Unilateral adrenalectomy as a treatment for adrenocortical tumors in ferrets: Five cases (1990-1992)
Howard J. Lawrence, DVM; Willard J. Gould, DVM; James A. Flanders, DVM; Peter H. Rowland, DVM; Amy E. Yeager, DVM
Summary: 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. Dur- ing abdominal ultrasonography, irregular masses, be- lieved 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 sam- ples, 4 ferrets were found to have adrenocortical ad- enomas, and 1 ferret was found to have an adrenocor- tical adenocarcinoma. All clinical signs resolved after adrenalectomy, suggesting that the adrenocortical tu- mors had been secreting adrenocortical hormones.
T here is little information published concerning diagnosis or treatment of adrenocortical tu- mors in ferrets other than individual case re- ports.1-4 These reports describe a 7-year-old male ferret with hyperadrenocorticism secondary to adrenocortical adenocarcinoma,1 a 5-year-old spayed ferret with a functional adrenocortical ad- enoma,2 and a 3- to 4-year-old adult spayed ferret with signs of estrus that had an adrenocortical ad- enoma.3 In our experience, unilateral adrenalec- tomy has been a successful treatment for functional adrenal tumors in ferrets, and the purpose of the study reported here was to describe surgical treat- ment and long-term outcome of 5 ferrets with adrenocortical tumors.
Criteria for Selection of Cases
The medical records of 5 ferrets that had adre- nalectomy for treatment of an unilateral adreno- cortical tumor at the veterinary teaching hospital were reviewed. Records were examined to deter- mine signalment, history, physical examination findings, clinicopathologic abnormalities, ultra- sonographic findings, anesthetic protocol, surgical
technique, histologic findings, and postoperative progress. Follow-up information on all surviving ferrets was obtained by telephone interview with the owners.
Tests and Procedures
History, physical examination, and clinicopatho- logic findings-For 4 ferrets, the mean age when clinical signs were first noticed was 5.4 years (range, 4.75 to 6.75 years). The age of 1 ferret was unknown, but the ferret was believed to be between 3 and 5 years old. Clinical signs had been seen for 1 to 6 months before the ferrets were evaluated at the veterinary teaching hospital. Four ferrets were evaluated because of symmetrical alopecia, and 1 because of hemorrhagic vaginal discharge. All an- imals were alert, and their attitude, appetite, and activity level had not changed. All 5 ferrets had been spayed. Mean body weight was 0.71 kg (range, 0.6 to 0.84 kg). All ferrets had been fed commercial dry or canned cat food.
Abnormalities detected on physical examina- tion included alopecia of the ventral portion of the abdomen, caudal femoral region, and tail base (n = 4), alopecia of the feet (n = 1), pruritus (n = 3), prominent vulvar swelling (n = 3), mild vulvar swelling (n = 2), purulent vaginal discharge (n = 1), and hemorrhagic vaginal discharge (n = 1). A CBC and serum biochemical analysis were performed on each ferret. Results were within reference ranges except that serum alanine ami- notransferase activity was 331 U/L in 1 ferret (nor- mal; 82 to 289 U/L).5 A urinalysis was performed on 2 ferrets; both had urine specific gravity > 1.030. One ferret had WBC (5 to 20/hpf) in the urine sed- iment, but bacteria were not seen. Vaginal smears were obtained from 1 ferret with a purulent vagi- nal discharge. Gram-negative rods were seen on cytologic examination, and Escherichia coli was obtained on bacteriologic culture. Skin scrapings were performed on 2 ferrets to obtain samples for microscopic examination and fungal culture. There was no evidence of ectoparasites or dermatophy- tosis.
Abdominal ultrasonography-A unilateral mass, believed to involve the adrenal gland, was seen
From the Departments of Clinical Sciences (Lawrence, Gould, Flanders, Yeager) and Pathology (Rowland), New York State College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. Dr. Lawrence’s present address is Veterinary Referral Services, 21 E Mission Ave, Spokane, WA 99202.
during abdominal ultrasonography of each ferret (Fig 1). The mass appeared to involve the left ad- renal gland in 3 ferrets, and the right adrenal gland in 2. The masses had a round or irregular shape and ranged from 8 × 7 × 7 mm to 18 × 6 × 6 mm. Four were uniformly hypoechoic, and 1 had hy- perechoic foci. The contralateral adrenal gland was considered small in 1 ferret, to be of normal size in a second ferret, and could not be imaged in 3 fer- rets. Two ferrets had a large, tubular, fluid-filled structure dorsal to the bladder that was presumed to be the uterine stump. Abdominal radiography of 1 ferret revealed a 15 × 5-mm soft tissue mass, cranial to the left kidney, consistent with what was seen on ultrasonography.
Surgical techniques and postoperative care- General anesthesia was induced, and ventral midline celiotomy was performed in all ferrets. Metastases were not grossly evident. In 2 ferrets, the tubular, fluid-filled structure seen during ultra- sonography was identified as an incompletely ex- cised uterine body and was removed.
In each ferret, the affected adrenal gland was larger than normal and irregular in shape.7,8 Uni- lateral adrenalectomy was uncomplicated in 4 fer- rets. In 1 ferret, the caudal vena cava was lacerated during right adrenalectomy. The vessel was re- paired with 6-0 polybutester, and the ferret recov- ered without further complications.
To prevent hypoadrenocorticism secondary to atrophy of the unaffected adrenal gland, ferrets were given, during surgery, either dexamethasone sodium phosphate (0.014 mg/kg of body weight to 0.3 mg/kg, Iv) or dexamethasone (0.08 to 0.1 mg/
kg, Iv, or 0.2 mg/kg, IM) on the basis of the surgeon’s preference. In 4 ferrets, a second dose was given 3 to 6 hours later.
Prednisone was given PO to all ferrets after surgery. Dosages ranged from 1 mg/kg/d tapered to 0.5 mg/kg every other day over 3 weeks to 1 mg/ kg/d tapered to 0.25 mg/kg every other day over 3 months to 0.25 mg/kg/d tapered to 0.1 mg/kg ev- ery other day over 3 weeks.
Results
In 4 ferrets, the affected adrenal gland con- tained 1 or 2 compressive, moderately well-de- marcated nodules ranging from 3 to 8 mm in diameter. On histologic examination, the nodules
contained uniform, polygonal cells with abundant, eosinophilic, often slightly foamy cytoplasm (re- sembling adrenocortical cells) and smaller, round- to-polygonal cells with less-abundant basophilic to amphophilic cytoplasm (Fig 2). Individual neo- plastic nodules had a predominance of 1 cell type or contained intermixed clusters of both cell types. There was scant to moderately abundant fibrous connective tissue associated with the neoplasms. Except in 1 tumor, the mitotic index was low. This tumor contained mainly smaller, basophilic cells, surrounded by a fine fibrovascular stromal net- work. In these 4 ferrets, the tumor was diagnosed as an adrenocortical adenoma. In the fifth ferret, the tumor was poorly demarcated and invaded ad- jacent adipose tissue. Histologically, it contained a mixed-cell population with moderate cellular pleo- morphism and abundant fibrous connective tissue, and was diagnosed as an adrenocortical adenocar- cinoma.
The uterine body of 1 ferret was distended and friable and contained purulent fluid; a diagnosis of stump pyometra was made. On histologic exami- nation of the uterine body that was removed from the other ferret, a diagnosis of cystic endometrial hyperplasia was made.
All 5 ferrets had complete hair regrowth and regression of vulvar enlargement by 1 to 2 months after surgery. Four ferrets were reported by their owners to be clinically normal 5 to 8 months after surgery. The fifth ferret was evaluated 3 months af- ter surgery because of progressive abdominal dis- tension. Ultrasonography revealed pleural and peritoneal effusion, with apparent right atrial and ventricular enlargement and tricuspid valve insuf- ficiency. The effusion was a modified transudate, and neoplastic cells were not seen during cytologic examination. A tentative diagnosis of right-sided heart failure and possible metastatic carcinoma was made, and the owner elected to have the ferret eu- thanatizied. At necropsy, a diagnosis of right-sided heart failure was made; there was no evidence of recurrence of the adrenocortical tumor.
Discussion
In all 5 ferrets in this study, 1 of the predom- inant clinical signs was alopecia. Seasonally, ferrets will undergo shedding in the early summer, result- ing in a thinner hair coat than during the winter months.1,9 Biotin deficiency, secondary to exces- sive raw egg consumption also may result in hair loss.10,11 Bilaterally symmetrical alopecia of the tail, ventral portion of the abdomen, and femoral region is common in ferrets in estrus (March to August) and also has been observed in male ferrets during the breeding season.5,6,10 However, none of these aforementioned reasons seemed to be a likely cause of the alopecia of the ferrets in this study, and the changes were most consistent with endocrine alopecia.
Symmetrical hair loss may be associated with
higher than normal serum concentrations of estro- gen or cortisol,12 and functional adrenocortical tu- mors in dogs and cats are commonly associated with excessive secretion of cortisol.13,14 However, the ferrets in this study did not have other clinical signs, such as polyuria, polyphagia, weakness, and lethargy, or biochemical and hematologic abnor- malities characteristic for cortisol excess. Although adrenal function tests were not performed because protocols for these tests had not been established at the time that these ferrets were evaluated, 15,16 it seems unlikely that the alopecia was caused by cortisol excess.
The vulvar swelling, stump pyometra, and cystic endometrial hyperplasia that were seen could have been caused by excessive amounts of estrogen or an estrogen-like substance. In human beings, adrenocortical tumors may induce clinical signs of feminization either because of production of estrogen by the adrenocortical tumor or because of conversion of excessive androgens to estrogens in other tissues,17 and a similar mechanisms may have been the cause of the clinical signs in the fer- rets in the present study.
A diagnosis of adrenocortical tumor in the fer- rets of this study was supported by abdominal ul- trasonography. Inability to image the contralateral gland does not imply atrophy, because normal ad- renal glands in ferrets may be too small for consis- tent detection by ultrasonography. In 1 report, ul- trasonography was found to be the single most reliable test, other than surgery, for identifying adrenocortical tumors in dogs.18 Masses could be seen by use of ultrasonography in 18 of 25 dogs with adrenocortical tumors. In a more recent eval- uation, x-ray computed tomography enabled accu- rate localization of functional adrenocortical tu- mors in 13 of 13 dogs evaluated.19
The 2 most common approaches for adrena- lectomy are ventral midline celiotomy and the paracostal (retroperitoneal) approach.20-23 The paracostal approach involves minimal dissection and provides the best exposure of a single adrenal gland, the ipsilateral kidney and the retroperito- neal space, but exposure of the rest of the abdomen is extremely limited. Ventral midline celiotomy al- lows exposure of both adrenal glands as well as the rest of the abdominal contents, permitting inspec- tion for gross evidence of metastases.2º In a report of adrenalectomy in 25 dogs, the preferred ap- proach was ventral midline celiotomy with para- costal extension of the incision if needed.20 Adre- nalectomy of the ferret by use of a paracostal approach has been reported; however, this proce- dure has not been evaluated in ferrets with diseased adrenal glands.21 The ventral midline celiotomy used in the ferrets of the present study allowed full exposure of the abdomen and retroperitoneal space, evaluation of the contralateral adrenal gland, and inspection for metastatic disease. Surgical ex- cision of the right adrenal gland in 2 ferrets was
technically more difficult because of the proximity of the right adrenal gland to the caudal vena cava and liver. Reported intraoperative complications of adrenalectomy in dogs and cats include hemor- rhage from the adrenal arterial supply and lacera- tion of major vessels close to the adrenal glands, such as the caudal vena cava.
Corticosteroids were given postoperatively be- cause of the possibility that the tumors were secreting excessive amounts of cortisol. If these were cortisol-producing tumors, one would expect contralateral adrenal gland atrophy secondary to negative feedback effects on the pituitary gland and decreased ACTH secretion.13 On the other hand, if the adrenocortical tumors were estrogen-secreting tumors rather than cortisol-secreting tumors, there would be no adrenocortical suppression of the contralateral gland, and, therefore, no supplemen- tation would be needed. In 2 of the 5 ferrets, the contralateral adrenal gland was difficult to identify at surgery, suggesting adrenal gland atrophy. How- ever, none of the ferrets had clinical signs of hypoadrenocorticism after surgery.
In 1 ferret, the tumor was initially diagnosed as a pheochromocytoma; however, the lack of argy- rophilic granules suggested that the tumor origi- nated from adrenal cortex, and the final diagnosis was adrenocortical adenoma. Definitive differenti- ation between cortical and medullary tumors de- pends on chromate fixation and the demonstration of a positive chromaffin reaction.24,25 Unfortu- nately wet tissues were not available for this stain- ing procedure at the time of this study.
All of the ferrets in this study, and 2 of the 3 other ferrets with adrenal tumors that have been reported, were middle-age to older spayed ferrets. Ovariectomy of 1- to 3-day old mice of a specific strain (JAX ce) resulted in the appearance of adrenocortical carcinomas in all ovariectomized mice > 6 months old.26 Adrenal tumors were not identified in control animals. The uterus, vaginal epithelium, and mammary glands did grow and develop, and investigators attributed this to estro- genic or androgenic hormone production.27 It is common practice for commercial vendors to neu- ter ferrets at 5 to 6 weeks of age before delivering them to pet stores, and it is possible that this is as- sociated with the development of adrenocortical tumors.
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