Surgical treatment and long-term outcome of ferrets with bilateral adrenal tumors or adrenal hyperplasia: 56 cases (1994-1997).

OBJECTIVE: To determine signalment, clinical signs, concurrent diseases, response to surgical treatment, and long-term outcome of ferrets with bilateral adrenal tumors or adrenal hyperplasia. DESIGN: Retrospective study. ANIMALS: 56 ferrets with bilateral adrenal tumors or adrenal hyperplasia confirmed histologically following subtotal bilateral adrenalectomy. PROCEDURE: Medical records of all ferrets with bilateral adrenal tumors or hyperplasia examined between 1994 and 1997 were reviewed. Ferrets underwent a subtotal bilateral adrenalectomy or a unilateral adrenalectomy initially, followed by a unilateral subtotal adrenalectomy when tumors or hyperplasia later developed on the contralateral adrenal gland. A long-term follow-up of a minimum of 18 months after final adrenal gland surgery was obtained by examination of medical records and follow-up telephone conversations. RESULTS: Clinical signs of hyperadrenocorticism included bilaterally symmetric alopecia, return to male sexual behavior in castrated male ferrets, or swollen vulva in spayed female ferrets. Surgical treatment of bilateral adrenal disease by subtotal bilateral adrenalectomy (or unilateral adrenalectomy followed by contralateral unilateral subtotal adrenalectomy) was effective with a mortality rate of < 2%. Only 3 (5%) ferrets required glucocorticoid or mineralocorticoid replacement following subtotal bilateral adrenalectomy. Recurrence after bilateral adrenalectomy was 15% with a mean long-term follow-up period of 30 months. CONCLUSIONS AND CLINICAL RELEVANCE: Bilaterally symmetric alopecia, return to male sexual behavior in castrated male ferrets, or swollen vulva in spayed female ferrets are indicative of adrenal tumors or adrenal hyperplasia in ferrets. Surgical treatment of bilateral adrenal disease by subtotal bilateral adrenalectomy is effective, with a low rate of complications and postoperative recurrence rate.     

Adrenal gland disease in ferrets.

Adrenal gland disease in ferrets is unique to this species, with clinical signs and pathophysiology different from those seen in the dog. Its prevalence is increasing; 70% of pet ferrets in the United States were affected in 2003. The exact causes of the adrenal gland changes that lead to the disease are not known. Early oophorohysterectomies and neutering, combined with the artificially prolonged photoperiod experienced by indoor pet ferrets, and a possible genetic component, may be contributing factors. Signs of adrenal gland disease include progressive hair loss, pruritis, lethargy, atrophy, and, in female ferrets, vulvar swelling. An understanding of the signs and physiologic changes is necessary for diagnosis and treatment. A review of anatomy, physiology, and current surgical and medical options is presented.     

Leuprolide acetate treatment of adrenocortical disease in ferrets

OBJECTIVE: To determine the effects of leuprolide acetate, a long-acting gonadotropin-releasing hormone analog, in ferrets with adrenocortical diseases. DESIGN: Case series. ANIMALS: 20 ferrets with adrenocortical disease diagnosed on the basis of clinical signs and plasma sex hormone concentrations. PROCEDURE: Ferrets were treated with leuprolide (100 microg, IM, once), and plasma hormone concentrations were measured before and 3 to 6 weeks after treatment. RESULTS: Leuprolide treatment resulted in significant reductions in plasma estradiol, 17 alpha-hydroxyprogesterone, androstenedione, and dehydroepiandrosterone concentrations and eliminated or reduced clinical signs associated with adrenocortical disease. Decreases in vulvar swelling, pruritus, and undesirable sexual behaviors and aggression were evident 14 days after treatment; hair regrowth was evident by 4 weeks after treatment. The response to treatment was transitory, and clinical signs recurred in all ferrets. Mean +/- SEM time to recurrence was 3.7 +/- 0.4 months (range, 1.5 to 8 months). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that leuprolide can be safely used to temporarily eliminate clinical signs and reduce sex hormone concentrations in ferrets with adrenocortical diseases. However, the safety of long-term leuprolide use in ferrets has not been investigated, and the long-term effects of leuprolide in ferrets with nodular adrenal gland hyperplasia or adrenal gland tumors are unknown.     

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.     

Clinical and endocrine responses to treatment with deslorelin acetate implants in ferrets with adrenocortical disease

OBJECTIVE: To evaluate the clinical and endocrine responses of ferrets with adrenocortical disease (ACD) to treatment with a slow-release implant of deslorelin acetate. ANIMALS: 15 ferrets with ACD. PROCEDURE: Ferrets were treated SC with a single slow-release, 3-mg implant of deslorelin acetate. Plasma estradiol, androstenedione, and 17-hydroxyprogesterone concentrations were measured before and after treatment and at relapse of clinical signs; at that time, the adrenal glands were grossly or ultrasonographically measured and affected glands that were surgically removed were examined histologically. RESULTS: Compared with findings before deslorelin treatment, vulvar swelling, pruritus, sexual behaviors, and aggression were significantly decreased or eliminated within 14 days of implantation; hair regrowth was evident 4 to 6 weeks after treatment. Within 1 month of treatment, plasma hormone concentrations significantly decreased and remained decreased until clinical relapse. Mean time to recurrence of clinical signs was 13.7 +/- 3.5 months (range, 8.5 to 20.5 months). In 5 ferrets, large palpable tumors developed within 2 months of clinical relapse; 3 of these ferrets were euthanatized because of adrenal gland tumor metastasis to the liver or tumor necrosis. CONCLUSIONS AND CLINICAL RELEVANCE: In ferrets with ACD, a slow-release deslorelin implant appears promising as a treatment to temporarily eliminate clinical signs and decrease plasma steroid hormone concentrations. Deslorelin may not decrease adrenal tumor growth in some treated ferrets. Deslorelin implants may be useful in the long-term management of hormone-induced sequelae in ferrets with ACD and in treatment of animals that are considered at surgical or anesthetic risk.     

Effects of melatonin administration on the clinical course of adrenocortical disease in domestic ferrets

OBJECTIVE: To evaluate the effect of oral administration of melatonin on clinical signs, tumor size, and serum steroid hormone concentrations in ferrets with adrenocortical disease. DESIGN: Noncontrolled clinical trial. ANIMALS: 10 adult ferrets with clinical signs of adrenocortical disease (confirmed via serum steroid hormone concentration assessments). PROCEDURES: Melatonin (0.5 mg) was administered orally to ferrets once daily for 1 year. At 4-month intervals, a complete physical examination; abdominal ultrasonographic examination (including adrenal gland measurement); CBC; serum biochemical analyses; and assessment of serum estradiol, androstenedione, and 17alpha-hydroxyprogesterone concentrations were performed. Serum prolactin and dehydroepiandrosterone sulfate concentrations were evaluated at the first, second, and last examinations, and serum cortisol concentration was evaluated at the first and last examinations. RESULTS: Daily oral administration of melatonin greatly affected clinical signs of adrenocortical disease in ferrets; changes included hair regrowth, decreased pruritus, increased activity level and appetite, and decreased vulva or prostate size. Mean width of the abnormally large adrenal glands was significantly increased after the 12-month treatment period. Recurrence of clinical signs was detected in 6 ferrets at the 8-month evaluation. Compared with pretreatment values, serum 17alpha-hydroxyprogesterone and prolactin concentrations were significantly increased and decreased after 12 months, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that melatonin is a useful, easily administered, palliative treatment to decrease clinical signs associated with adrenocortical disease in ferrets, and positive effects of daily treatment were evident for at least an 8-month period. Oral administration of melatonin did not decrease adrenal gland tumor growth in treated ferrets.     

The Treatment of Adrenal Cortical Disease in Ferrets with 4.7-mg Deslorelin Acetate Implants

Thirty pet ferrets with adrenocortical disease (ACD) of varying severity and duration were evaluated for response to a single administration of a slow release 4.7 mg deslorelin acetate implant. Clinical response to deslorelin was monitored via a physical examination performed every 3 to 4 months. Adrenal ultrasound measurements were taken every 3-4 months until clinical relapse. At clinical relapse, duration of symptom suppression and adrenal size and growth were determined. Administration of a single 4.7 mg implant of deslorelin acetate resulted in significant decreases in the clinical signs and hormonal concentrations associated with ACD. Within 14 days post-implant, vulvar swelling, pruritus, sexual behaviors and aggression decreased or disappeared. Hair re-growth was evident by 4-6 weeks post implant. Within two months post deslorelin implant, plasma concentrations of steroid hormones decreased: mean estradiol concentration decreased 28%; 17-hydroxyprogesterone levels decreased 89% and androstenedione levels decreased 88%. The response to a single 4.7 mg implant of deslorelin acetate was transitory. The mean ± SD time to recurrence of clinical signs was 17.6 ± 5.0 months (range, 8.0-30.0 months). Repeated ultrasound measurements revealed no statistical difference in size of the adrenals (right or left) before, during the months of deslorelin implant and at clinical relapse. Slow release 4.7 mg deslorelin implants can effectively be used to temporarily eliminate the clinical signs and reduce steroid hormone concentrations in ferrets with ACD. This dose of deslorelin does appear to influence adrenal tumor growth causing a decrease in adrenal size in some ferrets, and mild enlargement of adrenal glands in most ferrets with 2 of 30 implanted animals developing large tumors before clinical relapse. The long-term effect of treatment with deslorelin on adrenal tumor pathology requires additional investigation. At this time, surgical removal of the adrenal tumor remains the only curative treatment; however, 4.7 mg deslorelin implants are useful in the long-term management of ACD hormone-induced sequelae and may be as effective assurgical management.     

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

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

Diagnosis and surgical treatment of a primary splenic torsion in a domestic ferret (Mustela putorius furo)

A 4-year-old female spayed domestic ferret (Mustela putorius furo) presented with a history of vomiting over 24 hours. On physical examination, a significantly enlarged, firm spleen was palpated. Abdominal radiographs and abdominal ultrasound were suggestive of a splenic torsion or splenic infarction. An exploratory laparotomy confirmed the initial diagnosis and splenectomy was performed using a vessel sealing device. Histologic evaluation and culture of the spleen were consistent with primary torsion without evidence of infection or neoplasia. The patient recovered from surgery without complications. Based on a literature search, this is the first report of the clinical diagnosis and successful surgical treatment of a primary splenic torsion in a ferret. Although it appears to be a rare and potentially life-threatening disease in ferrets, splenic torsion should be considered as a differential diagnosis in ferrets that present with non-specific signs and a palpably enlarged spleen.     

Correlation between age at neutering and age at onset of hyperadrenocorticism in ferrets

OBJECTIVE: To determine prevalence of hyperadrenocorticism in ferrets in The Netherlands and evaluate age, sex, and age at neutering in affected ferrets. DESIGN: Prevalence survey and retrospective study. ANIMALS: 50 ferrets with hyperadrenocorticism and 1,267 ferrets without hyperadrenocorticism. PROCEDURE: A questionnaire was sent to 1,400 members of a ferret-owners organization in The Netherlands; 492 (35%) owners returned the questionnaire, providing usable data on 1,274 ferrets. Seven of these ferrets developed hyperadrenocorticism during the survey period; medical records for these ferrets and 43 ferrets with confirmed hyperadrenocorticism were reviewed. Hyperadrenocorticism was confirmed by histologic examination of an excised adrenal gland (92% of ferrets) or clinical improvement after excision. RESULTS: Prevalence of hyperadrenocorticism in the survey population was 0.55%. Sex was not associated with prevalence of disease. Median time interval between neutering and diagnosis of hyperadrenocorticism was 3.5 years. A significant linear correlation between age at neutering and age at time of diagnosis was detected. CONCLUSIONS AND CLINICAL RELEVANCE: Age at neutering may be associated with age at development of hyperadrenocorticism in ferrets.     

ADRENAL NEOPLASIA IN SEVEN FERRETS

Medical records from 7 ferrets presented to the VMTH with histologically confirmed adrenal neoplasia were reviewed. Three neutered female ferrets had adrenal cortical adenoma; four ferrets (2 neutered females, 2 neutered males) had adrenal cortical carcinoma. Ultrasound identified unilateral enlargement or abnormal shape of the adrenal gland in all ferrets. Only 1 ferret had adrenomegaly on abdominal radiographs. Adrenomegaly was identified in 1 ferret by magnetic resonance imaging (MRI). All ferrets were treated by adrenalectomy followed by a tapered dose of prednisone. Surgical complications were limited to fatal hemorrhage from the caudal vena cava in 1 ferret. Remission of clinical signs occurred in all 6 ferrets which survived surgery. The time of follow up varied from 3 to 16 months. The 3 ferrets with adrenal adenomas were still alive 3 to 7 months after surgery. AH 3 ferrets with adrenal carcinoma developed metastasis and were euthanized from 2 to 16 months after surgery.     

Ultrasonographic features of insulinoma in six ferrets

Insulinoma is a functional, insulin‐secreting tumor, arising from the beta islet cells of the pancreas. It is one of the most common neoplasms in ferrets and has been associated with clinical signs of hypoglycemia, such as ptyalism, pawing at the mouth, seizures, lethargy, and coma. The ultrasonographic features of insulinoma in ferrets have not been previously reported. The purpose of this retrospective case series study was to describe the ultrasonographic features of confirmed insulinoma in a group of ferrets. Inclusion criteria were abdominal ultrasound examination and histological confirmed insulinoma by surgical biopsy. Six ferrets met the inclusion criteria, all of which had multiple hypoglycemic episodes. Ultrasonographic images were reviewed and the characteristics of the pancreatic nodules were recorded. Twenty‐eight pancreatic nodules were observed in the six ferrets and were primarily hypoechoic (89.3%, 25/28) and homogenous (46.4%, 13/28) with a smooth margin (78.6%, 22/28). The distribution of the pancreatic nodules was 46.4% in the left lobe, 50% in the right lobe, and 3.6% in the body of the pancreas. The sizes of the pancreatic nodules varied from 1.5 × 1.5 to 4.1 × 5.6 mm. All of the pancreatic nodules removed from surgery were histopathologically confirmed as insulinoma. The findings indicated that insulinoma in ferrets could be detected through ultrasonography, which may facilitate diagnosis and preoperative surgical planning.     

Two cases of pancreatic neoplasia in British ferrets (Mustela putorius furo)

Two six-year-old male neutered polecat ferrets (Mustela putorius furo) were presented for the investigation of acute collapse or periodic weakness and weight loss. While blood biochemistry revealed hypoglycaemia in both cases, diagnosis of an insulin-secreting neoplasia was confirmed by exploratory surgery in one case and supported by the use of an insulin assay in the other. Subsequent histopathological examination showed the former to be a pancreatic islet cell carcinoma and the latter to be a pancreatic islet cell adenoma. While neoplasia of the pancreas commonly affects ferrets in the USA, there appears to be only one previous report from the UK.     

IMAGING DIAGNOSIS—RADIOGRAPHY AND ULTRASONOGRAPHY OF BILATERAL CONGENITAL URETEROVESICAL JUNCTION STENOSIS CAUSING HYDRONEPHROSIS AND HYDROURETER IN A FERRET (MUSTELA PUTORIUS FURO)

An 8‐month‐old neutered male ferret was presented for vaccination and preventive treatment for adrenal gland disease. Abdominal ultrasound revealed severe bilateral hydronephrosis and hydroureter. Excretory urography and negative contrast cystography showed bilateral ureterovesical junction stenosis. Positive retrograde cystography demonstrated right ureteral reflux. A subcutaneous ureteral bypass was placed in the left kidney; however, it had to be removed 3 months later due to an obstruction and persistent urinary tract infection. Bilateral ureteroneocystotomy was performed. Although congenital strictures are uncommon in veterinary patients, they should be included in the differential diagnosis in ferrets presenting with hydronephrosis and hydroureter of undetermined cause.     

Diseases of the nictitating membrane of the dog

The clinical signs and treatment of the following conditions of the nictitating membrane are described–prominence of the nictitating membrane due to various causes, injuries and foreign bodies, conjunctivitis, plasma cell infiltration, disorders of the nictitans gland, neoplasia, and deformity of the cartilage. The surgical removal of the third eyelid is also discussed.     

Adrenal teratoma in four domestic ferrets (Mustela putorius furo)

Teratomas are histologically complex neoplasms that are composed of structures derived from multiple germ cell layers (ectoderm, mesoderm, and endoderm). These neoplasms are uncommon in domestic animals and are usually found in the gonads. This paper describes teratomas of the adrenal gland in four domestic ferrets (Mustela putorius furo). Three of four of the neoplasms contained tissues from ectodermal, mesodermal, and endodermal germ cell layers; two of four contained rudimentary teeth. In one case, malignant epithelial cells had metastasized to local lymph nodes. Teratomas, although uncommon, should be included in the differential diagnosis for adrenal neoplasms in domestic ferrets.     

Primary Hyperparathyroidism in a Quarter Horse Mare Associated With a Chief Cell Adenoma

Primary hyperparathyroidism is rare in large animal species, and little is known regarding its pathophysiology, endocrine and electrolyte derangements, diagnosis, medical management, and prognosis. This report describes the clinicopathologic diagnosis of a parathyroid (PT) gland chief cell adenoma in a 12-year-old Quarter Horse mare, including PT hormone (PTH) and electrolyte disarrangements associated with the neoplasia, the surgical removal of the adenoma, and medical management of the case. This report also describes for the first time the use PTH immunohistochemistry to confirm the nature of this neoplasia in a horse.     

Omentalization of Prostatic Abscesses and Large Cysts in Ferrets (Mustela putorius furo)

Neutered male ferrets are occasionally presented with cystic prostatic disease or prostatic abscesses, most often secondary to elevated, circulating sex steroid hormones caused by adrenocortical disease. Useful features of the omentum, such as tissue adhesion, angiogenesis, and stimulation of the immune system, can be used for surgical treatment of large prostatic cysts and abscesses. Two cases of prostatic abscess omentalization are described. In one case, the underlying cause was a sustentacular (Sertoli cell) tumor associated with a retained testicle. In the other case, adrenocortical disease was determined to be the underlying disease. The first ferret had a residual prostatic abscess 5 months after omentalization. A small, residual prostatic cyst was detected by ultrasound in the second ferret 9 weeks after surgery. Although omentalization may be an effective technique to surgically manage large prostatic cysts and abscesses in ferrets, clinical studies comparing omentalization with other surgical and nonsurgical methods are needed in this species.     

Canine hyperadrenocorticism

Hyperadrenocorticism is a common endocrinopathy which results from the excessive production of cortisol by the adrenal cortex. In the majority of cases, this increased secretion of cortisol results from stimulation of the adrenal cortex by adrenocorticotrophic hormone secreted from the pituitary gland. In a smaller number of cases adrenal tumours are present. Clinical signs are variable but commonly include polydipsia and polyuria, polyphagia, obesity, a pendulous abdomen, hepatomegaly, alopecia, lethargy, weakness and anoestrus. Haematology, serum chemistry analysis and urinalysis should be performed on a dog with suspected hyperadrenocorticism. Finding a significant number of changes that are consistent with hyperadrenocorticism often allows a presumptive diagnosis to be made. Other tests can then be used to confirm the diagnosis and to help localise the cause, including liver biopsy, radiology, ultrasonography, gamma camera imaging, computed tomography, and measurement of blood and urine hormone levels. The ACTH stimulation test, low dose dexamethasone suppression test and measurement of the urine cortisol:creatinine ratio are used to assess whether hyperadrenocorticism is present. The high dose dexamethasone suppression test, measurement of plasma ACTH, corticotropin-releasing hormone stimulation test, and a modification of the urinary cortisol:creatinine ratio test are then implemented to determine the aetiology. The treatment of choice for adrenal neoplasia is surgical removal of the affected adrenal. On the other hand, pituitary hyperplasia or neoplasia may be treated either surgically, by bilateral adrenalectomy or hypophysectomy, or medically. The drug which is chosen most commonly for medical management is 1,1-dichloro-2(O-chlorophenyl)-2-(P-chlorophenyl) ethane (op'-DDD), which can be used to suppress adrenal function or to completely destroy the adrenal cortex. The antifungal agent ketoconazole also suppresses adrenal steroid synthesis and provides an alternative form of medical treatment for hyperadrenocorticoid dogs.     

Solitary dermal leiomyosarcomas in 12 ferrets.

Twelve 3-6-year-old ferrets (8 males, 3 females, 1 unknown) were presented with single cutaneous nodules. These dermal tumors were characterized histologically by nodular proliferation of neoplastic smooth muscle fibers with marked anisokaryosis and a mitotic rate of >2 mitoses per 10 high-power fields. Neoplastic cells stained strongly for vimentin in all tumors and for smooth muscle actin and desmin in all but 1 tumor. Histologic and immunohistochemical findings suggested a diagnosis of piloleiomyosarcoma for these tumors. Excision was curative in all animals available for follow-up. However, 3 of 5 animals developed adrenal disease within 7 months after removal of the dermal leiomyosarcoma.