustela putorius furo). The adrenal tissues of these ferrets develop hyperplasia, adenomas, or adenocarcinomas, which produce steroid hormones including estradiol, 17-hydroxyprogesterone, and androstenedione. Major clinical signs attributable to overproduction of these hormones are alopecia (hair loss) in both sexes and a swollen vulva in females. Pruritus, muscle atrophy, hind limb weakness, and sexual activity or aggression are also observed in both sexes. Males can develop prostatic cysts, prostatitis, and urethral obstruction. ACD is thought to be linked to continuous and increased LH secretion, due to lack of gonadal hormone feedback in neutered ferrets. This continuous elevated LH acts on adrenal cortex LH receptors, resulting in adrenal hyperplasia or adrenal tumor. This study investigated whether the immunocontraceptive vaccine GonaCon, a GnRH vaccine developed to reduce the fertility of wildlife species and the spread of disease, could prevent or delay onset of ACD and treat alopecia in ferrets with existing ACD. Results showed that GonaCon provided relief from ACD by causing production of antibodies to GnRH, probably suppressing production and/or release of LH. Treatment caused many ACD symptoms to disappear, allowing the ferrets to return to a normal life. The study also found that the probability of developing ACD was significantly reduced in ferrets treated with GonaCon when young (1-3 years old) compared to untreated control animals. GonaCon caused injection site reaction in some animals when administered as an intramuscular injection but caused few side effects when administered subcutaneously. Both intramuscular and subcutaneous vaccination resulted in similar levels of GnRH antibody titers. Subcutaneous vaccination with GonaCon is thus recommended to prevent the onset of ACD and as a possible treatment for ACD-signs in domestic ferrets.

Leishmania amastigotes in neoplastic cells of 3 nonhistiocytic canine tumors.

Concurrent leishmaniasis and neoplasia has been reported in dogs. This study describes the presence of the protozoa within the cytoplasm of neoplastic cells in 3 different types of tumors. Leishmania amastigotes were detected by light and transmission electron microscopy and immunohistochemistry in a fibrosarcoma, a T-cell lymphoma, and an adrenocortical adenoma.

Histologic and immunohistochemical classification of 41 bovine adrenal gland neoplasms.

Tumors of the adrenal glands are among the most frequent tumors in cattle; however, few studies have been conducted to describe their characteristics. The aim of this study was to classify 41 bovine adrenal neoplasms from 40 animals based on macroscopic and histologic examination, including electron microscopy and immunohistochemistry for melan A, synaptophysin, chromogranin A, vimentin, pan-cytokeratin, 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNPase), and Ki-67. The tumors were classified as 23 adrenocortical adenomas, 12 adrenocortical carcinomas, 2 schwannomas, 2 pheochromocytomas (1 malignant), and 1 ganglioneuroma. Five histologic features were characteristic of metastasizing adrenocortical tumors: invasion of the capsule, vascular invasion, diffuse growth pattern, spindle-cell morphology, and nuclear pleomorphism. Adrenocortical tumors with at least 3 of these features were classified as malignant. Immunohistochemically, adrenocortical tumors expressed melan A (16/19), vimentin (14/26), cytokeratin (11/26), and chromogranin A (9/27), whereas pheochromocytomas expressed chromogranin A (2/2), synaptophysin (2/2), and vimentin (1/2). Both schwannomas expressed CNPase. An immunohistochemistry panel consisting of antibodies against melan A, synaptophysin, and CNPase was considered most useful to classify bovine adrenal tumors. However, the distinction between benign and malignant adrenocortical tumors was based on histologic features as in human medicine.

Adrenal pheochromocytoma with contralateral adrenocortical adenoma in a cat.

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.

Cytochrome b5 expression in gonadectomy-induced adrenocortical neoplasms of the domestic ferret (Mustela putorius furo).

Whereas the adrenal glands of healthy ferrets produce only limited amounts of androgenic steroids, adrenocortical neoplasms that arise in neutered ferrets typically secrete androgens or their derivative, estrogen. The 17,20-lyase activity of cytochrome P450 17alpha-hydroxylase/17,20-lyase (P450c17) must increase to permit androgen biosynthesis in neoplastic adrenal tissue. We screened ferret adrenocortical tumor specimens for expression of cytochrome b(5) (cyt b(5)), an allosteric regulator that selectively enhances the 17,20-lyase activity of P450c17. Cyt b(5) immunoreactivity was evident in 24 of 25 (96%) adrenocortical adenomas/carcinomas from ferrets with signs of ectopic sex steroid production. Normal adrenocortical cells lacked cyt b(5), which may account for the low production of adrenal androgens in healthy ferrets. Other markers characteristic of gonadal somatic cells, such as luteinizing hormone receptor, aromatase, and GATA4, were coexpressed with cyt b(5) in some of the tumors. We concluded that cyt b(5) is upregulated during gonadectomy-induced adrenocortical neoplasia and is a marker of androgen synthetic potential in these tumors.

Primary hyperaldosteronism in a domestic ferret with an adrenocortical adenoma.

CASE DESCRIPTION: A 6-year-old spayed female domestic ferret was evaluated because of lethargy, alopecia, pruritus, and an abdominal mass. CLINICAL FINDINGS: On initial examination, nonregenerative anemia, mild azotemia, and a large left adrenal gland mass were identified. However, deterioration of the ferret's general condition prevented excision of the mass, and dyspnea, weakness, hypertension, and severe hypokalemia developed. Plasma aldosterone concentration was >3329 pmol/L, confirming a provisional diagnosis of hyperaldosteronism. High concentrations of sex hormones were also observed, but baseline cortisol concentration was within reference limits. TREATMENT AND OUTCOME: Medical treatment included oral administration of spironolactone, potassium gluconate, leuprolide acetate, amlodipine, and benazepril. Inhalation of albuterol proved effective in reducing the dyspnea. In the following weeks, serum potassium concentration returned to within reference limits and hypertension decreased, but dyspnea persisted. Two months after initial examination, the ferret became anorectic and was euthanized. Histologic examination revealed a large left adrenal gland adenoma, progressive chronic nephropathy, severe pulmonary edema, and focal fibrosis in the left ventricle. Immunohistochemical staining of the adrenal gland mass revealed aldosterone within neoplastic adrenocortical cells. CLINICAL RELEVANCE: Findings suggested that primary hyperaldosteronism should be considered as a possible cause in ferrets with hypokalemia, hypertension, and an adrenal gland mass. Early detection of aldosterone-secreting masses might allow for removal of the tumor before irreversible complications occur.

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.

Surgical management of adrenal gland tumors with and without associated tumor thrombi in dogs: 40 cases (1994-2001).

OBJECTIVE: To compare pathologic findings and results of adrenalectomy for adrenal gland tumors in dogs with and without vena caval tumor thrombi. DESIGN: Retrospective study. ANIMALS: 40 dogs with adrenal gland tumors. PROCEDURE: Medical records were examined. An exact logistic regression analysis was used to evaluate associations between tumor type or right-sided versus left-sided tumor involvement and development of caval tumor thrombi and associations between tumor thrombi, tumor type, or right- versus left-sided location and perioperative complications and mortality rate. Survival was compared between dogs with and without tumor thrombi. RESULTS: Caval thrombi were detected in 25% of dogs, including 3 of 28 (11%) dogs with an adrenocortical tumor and 6 of 11 dogs with a pheochromocytoma. A caval tumor thrombus was detected in 6 of 17 right-sided and 4 of 20 left-sided tumors. Sensitivity and specificity of abdominal ultrasonography for detection of caval thrombi were 80 and 90%, respectively. Intraoperative and postoperative complications developed in 15 and 51% of dogs, respectively. The mortality rate was 22%. There were no significant differences in perioperative morbidity and mortality rates between dogs with and without tumor thrombi. CONCLUSIONS AND CLINICAL RELEVANCE: Caval thrombi associated with adrenal gland tumors are amenable to adrenalectomy and thrombectomy without significantly increased perioperative morbidity and mortality rates, assuming the surgeon is experienced in appropriate techniques.

Temporary tube cystostomy as a treatment for urinary obstruction secondary to adrenal disease in four ferrets.

Adrenal neoplasia is a common problem in middle-aged to older ferrets. Male ferrets may present for stranguria and dysuria due to prostatic/paraurethral tissue enlargement secondary to elevation in androgens produced by the neoplastic tissue. Progressive urethral compression followed by complete urinary obstruction can result. Urinary obstruction can persist for days following surgery requiring urinary diversion. Four ferrets presenting with signs consistent with urinary obstruction secondary to adrenal disease were immediately treated with urethral catheterization or cystocentesis followed by adrenalectomy and temporary tube cystostomy. The tube cystostomy placement and use were associated with minimal complications and allowed recovery from surgery.

Surgical treatment of adrenocortical tumors: 21 cases (1990-1996).

Twenty-four adrenocortical tumors were surgically removed from 21 dogs. Histopathological examination confirmed 18 carcinomas and six adenomas. Four dogs died in the perioperative period. Fifteen of the 17 dogs that survived the perioperative period had long-term resolution of their clinical signs. Two dogs with incompletely resected tumors were treated with mitotane to control their clinical signs. Overall median Kaplan-Meier life-table survival for dogs with carcinomas was 778 days (range, one to 1,593 days). Median survival for dogs with adenomas was not reached (range, 11 to 730 days). Histopathological diagnosis, histopathological cellular features, age of the dog, and tumor size were not prognostic of outcome.

Use of low- and high-dose dexamethasone tests for distinguishing pituitary-dependent from adrenal tumor hyperadrenocorticism in dogs.

OBJECTIVE: To evaluate low- and high-dose dexamethasone suppression tests for differentiating pituitary dependent hyperadrenocorticism (PDH) from adrenal tumor hyperadrenocorticism (ATH) in dogs. DESIGN: Prospective study. ANIMALS: 181 dogs with PDH and 35 dogs with ATH. PROCEDURE: Plasma cortisol concentrations from dogs with naturally developing hyperadrenocorticism were evaluated before, and 4 and 8 hours after administration of standard low- and high-doses of dexamethasone (0.01 mg/kg of body weight, i.v., and 0.1 mg/kg, i.v.; respectively). RESULTS: In response to the low-dose test, all but 3 dogs had an 8-hours post-dexamethasone plasma cortisol concentration that was consistent with a diagnosis of hyperadrenocorticism, that is, > or = 1.4 micrograms/dl. Criteria used to distinguish PDH from ATH in response to low-dose dexamethasone included a 4-hour post-dexamethasone plasma cortisol concentration < 50% of the basal value or < 1.4 micrograms/dl, or an 8-hours post-dexamethasone plasma cortisol concentration < 50% of the basal concentration. Criteria used to distinguish PDH from ATH in response to high-dose dexamethasone included 4- or 8-hour post-dexamethasone plasma cortisol concentrations < 50% of the basal concentration or < 1.4 micrograms/dl. In response to the low-dose test, 111 dogs met criteria for suppression (each had PDH). In response to the high-dose test, 137 dogs met criteria for suppression (2 had ATH, 135 had PDH). Twenty-six dogs with PDH (12%) had indications of adrenal suppression in response to high-dose but not low-dose testing. CLINICAL IMPLICATIONS: Low-dose dexamethasone test has value as a discrimination test to distinguish dogs with PDH from those with ATH. The high-dose test need only be considered in dogs with hyperadrenocorticism that do not have adrenal suppression in response to the low-dose test.

Estradiol-17 beta-secreting adrenocortical tumor in a ferret.

Severe generalized alopecia and marked vulvar enlargement were observed in a 5-year-old spayed ferret with high serum estradiol concentrations. A neoplastic left adrenal gland was removed. Staining of the neoplastic cells for estradiol was demonstrated by use of immunohistochemistry. Clinical findings in this ferret were typical of adrenal-associated endocrinopathy, a syndrome characterized by increased secretion of adrenocortical hormones by hyperplastic or neoplastic adrenal glands.

Unilateral adrenalectomy as a treatment for adrenocortical tumors in ferrets: five cases (1990-1992).

Adrenocortical tumors were diagnosed in 5 adult spayed ferrets. Four ferrets had bilaterally symmetrical alopecia of the caudal femoral region, abdomen, and tail, and 1 had alopecia of the distal limbs and feet. All 5 ferrets had vulvar swelling. During abdominal ultrasonography, irregular masses, believed to involve the adrenal glands, were seen in all 5 ferrets. Unilateral adrenalectomy was performed successfully in each ferret by use of ventral midline celiotomy. On histologic examination of biopsy samples, 4 ferrets were found to have adrenocortical adenomas, and 1 ferret was found to have an adrenocortical adenocarcinoma. All clinical signs resolved after adrenalectomy, suggesting that the adrenocortical tumors had been secreting adrenocortical hormones.

Hyperadrenocorticism associated with adrenocortical tumor or nodular hyperplasia of the adrenal gland in ferrets: 50 cases (1987-1991).

Adrenocortical adenoma, nodular hyperplasia, or carcinoma was diagnosed in 50 ferrets. Thirty-five (70%) ferrets were female and 15 (30%) were male. The mean age at which clinical signs were first noticed was 3.4 years (range, 1 to 7 years). Clinical signs included large vulva (n = 31; 89% of females), alopecia (n = 43; 86%), pruritus (n = 20; 40%), and increased consumption of water and increased urine output (n = 4; 8%). A mass was palpated at the cranial pole of the kidney during physical examination of 17 (34%) ferrets. Ultrasonography, performed on 39 of 50 ferrets, revealed a unilateral adrenal gland mass in 19 (49%). Four ferrets were anemic, and 2 ferrets were thrombocytopenic. Baseline plasma concentrations of cortisol and corticosterone were within or below the reference range in all 17 ferrets tested, whereas baseline plasma estradiol concentrations were high in 4 of the 11 ferrets (36%) tested. AFter adrenocorticotropic hormone (ACTH) administration, only 1 ferret had a slightly exaggerated response on the basis of plasma cortisol concentrations, and all 17 had normal responses on the basis of plasma corticosterone concentrations. There was little or no increase in plasma estradiol concentrations after ACTH administration. Of the 50 ferrets, 39 were treated by adrenalectomy. Unilateral adrenalectomy was performed in 34 ferrets in which 1 adrenal gland was large, whereas subtotal bilateral adrenalectomy was performed in 5 ferrets with bilateral adrenal disease. Five ferrets died in the immediate postoperative period, and follow-up information was available for the remaining 34, 1 to 34 months after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)