Surgical Diseases of the Ferret

It is estimated that 7 to 10 million ferrets are owned as pets in the United States [1]. Besides traumatic injuries and gastrointestinal foreign bodies, the majority of surgical diseases in ferrets are neoplastic conditions. A group of black-footed ferrets that spent their entire lives in a captive setting had a 100% incidence of cancer at necropsy [2]. It is also common for more than one type of tumor to be present simultaneously in a ferret, with one type usually diagnosed as an incidental finding at surgery [3-8]. The most commonly reported tumors in ferrets are endocrine tumors, with an incidence of 39.7% to 53% [6,7,9,10]. Pancreatic beta-cell tumors or insulinomas are the most common endocrine tumors, and adrenal tumors are the second most common [8-10].

Surgical procedures in ferrets are similar to those performed in dogs and cats. Because of the small body size of ferrets, microsurgical instruments, magnifying loupes, smaller suture sizes, body-temperature support devices, and smaller retractors (Lone Star retractor, Lone Star Medical Products, Stafford, TX) are important (Fig. 118-1). For a majority of the surgical diseases described in this chapter, a ventral midline laparotomy is indicated. Ferrets have relatively thick skin, little subcutaneous tissue, and a wide, thin linea alba [11].

Figure 118-1. Lone Star retractor being used in the abdomen of a ferret.

In the United States, 2 years represents 25% of the average lifespan of ferrets [8]. If the goal of treatment is to prolong life and improve the quality of life of the ferret, then a 1- to 2-year survival with a good quality of life is considered a success.

Insulinoma

Pancreatic beta-cell tumors are the most commonly reported endocrine tumors in ferrets, with a reported incidence of 21.7% to 25% [6,7,10,12-16]. The median age of ferrets with insulinomas is 5 years (range 2-7 years), with males being diagnosed more frequently than females [7,17,18].

Disease Mechanism

The four types of islet cells are beta cells (insulin secretion), alpha cells (glucagon secretion), delta cells (somatostatin secretion), and F cells (pancreatic polypeptide secretion) [19]. Islet cell tumors in ferrets arise from the beta cells and produce insulin, which, when present in excess amounts, leads to hypoglycemia [6,8,9,19,20]. Functional insulin-secreting conditions in ferrets include pancreatic hyperplasia, adenoma, and adenocarcinoma [6,7,17,21]. Neuroglucopenic signs occur because cells in the central nervous system have a higher metabolic rate and glucose is their primary energy source [19,22]. Prolonged and severe hypoglycemia can cause brain damage and, clinically, patients present with neurologic dysfunction [9,19,22].

Clinical Signs

Clinical signs may not be apparent and the tumor is sometimes diagnosed on health screen biochemical examination or at exploratory laparotomy for another reason. Clinical signs are related to the systemic effects of hypoglycemia, the rate of decline of the blood glucose concentration, and the duration and degree of hypoglycemia.19 Clinical signs in ferrets with hypoglycemia include hind limb ataxia, paresis or paralysis, seizures, weight loss, ptyalism, gagging, vomiting, and pawing at the mouth. [6,7,12,14,17,21,23,24]. Pawing at the mouth is thought to be associated with nausea, but may lead owners and clinicians to believe there is a foreign object in the mouth or throat [8,25]. Owners may report a prolonged waxing and waning history of lethargy and episodes of collapse. They often describe the ferret as having a "glazed" eye appearance [19]. Physical examination of ferrets with an insulinoma may be unremarkable as the hypoglycemia can be episodic.

Diagnostics

The reference range for resting blood glucose concentration in ferrets is 94 to 207 mg/dL and normal fasting blood glucose levels are 90 to 125 mg/dL [19]. Insulin levels can be run concurrently but will only be diagnostic if the patient is hypoglycemic at the time of sampling [19,26,27]. If serum glucose levels are normal and a high clinical suspicion for insulinoma exists, a controlled fast can be performed for no more than 4 hours to better establish hypoglycemia. It is best to fast the ferret in the hospital in case a hypoglycemic crisis occurs. Because ferrets have a rapid gastrointestinal transit time (3-4 hours), a shorter fast than in dogs and cats is diagnostic. A 4-hour fasting glucose concentration less than 60 mg/dL is consistent with a pancreatic islet cell tumor in a ferret [20,21,27]. Typically, abdominal radiography and ultrasonography are not helpful in detecting these masses as they are usually only millimeters in diameter [8,19].

Treatment

Treatment is aimed at increasing blood glucose levels by both medical and surgical means. It is common (> 50% of surgical cases) that after surgical excision, medical management is still indicated [17]. Only 14% to 15% of ferrets with insulinoma are cured long-term with surgery [7,17,19,28]. This may be due to the high recurrence rate or micrometastatic rate of ferret insulinoma to other regions of the pancreas, regional lymph node, spleen, or liver; however, some have found the metastatic potential to be low [17,24].

Surgical excision is the treatment of choice for ferrets under 6 years of age or for those suspected of having concurrent adrenal disease [19]. Surgery is indicated for confirmation of insulinoma, for decreasing the tumor burden, and to better evaluate for metastatic and concurrent disease (Fig. 118-2) [27]. Removal of the left lobe of the pancreas is technically less challenging than removal of the right lobe because of the close proximity of the right lobe to the pancreatic ducts, duodenum, and adjacent blood vessels [21,29].

Figure 118-2. An insulinoma removed from the left limb of the pancreas of a ferret. This was an unusually large tumor. Most insulinomas in ferrets are less than a centimeter in diameter.

The pancreas of ferrets is similar to that of cats in that there is typically a common pancreatic duct that joins with the common bile duct and enters the duodenum at the major duodenal papilla. An accessory pancreatic duct is present in about 2.5% of ferrets [11,13]. Medical management can be used concurrently with surgery or as the sole modality for treatment. Ferrets with insulinomas managed medically without surgery have a shorter survival than those treated with surgery or a combination [17]. Medical management is aimed at increasing blood glucose levels. Glucocorticoids increase hepatic gluconeogenesis and decrease glycogenolysis [19,27,30]. Liquid formulations of prednisone or prednisolone are available for more accurate dosing. It is important that the solution does not contain sugar or alcohol that can exacerbate the hypoglycemia. [8,19].

Diazoxide is a nondiuretic benzothiadiazide that effectively increases serum glucose levels by different mechanisms. It inhibits pancreatic islet cell insulin secretion and enhances hyperglycemia by stimulating the beta-adrenergic system and inhibiting the uptake of glucose by cells [15,31,32]. Diazoxide has no antineoplastic activity nor does it affect the synthesis of insulin [31,32]. Glucocorticoids and diazoxide can be given alone or in combination as needed to combat the effects of systemic hypoglycemia. Streptozotocin is a chemotherapeutic agent that exhibits a diabetogenic effect on pancreatic beta cells in dogs but not in humans and has not been evaluated in ferrets [8,32].

Diet is also important in the medical management of insulinomas in ferrets. Feeding a high-protein, low-carbohydrate diet at frequent intervals is necessary. Treats and snacks, especially those containing sugar, should be avoided [8,19,27]. It has been recommended that serial blood glucose concentrations be taken at 2 weeks postsurgery and at 1-4-month intervals for the life of the ferret [11,19].

Prognosis

The prognosis for ferrets with insulinomas varies but is generally better than for that of dogs with insulinomas [7,12,21,23,24,26]. Young ferrets without metastatic disease that are diagnosed early in the disease process have the best prognosis [27]. With partial pancreatectomy, mean survival time is 668 days; multiple surgeries are sometimes needed to achieve longer survival times [7,8]. The duration of clinical signs before diagnosis may negatively affect survival time and disease-free interval after surgery [14]. No difference in survival time has been identified between ferrets with benign versus metastatic disease [12,17].

Adrenal Disease

Adrenocortical cell tumors are the second most common tumors in ferrets [3,6,10,18,30,33-36]. The occurrence of hyperadrenocorticism in domestic ferrets in the United States is common and may be present in up to 25% of all ferrets. [3,6,37]. The first report of hyperadrenocorticism in a domestic ferret was in 1987 [38]. Since then several reports identifying the hormones elevated in ferret hyperadrenocorticism and the pathophysiology of the disease have been published [3,33,34,39]. The mean age of affected ferrets is 3.4 to 4.8 years, with females having a predilection for the disease [3,30,35], although one study refutes this finding [37].

Disease Mechanism

These are adrenal cortical reticularis tumors, which produce excessive levels of androgenic hormone precursor and estrogenic hormones. Increases in serum cortisol levels are typically not a feature of this disease in ferrets, nor is primary pituitary disease likely [8,19,27,35,40-42]. These tumors histologically are characterized as adrenal cortical hyperplasia, adenomas, or adenocarcinomas, and it is possible that this is a continuum of a disease process [3,43]. The clinical signs and prognosis are the same regardless of the histopathologic diagnosis [2,3,8,30,37]. Adrenocortical spindle-cell tumors and pheochromocytomas have also been reported alone and concurrently with functional adrenocortical cell neoplasms in ferrets [9,18,19,30,44]. The incidence of adrenal disease in ferrets in Europe and Australia appears to be much lower than in the United States. It has been speculated that adrenal gland hyperplasia and tumor development are due to the early neutering of ferrets [27,45,46]. This has been shown to occur in mice [45]. Other suggested causes include feeding a commercial brand ferret food (instead of whole prey items), inbreeding, and the lack of a natural light cycle for ferrets in the United States [19].

Clinical Signs

Clinical signs in ferrets with functional adrenocortical tumors are primarily a result of the hypersecretion of estrogenic and other steroid hormones by tumor cells [9]. Clinical signs are variable in affected animals and may include a bilaterally symmetrical endocrine alopecia which may be seasonal, pruritis (sometimes the only clinical sign), vulvar enlargement in females, prostatic enlargement in males, aggressive sexual behavior, comedones on the tail, and mammary gland enlargement (Fig. 118-3). [3,19,20,28,33,37,39,47]. Males with prostatic disease secondary to hyperadrenocorticism may present with dribbling urine or straining to urinate and defecate. Prostatic abscessation, paraurethral cysts, and urinary obstruction can also accompany the disease in males. Large tumors can be palpated in the cranial abdomen.

Figure 118-3. The ventral abdomen of a female ferret diagnosed with hyperadrenocorticism. Notice the alopecia of the ventral tail and abdomen. Moderate swelling of the vulva is secondary to an increase in circulating estrogens and androgens.

Diagnostics

Hyperadrenocorticism in ferrets is diagnosed based on a combination of clinical signs, abdominal ultrasound, and plasma concentrations of estrogens and androgens [19,34,35,40,41]. Serum chemistry and hematologic profiles are usually normal except for the occasional thrombocytopenia and anemia, thought to occur owing to estrogen-induced bone marrow suppression [3]. In ferrets with anemia and pancytopenia, a packed cell volume less than 15% is associated with a grave prognosis [19]. A serum androgen profile has been established and is commercially available at the University of Tennessee. The assay measures levels of 17-hydroxyprogesterone, androstenedione, and estradiol. An elevation of any one of these hormones is considered diagnostic for hyperadrenocorticism in ferrets [19,33,34]. Elevations in dehydroepiandrosterone may also be detected in ferrets with adrenal disease [40]. Urine cortisol:creatine ratios are not useful in diagnosing hyperadrenocorticism in ferrets because serum cortisol is not elevated in these patients, [3,41], although one study disagrees with this [35].

History and physical examination appear to be the most useful in diagnosing the disease. Abdominal radiographs are usually unremarkable unless the mass is large or if mineralization of the affected adrenal gland has occurred [3]. Adrenal lesions are the most commonly found ultrasonographic abnormalities in ferrets [8,48,49]. Ultrasound has been reported to have an 84% sensitivity for detecting adrenal disease in ferrets, with histopathology being the gold standard [43]. Ultrasound findings in ferrets with hyperadrenocorticism may also include a prominent uterus or uterine stump, or a prominent prostate with or without prostatic cysts [43]. The authors have also observed ultrasonographic evidence of urinary tract dilation (urethra, bladder, and ureters) owing to an enlarged prostate obstructing the prostatic urethra.

Treatment

Currently, medical management of adrenal disease in ferrets is focused on controlling abnormal hormone levels and their effects. These treatments do not cure the condition but may help alleviate clinical signs. Medical management is recommended if the owner is unable to afford surgery, if the ferret is a poor surgical candidate, or if the ferret has bilateral adrenal tumors that cannot be resected [19]. The use of leuprolide acetate, a repositol gonadotropin releasing hormone (GnRH) analog, causes a transient increase and then a rapid decrease in luteinizing hormone, follicle-stimulating hormone, and testosterone levels [19,50]. It is rare that patients become refractory to leuprolide acetate treatments [8]. Other hormone therapies include bicalutamide, anastrazole, and melatonin [8,19,51].

A ventral midline and a lateral celiotomy have been described for adrenalectomy in ferrets (Fig. 118-4) [20,52-59]. In 85% of ferrets with hyperadrenocorticism, one adrenal gland is enlarged and the other is small to normal. In the remaining 15% of cases, bilateral adrenal enlargement is identified [3,37]. In unilateral enlargement, disease may occur in the contralateral gland after the affected adrenal is removed [37]. In some cases, both adrenal glands will appear grossly normal and direct visualization of the entire gland via careful dissection of surrounding retroperitoneal fat is necessary. Historically, the recommended surgical treatment for bilateral adrenal disease in ferrets has been total adrenalectomy of the one side and partial resection of the contralateral side [40,57]. This will ultimately lead to recurrence of the disease as the remaining adrenal tissue proliferates, and it may not even temporarily relieve clinical signs.

Figure 118-4. A 2 cm x 1.5 cm right adrenal mass is being removed from the caudal vena cava and liver. A combination of blunt dissection with sterile cotton tip applicators, hemoclips, and bipolar electrocautery facilitate removal of these tumors.

The prostate is not grossly visible in a normal male ferret. If the ferret presented with a urinary obstruction from prostatic disease, a urinary catheter should be left in place for a couple of days until voluntary urinary function returns.

If both glands are abnormal, bilateral adrenalectomy is achievable and preferred. Removing both adrenal glands can lead to iatrogenic hypoadrenocorticism (Addison’s disease); however, most ferrets do well on glucocorticoid supplementation only and do not need long-term mineralocorticoid therapy. Most ferrets will not require long-term steroid administration [20]. Many ferrets are concurrently diagnosed with insulinoma and already on glucocorticoid therapy for that disease process. Periodic electrolyte analysis of ferrets having had a bilateral adrenalectomy is recommended because some patients will require mineralocorticoid therapy.

Prognosis

Following complete surgical removal of the affected gland or glands, prostatic and vulvar enlargement decreases within days and hair regrowth occurs within 3 months [8]. The prognosis for adrenal gland disease in ferrets is good, if the gland is completely excised, owing to a low metastatic potential [3,8,27,30].

Splenomegaly

Splenomegaly is a common finding in adult ferrets but is poorly understood [11,60,61]. The spleen in ferrets increases gradually and slightly in size with increasing age [30] but can also enlarge owing to proliferative lesions, reactive processes, compensatory mechanisms, or certain anesthetics [29,60]. The most common cause of splenomegaly is extramedullary hematopoiesis (EMH) in the presence or absence of anemia or other hematologic dyscasias [60-62]. Other causes include lymphoma, insulinoma, cardiomyopathy, adrenal disease, systemic mast cell tumors, Aleutian disease, eosinophilic gastritis, hemangiosarcoma, primary splenic neoplasia, hypersplenism, and splenitis [54]. Most causes of splenomegaly are not surgical diseases and should be evaluated with clinicopathologic data and imaging modalities before splenectomy is considered. Percutaneous splenic biopsy is contraindicated in ferrets suspected of having splenic hemangiosarcoma, although this condition is rare in ferrets [54]. Ultrasound is useful in determining the safety of percutaneous biopsy. Ultrasound is also useful in guiding biopsy needles or smaller gauge needles for obtaining a sample of the spleen. Fine-needle aspiration is simple, carries little risk, is associated with low morbidity, and provides useful samples.

Indications for splenectomy in ferrets include splenic neoplasia, splenomegaly or hypersplenism causing compression of abdominal viscera, splenic torsion, and non-self-limiting traumatic fractures of the spleen. Splenectomy is contraindicated in ferrets with bone marrow hypoplasia because the spleen is the primary site of hematopoiesis in these patients [54]. Ferrets with splenic extramedullary hematopoiesis may develop chronic anemia after splenectomy because of the absence of splenic production of erythrocytes.

Gastrointestinal (GI) Foreign Body

In pet ferrets, foreign body ingestion is common [11,63]. Ferrets are inquisitive and have a propensity to chew on rubber and plastic [64,65]. Ingestion of foreign objects usually occurs in ferrets under the age of 2 years, whereas trichobezoars are more commonly observed in older ferrets [64]. Linear foreign bodies are rarely seen in ferrets.

Disease Mechanism

Ferrets have a rapid GI transit time compared with other carnivores [25]. This is likely owing to a lack of the proximal-to-distal digestive-enzyme gradient seen in other carnivores, resulting in a continuous exposure of nutrients to digestive enzymes during GI transit [25]. Most GI foreign bodies lodge in the stomach or jejunum [64].

Clinical Signs

Clinical signs of gastrointestinal foreign bodies in ferrets include anorexia or inappetence, diarrhea, ptyalism, facial rubbing, and vomiting (although this is not commonly reported by the owners) [63-65]. Abdominal palpation may elicit discomfort. Palpation of the foreign body is usually possible, especially if it is in the intestinal tract [10,63-65].

Diagnostics

Diagnosis is based on signalment, history, and physical examination. Ferrets have an abdomen that is easy to palpate, making most foreign bodies readily palpable within the gastrointestinal tract [54]. A complete blood count, serum biochemistry panel, and urinalysis should be performed. Abdominal radiographs and ultrasonography are useful in confirming the diagnosis and determining the location of the obstruction (Fig. 118-5). The ferret should be stabilized with intravenous fluids before surgical removal is pursued.

Figure 118-5. A right lateral abdominal radiograph of a 1-year-old ferret with decreased appetite and lethargy. Notice the numerous, circular, soft-tissue opacities in the jejunum. Fluid and gas dilation of the small intestine is present. This ferret had a jejunal foreign body obstruction.

Treatment

Most GI foreign bodies in ferrets must be removed surgically. Gastrointestinal foreign bodies in ferrets rarely pass on their own. The use of gastrointestinal lubricants and fluid replacement therapy may allow smaller nonobstructive materials to pass, especially hairballs [65].

A ventral midline abdominal exploratory surgery should be performed in any ferret with a GI foreign body. Ferrets lack a grossly obvious ileum, and the jejunoileum extends from the duodenojejunal flexure to the ascending colon [11,13]. A gastrotomy and/or enterotomy are usually indicated, with intestinal resection and anastamosis less frequently necessary.

Prognosis

In general, ferrets have an excellent prognosis after surgery for foreign body removal as long as a perforation and septic peritonitis are not present. Intestinal necrosis or perforation seem to occur less frequently in ferrets compared with dogs and cats with foreign body obstruction. Preventing foreign body ingestion can be difficult in ferrets. Usually by 2 years of age, ferrets ingest foreign bodies less frequently. The routine use of GI lubricants to prevent trichobezoars is helpful.

Gastrointestinal Neoplasia

GI neoplasia has been reported in ferrets [6,10,18,30,66-69]. but it is not a common site for primary neoplasia [65]. Pyloric adenocarcinoma has been described in ferrets and clinical signs include those associated with an upper GI obstruction: vomiting, weight loss, anorexia, and lethargy [6,67,68].

The anatomy of the ferret stomach is similar to that of dogs, but is physiologically more like the human stomach [13,25]. Blood gas analysis commonly reflects a hypochloremic metabolic alkalosis. Ultrasound is useful in diagnosing the presence and location of the mass. Attempts at surgical resection with a Bilroth have been made but were unsuccessful [67,68]. Palliative stenting across the pylorus of a ferret with adenocarcinoma was successfully performed and alleviated clinical signs [69].

Obstructive Urolithiasis

Urolithiasis in ferrets can be characterized by solitary or multiple renal or cystic calculi or by the presence of sandy material in the urinary bladder and urethra [70]. Clinically, obstructive urolithiasis tends to be less common now than it was 10 years ago [70]. Obstructive urolithiasis is more common in male ferrets than in female ferrets owing to the narrow diameter of the urethra as it passes through the os penis in males. The most common type of stone identified in ferrets is magnesium ammonium phosphate (struvite) [70].

Disease Mechanism

Although not studied as extensively as in dogs and cats, the pathogenesis of struvite urolithiasis in ferrets is probably related to diet [70]. Ferrets are carnivores with a normal urine pH of about 6.0 [71]. Struvite crystallizes when the urine pH rises above 6.4. Although the mineral content of the food was once thought to be the cause of urolithiasis in ferrets, it is now thought to be caused by ingestion of plant proteins [70]. The metabolism of organic acids in plant protein produces an alkaline urine that results in the formation of struvite crystals [71]. This was demonstrated in a group of pregnant jills fed a diet high in plant protein (mainly corn) and in a group of ferrets fed a commercial dog food [71,72]. Historically, the prevalence of the disease in the American ferret population was probably related to feeding poor quality dog and cat diets that contained a high percentage of plant-based protein. In recent years, many commercial ferret diets have become available and ferrets are not commonly fed dog and cat foods with plant proteins.        

Clinical Signs

The systemic effects of obstructive urolithiasis in ferrets are the same as those in dogs and cats. Dysuria, hematuria, stranguria, frequent licking of the perineum, and urine dribbling are reported clinical signs in ferrets with urolithiasis [70]. Ferrets with obstructive urolithiasis may strain violently or cry when attempting to urinate, or they may present depressed, moribund, or comatose. Rarely, ferrets present with lethargy and inappetence without lower urinary tract signs.

Diagnostics

The presence of lower urinary tract signs and palpation of a firm, distended, unexpressable urinary bladder confirms an obstruction. Obstructive urolithiasis can be identified with abdominal radiographs because struvite stones are radioopaque. However, sand is not always visible radiographically. Abdominal ultrasound is often useful as the fine sand-like crystals are easily identified. It is also helpful if another cause is suspected (prostate disease secondary to adrenal neoplasia) and to identify radiolucent urinary calculi. Serum chemistry and hematologic profiles should be run to determine the extent of azotemia and electrolyte abnormalities, as well as to look for concurrent disease.

Treatment

If severe cardiac arrhythmias and electrolyte abnormalities are present, they are treated before attempting to unobstruct the urethra. Once intravenous fluids and supportive care have been initiated, the urethra should be unblocked. The treatment of obstructive urolithiasis in male ferrets is challenging because it is difficult to pass a urinary catheter in males. Males have an operculum covering the distal urethra and a hook directed dorsally at the tip of the os penis, making it difficult to identify the urethral opening [58]. The technique for urinary catheterization in ferrets has been described [54,73].

If the distal urethra cannot be cleared of stones or if the ferret has recurrence of obstruction, an emergency cystotomy, percutaneous tube cystostomy, or perineal urethrostomy (PU) can be performed if the ferret is stable.

The anatomy of a ferret penis is similar to that of a dog [58]. The penis exits the pelvic canal, runs subcutaneously along the ventral pelvis, and lies along the caudal ventral abdominal body wall [58]. The opening of the prepuce is just caudal to the umbilicus. The PU site should be between the caudal portion of the os penis and the pelvic urethra. The stoma should be perineal and not ventral to avoid trauma to the site during normal ambulation. The penis is not resected as is done in cats. A 3.5 to 5.0 Fr red rubber catheter is then placed in the proximal urethrostomy site to assess the diameter of the urethra and make sure it is patent. Fine monofilament suture (6-0 to 8-0) is used to appose the mucosa of the urethra to the skin. The urethral drain board should be at least 1 cm. This technique works well in ferrets and is well tolerated long term.

Prognosis

If the ferret is on an inappropriate diet it should be changed to a commercial ferret diet with no plant protein source. The ferret should be monitored for struvite urolithiasis every 3 to 6 months with a urinalysis and abdominal radiographs. The prognosis is good for ferrets with obstructive urolithiasis if they are stabilized before general anesthesia. Recurrence can happen but is uncommon when dietary changes are made.

Blood Products

Many of the surgical diseases presented in this chapter require aggressive and challenging operative procedures. The use of perioperative blood products may be needed in some cases. Whole blood or packed red blood cell transfusions have been used in clinical patients. Ferrets have only one blood type and transfusion reactions have not been reported in ferrets, but minor cross-matches are still recommended by some [8,25,74]. Oxyglobin (Biopure, Cambridge, Massachusetts) is a hemoglobin replacement product that increases the oxygen carrying capacity of the blood and has been used in ferrets with no reports of adverse reactions. The beneficial effects are still speculative.