Adrenocortical Disease - Ferret

Introduction

Adrenal gland disease associated with adrenocortical hyperplasia, adenoma or adenocarcinoma occurs commonly in middle-aged ferrets in the USA and its incidence is increasing in Europe.

Pituitary-dependent hyperadrenocorticism, which is the most common cause of hyperadrenocorticism in dogs, has not been recognised in ferrets.

In ferrets, adrenal disease is associated with elevation of sex hormone concentrations, most commonly oestradiol, androstenedione and 17-hydroxyprogesterone.

The practice of early neutering, common in the USA (neutered as early as 6 weeks of age), has been shown to be strongly correlated with the development of the disease.

Since the adrenal glands and the gonads are in close proximity during early development, undifferentiated gonadal cells may migrate in the embryo with the adrenal gland cells. These undifferentiated cells may later become functional steroidogenic cells.

Surgical removal of the gonads is thought to reduce the appropriate negative feedback mechanism on the hypothalamic-pituitary axis. Thus, the functional gonadal cells secrete hormones in excess. Over time, the excess hormonal secretion and lack of negative feedback control is what is thought to lead to neoplastic transformation of these aberrant adrenal cells.

Other potential risk factors include genetics, as most American ferrets are derived from a limited gene pool, and diet and husbandry, whose roles have not yet been fully investigated.

Clinical Signs

Alopecia: one of the most common clinical signs, presenting as bilaterally symmetrical alopecia, localised to the tail, dorsum or ventrum, or leading to complete baldness.

Return to male sexual behaviour: neutered males may be seen to attempt to mate with spayed females and occasionally males.

Stranguria in males: associated with prostatic or periurethral cysts that occlude the urethra. The prostatic tissue becomes swollen under the influence of sex hormones.

Vulval enlargement in females: due to the high circulating concentrations of sex hormones. Increased vulval discharge is an ideal medium for the growth of bacteria and this increases susceptibility to urinary tract infections.

Other signs include: lethargy and muscle atrophy.

Rarely, the enlarged adrenal gland may be palpated on physical examination.

Diagnosis

A presumptive diagnosis may be made based upon the history, clinical signs and physical examination.

However it must be remembered that sexually intact females in oestrus or females with retained ovarian remnants may demonstrate similar clinical signs.

Further investigation should include:

Haematology and biochemistry: in severe cases, pancytopenia may be present due to oestrogen toxicosis and myelosuppression. Aspartate aminotransferase (AST) levels are frequently elevated. The ACTH stimulation test and the Dexamethasone suppression test are useless in ferrets because, unlike in dogs, their disease is rarely associated with an increase in cortisol levels.

Sex hormone diagnostic panel: A diagnostic test is available through the University of Tennessee which measures levels of estradiol, androstenedione and 17-hydroxyprogesterone, which are the most commonly elevated sex hormones in adrenal disease of ferrets. This diagnostic panel has consistently identified ferrets with adrenal disease.

Abdominal ultrasonography: this can reveal enlarged adrenal glands and enables any concurrent abdominal problems (insulinoma, splenic enlargement) to be identified. It has been found that only one adrenal gland was affected in 84% of diseased ferrets and that the left adrenal was most commonly affected.

Exploratory laparotomy: direct visualisation of the adrenal glands is also an option and an incisional or excisional biopsy can then be performed.

Differential diagnosis: hyperoestrogenism

Treatment

Surgical removal of the affected adrenal gland or debulking is the treatment method of choice.

The left adrenal gland is most easily resected due to its anatomical location. The right adrenal is very closely associated with the caudal vena cava and complete surgical excision can be difficult. The incidence of surgical complications is higher and the disease can recur.

Generally, complete adrenalectomy in ferrets has a favourable prognosis. Malignant adrenal tumours metastasise rarely and have a similar prognosis to benign ones.

There are medical options, which include:

Leuprolide (GnRH analogue) and melatonin injections which may temporarily reduce the ferret's clinical signs and disease but will not cure the underlying condition. Repeat injections are often required, but this is an option for ferrets that are high-risk anaesthetic and surgery candidates.

Mitotane is used in dogs for the treatment of hyperadrenocorticism and has been used in ferrets. It is not currently recommended due to its unpredictable results and low margin of safety.

Clinical signs should resolve shortly after appropriate treatment.

References

Bielinska M, Kiiveri S, Parvianinen H, et al. (2006) Gonadectomy-induced adrenocortical neoplasia in the domestic ferret (Mustela putorius furo) and laboratory mouse. Vet Pathology 43:97-117.

Carpenter JW, Quesenberry KE. (2003) Ferrets, Rabbits and Rodents: Clinical Medicine and Surgery, 2 nd ed. W B Saunders, St. Louis pp. 83-87

Keeble, E. (2001) Endocrine diseases in small mammals In Practice 23:570-585

Lewington, J. (2000) Ferret husbandry, medicine and surgery Elsevier Health Sciences