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Authors: Joerg Mayer, D.V.M., Gretchen Kaufman, DVM
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OCW Zoological Medicine 2008
Ferret Medicine (2009)
J. Mayer, DVM, G. Kaufman, DVM
Cummings School of Veterinary Medicine at Tufts University

1. Learning Objectives and Review

1.1. Learning Objectives

This section on Ferret Medicine will give you a good review of the major husbandry challenges, diseases, and clinical approaches to ferret health issues. Color coded topics indicate learning objectives that the student should become familiar with. Cases will be presented in class to illustrate these topics. At a minimum, you will be expected to be familiar with the following:

  • Gain an appreciation for the conservation issues for Black-footed ferrets

  • Be familiar with the husbandry and preventative medicine recommendations of domestic ferrets

  • Be able to interpret ferret serum chemistry profiles

  • Understand the reasons for and consequences of neutering male and female ferrets

  • Be able recognize, diagnose and provide treatment options for the three main neoplastic diseases of domestic ferrets: insulinoma, hyperadrenocorticism and lymphoma

  • Be able to recognize and provide treatment options for the major GI disorders of domestic ferrets

  • Be familiar with the other common disorders of the domestic ferret mentioned in the text

1.2. Review

Review material presented in the Reproductive Physiology course on ferret reproduction

References and Resources

Conservation Medicine Challenges

Supplemental Readings

1

2. Taxonomy

Order Carnivora

Family Mustelidae

Ferret

Otter

Badger

Weasel

Mink

Polecat

3. Basic Ferret Information

Species: Mustela nigripes, Mustela putorius furo

Mustela nigripes is the black-footed ferret, our only native wild ferret. It is native to the Northwestern plains but is currently highly endangered and close to extinction. The black-footed ferret preys mainly on prairie dogs in the wild and often lives in old prairie dog burrows. Numbers have declined rapidly over the last century following agricultural development of the western plains and large scale poisoning (attempts at control) of prairie dog populations. Due to their severely endangered status the US Fish & Wildlife Service is coordinating a recovery program including a very successful captive breeding programs and recent attempts to reintroduce animals to previous habitat areas. Disease, management, and political problems continue to interfere with the reintroduction program. Mortalities most often involve canine distemper, plague or predator problems (coyotes). The goals of the recovery program are to establish a population of 1500 free living ferrets in 10 or more locations with a minimum of 30 breeding pairs per site (year 2010?).

Mustela putorius furo is the European ferret, related to the wild European polecat. The European ferret has been domesticated for 2,000 years. It was brought to North America by English settlers in the 17th century. It has been used for hunting, biomedical research and as a companion animal. There are an estimated 1 million pet ferrets in the US.

Domestic ferrets in the United States occur in two main coat colors: sable or fitch (wild type color) and albino (English). In addition there are over 30 color variations recognized among ferret fanciers.

Recognition of ferrets as legitimate pets has been a gradual process over the last 50 years. At this point in time ferrets are legal in every state except California and Hawaii, and New York City. They were declared legal in this state in February of 1996. Arguments against making ferrets legal included: their erroneous classification as a wild animal, concerns of establishing wild populations and displacing native wildlife, their reputation as "baby biters", and humane societies fears of another unwanted pet species they would have to deal with.

4. Basic physiologic and anatomic parameters

Body weight range

500-2,000 grams

Life span

5-11 years (typically 6-8 years)

Age at weaning

6-8 weeks

Reproductive maturity

first spring after birth

Gestation

41 - 42 days

Body temperature (avg.)

99 -103 F

Heart rate

180-250 bpm

Respiratory rate

33-36 per minute

  • In general, intact males are appreciably larger than intact females.

  • Most neutered ferrets weigh 800-1200g. They may experience seasonal weight fluctuations due to deposition of subcutaneous fat in the winter.

  • Ferrets may become very excited during a routine examination. An erratic heart rate will often be detected in this excited state. This is considered a normal finding and classified as a pronounced sinus arrhythmia.

4.1. Ferret dentition

  • Incisors 3/3

  • Canines1/1

  • Premolars 4/3

  • Molars 1/2

Teeth
Teeth

4.2. Complete Blood Count (Normal mean values for Fitch or Albino ferrets)

RBC

Male

Female

WBC

Male

Female

PCV (%)

36-50

47-51

WBC (103/μl)

7.7 - 15.4

2.5 - 8.6

RBC (106/μl)

9.7-12.4

NA

Neutrophil (%)

24 - 78

12 - 41

Hb (g/dl)

12-16.3

15.2-17.4

Lymphocyte (%)

28 - 69

25 - 95

MCV (fl)

42 - 55.9

NA

Monocyte (%)

3.4 - 8.2

1.7 - 6.3

MCHC (%)

26.9 - 35

NA

Eosinophil (%)

0 - 7

1 - 9

MCH (pg)

14 - 16.4

NA

Basophil (%)

0 - 2.7

0 - 2.9

Reticulocytes (%) (albinos)

1-12

2-14

Platelets (103/μl) (albinos)

297 - 730

310 - 910

The PCV in a normal healthy ferret may be as high as 60-70%. The WBC often runs significantly lower than expected in other carnivore species. Isoflurane may cause all values to be significantly decreased with 15 minutes due to splenic sequestration.

4.3. Serum Biochemistry (Normal values for the Fitch ferret)

Chemistry compound

Mean value

Alk. Phos. (U/l)

30 - 120

ALT (U/l)

82 - 289

AST (U/l)

57 - 248

LDH (U/l)

221 - 752

Total protein (g/dl)

5.3 - 7.2

Albumin (g/dl)

3.3 - 4.1

Globulin (g/dl)

1.8 - 3.1

BUN (mg/dl)

12 - 43

Creatinine (mg/dl)

0.2 - 0.6

Total Bilirubin (mg/dl)

0 - 0.1

Glucose (mg/dl)

62.5 - 134

Cholesterol (mg/dl)

119 - 209

Triglycerides (mg/dl)

10 - 32

Sodium (mEq/l)

146 - 160

Chloride (mEq/l)

102 - 121

Potassium (mEq/l)

4.3 - 5.3

Calcium (mg/dl)

8.6 - 10.5

Phosphorus (mg/dl)

5.6 - 8.7

Note the low creatinine levels compared with other carnivores. Normal bile acid levels have not been published for the ferret.

Jugular venipuncture
Jugular venipuncture

4.3.1. Interpreting the chemistry profile in ferrets

While the ferret is not considered to be a particularly exotic pet and in general its clinical medicine is very similar to feline clinical medicine, the interpretation of the ferret chemistry profile deserves special attention as there can be several pitfalls if ferret profiles are interpreted by comparing with cat or dog normal values. This lecture and handout will focus on some of the most important clinical pathology parameters and their interpretation.

As in other species, an exact diagnosis of a clinical problem should never be based on blood work alone, but should include an evaluation of other diagnostic tools such as biopsies. One abnormal parameter is rarely pathognomic for a problem, and often 2 or 3 clinical pathology parameters need to be assessed in order to better locate the potential origin of the clinical problem, especially if it is sub-clinical. If several different parameters are significantly altered a preliminary diagnosis can be with a high degree of certainty and then pursued with further diagnostics. Further diagnostics approaches, e.g. biopsies, should be recommended. The lecture presents clinical cases, which highlight the need to harvest biopsies early on in the diagnostic process in order to come to a definitive diagnosis and to establish an accurate treatment plan early on.

The recommended reading for a detailed discussion on GI and liver diseases of ferrets is the chapter “Ferret gastrointestinal and hepatic diseases” in the new edition of the “Ferret Husbandry, Medicine and Surgery” book (Lewington J. 2007) or the AFA proceeding 2006 (Burgess M. 2006).

4.3.2. Biochemical Parameters to evaluate different organ function:

4.3.2.1. Pancreas

  • Glucose:

    • Normal values 90-200 mg/dl

    • An extremely important parameter, as insulinoma is the most common form of cancer affecting the ferret in the USA. In ferrets older then 4 years, the blood glucose should be checked at least once a year.

    • Care has to be taken when using a human glucometer as these devices will artificially read out lower values then the true value, usually 15-20 mg/dl lower). In addition the inaccuracy of these units is around 20 mg/dl.

    • The fasting glucose (4-6 hr fast) should be between 90-120 mg/dl.

    • If animal has been fasting for longer periods of time, the glucose will be low and is not considered diagnostic for insulinoma.

    • If the animal was eating with the last 4 hours and the glucose is below 90 mg/dl (< 60 mg/dl on the human glucometer) this is diagnostic for insulinoma.

    • Blood glucose alone is diagnostic for insulinoma, no other parameters need to be taken into consideration.

    • Repeated levels above 350 mg/dl might indicate diabetes mellitus. Which is rare in my experience.

    • it can also develop after a partial pancreactomy was performed.

4.3.2.2. Liver

  • ALT (Alanine Aminotransferase):

    • Liver specific in ferrets (not in rabbits!) is released when liver cells are damaged. Activity in liver is 3-10 higher than in other tissues (in ferret).

    • Normal value 80-290 IU/L

    • High normal value than in other species

    • Steroids can increase ALT very fast.

    • Hepatic lipidosis, lymphocytic hepatitis, other forms of hepatitis and gastritis often produce values up to 800 mg/dl, with Alk. Phos. up to 100 mg/dl. Will see increase in AST as well

    • Careful when diagnosing primary liver disease on blood work alone.

      • Check for increased bilirubin, low total protein and icterus

      • Suggest biopsy in order to characterize liver lesion.

        • Lymphocytic hepatitis

        • Suppurative hepatitis

        • Vacuolar hepatopathy

        • Hepatic lipidosis

        • Cirrhosis

        • Hepatic neoplasia

        • Biliary cystadenoma

  • GGT:

    • The biliary system is the primary source of plasma GGT. In addition to biliary GGT, significant levels of renal epithelial GGT can be found in the urine.

    • Normal around 5 IU/L

    • Over 10 IU/L high index of suspicion for liver problems.

      • Need to differentiate nature of elevation

      • Recommend abdominal ultrasound +/- US guided biopsy of liver to rule out primary liver pathology

      • Liver involvement is sometimes secondary to ascending inflammation from gut.

        • Suggest exploratory with multiple biopsies (GI tract, liver, lymph node)

4.3.2.3. Kidney

  • BUN:

    • Blood urea nitrogen (BUN) measures the amount of urea nitrogen, a waste product of protein metabolism, in the blood.

    • Normal range 10-40 mg/dl

    • BUN considered a relatively insensitive test for evaluating renal disease in ferrets due to:

      • Pre renal factors influencing the BUN in ferrets include

        • High protein diet

        • Tendency to develop gastric ulcers very fast

      • Post renal elevations include

        • Urinary tract problems such as

          • Urinary obstructions.

          • Infections (prostatitis, etc) - Often due to adrenal disease!!

      • Might go up to 200-300 mg/dl with normal or mildly elevated creat.

    • Drug interaction:

      • drugs such as steroids or NSAIDS may cause GI ulcers, therefore increasing the BUN value

      • Levels have been shown to decrease with the administration of diuretics, aminoglycosides, amphotericin B and chloramphenicol (not a ferret specific fact)

  • Creatinine:

    • Creatinine is a nitrogenous waste product produced by the breakdown of creatine, which is an important part of muscle. A serum creatinine test measures the amount of creatinine in the blood and is an indirect indicator of renal glomerular filtration rate and can estimate renal function.

    • It has been demonstrated that creatinine is an insensitive indicator of renal failure in ferrets perhaps related to their capacity for extrarenal elimination of creatinine. Ferrets also have a considerably lower and narrower range of creatinine in the blood than other mammals.

    • Narrow range at normal 0.2 – 0.6 mg/dl

    • Is considered relatively insensitive as an indicator of renal failure.

    • The normal creatinine level averages approximately half the level of the dog and cat.

    • If > than 0.8 mg/gl than renal suspect

      • Elevations of BUN up to 300 mg/dl have been seen with a mild increase of creat. to 2-3 mg/dl

      • Three-fourths of renal function must be lost before abnormalities in creatinine concentration are seen

      • In contrast to BUN, Creatinine is not influenced by diet or GI ulcers

    • Lab artifacts:

      • Elevated levels: False-high serum test values can result when using Jaffe’s reaction, a chromogen color reaction when the sample contains non-creatinine chromagens, such as ketones, glucose, fructose, ascorbic acid, protein, urea, and ascorbic acid

      • Decreased levels: Creatinine deteriorates in plasma samples older than 24 hours leading to unreliable results. Bilirubin can also cause sampling errors.

  • Phosphorus, Calcium, Potassium

    • These three parameters can be used to assess renal function

    • In conjunction with BUN and Creat.

    • Suspect true renal failure if:

    • Phosphorus > 10 mEq/L AND

    • Calcium < 8 mg/dl AND

    • Potassium > 6 mEq/L

4.3.2.4. GI tract

  • Lipase:

    • Enzyme that breaks down triglycerides into monoglycerides and free fatty acids.

    • Normal values 0-200 U/L

    • While in other species, lipase is primarily produced in the pancreas, with a small amount being produced by the gastric mucosa, it appears that the ferret produces more lipase in the stomach than in the pancreas1.

      • Therefore elevations of lipase appear more diagnostic for GI problems than for pancreatic problems.

    • Elevated if > 500 IU/L from commercial labs. or > 1000 IU/L from the IDEXX Vet-test)

    • Significant elevation most commonly seen cases of mild to severe GI disease like IBD and/or Eosinophilic Granulomatous Disease

      • Check Globulin for evaluation as well.

      • Run CBC to check for peripheral eosinophilia

    • In my opinion, lipase is one of the most commonly underused clinical pathology parameter to date.

    • Steroids will increase lipase levels in other species (dogs, etc.)

      • Most likely in ferrets as well.

  • Globulin:

    • Globulins are proteins that are mostly involved the immune defense system. Any protein that is not albumin is classified as a globulin

    • Normal values 2-2.9 mg/dl

    • Often elevated with chronic inflammatory conditions such as IBD

      • Check Lipase for elevation in cases of IBD

      • Most confirmed cases of IBD have high levels (> 3-5 mg/dl)

      • Consider Aleutian disease if elevation goes beyond 6 mg/dl

      • Increases in dehydration

    • Decreased globulins are generally the result of decreased production (i.e. liver failure) or increased loss.

  • Lipase and Globulin should always be interpreted with each other to check for signs of IBD

  • I usually recommend GI biopsies to diagnose IBD in these cases.

  • It has been speculated that chronic unmanaged cases of IBD might develop into GI lymphoma.

    • Lab error:

      • Globulin levels are often calculated by subtracting albumin from the total protein. Any error in the measurements of albumin or total protein will give you erroneous globulin levels.

4.4. Anatomic features

  • The elongate body of the ferret allows for excellent abdominal palpation of most visceral organs.

  • The spleen is often considered enlarged for a variety of reasons (see below).

  • The chest is also elongated which places the heart somewhat more caudal than expected relative to dogs and cats.

  • Other anatomical features are very similar to the cat.

  • Intubation for anesthesia is not difficult.

  • Venous access points are similar to those in a cat except that the jugular veins are located more laterally on the ventral neck than expected. In general, jugular or anterior vena cava venipuncture are preferred for blood sampling, and the cephalic or saphenous vein is preferred for intravenous catheter placement. Other venipuncture sites (not all suitable for pets) include the retro-orbital sinus, the caudal tail vein and a cardiac puncture.

  • Male ferrets have an os penis and the penis is directed caudal as in a cat. The urethra is very difficult to catheterize (especially males neutered at a very young age). A 3.5 french urinary catheter or special catheter, available from Global Veterinary Products (Slippery Sam®), should be used.

Burrito restraint
Burrito restraint

4.5. Reproduction

Jills, hobs and kits (also review Reproductive Physiology notes)

Gestation

41-42 days

Litter size

1-18 (average 8)

Size at birth

8-10 grams

Eyes open

30-35 days

Weaning age

6-8 weeks of age (300 grams)

Permanent canine teeth erupt

52 days

Deciduous canine teeth lost

56-70 days

  • Ferrets reach sexual maturity normally in the first spring after birth.

  • They are seasonal breeders with a breeding season from December-July (hob), and March-August (jill).

  • The female is an induced ovulator and will remain in estrus for long periods of time if not allowed to breed.

  • Ferrets not used for breeding should be neutered to avoid estrogen toxicity (see below).

  • At the large ferret breeding farms, ferrets are neutered and descented at 6 weeks of age.

4.6. Nutrition

The exact nutrient requirements of ferrets are pretty well understood. They are carnivores with dietary needs similar to cats and mink. Their protein and fat requirements are in fact higher than the cat (recommended protein: 30-40% DM with a recommended fat content of 18-30% DM; 18-20% fat for nonbreeding ferrets). Dietary fat is the primary energy source for the ferret, not carbohydrates. In general, ferrets are given formulated ferret diets or high-quality animal protein based kitten foods.

4.7. Husbandry and Behavior

Pet ferrets are usually housed in a cage with a private "den" area. They spend a good deal of their time sleeping in the den. They can be housed in groups. Ferrets can also be caged outdoors but require adequate shelter and shade. They are prone to heat exhaustion since they do not have well developed sweat glands. Ferrets are easily trained to a litter box similar to a cat. It is advisable to keep them caged when unsupervised. They will often get into unexpected places and will readily swallow a variety of foreign objects! They will also tend to hoard things that they like and will stash their hoard in one or several places (e.g. under the refrigerator). It is not advisable to keep ferrets as pets in households with infants.

5. Basic therapeutic approaches

  • Intravenous catheters - Jugular catheters are difficult to place and this vein is best saved for obtaining blood samples. Short catheters (Jelco) can be placed relatively easily in either the cephalic or lateral saphenous veins.

  • Intraosseous catheters work just as well as intravenous catheters and are useful in many situations, especially when IV access has failed. A 20 or 22 ga. spinal needle can be placed in the femur.

  • IM and SQ injections are given as in dogs and cats

Chest tap - Thoracocentesis in a ferret with pleural effusion
Chest tap - Thoracocentesis in a ferret with pleural effusion

6. Anesthesia and surgery

There are many surgical diseases in the ferret. Consequently sedation and anesthesia are frequently performed in a variety of situations. Pre-anesthetic workups and health status concerns are the same as for dogs and cats.

6.1. Sedation

Sedation may be indicated for adequate restraint for short procedures such as venipuncture, radiographs, or ultrasound examination. Sedation is usually accomplished with an intramuscular injection of ketamine combined with diazepam (see below).

6.2. Tranquilization

Tranquilization or short anesthesia may be utilized for induction of inhalation anesthesia, short surgical procedures such as castration, skin tumor removal, or dentistry. Ketamine combined with xylazine is usually used in these cases, with the option of adding inhalation anesthetics if needed. Do not use this combination in older animals

6.3. Anesthesia

Anesthesia for a variety of major surgical procedures is often performed. Isoflurane gas is most often used. Intubation is easily and routinely performed.

Common Anesthetic Doses for Ferrets

Ketamine (sedation)

10-20 mg/kg IM

Diazepam

1-2 mg/kg IM, IV

Midazolam

0.1-0.5 mg/kg IM

Ketamine/diazepam

10-30/2-3 mg/kg IM

Ketamine/xylazine

10-30/1-4 mg/kg IM

Telazol

22mg/kg IM

6.4. Surgery

Surgery as indicated below is often required in ferrets. Health concerns pre-operatively are similar to those in cats and dogs. It should be noted that older ferrets (>4 years) often have multiple problems occurring simultaneously and a full evaluation of the animal should be performed before proceeding with surgery for any particular condition. Heart disease, various endocrine disorders, and lymphoproliferative diseases can seriously affect any surgical procedure.

Perioperative management of the surgical patient is also similar to cats and dogs, and is very important. Fluid maintenance in ferrets is about twice that of a dog or cat dose . It is usually calculated at 100-120 ml/kg/24 hours. This equals to 4-5 ml/kg/h. Their small size makes the ferret a little more challenging.

Fluid maintenance during surgery is about 2 x that of the dog or cat and is usually calculated at 100-120 m./kg/24hours or 4-5 ml/kg/hour.

Surgical protocols for gastrotomy, abdominal surgery, orthopedics, tissue handling, suture etc. are similar to other carnivore species (dogs, cats), taking into account the ferrets very small size. Ferret spay, castration and anal sacculectomy are commonly performed when the animals are very young. Neutering is similar to a cat. Anal sacculectomy will reduce the ferret odor, but will not eliminate it.

Perineal area in a male ferret in preparation for castration
Perineal area in a male ferret in preparation for castration

7. Preventative medicine

7.1. Vaccinations

Only use products approved for ferrets. Vaccinations should be performed regularly as indicated to protect against canine distemper and rabies viruses. Vaccines are often given separately because vaccine reactions have been seen fairly frequently, especially with the Fervac D. Reactions range from injection site irritation to full blown anaphylaxis and even death. Fewer reactions are expected with the new vaccine. Owners should be warned of the possibility of a reaction and are often asked to stay in the veterinary clinic for 30 minutes following a vaccination. Ferrets are exquisitely sensitive to canine distemper virus. Timing of vaccinations is important because it has been shown that kits are refractory to vaccination until 36-47 days of age. Ferrets are not susceptible to feline panleukopenia or rhinotracheitis, mink virus enteritis, canine hepatitis or canine parvovirus.

  • Canine distemper

    • Purevax D (Ferret Approved, recombinant canarypox vectored nonadjuvant vaccine) - As of 2008 this vaccine has been withdrawn from the market.

    • Galaxy D can also be used once client is educated that the vaccine is not approved for ferrets and the owner signed an informed consent form.

    • 8 weeks, then every 3 weeks for at least 2 boosters then annually

    • Due to severe reactions, owner might elect not to vaccinate the ferret against distemper. If the animal received 3-4 shots in its lifetime, the immunity might be considered enough to prevent a clinical outbreak.

  • Rabies

    • Imrab (Rhone-Merieux)

    • 3 months of age, then annually (not every 3 years)

    • This vaccine is required in MA, even if the animal has had a strong adverse reaction in the past.

7.2. Heartworm prevention

Prevention with monthly ivermectin for all animals in endemic areas. Recommended dosage: 6μg/kg PO once a month (or 1/4 of the smallest size of dog/cat preventative)

8. Common problems/diseases

8.1. Viral diseases

8.1.1. Canine distemper

  • Highly susceptible to infection with mortality approaching 100%

  • Incubation period 7-10 days

  • Clinical signs: anorexia, pyrexia, nasal and ocular discharge (often mucopurulent), chin rash, photophobia, generalized dermatitis, hyperkeratotic foot pads

  • Neurologic signs seen in ferrets that survive the catarrhal phase

  • Diagnosis: clinical signs, FA test on blood smear, histopathology

  • Treatment: supportive, hyperimmune serum (?) - euthanasia generally advisable

  • Prevention with vaccination is essential!

8.1.2. Influenza virus

Human influenza virus: many strains (usually influenza A)

  • Transmission: human to ferret (usually) and ferret to human

  • Clinical signs: lethargy, pyrexia, sneezing, coughing, nasal discharge, conjunctivitis

  • R/O early signs of distemper

  • Symptoms last 5-14 days

  • Treatment: symptomatic - can use pediatric cough suppressants, antihistamines and antibiotics to prevent secondary bacterial complications.

8.1.3. Aleutian disease virus

Aleutian disease is a parvovirus causing persistent viremia in mink and in ferrets. Mink are very susceptible, while ferrets are often carriers of the disease, but some will become affected. The ferret strains of this virus are likely mutations of the mink virus. The pathology of the virus is directly related to the strain. It appears that only one strain of the virus is causing severe clinical signs in the ferret (4 mink strains, 1 ferret strain).

Only counter current immuno-electrophoresis is able to differentiate the strains. In Mink, susceptibility is related to genetics and the disease produces immune mediated glomerulonephritis. Do not house ferrets with mink

Many ferrets will show up as positive on routine testing. A positive test result has little prognostic value.

In ferrets:

  • many are asymptomatic, subclinical (mink strains?)

  • wide variety of clinical syndromes reported : chronic wasting, weight loss, weakness, ataxia, progressive posterior paralysis, muscle wasting, tremors

  • may be associated with splenomegaly, hepatomegaly

  • diagnosis based on hypoalbuminemia and severe hypergammaglobulinemia (20-60% of total protein) and serology (United Vaccines, Madison WI; Avecon Diagnostics )

  • treatment: none

8.1.4. Epizootic Catarrhal Enteritis (ECE)

  • "Green slime diarrhea"

  • Coronavirus, highly contagious

  • Vomiting, dehydration and profuse diarrhea with mucous ; older ferrets most severely affected

  • Diagnosis based on history (new animal?), clinical signs and ruling out other diseases

  • Treatment includes supportive care: fluids, antibiotics for secondary bacterial infections, and a bland diet.

8.2. Bacterial diseases

Bacterial diseases of major concern are discussed below. Some other reported diseases include: salmonellosis, leptospirosis, listeriosis, atypical tuberculosis, botulism, and subcutaneous abscesses.

8.2.1. Bacterial pneumonia

  • relatively uncommon

  • seen usually secondary to megaesophagus (rare condition)

  • Streptococcus zooepidemicus, E. coli, Klebsiella pneumoniae, Pseudomonas, Bordetella

8.2.2. Helicobacter mustelae

  • Chronic gastritis and gastric and duodenal ulcers

  • Clinical signs often vague: lethargy, anorexia, hypersalivation, tooth-grinding, halitosis, melena

  • Ferrets used as experimental model for Helicobacter pylori in humans

  • Diagnosis: endoscopy or exploratory surgery with full thickness biopsies

  • Treatment: triple therapy as in humans

Treatment for Helicobacter in ferrets
(tx 2 weeks)

Clavamox

20 mg/kg q12h

Metronidazole

20 mg/kg q12h

Sucralfate

100 mg q 8h

Major Rule-outs for Ferret Gastroenteritis

Helicobacter

Cryptosporidiosis

ECE (coronavirus)

Coccidiosis

Inflammatory bowel disease

GI foreign body

Lymphoma

-

8.3. Fungal diseases

Blastomycosis, cryptococcosis and histoplasmosis have been reported. Dermatophyte infections most frequently involve Microsporum canis. Diagnosis and treatment is as for the cat.

8.4. Parasitic diseases

As in other carnivores, fleas and ear mites can be found on ferrets, and are contagious among other household pets (cats and dogs). Treatment is the same as for cats. Gastrointestinal parasites are not commonly seen. Cryptosporidiosis has been reported and may be zoonotic. Coccidia or Giardia are occasionally diagnosed in young ferrets.

8.4.1. Scabies

  • Sarcoptes scabei

  • signs: alopecia, pruritus

  • diagnosis: clinical signs, skin scraping

  • treatment: ivermectin 0.4 mg/kg SC once; repeat in 2 weeks ; selemectin has also been used

8.4.2. Heartworm - Dirofilaria immitis

  • Can be severe disease in ferrets, may involve only 1 worm - easier to prevent than to treat

  • Prevention: ivermectin, 1/4 smallest available canine/feline tablet

  • Clinical signs: (pre-caval syndrome) fulminant cardiac failure with lethargy, tachypnea, dyspnea, cough, ascites, melena

  • Diagnosis: clinical signs, radiographs, cardiac ultrasound, ELISA to test for HW antigen (Snap Heartworm Antigen Test Kit, IDEXX Labs, Inc.)

  • Rarely become microfilaremic

  • Treatment: may be successful if detected early; PROGNOSIS GUARDED. Safety and efficacy of melarsamine has not been established, although mortalities have been reported in North American river otters and red panda with this drug.

Suggested treatment protocol for heartworm in a ferret

Ivermectin
to resolve microfilaremia
(if present)

50 μg/kg SQ q 30d

Melarsamine,
single dose

2.5 mg/kg IM

Melarsomine,
follow-up doses 1 month later

2.5 mg.kg IM x 2 ; 24 hours apart

Cardiac failure

Treat as necessary for cardiac failure, restrict to cage rest

Perform follow-up ELISA 3 months after adulticide therapy, then monthly until negative

8.5. Neoplastic diseases

Neoplastic disorders are the most common diseases seen in the domestic ferret. In-breeding with limited genetic stock has likely artificially produced this trend. Many of the neoplastic diseases are not characteristic of their counterparts in other carnivores (dogs and cats).

Some Neoplasias Reported in the European Ferret

Tumor type

Location

Age

Squamous cell carcinoma

Multiple

3-5 yrs

Basal cell carcinoma

Multiple

3+ yrs

Ceruminous gland adenocarcinoma

Ear (base)

7 yrs.

Sebaceous carcinoma

Tail and perineum

6+ yrs

Adenocarcinoma

Prepuce, Perianal gland, Liver, Pancreas (exocrine), Stomach, Adrenal cortex

4 yrs 2+

Insulinoma

Pancreas (β-cell)

3+

Bile Duct Cystadenoma

Liver

Adult

Cortical adenoma

Adrenal gland

2+ yrs

Transitional cell carcinoma

Kidney

2 yrs

Mastocytoma

Multiple

3+ yrs

Myxosarcoma

Thorax, tail

-

Chordoma

Caudal, cervical spine

4 yrs

Chondroma, Chondrosarcoma

Tail tip

NA

Osteoma

Base of skull, larynx, vertebrae

5 yrs

Rhabdomyosarcoma

Thorax

1 yr

Neurofibroma, Neurofibrosarcoma

Neck, Eyelid

-

Papillary cystadenoma

Kidney

Adult

Papillary cystadenocarcinoma

Mammary

12+

Theca cell, granulosa cell tumor

Ovary

3

Fibroma, fibromyoma, myoma

Ovary

Adult

Leiomyoma

Ovary, Uterus

1-5 yrs

Interstitial cell tumor, Sertoli cell tumor

Testes

6 yrs

Hemangioma, hemangiosarcoma

Spleen, liver, leg

2-5 yrs

Lymphosarcoma complex

Multiple

6 mos+

Myeloma

Lumbar spine

3 yrs

Sarcoma

Orbit

-

Myelosarcoma

Skin

-

Mesothelioma

Abdomen

1.5+ yrs

Histiocytoma

Thorax

-

8.5.1. Mast cell tumors

  • Common benign skin tumors; visceral mast cell tumors are rare and do not occur with cutaneous tumors ; very different disease from the dog!

  • Clinical signs: small round raised tan lesions anywhere on the body, with or without pruritis or alopecia

  • Diagnosis: physical appearance of the lesion, excisional biopsy

  • No special treatment is required following excision

  • Monitor any un-excised lesions

8.5.2. Insulinoma

  • Seen in middle-aged to older ferrets (3 years and older, typically 5-6 yr)

  • Very common: assume all ferrets 5 years or older have insulinoma until proven otherwise!

  • Clinical signs: episodic weakness or collapse (minutes to hours), hind limb paresis, abnormal mentation, hypersalivation, pawing at the mouth

  • Seizures uncommon but do occur

  • Common emergency call!

  • Diagnosis: hypoglycemia <60 mg/dL; hyperinsulinemia >250 pmol/L (>35 μU/mL)

  • Surgical treatment: remove all nodules (histology: hyperplasia, adenoma, adenocarcinoma)

  • Medical treatment:

    • Prednisone 0.5-2 mg/kg q12h (start low), later add diazoxide 5-30 mg/kg q12 h (start low)

    • Alternatively, consider starting therapy with the diazoxide (expensive at about $ 4-5/ml) in order to avoid side effects of the steroids (very cheap at about $ 0.5/ml). A benefit of avoiding steroids is in case the animal develops lymphoma later on, successful chemotherapy will be much more likely. A lymphoma that has been exposed to steroids (from the insulinoma treatment) is considered a multi drug resistant lymphoma.

  • Prognosis guarded: survival rates vary from 3 months to 1+ years

  • Surgery (partial pancreatectomy) is often palliative, but rarely curative: microscopic neoplasia and metastasis have probably occurred at time of surgery. Recurrance of the problem WILL happen. Inform the owner of this prior to surgery.

  • Chemotherapy with doxyrubicin is possible when cases have been diagnosed prior to the onset of clinical signs of the severe hypoglycemia (i.e. during routine yearly exams, check a BG in every ferret over 4 years of age). The treatment is unrewarding in cases where the insulinoma has been long standing and medicated already.

Summary of Insulinoma (pancreatic islet cell tumors):

Insulinomas are considered the most frequently encountered neoplasia in ferrets. The most common clinical signs of insulinoma in the ferret are lethargy and hind limb weakness. Ferrets as young as 2 years should be screened for this problem with a blood glucose level. A severe hypoglycemia (< 60 mg/dl) after a 4-6 hour fast is indicative of this condition, however, care must be taken not to over interpret a low blood glucose finding. It is not uncommon for any sick ferret t to not have been eating well, or at all, for long periods of time at the time of presentation to the veterinary clinic. A low blood glucose level after an 8-10 hour fast is not diagnostic for insulinoma. However, if the animal has been eating within the last 4 hours prior to having blood drawn, and the blood glucose level is below the threshold (< 60 mg/dl), this level can be considered as a true indication of an insulinoma. Interestingly, in only about 80% the cases are blood insulin levels an indicator for this disease.

Ultrasonography has been used to screen for pancreatic nodules but it is not an ideal tool since many of these cases do not produce nodules at all, or the nodules cannot be recognized with ultrasound. In one study only about 22% of confirmed cases were positive using an ultrasound exams.

Pancreatic islet cell tumors can occur as hyperplasic regions, as carcinomas or as adenomas, and these different forms can only be differentiated by histopathological examination.

Once the diagnosis of insulinoma has been made, there are several treatment options available.

Medical treatment can be started with daily doses of oral prednisolone to stimulate gluconeogenesis. A low dose of 0.2 mg PO SID or BID can be used initially, but the dose must be tailored to both eliminate the clinical signs and to achieve euglycemia. While prednisolone therapy will make the animal symptom free and restore a good quality of life, it is important to keep in mind that this therapy will not reduce the growth of the primary tumor and the animal will eventually become hypoglycemic again, unless the steroid dose is readjusted. The prednisolone dose can be gradually increased as needed but once it has reached approximately 2 mg/kg a second drug should be added in order to help control glucose levels. Diazoxide (Proglycem® by Baker Norton) is a drug, which can be used either alone or in conjunction with the prednisolone. (As mentioned earlier, I prefer to use the drug as a first drug of choice instead of the steroids). This drug helps to raise blood glucose levels by directly inhibiting pancreatic insulin secretion. It is available in a liquid form at a concentration of 50mg/ml. The usual starting dosages are approximately 10 mg/kg. This drug is relatively expensive for the owner (about $5/ml), however it can extend the efficacy of the steroids for a reasonable amount of time. Once diazoxide is started, the dosage of the prednisolone can usually be reduced. Remember that as with the steroids, this drug will not interfere with the growth of the primary tumor and ‘resistance’ to the drug, resulting in recurrence of the hypoglycemia.

Surgical treatment is the other option. Excision of the nodules from the pancreas is straight forward and a partial pancreatectomy is often performed at the same time. This combination of nodule removal and partial pancreatectomy has shown to significantly prolong the euglycemic state in the post-surgical period over nodule removal alone. However, it is important to inform the owner that despite aggressive treatment and the partial removal of the pancreas, this treatment is not considered to be a cure, and there is a high likelihood of recurrence of the tumors after some time.

8.5.3. Hyperadrenocorticism

  • Extremely common, ages 3 and up

  • Very different disease than seen in the dog (Cushing's)

  • Mostly androgen secreting tumors ; influence of early neutering?

    • Hypothesis that early neutering and domestication have interfered with the normal hormonal feedback mechanisms (highly seasonal animals) and produced animals under constant hormonal stimulation. This triggers hyperplasia >>adenoma >> adenocarcinoma in other animals, and is possibly related to high rate of adrenal tumors, insulinoma, mast cell tumors and lymphomas in ferrets (For more on this go to Nico Schoemaker chapter).

  • Adrenal cortical hyperplasia, adenoma, and adenocarcinoma

  • Clinical signs: vulvar swelling in females, symmetric hair loss beginning on the tail and spreading up the trunk, pruritus (PU/PD, pendulous belly uncommon), anemia very rare, stranguria or urinary obstruction in males

    • Prostatic enlargement (hypertrophy, cysts, prostatitis) secondary to adrenal neoplasia is a common cause of partial or complete urethral obstruction in male ferrets. Emergency treatment is often necessary to relieve an acute obstruction. Urethral catheterization is challenging: a special urinary catheter is available from Global Veterinary Products (Slippery Sam®). Adrenalectomy usually reduces prostate size within days, but complicated cases involving infection will be more difficult to deal with.

  • Diagnosis: clinical signs, adrenal ultrasonography, sex steroid hormone analysis (estradiol, androstenedione, 17-hydroxyprogesterone, estradiol: University of Tennessee )

    • At Tufts we rely on the abdominal ultrasonography for the diagnosis of this disease.

    • Very commonly the adrenal gland is not grossly enlarged but only produces a large mount of hormones (e.g. patients with hyperthyroidism do not have a large thyroid)

    • If no large gland can be seen on ultrsound, the disease needs to be managed with lupron for 3 months and a repeat ultrasound is indicated to document a change in one (or two) glands.

  • ACTH stimulation and dexamethasone suppression tests rarely helpful WHY?

  • Surgical treatment is the preferred therapy: adrenalectomy (Figure), cryosurgery

    • Major risks associated with R adrenalectomy and its relationship with the vena cava

    • Have blood transfusion (buddy) or oxyglobin on hand

    • Always warn the owner of risks associated with surgery

    • A pheochromocytoma might be fatal due to secretion of excessive amounts of catecholamines

  • Medical treatments are only temporary and reduce clinical signs but do not effect tumor growth

    • GnRH analogs (lupron) - down regulates release of LH and FSH

    • Androgen receptor blockers (Flutamide) - only works in some ferrets

    • Aromatase inhibitors (Arimidex) - blocks production of estrogen and testosterone

    • Ketoconazole and Lysodren are not effective

Summary on Adrenal gland disease (hyperadrenocorticism):

The pathophysiology of adrenal gland disease in ferrets is significantly different from that in domesticated animals known as Cushings disease and therefore it should not be called Cushings disease in the ferret. Adrenal gland disease is considered the second most common disease in the ferret after insulioma1. While several different hypothesis regarding the etiology of ferret adrenal disease have been put forward in the literature, it appears that there is a direct link between the early age of neutering and the onset of this disease2.

The difference between the ferret adrenal disease and the typical Cushings presentation and pathophysiology, is the fact that in the ferret the adrenal cortex does not produce significant levels of cortisol from the zona fasciculata, and instead the tumor produces a significant increase of the sex steroids produced by the zona reticularis. The sex steroids that are usually elevated are estradiol, 17-hydroxyprogeterone, testosterone and androgesterone.

These hormones can be measured in the blood. T University of Tennessee offers this test. Besides as a primary diagnostic tool, this test can also be a useful aid in the differentiation between a seasonal shed and the disease.

The primary clinical signs in ferrets are directly related to the increase of these sex steroids in the blood resulting in estrogen toxicity. Enlargement of the vulva in females, prostatic enlargement, prostatitis and cystitis in males, as well has alopecia and pruritis are all extremely common clinical signs. If the elevation of the estrogen precursors are allowed to continue for a prolonged period of time, anemia will often follow and it usually non-regenerative, because the bone marrow undergoes fatty degeneration.

At Tufts University we use abdominal ultrasound exam as the primary tool for the diagnosis of the disease.

The clinical signs of the animal have no direct correlation with the size of the gland. It is not an uncommon scenario, to be presented with an animal with severe clinical signs and neither of the adrenal gland are physically enlarged or appear abnormal to the naked eye to the surgeon. In this case it is extremely difficult to decide which gland should be surgically removed. An ultrasound exam can evaluate this situation before the animal is presented for the surgical procedure.

In case none of the adrenal glands are enlarged, the owner is advised to start with the medical treatment of the disease and to repeated the ultrasound exam in 3 months. If one of the glands is mildly larger than before, even if still within normal limits, surgical removal of this gland is then recommended. It is important to submit the removed tissue for histopathological evaluation in order to document the pathological nature of the tissue to the client and to differentiate the degree of pathology of the tissue in order to provide the owner with a realistic prognosis of expected recurrence.

Histologically the lesion of the adrenal gland can be differentiated as benign hyperplasia, adenoma or carcinoma. The reason for using the ultrasound exam as a viable tool to work up the ferret presented for a suspected adrenal gland disease process is outlined below.

Medical treatment of the condition can be achieved with monthly injections of Lupron® (leuprolide acetate) at 0.1 mg/animal if less than 1 kg, and 0.2 mg/animal if over 1 kg of bodyweight. The drug is considered a GnRH superagonist and will stop the production of LH and FSH due to negative feedback from persistent stimulation of the hypophysis. This process is call “desensitization”. This treatment should be done monthly for at least 3 months. It is then potentially possible to reduce the frequency of injections depending on the clinical signs, however, the continuation of the monthly injections can be recommended. The advantages of this treatment choice are obvious, it is both non-invasive and relatively inexpensive. Each injection costs the client approximately $30-50. However there are disadvantages, which also need to be explained to the owner before treatment is started. This treatment does not interfere at all with tumor growth. It only affects response to the hormones and does not affect cell growth. In addition, these treatment need to be life-long and so in the long run this option may end up being as expensive as a surgical removal of the diseased tissue. It has also been noted that a ‘resistance’ seems to develop over time and higher doses are needed in order to control the clinical signs. In rare cases the adrenal gland will produce hormones independent of LH and FSH regulation, in these cases the lupron treatment is completely ineffective.

The second option for medical treatment is the use of melatonin to suppress the hormone release. Melatonin is a hormone which is normally released during the dark phase of the day by the pineal gland. It directly inhibits GnRH release and therefore suppresses LH and FSH production. The importance of the pineal gland and its influence on gonadal activity has been validated as long as 30 years ago in the ferret 3 4.

Melatonin treatment is done using a commercially available melatonin implant that can be injected under the skin, similar to a microchip, and which will release enough melatonin for three months. The implant can be ordered through Melatek (www.melatek.net or 1-877-MELATEK) and the cost to the owner is similar to those for the lupron treatments. Melotonin has been reported to be extremely effective even in cases where lupron treatment did not produce a satisfactory response (Murray J., pers. com). Melatonin also appears to be very safe and can be used in combination with other drugs including lupron.

The surgical approach is always a treatment possibility with the goal of removal of the pathological gland.

Against popular belief it is possible to remove both adrenal glands at the same time without creating significant hormonal problems5. It is best to medicate these animals with dexamethsone (1mg/kg IM) during post-op recovery, and then to continue medication with oral prednisone (1 mg/kg SID PO) for a few weeks. Supplementation with glucocorticoids is usually not needed with unilateral removal of the gland.

The owner should always be informed that it is possible for the disease to recur even if both adrenal glands have been removed. As mentioned above, the excised tissue should be submitted for histopathological evaluation in order to differentiate between hyperplasia, carcinoma and adenoma. This will help in discussions of the long-term prognosis with the owner.

An interesting new surgical approach has been developed in an exotics practice in Italy. Good results are being achieved after alcohol injection into the diseased gland (Selleri, P. pers. comm., 2005). The injection of alcohol into the adrenal and other tumor sites has been used in human medicine and is well published 6, 7. The treated gland appears to shrink, and this has been documented with abdominal ultrasound examinations. This localized treatment option may provide an exciting new solution to cases where complete excision is not possible. Frequently a tumor of the right adrenal will have invaded significantly into the vena cava making partial resection the only option short of removal of vena cava at this site..

It is important to mention that it is sometimes possible to successfully completely resect the vena cava if it is too badly damaged during removal of the right adrenal gland. Ferrets have many collateral vessels into which blood will be diverted into the vertebral sinuses. Data available indicate that approximately 25% of animals will die during surgery with this aggressive procedure. Survivors must be treated with aggressive fluid therapy for 2-3 days post-op, and renal values should be closely monitored for signs of renal failure due to impaired perfusion.

Adrenal gland disease is one of the easiest diseases to recognize in the ferret due to the striking clinical signs. Care has to be taken not to correlate clinical signs with the physical size of the gland. Only after an appropriate diagnostic workup, should the patient be submitted for surgery. Abdominal ultrasound exams appear to be the most reliable diagnostic tool in order to decide if the disease should be treated medically or surgically.

8.5.3.1. Adrenal gland disease bibliography:

  • Fox JG. Biology and diseases of the ferret. 2nd ed. Baltimore: Williams & Wilkins; 1998.

  • Shoemaker NJ, Schuurmans M, Moorman H, Lumeij JT. Correlation between age at neutering and age at onset of hyperadrenocorticism in ferrets. J Am Vet Med Assoc 2000;216(2):195-7.

  • Baum MJ, Lynch HJ, Gallagher CA, Deng MH. Plasma and pineal melatonin levels in female ferrets housed under long or short photoperiods. Biol Reprod 1986;34(1):96-100.

  • Thorpe PA, Herbert J. Studies on the duration of the breeding season and photorefractoriness in female ferrets pinealectomized or treated with melatonin. J Endocrinol 1976;70(2):255-62.

  • Weiss CA, Williams BH, Scott JB, Scott MV. Surgical treatment and long-term outcome of ferrets with bilateral adrenal tumors or adrenal hyperplasia: 56 cases (1994-1997). J Am Vet Med Assoc 1999;215(6):820-3.

  • Wang P, Zuo C, Qian Z, Tian J, Ren F, Zhou D. Computerized tomography guided percutaneous ethanol injection for the treatment of hyperfunctioning pheochromocytoma. J Urol 2003;170(4 Pt 1):1132-4.

  • Wang P, Zuo C, Tian J, Qian Z, Ren F, Shao C, et al. CT-guided percutaneous ethanol injection of the thymus for treatment of myasthenia gravis. AJR Am J Roentgenol 2003;181(3):721-4.

Adrenal ds.
Adrenal ds.

Ultrasound
Ultrasound

8.5.4. Lymphoma

  • One of the most common neoplasms (following insulinoma and adrenal tumor)

  • Fulminant aggressive disease in juvenile animals

    • may affect different organs: liver, spleen and thymus >>>bone marrow

    • Acute clinical signs may include pleural or abdominal effusion, leukemia

    • Response to tx. poor, prognosis poor

  • Smoldering, chronic disease in older animals 2-9 years of age

    • chronic, cyclical ds.

    • lethargy, inappetance, weight loss

    • lymphadenopathy most common form detected on exam - R/O prominent fat pads!

    • Prognosis better than juvenile disease, may respond to minimal prednisone therapy

  • Diagnosis: tissue biopsy for definitive diagnosis (eg, lymph node, fluid aspirate, etc.)

  • Treatment: chemotherapy protocols as for other animals ; many available in the literature

Summary of Ferret Lymphoma

Lymphoma is one of the most commonly diagnosed conditions in ferrets in the USA1. A viral etiology of the disease, like the viral leukemia in cats, has recently been proposed2 but no scientific evidence of this proposed etiology exists to date.

Unfortunately, in spite of the frequency of occurrence, lymphoma is one of the more difficult diseases to accurately diagnose. Two distinct forms of this disease are commonly discussed in the literature. The first form often described is the ‘juvenile’ form, which usually affects ferrets younger than 2-3 years. It is also known as the ‘lymphoblastic’ form. In this case many visceral organs are infiltrated by lymphocytes with resulting enlargement of these organs. The most common presentation is a young ferret with respiratory distress. This is due to significant enlargement of the thymus, and can be clearly seen on chest radiographs.

The second form of lymphoma mentioned in the literature is often described as the ‘lymphocytic’ form, or the adult/chronic presentation. It is reported to be usually seen in ferrets older than 3 years. In this form of the disease the most common presentation is a ‘healthy’ animal with significantly enlarged peripheral lymph nodes. Over time lymphocytes will eventually infiltrate every organ and the cause of death in the advanced state is usually organ failure.

While the distinction between the two forms of the disease can every useful, in reality it is possible for this disease to present in many different ways. It is therefore important to include lymphoma in the differential list for most sick ferret patients until proven otherwise. The author has seen many different presentations of lymphoma and thinks that the classical description of ferret lymphoma, mentioned above is an over simplification.

It is unclear why this difference between the literature and the real world exists. It is possible that early descriptions of the ferret lymphoma were based on the description of the feline lymphoma. The feline Non-Hodgkin Lymphoma is one of the most common neoplasias in cats and shows a bimodal age distribution ( ~ 2 years and ~ 6.5 years). Young cats show often the mediastinal form (which is often FELV +) and older cats often present with the abdominal form (which is often FELV -). In addition the terminology of lymphoblastic and lymphocytic can be confusing, the old way of defining a lymphoblast was to refer to a large lymphocyte which does not show signs of a well differentiated cell. However the WHO classification of a lymphoblast refers to a small but aggressive lymphocyte. This can lead to confusion regarding which definition the clinician or the clinical pathologist refers to. In order to avoid confusion the histology report should read small cell type or large cell type. In addition to this confusion a new type of lymphoma has recently been described in dogs. The (-( (Gamma Delta) hepatosplenic lymphoma has recently been seen in dogs. This form of lymphoma was first described in humans in 1990 (40 cases reported from 1990-2003). People usually present with systemic signs, anemia and thrombocytopenia. Histologically the infiltration of liver, spleen and bone marrow with T cells expressing the (-( T-cell receptor is common. Neoplastic cells are found in most tissues, the cells are large, round, and pleomorphic where about 5% of neoplastic cells exhibited erythrophagocytosis with 1-4 mitotic figures /hpf. There is generally an absence of peripheral lymphadenopathy. This form of lymphoma usually follows and aggressive clinical course. Clinically a hepatomegaly (5.8% of body weight) and a splenomegaly are commonly noted. In 2003 the first report in dogs was published7.

This form might soon be described in ferrets.

In order to appropriately diagnose lymphoma in a ferret, a biopsy is needed. In only in a few cases can the diagnosis be made with a fine needle aspirate, and almost never based on the complete blood count alone. The popliteal lymph node is easily removed and biopsy of this tissue is often the best diagnostic choice. Fine needle aspirates obtained via the ultrasound exam can be suggestive of lymphoma but often don’t provide a definitive diagnosis.

Several different treatment options are available and before starting any particular treatment the owner should be informed about the character of this disease and warned that a complete cure is rarely achieved.

Chemotherapy is one option and the simplest form is the use of prednisolone alone. This is an extremely effective treatment resulting in rapid remission even within a few days. Therefore it should never be started before a biopsy is taken. However, in most cases, if not all, the lymphoma will recur within a few months after initiation of this treatment and then can be considered as a multi-drug resistant (MDR) lymphoma. These animals will usually lose ground rapidly and euthanasia is often indicated due to quality of life issues.

Other chemotherapeutic protocols have been published for ferrets and are usually modified from canine or feline protocols3, 4. All of these published protocols include chemotherapeutic agents, which are extremely caustic to tissue and must be given intravenously with strict care. For example one of the most popular protocols consists of vincristine, asparaginase, cyclophosphamide and doxorubicin. Any extravasation of these drugs has the potential to cause tissue necrosis leading to sloughing or self-mutilation resulting in severe damage. Repeated careful venous access can sometimes be a challenge in the small ferret patient. The use of subcutaneous venous access-ports can be helpful in this regard and techniques for their use have been published previously.

Often however, owners may shy away from treatment choices involving either invasive surgeries or these aggressive chemotherapeutic agents. A novel lymphoma protocol has been developed at the Tufts Cummings School of Veterinary Medicine and includes drugs that are given only by oral or subcutaneous routes, completely avoiding the need for weekly venipuncture or surgical procedures. The preliminary results over the last 3 years of trials are promising and owners have been very pleased with the efficacy of the drugs. The only drawback of this protocol is that it extends over a 26 week period and 19 visits are required during this time, making it relatively involved for the owner.

For this protocol we stage the disease prior to treatment. The staging process should include a complete blood count with a platelet count, a chemistry profile, whole body radiographs (2 views), abdominal ultrasonography, a biopsy of affected tissue and a bone marrow aspirate. Currently, we distinguish four stages in the manifestation of lymphoma:

Stage 1: the tumor involves only a single site

Stage 2: multiple sites are involved, on the same side of the diaphragm

Stage 3: spleen, and lymph nodes on both sides of the diaphragm are involved.

Stage 4: multiple sites on both sides of the diaphragm are affected

Blood work (CBC only in most cases) is repeated 7 times during the protocol to monitor the affect of the myelosuppressive drugs (cyclophosphamide, chlorambucil, procarbazine and cytarabine). Also, depending on the location of the disease, imaging of the abdomen or chest may need to be repeated to assess response to therapy.

This protocol appears promising although considering it appears that the protocol can be very effective however, due to the low number of animals that have been treated so far, conclusions are only preliminary. It does appear also that in animals that have been treated previously with prednisone for an extended period of time, the protocol appears not to be as effective.

In cases where the lymphoma is resistant to drugs and or the owners do not feel comfortable with chemotherapy, the option of radiation treatment is also available. The use of radiation treatment in ferrets has been reported in the literature. The author has managed different neoplastic conditions in ferrets with the help of radiation therapy including an animal with MDR lymphoma. While the treatment is not curative, it is simple to use if a radiation therapy facility is available and side effects are negligible.

Conclusion:

While lymphoma remains a very common diagnosis in the ferret patient, it is important not to over diagnose the disease by CBC results. For a definitive diagnosis of lymphoma, a tissue biopsy or sometimes a fine needles aspirate is needed as a minimum diagnostic workup. Different chemotherapy options are available to the client including radiation therapy.

CHEMOTHERAPY PROTOCOL FOR LYMPHOMA IN FERRETS

Week 1:

L-ASP

____

Week 13:

CTX

____

CTX

____

Week 15:

PCB

____

PRED

____

Week 16:

CBC*

____

Week 2:

L-ASP

____

Week 17:

CBC

____

CBC*

____

Week 18:

CTX

____

Week 3:

L-ASP

____

Week 20:

CYTOSAR

____

CYTOSAR

____

LEUK

____

Cytosar x 2 days

____

X 2 Days

____

Week 4:

CBC *

____

Week 23:

CTX

____

Week 5:

CTX

____

Week 26:

PCB

____

Week 7:

MTX

____

Week 27:

CBC

____

CBC

____

CHEM

____

Week 8:

CBC*

____

IF NOT IN REMISSION
CONTINUE WEEKS 20-26
FOR 3 CYCLES

Week 9:

CTX

____

Week11:

CYTOSAR

____

LEUK

____

Week 12:

CBC*

____

Key:

PRED

=

Prednisone

1 mg/kg PO daily

L-ASP=

=

L-asparaginase

10,000 iu/m2 SQ

PRED

=

Prednisone

1 mg/kg PO daily

CTX

=

Cytoxan elexir

250 mg/m2 PO GIVE WITH
50ml/kg of NaCl SQ

CYTOSAR

=

Cytosar

300 mg/m2 SQ X 2 days
(dilute 100mg with1 ml H20)

MTX

=

Methotrexate

0.8 mg/kg IM

LEUK

=

Leukeran

1 tab ferret PO (or ½ tablet daily for 2 days)

PCB

=

Procarbazine

50mg/ m2 PO daily for 14 days

Dose Reductions: If CBC * indicates severe myelosuppression, reduce dosage by 25% for all subsequent treatments of the myelosuppressive drugs.

STAGING PROTOCOL FOR FERRET LYMPHOMA

¨

CBC + platelet count

¨

Thoracic Radiographs – 2 Views

¨

Chemistry Profile

¨

Abdominal Ultrasound

¨

UA (Culture if Indicated)

¨

Bone Marrow Aspirate

¨

freeze serum for later viral assay

¨

Histopathology

Instructions and remarks for the CHEMOTHERAPY PROTOCOL FOR LYMPHOMA IN FERRETS

  1. Please adhere strictly to the protocol and make a note of any side effects which are observed during the treatment.

  2. The myelosuppression is the most important factor in monitoring. Other side effects might include vomiting, diarrhea or nausea. Systemic antibiotic therapy might be indicated very early in the protocol. L-ASP has the potential to cause anaphylaxis (I have not seen it, yet.). In case any reaction is noticed after the first dose, premedicate with Dexamethasone (1 mg/kg s.c.) 10 min before the subsequent treatments.

  3. As indicated in the protocol, a 25% reduction of the myelosuppressive drugs should be initiated if the CBC shows a severe drop (segmented neutrophil count < 1,000 /µl). The myelosuppressive drugs are CTX, CYTOSAR, MTX, LEUK and PCB. Start antibiotic therapy to prevent secondary infection!

  4. When toxic side effects occur please use the scale below in order to Grade the toxicity, so that we can have objectively comparable data.

  5. The Cytoxan elixir (injectable drug prepared as oral medication) is usually prepared by a compounding pharmacy.

  6. Eventually we would like to publish results and kindly ask you to share your findings (toxicity, blood work results, and outcome) with us.

  7. If an animal should pass during the therapy, please try to get a necropsy, as any information available is vital for us.

Toxic Effect
& Grade

Signs

Neutropenia

0

None

1

1,500-3,000 neutrophils

2

1,000-1,500 neutrophils

3

500-1,000 neutrophils

4

<500 neutrophils

Plts

0

None

1

100,000-200,000

2

50,000-100,000

3

15,000-50,000

4

<15,000

Vomiting/ Darrhea

0

None

1

Nausea, Inapp., Soft stool

2

Sporadic V, Anorexia<2 days,
1-4 watery stools/day for <2 days

3

1-5 V. episodes/day <2 days,
Anorexia >3 but< 5 days,.
4-7 watery stools /day for > 2days

4

Hospitalization for V or D,
Anorexia > 5 days w/ 10% wt loss

8.5.4.1. Lymphoma Bibliography:

  • Li X, Fox JG, Padrid PA. Neoplastic diseases in ferrets: 574 cases (1968-1997). J Am Vet Med Assoc 1998;212(9):1402-6.

  • Erdman SE, Reimann KA, Moore FM, Kanki PJ, Yu QC, Fox JG. Transmission of a chronic lymphoproliferative syndrome in ferrets. Lab Invest 1995;72(5):539-46.

  • Carpenter JW, Quesenberry KE. Ferrets, rabbits, and rodents: clinical medicine and surgery: includes sugar gliders and hedgehogs. 2nd ed. Philadelphia, Pa. London: Saunders; 2004.

  • Lloyd M. Ferrets: health, husbandry, and diseases. Oxford; Malden, MA: Blackwell Science; 1999.

  • Rassnick KM, Gould WJ, 3rd, Flanders JA. Use of a vascular access system for administration of chemotherapeutic agents to a ferret with lymphoma. J Am Vet Med Assoc 1995;206(4):500-4.

  • Miller TA, Denman DL, Lewis GC, Jr. Recurrent adenocarcinoma in a ferret. J Am Vet Med Assoc 1985;187(8):839-41.

  • Fry MM, Vernau W, Pesavento PA, Brömel C, Moore PF. Hepatosplenic lymphoma in a dog. Vet Pathol. 2003 Sep; 40(5):556-62.

Mediastinal lymphoma in a ferret
Mediastinal lymphoma in a ferret

8.6. Estrogen toxicity due adrenal disease (common in the US) or to prolonged estrus (common anywhere else in the world)

  • Seen in cases with adrenal cancer (due to sexual steroid production in adrenals)

  • Seen in approx. 50% of unspayed females if not bred, uncommon now that most pet ferrets neutered at 6 wks

  • Clinical signs: inappetence, lethargy, melena, hairloss over dorsum (pelvis and neck region)

  • Physical exam: swollen vulva, pallor, petechiae, ecchymoses

  • Diagnosis: PCV, CBC, platelet count

  • Prognosis varies according to PCV

    • grave if PCV <15%

    • guarded if PCV 16-24%

  • Treatment: varies according to stage of disease

    • if adequate PCV and platelet count: ovariohysterectomy if intact

    • diagnose adrenal gland disease and treat, either medically or with surgery

    • safer approach in most cases: induce ovulation with human chorionic gonadotropin 100 IU or 1,000 USP units IM (functions only after day 10 of estrus) ; may need repeat injection in 7-14 days

  • Other therapy: blood transfusion(s), iron, androgens, steroids, antibiotics

4Vulvar swelling in response to estrogen in the female ferret
Vulvar swelling in response to estrogen in the female ferret

8.7. Cardiomyopathy

  • Seen in middle-aged ferrets

  • Clinical signs variable: lethargy, inappetence, dyspnea, coughing, ascites

  • Dilatative cardiomyopathy most common

  • Diagnosis and treatment: as for cats

    • Echocardiogram, radiographs, ECG

    • Acute: Oxygen, diuretics, nitroglycerin,

    • Chronic or stabilized: Diuretics, ACE inhibitors, digoxin

  • Prognosis good with therapy (better than dogs and cats)

8.8. Noninfectious GI disorders

8.8.1. Inflammatory Bowel Disease

  • Lymphoplasmacytic and eosinophilic

  • One of the most common problems seen in clinics

  • May be complication associated with other chronic disease (other GI diseases, lymphoma, megaesophagus)

  • Clinical signs

    • Abnormal stool

    • Thin, poor muscle mass

    • Nausea, vomiting, regurgitation

    • Prominent mesenteric lymph nodes

  • Elevated serum lipase, globulins, liver enzymes

  • Diagnosis through history and clinical presentation, blood work, intestinal and lymph node biopsy.

  • Treatment includes anti-inflammatories (azathioprine, prednisone, etc.) and treating other associated conditions

The importance of the GI pathology affecting other organ systems in the ferret is extremely important

8.8.2. Splenomegaly

  • Common physical finding in ferrets

  • Reported causes in ferrets:

    • lymphoma

    • plasma cell myeloma

    • megakaryocytic myelosis

    • Aleutian disease virus infection

    • chronic helicobacter

    • idiopathic hypersplenism

  • Found often in association with insulinoma and adrenal disease

  • May not be associated with clinical signs

  • Recommended work-up: CBC, platelet count, reticulocyte count if indicated, splenic aspirate

  • Look for other diseases: serum chemistry, urinalysis, radiographs, cardiac or endocrine evaluation

  • Treatment and prognosis: depend on primary disorder if any determined

  • Splenectomy indicated only if: rupture, neoplasia, true hypersplenism

8.8.3. Gastrointestinal foreign bodies

Gastrotomy to remove a foreign body in a ferret
Gastrotomy to remove a foreign body in a ferret

  • Very common because of ferrets' inquisitive nature

  • Rubber FB most common in younger animals (ear plugs, toys, etc.)

  • Trichobezoars seen in older animals

  • Clinical signs: chiefly anorexia also vomiting, melena, weight loss

  • Diagnosis: palpation, radiography

  • Treatment: surgery immediately

8.9. Urinary tract disorders

8.9.1. Urethral obstruction/Urolithiasis

  • Both sexes affected

  • Struvite calculi most common

  • Role of diet?

    • urine pH should be about 6.0 on a good meat-based diet

    • urine pH is higher on poor-quality diet with plant protein (eg, corn, cat food diets)

    • pH > 6.4 predisposes to struvite urolithiasis

  • Diagnosis: clinical signs, palpation, radiographs, urinalysis

  • Treatment: surgical removal of uroliths, urethral catheterization may be difficult, use antibiotics as necessary and correct diet (gradually) emergency perineal urethrostomy may be required

  • REMEMBER: stranguria is most often associated with hyperadrenocorticism and prostate enlargement -

    • Adrenalectomy resolves (1-2 days)

    • Aspirate prostate during surgery to relieve pressure and re-establish patent urethra

8.9.2. Polycystic kidneys

Polycystic kidneys are commonly diagnosed as an incidental finding but may cause terminal renal failure if severe.

8.9.3. Chronic Interstitial nephritis

Chronic interstitial nephritis may be seen in animals as young as 2 years of age. Syndrome similar to the disease in older cats.

DIAGNOSTIC TIP: Middle-age to older ferrets often have more than one "important" disease concurrently. KEEP YOUR EYES OPEN FOR MORE THAN ONE PROBLEM!

9. References and Resources

Conservation Medicine Challenges 1

Supplemental Readings

9.1. Professional Organizations

9.2. Websites

9.3. Texts and Articles

  • Abou-Madi, N. Anesthesia and analgesia of small mammals. In: Recent Advances in Veterinary Anesthesia and Analgesia: Companion Animals , Gleed R.D. and Ludders J.W. (Eds.). International Veterinary Information Service, Ithaca NY (www.ivis.org)

  • Beeber, Neal L. and Holly S. Mullen. Abdominal and miscellaneous surgery in ferrets. In: Veterinary Clinics of North America Exotic Animal Practice, 3:3, 2000 : 647-671.

  • Besch-Williford CL. Biology and medicine of the ferret. Vet Clin NA: SAP 1987;17(5):1155-1183.

  • Burgess, Mark and Michael Garner. Clinical aspects of inflammatory bowel disease in ferrets. Exotic DVM 4.2, 2002 : 29-34.

  • Burgess, M. (2006) Gastrointestinal and hepatic diseases in A comprehensive Veterinary Symposium, Advanced Course. Management of the Ferret. AFA meeting Pittisburgh, Pennsylvania. Oct 6-7 2006 pp. 79-97 (order online at www.ferret.org)

  • Fox JG. Biology and Diseases of the Ferret, 2nd ed.. Philadelphia:Williams & Wilkins, 1998.

  • Fudge, Alan M. Laboratory Medicine, Avian and Exotic Pets. Philadelphia : W.B. Saunders Co., 2000.

  • Hamosh, M., T.R. Henderson, and P. Hamosh, Gastric lipase and pepsin activities in the developing ferret: nonparallel development of the two gastric digestive enzymes. J Pediatr Gastroenterol Nutr, 1998. 26(2): p. 162-6

  • Johnson-Delaney, Cathy A. Exotic Companion Medicine Handbook for Veterinarians. Wingers Pub. Inc., 1996.

  • Johnson-Delaney, Cathy A. Update on ferret adrenal research. Exotic DVM 4.3, 2002 : 61-64.

  • Lair, Stephane. Pathology and epidemiology of neoplasia in the captive population of black-footed ferrets (Mustela nigripes). Proc. of the Joint Conference of AAZV and AAWV, 1998.

  • Lewington J (2007) Ferret Husbandry, Medicine and Surgery, Second edition, Saunders, Elsevier 2007.

  • Mann FA et al. Reference intervals for insulin concentrations and insulin:glucose ratios in the serum of ferrets. Journal of Small Exotic Animal Medicine, 2 (2), 1993, pp. 79-83.

  • Marini, RP, et al. Functional islet cell tumor in six ferrets. JAVMA, 202 (3), 1993, pp.430-433.

  • Morrisey, James K. and Jan C. Ramer. Ferrets : clinical pathology and sample collection. In: Veterinary Clinics of North America Exotic Animal Practice, 2:3, 1999 : 553-564.

  • Neiffer, Donald L., et al. Mortality associated with melarsomine dihydrochloride administration in two North American river otters and a red panda. Journal of Zoo and Wildlife Medicine 33 (3), 2002 : 242-248.

  • Nelson WB. A simple method for removal of ferret musk glands. Avian/Exotic Prac 1985;2(4):6-10.

  • Neuwirth, L., et al. Adrenal neoplasia in seven ferrets. Veterinary Radiology & Ultrasound, 34 (5), 1993, pp.340-346.

  • Orcutt, Connie. Treatment of urogenital disease in ferrets. Exotic DVM 3.3, 2001: 31-37.

  • Palley, Lori S. Parvovirus-associated syndrome (Aleutian disease) in two ferrets. JAVMA, 201 (1), 1992, pp.100-106.

  • Quesenberry, Katherine E., James W. Carpenter, Peter Quesenberry. Ferrets, Rabbits and Rodents: Clinical Medicine and Surgery Includes Sugar Gliders and Hedgehogs. 2nd ed. Philadelphia: WB Saunders Co., c2003

  • Rosenthal, K., et al. Hyperadrenocorticism associated with adrenocortical tumor or nodular hyperplasia of the adrenal gland in ferrets. JAVMA, Vol. 203 (2), 1993, pp. 271-275.

  • Shoemaker, Nico J., et al. Correlation between age at neutering and age at onset of hyperadrenocorticism in ferrets. JAVMA, 216 (2), 2000: 195-197.

  • Shoemaker, NJ and PG Fisher. Hyperadrenocorticism in ferrets: an interpretive summary. Exotic DVM, 6 (1), 2004: 43-45.

  • Thorne, ET, Williams ES.1988. Disease and endangered species: the black-footed ferret as a recent example. Cons.Biol. 2(1):66-74.

  • Wagner, Robert A., et al. Leuprolide acetate treatment of adrenocortical disease in ferrets. JAVMA, 218 (8), 2001: 1272-1274.

  • Weiss, Charles A., et al. Surgical treatment and long-term outcome of ferrets with bilateral adrenal tumors or adrenal hyperplasia: 56 cases (1994-1997). JAVMA, 215 (6), 1999: 820-823.

  • Weiss CA. Cryosurgery of the ferret adrenal gland. Exotic DVM Magazine, 1 (5), 1999: 27-28.

  • Wimsatt, Jeffrey, et al. Efficacy of a commercial canine distermper vaccine in the domestic ferret (Mustela putorius): survival, PCR, and serologic evidence. Proceedings of the AAZV and IAAAM Joint Conference, 2000. pp. 238-239.

  • Xiantang, Li, et al. Neoplastic diseases in ferrets: 574 cases (1968-1997). JAVMA, Vo. 212 (9), 1998, pp. 1402-1406.