Infectious/Non-Infectious
Agent associated with the Disease
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Ferrets
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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)
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Infective
"Taxa" |
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Non-infective agents |
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Physical agents |
-- Indirect /
Secondary |
Detailed Clinical and Pathological Characteristics
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| General |
--
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Clinical
Characteristics |
Progressive
alopecia, sometimes with pruritis and skin thinning; vulval enlargement in
females, dysuria (prostatic enlargement) in males, weight loss and
abdominal swelling.
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| 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
- Muscle atrophy. (B627.12.w12,
B629.13.w13)
- Weight loss. (J60.11.w2)
- Development of a pendulous abdomen (pot-belly). (J60.11.w2.
B627.12.w12, B627.18.w18)
- Mammary gland enlargement in males. (B627.12.w12,
B627.18.w18)
- Increased sexual activity and swollen vulva may be presented in
females. (P120.2006.w5,
B339.9.w9,
B627.12.w12, B627.18.w18)
- Some females may have a vulva discharge (B627.18.w18)
and possible vaginitis.
(B627.12.w12,
B629.13.w13)
- Sometimes polydipsia/polyuria. (J60.11.w2,
B627.18.w18)
- Secondary disease:
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)
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Incubation |
-- |
| 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)
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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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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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| Related Techniques |
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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 µg
intramuscularly every thirty days, for ferrets weighing less than
one kg. For ferrets weighing over one kg 200 µg can be
given every thirty days. (P120.2006.w5,
B629.13.w13)
- A starting dose of 750 µg/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)
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| 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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| Related Techniques |
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