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.
Introduction
Adrenal disease is a common finding in middle-aged to older ferrets.1 The common diagnoses include adrenal nodular hyperplasia, adrenocortical adenoma, or adrenocortical adenocarcinoma affecting one or both adrenal glands. The disease is characterized by bilaterally symmetrical dorsal alopecia, with or without pruritis. It has been previously reported that >90% of affected ferrets have some degree of hair loss.23 In addition, approximately 90% of affected spayed females have vulvar enlargement, with or without vaginal discharge.23 Less commonly, neutered male ferrets have dysuria, urinary blockage, or both. Rosenthal, et al.3 reported that of 15 ferrets with adrenal disease, none had dysuria, while Wagner and Dorn2 reported that two of seven ferrets with adrenal disease had dysuria and cystic prostatic disease. Hyperplasia or cystic change in the tissue in the area of the prostate can cause urethral compression, which leads to stranguria and dysuria.1 Progressive compression can result in complete urethral obstruction, a life-threatening complication requiring immediate attention. Therapeutic choices include cystocentesis, urethral catheterization, and tube cystostomy. The purpose of this paper is to describe the use and outcome of temporary tube cystostomy in four ferrets for treatment of urinary obstruction secondary to adrenal disease.
Materials and Methods
Patients
The ferrets considered eligible for this procedure were suspected to have adrenal disease with secondary urinary obstruction based on clinical signs, clinical pathology, radiography, and ultrasonography. Urinary catheterization was successful in three of four ferrets, all of which reobstructed following catheter removal; in two ferrets, their catheters were removed prematurely and the third ferret had his catheter deliberately removed at 24 hours. The disease was confirmed by exploratory celiotomy.
Surgical Technique
The ferrets were induced by isoflurane mask, intubated, and maintained on isoflurane inhalant anesthesia. The ventral abdomen was clipped and prepared aseptically for surgery. An exploratory celiotomy was performed. The adrenal masses were treated by complete adrenalectomy of the affected gland, except in the case of bilateral disease, in which a complete right adrenalectomy (for the larger mass) and a partial left adrenalectomy were performed.4 The prostatic area of the proximal urethra just caudal to the neck of the bladder was examined during surgery and was thickened in all ferrets. Two ferrets were diagnosed with prostatic cysts based on gross findings. The prostate area was not biopsied due to low yield in recovering actual prostatic tissue in this scenario.5 The decision to perform a tube cystostomy was based on the identification of a nonexpressible bladder, an adrenal mass, and prostatomegaly, prostatic cysts, or paraurethral swelling at surgery and a history of urinary obstruction preoperatively. The cystostomy procedure performed was similar to that previously described in dogs.6 During exploratory celiotomy, a paramedian stab incision was made in the ventral body wall with a no. 15 scalpel blade, through which the cystostomy tube, a 5- or 8-French Foley catheter,a was passed. The bladder was then exteriorized, and a purse-string suture was placed in an avascular, ventral portion of the bladder wall with 3.0-poly-dioxanone suture.b A stab incision was made in the center of the purse-string suture entering the bladder lumen. The Foley catheter was then passed into the bladder through the stab incision, and the balloon was inflated with sterile saline. The purse-string suture was then tightened around the catheter and tied. Finally, the catheter was used to bring the bladder in close approximation to the body wall, and simple-interrupted tacking sutures between the body wall and the bladder were placed for additional security. The abdomen was closed routinely. The stab incision in the skin was closed with another purse-string suture, which continued as a Chinese finger-trap suture around the Foley catheter. The Foley catheter was capped with a catheter adapterc and intermittent injection cap.d A light abdominal wrap or body stockinet was applied, and an Elizabethan collar was placed to protect the tube from self-trauma. Intravenous (IV) fluid and antibiotic therapy were continued, and corticosteroid supplementation was given postoperatively if warranted (i.e., continuing lethargy or anorexia). The cystostomy tube was aspirated every 2 hours.
Results
Signalment, Clinical Signs, and Physical Examination
All four ferrets were castrated males and were evaluated because of unproductive stranguria [see Table]. The mean age at presentation was 3.7 years (range, 2 to 6 years). Lethargy and anorexia were noted in addition to stranguria in two ferrets. Abnormalities identified on physical examination included a moderate to large-sized, turgid, nonexpressible urinary bladder (n=4), dorsal or tail alopecia (n=3), dehydration (n=2), and dorsally located erythema (n=1).
Clinical Pathology, Radiography, and Ultrasonography
Results of a complete blood count and serum biochemical analyses in one ferret (case no. 2) revealed azotemia, hyperkalemia, hyperphosphatemia, and hypoglycemia. Urinalysis, collected by cystocentesis, revealed hematuria and pyuria (n=4), bacteriuria (n=2), and magnesium ammonium phosphate crystalluria (n=1). On whole-body radiographs from all ferrets, no urinary calculi were identified. Other radiographic findings included a midabdominal mass effect, pulmonary infiltrate, and equivocal cardiomegaly in one ferret (case no. 2). Thoracic and abdominal ultrasonography of this ferret were within normal limits, with the exception of an enlarged, homogeneous spleen and flocculent material within the urinary bladder, suspected to be urinary sand or blood clots. At surgery, prostatic fluid was drained from a prostatic cyst in one ferret (case no. 3) and was submitted for bacterial culture and sensitivity, which resulted in no growth.
Surgical Findings
At surgery, adrenal masses were identified in all four ferrets. Treatment included right adrenalectomy (n=2), left adrenalectomy (n=1), and right adrenalectomy and partial left adrenalectomy (n=1). Single, small (1 to 2 mm) or multiple pancreatic nodules (n=3) were identified and removed by blunt dissection. Prostatomegaly (n=4) and prostatic cysts (n=2) were also identified at surgery. One cyst had ruptured into the peritoneal cavity, causing a serosanguineous peritoneal effusion. The other cyst was drained via a needle and syringe, and the fluid was submitted for culture and sensitivity. An omental nodule (n=1) was identified and excised. The combination of prostatomegaly with urethral obstruction was the indication to perform the tube cystostomy.
Histopathology
The tissues submitted included left adrenal gland (n=1), right adrenal gland (n=2), left and right adrenal gland (n=1), pancreatic nodules (n=3), and omentum (n=1). Adrenocortical adenoma (n=2) and adrenocortical adeno-carcinoma (n=2) were diagnosed on histopathological examination. Pancreatic histopathology revealed benign acinar cell hyperplasia (n=1) and islet cell tumors (n=2). Omental histopathology revealed metastatic adenocarcinoma (n=1).
Postoperative Care
All ferrets recovered from anesthesia and received IV lactated Ringer’s solution at a rate of 20 to 40 mL/kg per hour, ampicillin (22 mg/kg body weight, IV, tid), and cystostomy tube aspiration every 2 to 3 hours. Two ferrets were treated with postoperative prednisone (1 mg/kg per day IV or subcutaneously [SC] for 2 to 3 days). One ferret (case no. 2) was treated with enrofloxacin (5 mg/kg body weight, SC, bid) and cimetidine (10 mg/kg body weight, IV, tid). Abdominal bandages or stockinettes were placed on all ferrets and were changed as necessary.
Outcome
Anorexia, originally seen in two ferrets, resolved postoperatively in 6 hours and 48 hours, respectively. Voluntary urination resumed in a median of 60 hours (range, 6 to 120 hours). One ferret was humanely euthanized 5 days after surgery because of the diagnosis of adrenocortical adenocarcinoma with omental metastasis. The remaining three ferrets were discharged 2 to 4 days after surgery. Hospital discharge occurred once the ferrets were eating and drinking and it was determined that the bladder could be adequately emptied via cystostomy tube aspiration or normal voiding. The owners were instructed to drain the bladder every 4 to 6 hours by aspiration of the tube with a syringe. An Elizabethan collar was used at all times to prevent premature removal of the cystostomy tube, and amoxicillin (22 mg/kg body weight, per os, bid) was dispensed. It was recommended that the ferrets be cage confined during the postoperative period. The owners reported that the tubes were easily managed at home, except for the occasional scratching or biting at the bandage and tube if the Elizabethan collar was removed. Cleaning of the tube exit site was not routinely required. Follow-up visits revealed minimal drainage and inflammation at the exit site of the cystostomy tubes. The cystostomy tubes remained in place for a median of 9.8 days (range, 5 to 14 days). Two of the four ferrets damaged their cystostomy tubes by self-trauma, one of which was beyond repair and was removed prematurely at 5 days postoperatively. All ferrets were urinating normally at the time of tube removal. Long-term outcome included recurrence of urinary obstruction in one ferret diagnosed with adrenal adenocarcinoma at 6 months, while the two remaining ferrets, diagnosed with adrenal adenoma, were euthanized for problems unrelated to urinary obstruction at 8 and 24 months.
Discussion
Adrenal disease commonly affects middle-aged to older ferrets. Ninety-five percent of generalized alopecia in the neutered ferret >3 years of age is secondary to adrenocortical hyperplasia or neoplasia.4 Other presenting clinical signs include vulvar enlargement in females and dysuria in males. The common clinical signs seen in dogs with hyperadrenocorticism are polyuria, polydipsia, weakness, and pot-bellied appearance, which are induced by glucocorticoid excess. Studies have shown that hyperadrenocorticism in ferrets is not commonly associated with increased glucocorticoids, as shown by normal baseline cortisol levels and adrenocorticotropic hormone (ACTH) stimulation tests.23 Androgens are the likely product of the hyperplastic or neoplastic adrenal gland, accounting for the difference in presentation. Rosenthal, et al.3 reported that plasma estradiol concentrations in male and female ferrets with adrenocortical disease were significantly higher than the mean plasma concentration in clinically normal ferrets, and four of 11 (36%) ferrets tested had high baseline values. Lipman, et al.7 detected high estradiol-17 β concentration in a ferret with an adrenocortical adenoma that presented for alopecia and vulvar enlargement. Two days postadrenalectomy, the level had returned to normal. Wagner and Dorn2 found high serum estradiol concentrations in 15 of 17 male and female ferrets with adrenal tumors, while cortisol, testosterone, and thyroxin concentrations were within the published reference ranges. It seems another androgen is also being produced by adrenal tumors, since not all male and female ferrets described in the previous studies have high estradiol levels.
Elevated androgen levels result in an adrenal-associated endocrinopathy in which bilaterally symmetrical alopecia, feminizing syndrome in spayed ferrets, and urogenital abnormalities in castrated males are seen.7 In castrated young dogs, prostatic hyperplasia, including cystic changes, can be induced by the administration of androgens, an effect markedly exacerbated by the simultaneous administration of estradiol.8 Androgen-associated prostatomegaly is suspected in these ferrets, resulting in urinary obstruction if severe. Urinary obstruction generally resolves within days after the removal of the diseased adrenal gland.9 There is some controversy regarding whether the involved tissue is truly prostatic tissue or not. One source states that ferrets lack a prostate gland,10 whereas authors of another report identify the prostate at the base of the bladder surrounding the urethra.11 Regardless, this prostatic or “paraurethral” tissue regresses in response to adrenalectomy.
Differential diagnoses for a ferret presenting with dysuria or urinary obstruction include urolithiasis, urinary tract infection, bladder neoplasm, and prostatic disease. Urolithiasis as well as urinary tract infections are rare in the ferret. If uroliths are present, the most common type is magnesium ammonium phosphate, which is easily identifiable on radiographs. Diseased prostatic tissue surrounding the urethra, including hyperplasia, cysts, infection, or neoplasia, can cause constriction of the urethra lumen. Sterile or infected prostatic cysts associated with adrenal disease and prostatic abscess associated with bladder neoplasia have been described in ferrets.11 In general, prostatic enlargement causes urinary obstruction more often than urolithiasis does and should be the primary rule-out in a male ferret. Urinalysis, urine culture and sensitivity, radiographs, and ultrasonography are useful diagnostic tools to investigate the cause of dysuria.
In the four cases presented here, urethral obstruction was suspected to be secondary to adrenal disease. Three of the four ferrets had alopecia, while the remaining ferret had pruritis in conjunction with dysuria, making adrenal disease with secondary prostatomegaly the most likely scenario. Biochemical analyses in one ferret revealed azotemia, hyperkalemia, and hyperphosphatemia, which were attributed to postrenal obstruction. Hypoglycemia was also identified. Sepsis or a pancreatic islet tumor was suspected; the latter was confirmed with histopathology. These abnormalities resolved in 3 days postoperatively. Radiographs of three ferrets revealed no urinary calculi. In the remaining ferret (case no. 2), radiographs were not obtained due to a previous diagnosis of adrenocortical adenoma and the decision to use exploratory laparotomy as a diagnostic and therapeutic tool. No calculi were found at surgery. In all ferrets, urinalysis revealed inflammatory sediment that could be attributed to urinary obstruction. In one ferret, the urinalysis revealed hematuria, pyuria, bacteriuria, and crystalluria (magnesium ammonium phosphate), and the abdominal ultrasound showed hyperechoic material in the urinary bladder. In this case, urolithiasis may have contributed to the urethral obstruction, but this was thought to be unlikely because of the ease of urethral catheterization.
Current recommendations include performing a complete blood count, serum biochemical analyses, urinalysis, urine culture and sensitivity, androgen levels, radiography, and ultrasonography when investigating a case of stranguria/dysuria in a ferret. Typical findings in a ferret with hyperadrenocorticism include a normal complete blood count and biochemical analysis, normal or inflammatory urinalysis, negative urine culture, increased androstenedione and estrogen levels, normal radiographs, and possible adrenal or prostatic changes on abdominal ultrasound. The described workup, with the exception of hormonal analysis and urine culture and sensitivity, was completed in only one ferret presented here. Estradiol and androgen blood levels can be used to strongly support a diagnosis of adrenocortical disease. The full workup was offered, but declined in most cases due to economic constraints. Exploratory laparotomy was chosen as a diagnostic and therapeutic tool and is typically rewarding. The most common ferret diseases (e.g., adrenal tumors, insulinomas, lymphoma, foreign bodies, etc.) can be diagnosed and treated via exploratory laparotomy. One must realize that the chance of a negative exploratory celiotomy rises without the aid of a full diagnostic workup, including hormone panels.
Treatment for a ferret with urinary obstruction and adrenal disease involves urinary diversion and adrenalectomy. Urinary obstruction secondary to simple cystic prostatic disease will resolve within days of adrenalectomy. Infected prostates may require drainage, debulking, or omentalization in order to achieve resolution.12 The options available for managing urethral obstruction include cystocentesis, urethral catheterization, and placement of a cystostomy catheter. Cystocentesis can be used, on an emergency basis, when catheterization is unsuccessful until more appropriate drainage by urinary catheterization or tube cystostomy is established. Urethral catheterization can be difficult in ferrets and has a high complication rate of blockage and self-induced removal. Urethral catheterization generally requires anesthesia. The urethral orifice is a very small slit in the ventral penis and is difficult to visualize. Catheterization was unsuccessful twice in one ferret (case no. 4) but was successful in the remaining three ferrets using a 22-gauge × 1.5-inch IV catheter, a 3.5-French Tom cat catheter, or a 3.5-French red rubber catheter. Complications included self-induced removal within 5 hours of placement in one ferret and obstruction and removal due to kinking of the catheter within 6 hours of the placement in another ferret, despite the use of Elizabethan collars. Repeated replacement of urinary catheters until voluntary voiding resumes may require many anesthetic periods and increased risk. Also, a catheterized ferret must remain hospitalized until catheter removal and normal urination is observed. Catheterization via urethrotomy is an additional option if the distal urethral opening cannot be identified. Because of the small nature of the ferret anatomy, this can be difficult. In addition, the catheter is still subject to blockage and removal. As described, the passage and maintenance of urinary catheters can be challenging, which may necessitate tube cystostomy in select cases.
Tube cystostomy was considered when complete urinary blockage was identified and urethral catheterization was unsuccessful or failed repeatedly. Indications for placement were identified at surgery (e.g., adrenal tumor with prostatic enlargement or cysts), and the owners accepted the responsibility for 10 days of postoperative care. Due to the complication rate of 100% with urethral catheters in these ferrets and the fact that urethral obstruction can take days to resolve, tube cystostomy was a sensible option. The placement of the cystostomy catheter was technically easy and did not significantly increase anesthetic times. In one study, complications of placing the cystostomy catheter included peritonitis (secondary to uroperitoneum), incisional swelling, cystitis, and catheter failure due to obstruction or balloon deflation.13 Rakeshaw, et al.,13 determined that balloon patency and failure were attributed to the process of resterilizing the Foley catheters for repeated use, so single use is recommended. The placement of an abdominal wrap and an Elizabethan collar were used to protect the cystostomy catheter, but diligent monitoring is required to prevent dislodgement, which occurred in one ferret. The guidelines for tube removal range from 5 to 10 days postoperatively.1314 Removal of the tube prematurely can result in uroperitoneum necessitating additional surgery. The complications identified in these ferrets were mild incisional swelling in one ferret and orally induced catheter damage in two ferrets. One damaged catheter was salvageable, and the other was removed prematurely at 5 days postoperatively. Peritonitis did not result. Normal urination resumed in 6 to 120 hours after catheter placement. The ferret with normal urination identified at 6 hours had evidence of a ruptured prostatic cyst at surgery (serosanguinous ascites). This may have attributed to the early return to normal voiding. In two ferrets, 4 to 5 days passed before normal voiding resumed. During this time period, the bladder was easily emptied through the cystostomy catheter. One ferret was discharged prior to the return of normal voiding. This would not have been possible if a urethral catheter was in place. In placing a cystostomy catheter, one must accept the risks associated with its placement and also the uncertainty of the duration of its use.
The use of postoperative antimicrobial therapy is very controversial. It may decrease the incidence of but will not necessarily prevent infection and can select for resistant bacteria. Antimicrobial therapy was instituted here because of the inflammatory urinary sediment and the inability to maintain an aseptic environment for the ferrets. It is recommended that urine culture and sensitivity be submitted at catheter removal.
Conclusion
Adrenocortical hyperplasia and neoplasia with secondary urethral obstruction due to prostatic hyperplasia or cysts are the primary differential diagnoses for ferrets presenting with stranguria/dysuria, especially with concurrent alopecia. Treatment may involve urinary diversion for days following adrenalectomy with urethral catheterization or tube cystostomy. Tube cystostomy is an easily performed procedure, and if carefully managed can result in an uneventful recovery with shorter hospital stays. Tube cystostomy should be considered when catheterization is unsuccessful or fails on repeated attempts or when prolonged recovery of normal urination is expected due to the severity of the prostatic disease.
Pediatric Foley catheter; Rusch, Duluth, GA
PDS II; Ethicon, Inc., Somerville, NJ
Catheter adapter; Becton Dickinson and Company, Franklin Lakes, NJ
Intermittent injection site; Kawasumi Laboratories, Inc., Tokyo, Japan
