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

Adrenocortical Neoplasia 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

Adrenocortical neoplastic disease affects the adrenal glands and is known as Cushing's disease in cats and dogs. (P120.2006.w5)
Ferrets Adrenocortical neoplastic disease is a common disease of neutered ferrets, involving increased production of sex hormones.

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Alternative Names (Synonyms)

  • Adenoma (B629.13.w13)
  • Adrenal gland disease
  • Adrenocarcinoma (B629.13.w13)
  • Adrenal hyperplasia (B629.13.w13)
  • Endocrinopathic disease (B629.13.w13)
  • Hyperadrenocorticism. (B339.9.w9)

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Disease Type

Miscellaneous / Metabolic / Multifactorial

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Infectious/Non-Infectious Agent associated with the Disease

Ferrets
  • This disease is thought to be associated with neutering (castration/ovariectomy) ferrets too early. (P120.2006.w5) The reason for this is thought to be unregulated stimulation of gonadal cells by hormones, which result in adrenal gland disease. (B629.13.w13)
    • However, there is a relatively high incidence in the Netherlands where ferrets are not neutered early, and it is suggested that all ferrets which have been neutered, whether early or later, are likely to develop adrenal disease. (B631.30.w30)
    • A study in the Netherlands found a significant correlation between age of neutering and age of onset of adrenal disease. Within the studied 1,274 ferrets, seven (0.55%) developed hyperadrenocorticism confirmed by histological examination of excised adrenal glands while a further seven were suspected cases based on clinical signs, but the owners did not allow further studies to confirm the diagnosis. (J4.216.w2)
    • Hyperadrenocorticism has been seen in entire (unneutered) ferrets, but only rarely. (J4.216.w2)
  • If a male is castrated, the negative feedback of testosterone and oestradiol on hypothalamic GnRH is lost. This then causes uninhibited secretion of GnRH, luteinizing hormone and follicle-stimulating hormone. These hormones then stimulate the adrenal gland, which results in hyperplasia and tumour development. (B339.9.w9)
  • An alternative theory is that ferrets kept in artificially prolonged light conditions indoors are more prone to develop this condition. The relatively low incidence in the UK may be associated with housing of ferrets outdoors, under natural light cycles, rather than indoors with longer periods of light from artificial lighting. (B631.30.w30, J60.11.w2)
  • There may be a genetic component. (B631.30.w30, J60.11.w2)
  • There may be a dietary component (complete pelleted diets rather than a carcass-based diet). (J60.11.w2)

Infective "Taxa"

  • --

Non-infective agents

--

Physical agents

-- Indirect / Secondary

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References

Disease Author

Bridget Fry BSc, RVN (V.w143)
Click image for main Reference Section

Major References / Reviews

Code and Title List

B339.9.w9, B627.12.w12, B627.18.w18, B629.13.w13
J60.11.w2
P120.2006.w5

Other References

Code and Title List

 

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Clinical Characteristics and Pathology

Detailed Clinical and Pathological Characteristics

General --

Clinical Characteristics

Progressive alopecia, sometimes with pruritis and skin thinning; vulval enlargement in females, dysuria (prostatic enlargement) in males, weight loss and abdominal swelling. 
Ferrets
  • Ferrets can show clinical signs without the adrenal glands being enlarged. (P120.2006.w5)
  • Clinical signs are similar to those found in cats and dogs. (B627.18.w18)

Dermatological

General

Clinical pathology
  • If oestrogen precursors are elevated for a long time, the ferret will develop non-regenerative anaemia. (P120.2006.w5)
  • A complete blood count should be normal, unless there is bone marrow toxicity. Anaemia may be present with pancytopaenia. (B629.13.w13)
  • Serum biochemistry may show elevated alanine aminotransferase. The biochemistry would also show concurrent diseases if present. (B629.13.w13)

Incubation

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Ferrets
  • --

Mortality / Morbidity

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Ferrets Morbidity
  • This disease is the second most common disease in ferrets. (P120.2006.w5)
  • This disease is much less common in populations of ferrets in Europe and Australia than in ferrets in the USA. (B602.9.w9, J60.11.w2)
    • The relatively low incidence in the UK may be associated with housing of ferrets outdoors, under natural light cycles, rather than indoors with longer periods of light from artificial lighting. (B631.30.w30)
    • In the Netherlands the prevalence is about 0.55%. (B631.30.w30)
    • A review in the USA found 25% of all neoplasms to be adrenocortical adenomas or adrenocortical adenocarcinomas. (B602.9.w9)
    • Incidence in the UK is increasing. (J60.11.w2)

Mortality

  • Generally a good prognosis (even if not treated). (B629.13.w13)
  • If the adrenal gland disease leads to metastasis or other complications such as bone marrow toxicity. or urinary obstruction, there is a poor to grave prognosis. (B629.13.w13)

Pathology

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Ferrets Gross pathology
  • Single or multiple masses, nodular, unilateral or bilateral. Adenomas are small (usually <1 cm) and slow-growing, whereas adenocarcinomas are large (more than 2 cm in diameter) and invasive. Nodules may be pale, friable, yellow to brown, encapsulated (variable); the adrenal medulla and cortex are compressed with adenomas while they may be replaced by adenocarcinomas. (B627.18.w18)
  • (B627.18.w18)
  • Metastases are uncommon, but may occur. (B627.18.w18) 
  • Concurrent pathological findings have included cystic urogenital abnormalities, mammary gland hyperplasia. and cystic prostatic disease. (B627.18.w18)

Histopathology

  • Histologically the tumours are categorised into hyperplasia, adenoma or carcinoma. (P120.2006.w5, B339.9.w9, B627.18.w18)
  • Adenomas have well-differentiated oval to polyhedral cells in nests, packets or cords, with fibrovascular stroma; there is usually an incomplete fibrous capsule. The cytoplasm is pale to eosinophilic, granular to vacuolated; the nucleus is round, small and hyperchromatic and there is usually one nucleolus. In adenocarcinomas, the cells are more pleomorphic, large and polyhedral, the cytoplasm eosinophilic and vacuolated, nuclei large and vesiculated with prominent nucleoli, and there may be conspicuous mitotic figures. There may also be small dark basophilic cells and large balloon cells with foamy vacuolated cytoplasm. Other findings have included focal necrosis, haemorrhage, and mineralisation. (B627.18.w18)

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Human Health Considerations

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Susceptibility / Transmission

General information on Susceptibility / Transmission

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Ferrets
Susceptibility
  • Neutered males or females are more likely to be susceptible to this disease than intact males and females. (B627.18.w18)
    • Ferrets that have been neutered at a young age have been found to be susceptible to adrenocortical neoplasia disease. (B629.13.w13)
  • Ferrets between the ages of one to seven years have been found to be affected. (B627.12.w12)
    • Ferrets are susceptibility to this disease at any age, but it is more likely between the ages of four and seven. (B627.18.w18)
    • In the UK, this is generally a disease of older ferrets (five years and over) while it is often seen in much younger ferrets in the USA. (J60.11.w2)
  • This disease can equally affect males or females. (B629.13.w13)

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

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

  • Adrenocortical neoplasia disease has been reported in ferrets in the USA. (B629.13.w13)
  • In the UK. (J60.11.w2)
  • In the Netherlands. (B631.30.w30)

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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 Diagnosis can be made by clinical signs (bilateral alopecia, vulvar swelling and masses cranial to the kidneys), history and a full work up. (B627.18.w18, B629.13.w13, J60.11.w2)
  • Palpation of enlarged adrenal glands: (B627.18.w18, B629.13.w13)
    • This can be difficult due to the fat that surrounds the glands. (B629.13.w13)
    • The left adrenal gland is more likely to palpable than the right. (B629.13.w13)
    • The left gland is found craniomedial to the left kidney and the right gland is found midline and under the caudal aspect of the liver. (B629.13.w13)

Blood tests

  • A complete blood count should be normal, unless there is bone marrow toxicity. (B629.13.w13)
  • Anaemia may be present with pancytopenia. (B629.13.w13) See: Clinical Pathology of Ferrets
    • Non-regenerative anaemia develops with time. (P120.2006.w5)
  • Serum biochemistry may show an elevated alanine aminotransferase. The biochemistry may also show concurrent diseases if present. (B629.13.w13)
  • Elevated sex steroids can be detected, such as androstenedione, dehydroepiandrosterone sulphate, oestradiol or 17- α-hydroxyprogesterone. (B339.9.w9, J60.11.w2)
    • Normal ranges for sex steroid hormones: 
      • Oestradiol (pmol/L) 30-180.  (B629.13.w13)
      • 17- α-hydroxyprogesterone (nmol/L) 0.0-0.8. (B629.13.w13)
      • Androstenedione (nmol/L 0.0-15.0. (B629.13.w13)
    • If one or more of these results are raised in a neutered ferret, this confirms hyperadrenocorticism.  (B629.13.w13, J60.11.w2)
    • Androstenedione is the most sensitive of the hormones above. (B339.9.w9)
  • Cortisol should be in the normal range. (B629.13.w13)

Imaging

  • Ultrasound scanning can assist in identifying adrenal disease, (P120.2006.w5, B339.9.w9, B627.18.w18) highlighting the thickness of the adrenal glands, size and shape. Note: If the adrenal glands appear normal, this does not necessarily rule out adrenal disease. (B629.13.w13)
  • Radiographs can help eliminate other diseases. (B629.13.w13, B627.18.w18)
  • See: Imaging in Ferret Diagnosis and Treatment

Surgery

  • An exploratory Laparotomy can help in the detection of a adrenal tumour. (B627.18.w18, J60.11.w2)
    • The adrenal glands should be pink, 6 - 8 mm long and 2-3 mm thick with "the texture of a cooked lentil. Increased size or firmness indicates disease. (B232.19.w19)
    • If both glands have hyperplasia and are the same size as each other, but only slightly enlarged, this may be difficult to evaluate. (J60.11.w2)

Histopathology

  • Histopathological findings confirm the diagnosis. (B627.18.w18)
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Similar Diseases (Differential Diagnosis)

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Ferrets
  • Female ferrets with Hyperoestrogenism may show similar clinical signs. (B629.13.w13)
  • Other masses which may be found on the adrenals include cortical cell nodular hyperplasia, myelolipoma and phaeochromocytoma. See Neoplasia in Ferrets. (B627.18.w18)

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Treatment and Control

Specific Medical Treatment

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Ferrets Treatment of adrenal disease includes medical or surgical therapy. (B629.13.w13)
  • Leuprolide acetate, which is a long acting gonadotropin-releasing hormone analogue; this can be given to the ferret as medical treatment for adrenal disease. (B629.13.w13, J60.11.w2)
    • Leuprolide acetate will suppress gonadotropins and reduces sex hormones, eliminating clinical signs. (P120.2006.w5, B339.9.w9, B629.13.w13) 
      • This process is known as desensitization. (P120.2006.w5)
      • This treatment will not stop tumour growth. (P120.2006.w5)
    • Leuprolide acetate 3.75 mg should be given at 100 g intramuscularly every thirty days, for ferrets weighing less than one kg. For ferrets weighing over one kg 200 g can be given every thirty days. (P120.2006.w5, B629.13.w13)
    • A starting dose of 750 g/kg bodyweight, monthly, is suggested. (J60.11.w2)
    • The response to this drug can be variable. (B629.13.w13, J60.11.w2)
    • Continuation of the drug is advised at least monthly for three months, and until clinical signs have ceased. Note: This treatment may have to be long term (life-long) and does not stop tumour growth. (P120.2006.w5)
      •  Increasing the dose rate over time may be necessary. (P120.2006.w5)
    • Leuprolide acetate can also alleviate urinary blockages, by reducing the sex hormones which trigger the prostatic enlargement. (B629.13.w13)
    • Some ferrets will produce other hormones by their adrenal glands, in these cases the treatment will be ineffective. (P120.2006.w5)

Other medical treatments

  • Bicalutamide, an androgen blocker, can also be used at 5 mg/kg orally once daily. (B629.13.w13)
  • Alternatively a melatonin implant can be used to suppress GnRH release and therefore suppress FSH and LH release. This implant should last three months and can be used instead of luprolide acetate. (P120.2006.w5)
    • Melatonin does not stop tumour growth, and may simply improve hair coat growth. (J29.13.w)
Related Techniques

 

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General Nursing and Surgical Techniques

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Ferrets Surgery
  • Surgery can be performed after histological pathology on the tumour is performed, with the view of removing a pathological gland. (P120.2006.w5, B339.9.w9)
  • If the affected adrenal tumour is removed at an earlier stage, this may be curative. (B627.18.w18)
    • The disease may recur even if both adrenals have been removed. (P120.2006.w5)
  • If surgery is performed, the left adrenal gland is easier to remove than the right. 
    • When a single gland is affected a unilateral adrenalectomy should be performed and if needed the contralateral gland should be debulked. (B339.9.w9, B629.13.w13)
    • If both adrenal glands need to be removed, it may be difficult to remove all adrenal tissue. (B339.9.w9, B629.13.w13)
    • It is, however, possible to remove both glands and for the ferret not to have significant hormonal problems.
      • Note: Post-surgical supplementation with glucocorticoids is required if both adrenal glands are removed. (B339.9.w9, B629.13.w13) These ferrets should be given dexamethasone (1 mg/kg intramuscularly) post surgery, then prednisolone (1 mg/kg once daily orally) for several weeks. (P120.2006.w5)
    • The right adrenal gland sits close to the caudal vena cava. Because of this a complete adrenalectomy of the left gland is advised and a partial adrenalectomy on the right side. (B339.9.w9, B629.13.w13)
    • Removal of the left adrenal gland:
      • Carefully dissect the adrenal gland from the surrounding fat. (B232.19.w19)
      • Ligate any minor vessels. (B232.19.w19)
      • Apply haemostatic dressings as required to stop ooze or haemorrhage from vessels in the fat. (B232.19.w19)
      • Take care not to affect the mesenteric blood supply when a large tumour extends towards the midline. (B232.19.w19)
    • Removal of the right adrenal gland.
      • This is more complex, because the gland often is attached to the caudal vena cava (as well as being more cranial and hidden below the right hepatic lobe. (B232.19.w19, J60.11.w2)
      • Incise the capsule and "shell out" the glandular tissue. (B232.19.w19)
      • If it is necessary to remove the capsule, ligate the caudal vena cava longitudinally alongside the gland at the attachment point to prevent haemorrhage from the vena cava when the gland is removed. (B232.19.w19)
    • If a right adrenal tumour has invaded into the vena cava, resection of this is possible. (P120.2006.w5)
      • 25% of animals will die during this procedure. If they survive then give aggressive fluid therapy (See: Treatment and Care - Fluid Therapy ) for two to three days and monitor for signs of renal failure. (P120.2006.w5)
      • Blood will be diverted via collateral vessels, which are plentiful in ferrets. (P120.2006.w5)
  • If the adrenal glands appear normal to the naked eye, the decision of which gland to remove can be difficult. In such cases, medical treatment and a repeat ultrasound in three months is recommended. (P120.2006.w5)
  • Note: There is a 17% chance of the disease recurring if unilateral adrenalectomy is performed and if a bilateral adrenalectomy is performed there is a 15% chance of the disease recurring between seven and twenty two months. (B629.13.w13)
  • Histopathological evaluation of the tissue that has been surgically removed is advised.  (P120.2006.w5)
    • These results will provide an indication of the degree of pathological change (hyperplasia, adenoma or adenocarcinoma) and thereby give an indication of prognosis. (P120.2006.w5)
    • If the adrenal is hyperplastic, function should return back to normal but with adenomas it does not; carcinomas might metastasize. (B339.9.w9)
  • There is no need for any hormonal supplements after the surgery. (J60.11.w2)

Other procedures

  • If males have urinary obstruction, the bladder should be emptied by manual expression, catheterisation or cystocentesis. (B629.13.w13)
  • In Italy a new surgical approach has been developed using alcohol injections into the adrenal glands, which shrinks them. This could be a successful treatment as it is currently widely used in human medicine. (P120.2006.w5)
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Preventative Measures

Vaccination --
Ferrets --
Prophylactic Treatment

--

Ferrets
  • Consider avoiding neutering (castration of males, ovariohysterectomy of females), particularly early neutering. (B339.9.w9, B629.13.w13, B631.30.w30, J60.11.w2, P120.2006.w5)
  • For alternatives to surgical neutering see Reproductive Management of Mammals - Control of Reproduction
Related Techniques
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Environmental and Population Control Measures

General Environment Changes, Cleaning and Disinfection --

Ferrets

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