Diseases / List of Miscellaneous / Metabolic / Multifactorial Diseases / Disease description:

Insulinoma in Ferrets

INFORMATION AVAILABLE

GENERAL INFORMATION

CLINICAL CHARACTERISTICS & PATHOLOGY

INVESTIGATION & DIAGNOSIS

TREATMENT & CONTROL

SUSCEPTIBILITY & TRANSMISSION

ENVIRONMENT & GEOGRAPHY

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General and References

Disease Summary

Tumours of the B-cells of the Islets of Langerhans of the pancreas, which can be adenomas or adenocarcinomas. This causes excessive insulin production, resulting in hypoglycaemia. It is a disease  of middle-aged ferrets.
Ferrets As in other species, this tumour of the pancreas causes excessive insulin production and therefore hypoglycaemia.

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Alternative Names (Synonyms)

Islet cell tumours. (B602.9.w9, B627.18.w18, B631.30.w30)

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Disease Type

Miscellaneous / Metabolic / Multifactorial

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Infectious/Non-Infectious Agent associated with the Disease

IInsulinoma is caused by excess levels of insulin being produced, which increases the glucose uptake by cells. This inhibits gluconegenesis and glycogenolysis, which results in hypoglycaemia. (B232.9.w9, B631.30.w30) 

Infective "Taxa"

--

Non-infective agents

--

Physical agents

-- Indirect / Secondary

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References

Disease Author

Bridget Fry BSc, RVN (V.w143)
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Major References / Reviews

Code and Title List

Ferrets
B232.9.w9, B602.8.w8, B602.9.w9 B602.12.w12, B629.13.w13, B631.30.w30

Other References

Code and Title List

 

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Clinical Characteristics and Pathology

Detailed Clinical and Pathological Characteristics

General --

Clinical Characteristics

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Ferrets Ferrets may be asymptomatic with insulinoma. (B629.13.w13)

Insulinoma can be acute or chronic in onset. (B232.9.w9) 

Clinical signs depend on not only the rate of decline of the blood sugar, but also the duration and level of hypoglycaemia. (B232.9.w9) Hypoxia can cause brain damage (B232.9.w9)

  • Neurological signs, which can  last from minutes to hours. 
    • Blindness (B232.9.w9)
    • Disorientation (B232.9.w9)
    • Ptyalism (excessive salivation) (B232.9.w9)
    • Muscle twitches (B232.9.w9)
    • Hind leg weakness (B602.12.w12)
    • Nervous (B232.9.w9)
    • Ataxia (B602.12.w12)
    • Seizures (B602.12.w12, B629.13.w13)
    • Collapse, with depression, recumbency, minimal responsiveness and glazed eyes. (B602.8.w8)

General

  • Tachycardia
  • Hypothermia 
  • Weight loss 
  • Tremors 
  • Lethargy (B602.12.w12)

(B232.9.w9, B629.13.w13)

  • Collapse 
  • Pawing at mouth
  • Glazed eyes 

(B602.8.w8, B629.13.w13, B631.30.w30)

(B232.9.w9)

Clinical pathology
  • Biochemistry (other than blood glucose levels) is typically within normal parameters, however the ALT can be raised. (B629.13.w13)

Incubation

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Ferrets
  • --

Mortality / Morbidity

  • --
Ferrets
  • Insulinomas are one of the most common neoplasms found in ferrets. (B602.9.w9, B602.12.w12, B631.30.w30)
  • Post-surgery, ferrets can survive up to twenty two months. (B631.30.w30)
  • Early diagnosis and treatment can improve the prognosis. (B629.13.w13)

Pathology

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Ferrets
Gross pathology
  • Pancreas: 
    • One or more nodules in the pancreas, perhaps 1-2 mm diameter. (B627.12.w12, B631.30.w30)
  • Metastases may be found in the liver, spleen or regional lymph nodes but are uncommon. (B627.12.w12).
Histopathology:
  • Cellular differentiation varies depending on whether the tumour is an adenoma or adenocarcinoma. The mitotic index is usually low. Adjacent pancreatic tissue may be compressed, there may be invasion of the tumour capsule, other tissue and/or local blood vessels. (B627.12.w12)
    • Immunostaining: Positive for insulin. (B627.12.w12)

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Human Health Considerations

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Susceptibility / Transmission

General information on Susceptibility / Transmission

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Ferrets
Susceptibility
  • Insulinomas are one of the most common neoplasms found in ferrets. (B602.9.w9, B602.12.w12)
  • This disease affects middle-aged and older ferrets (B629.13.w13)
    • Affects ferrets between the ages of three to eight years or more commonly in ferrets between four and five years of age. (B232.9.w9) 
  • Males are slightly more prone to the disease than females (B629.13.w13); males and females are equally affected. (B631.30.w30)

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Disease has been reported in either the wild or in captivity in:

  • Insulinomas are common in domestic ferrets. (B602.9.w9, B602.12.w12, B631.30.w30)

Further information on Host species has only been incorporated for species groups for which a full Wildpro "Health and Management" module has been completed (i.e. for which a comprehensive literature review has been undertaken). Host species with further information available are listed below:

Host Species List

(List does not contain all other species groups affected by this disease)

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Disease has been specifically reported in Free-ranging populations of:

  • --

Further information on Host species has only been incorporated for species groups for which a full Wildpro "Health and Management" module has been completed (i.e. for which a comprehensive literature review has been undertaken). Host species with further information available are listed below:

Host Species List

  • --

(List does not contain all other species groups affected by this disease)

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Environment/Geography

General Information on Environmental Factors/Events and Seasonality

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Regions / Countries where the Infectious Agent or Disease has been recorded

  • This disease is commonly reported in ferrets in the USA. This is thought to be due to intensive breeding and genetic selection. (B232.9.w9)

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Regions / Countries where the Infectious Agent or Disease has been recorded in Free-ranging populations

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General Investigation / Diagnosis

General Information on Investigation / Diagnosis

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Ferrets Clinical signs, history and hypoglycaemia on a blood test allow presumptive diagnosis of the disease. (B232.9.w9, B629.13.w13)

Lowered blood glucose levels. 

  • More than one sample is probably necessary for an accurate result. Fasting the ferret for four to six hours before hand is also useful for accuracy. Using a blood glucose test strip is the most practical way to test for this. (B232.9.w9, B232.9.w9, B631.30.w30) 
    • Normal resting blood glucose ranges are 94 to 207 mg/dL and fasting blood glucose are 90 to 125 mg/dL. (B629.13.w13)
    • Note: Human glucometers have not been validated for using on ferret blood. (B629.13.w13)
    • Where possible, an official laboratory should be used for measurement of glucose in venous plasma, for more accurate results. (B631.30.w30)
    • Note: A low glucose may be read from normal ferrets due to mishandling of samples before testing. (B629.13.w13)
Measurements of insulin levels.
  •  If insulin levels are raised from normal to 2000 pmoL/L and blood glucose is low, less than 70 mg/dL, this would suggest insulinoma. (B232.9.w9, B629.13.w13) Fasting for a further two hours at this stage, will show a glucose drop to below 3.4 mmoL/L (60 mg/dL). (B232.9.w9, B631.30.w30)

Imaging

  • Diagnostic imaging is not useful for detection of the primary insulinoma, because these tumours are very small, perhaps 1-2 mm diameter. (B631.30.w30)
  • Metastases on the liver can be seen on ultrasonography. (B631.30.w30)
  • Ultrasound and radiography are not necessarily recommended for the diagnosis of insulinomas. This is because the majority of insulinomas are benign and do not metastasize to other areas of the body. (B631.30.w30, B629.13.w13))
  • Ultrasonography can rule out other diseases causing hypoglycemia. (B602.8.w8, B629.13.w13)

Biopsy

  • Biopsy of the pancreatic tissue and histopathology can confirm diagnosis. (B629.13.w13)
Related Techniques
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Similar Diseases (Differential Diagnosis)

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Ferrets
  • Other Neoplasia in Ferrets. (B602.8.w8, B629.13.w13)
  • Hypoglycaemia may be seen in ferrets with liver disease, poor nutritional status, starvation or sepsis. (B602.8.w8, B629.13.w13)

Note: A low blood glucose level may be read from normal ferrets due to mishandling of samples before testing. (B629.13.w13)

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Treatment and Control

Specific Medical Treatment

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Ferrets
Immediate treatment of hypoglycaemia
  • If the ferret is hypoglycaemic then liquid glucose or honey can be given in a syringe orally. If the ferret is collapse then glucose can be rubbed on the ferrets gingiva. If there is no response a bolus 0.5-2 mL of 50% dextrose can be given slowly intravenously. Note: This must be given slowly to prevent further production of insulin. (B232.9.w9)
  • 5% dextrose can be given intravenously over a longer period of time, with diazepam 1-2 mg intravenously to effect (If the ferret is fitting). (B232.9.w9)
Long-term medical therapy
  • Medical treatment is recommended for ferrets with other diseases and for those over six years of age. (B232.9.w9)
  • Prednisone 0.5-2 mg/kg twice daily orally and/or diazoxide 5-10 mg/kg twice daily orally. This should control hypoglycaemia and inhibiting insulin release, but there is no effect on the progression of the disease. This can also be given post surgery. (B232.9.w9)
    • Orapred and Pediapred are paediatric formulas of prednisolone that work well for ferrets. (B629.13.w13)
    • Diazoxide inhibits insulin release. (B629.13.w13) Mixing with methylcellulose makes administration easier. (B631.30.w30)
    • Prednisolone (0.2-1.0 mg/kg orally every 24 hours) is usually added when diazoxide treatment reaches 15 mg/kg every twelve hours and is not controlling the hypoglycaemia. (B629.13.w13)
    • Another suggest dose rate of prednisolone is 0.25 mg/kg orally every twelve hours and increased up to 2 mg/kg every twelve hours. (B629.13.w13)
    • Note:
      • Neither of these drugs will stop the the tumour progressing, therefore an increased dose rate may have to be given over time. (B629.13.w13)
      • Side effects of both diazoxide and prednisolone treatment can be anorexia and vomiting. (B629.13.w13)
      • Cushing's disease has been reported in ferrets on long term prednisolone treatment. (B631.30.w30)
    • Octreotide, which is a somatostatin analogue that inhibits insulin secretion, can be given but requires subcutaneous injection every twelve hours, therefore is rarely used in ferrets. (B629.13.w13)
  • The effect of treatment can be monitored by the plasma glucose concentration. 
    • Blood should be taken four hours after giving diazoxide and weekly until the fasting blood glucose is in the normal range. Then every three months once the clinical signs have been eliminated. (B629.13.w13) 
      • During these four hours food should not be given. (B629.13.w13) 
      • The diazoxide can then be gradually increased. 10 mg/kg orally twice daily and can be increased up to 60 mg/kg twice daily. (B629.13.w13)

Note:

  • These treatments have been known to control hypoglycaemia and signs of the disease for 6-22 months. (B631.30.w30); for up to eighteen months. (B232.9.w9)
  • Recurrence of tumours and clinical signs are common. (B631.30.w30)
  • Prognosis is guarded, as local recurrence is likely. (B232.9.w9) 
  • The survival rate is an average of sixteen months post treatment. This can depend on the duration between clinical signs and the start of treatment. Early treatment is necessary increase the ferrets prognosis. (B629.13.w13)
  • Prognosis is considered to be better in ferrets than dogs. (B631.30.w30)
Related Techniques
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General Nursing and Surgical Techniques

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Ferrets
Surgery
  • Exploratory laparotomy should be performed if blood results suggest insulinoma. This will confirm if nodules in the pancreas are present. Removal of the tumours can be carried out if the ferret is young. (B232.9.w9) 
    • Fluid therapy and antibiotics should be given during and post surgery. (B232.9.w9)
    • Other organs should be examined for metastasis, whilst performing the exploratory laparotomy. (B629.13.w13)
    • Pancreatic surgery will slow the disease down, but not eradicate the disease. (B232.9.w9, B602.8.w8)
    • Surgery to remove the tumour is recommended, however, tumours may be difficult to remove if they are close to the pancreatic ducts, and some may be very small and not visible, therefore rather than nodulectomy, partial pancreatectomy (removal of a portion of the pancreas) is advised. This should increase the survival of the ferret. (B602.8.w8, B629.13.w13, B631.30.w30)
    • The body of the pancreas can only be viewed by its ventral surface. Visible masses can occur that are discoloured or small firm nodules. (B602.8.w8)
    • Disease free status after surgery usually last approximately one year and survival rate is twenty two months. (B631.30.w30)
    • Note:  
      • If a large section of pancreas is removed this can induce diabetes mellitus. This is more difficult to treat than insulinoma, so should be avoided. (B631.30.w30)
      • Reoccurrence of the disease may occur seven to ten months post surgery. (B629.13.w13)
      • Post surgery the blood glucose should be monitored at one month, and every three months thereafter. (B629.13.w13)
Long-term care
  • Give frequent small high protein meals. (B232.9.w9)
    • Foods high in protein and fat fed three to four times daily. (B629.13.w13)
  • Simple sugars/sugary foods should be avoided. (B232.9.w9, B629.13.w13)
  • Fasting should be avoided. (B232.9.w9)
Related Techniques
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Preventative Measures

Vaccination --
Ferrets --
Prophylactic Treatment

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Ferrets
  • Diets high in protein and fat, with reduced carbohydrate and fibre, have been suggested, although there is no evidence these actually prevent the development of insulinomas. (B631.30.w30)
Related Techniques
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Environmental and Population Control Measures

General Environment Changes, Cleaning and Disinfection --

Ferrets

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Population Control Measures --
Ferrets --
Isolation, Quarantine and Screening --
Ferrets --
Related Techniques
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