Endocrine Disease (Part II)

Courtesy of Anna Meredith MA VetMB CertLAS DZooMed MRCVS
Royal [Dick] School of Veterinary Studies

Hyperoestrogenism

This is probably the most common endocrine condition encountered in practice in ferrets in the United Kingdom, in the author's experience. The normal breeding season for ferrets is between March and September, during which time ferrets are seasonally polyoestrus with induced ovulation. Ovulation occurs approximately 30-40 hours following mating. If unmated or not stimulated to ovulate, then as many as 50% of females may develop aplastic anaemia after prolonged oestrus (up to six months). High levels of oestrogen lead to oestrogen suppression of the bone marrow and the resulting anaemia with pancytopaenia. Other causes of hyperoestrogenism include, rarely an ovarian remnant following ovariohysterectomy, or more commonly adrenal neoplasia. Pseudopregnancy following a sterile mating has been recorded in ferrets

Clinical signs include swelling of the vulva (indicative of oestrus), vulval discharge, weakness, anorexia, pallor of the mucus membranes, systolic murmurs, weak pulses, melaena, alopecia over the tail base, ecchymoses and petechiation of the mucus membranes and skin, posterior paresis (due to haemorrhagic myelomalacia) and systemic infections secondary to leukopaenia.

Diagnosis is based on history, clinical signs and haematology. Treatment with supportive care and a cessation of oestrus is indicated. Supportive care with intravenous fluids, syringe feeding, iron and vitamin B supplementation and prophylactic antibiotics should be commenced. A blood transfusion is indicated if the packed cell volume (PCV) is less than 15%. Normal PCV values in ferrets range from 46 61%. Blood groups have not been demonstrated in ferrets and therefore multiple transfusions from the same donor or a variety of donors without cross matching may be carried out without reactions occurring. With a PCV between 15 25% the prognosis is still poor since this value often continues to decrease over time. If greater than 25%, cessation of oestrus may be curative. Ovariohysterectomy is often too risky in such debilitated animals and human chorionic gonadotrophin has been successfully used instead at 100IU by intramuscular injection. The injection is repeated after 7 days if signs of oestrus are still apparent. Gonodotrophin-releasing hormone has also been used at 20ug dose intramuscular or subcutaneous injection repeated after 1 2 weeks. Once stabilised, ovariohysterectomy should be carried out.

This condition is easily prevented in female ferrets by routine ovariohysterectomy, mating with a vasectomised male or by use of proligestone ('Delvosteron' Intervet UK) subcutaneous injection, prior to the onset of the breeding season. Megoestrol Acetate can also be used to prevent the onset of oestrus, but it should be noted that both these drugs have been associated with the development of pyometra and liver disease. Tamoxifen has antioestrogenic effects in humans, however this is oestrogenic in ferrets and should therefore not be used. Altering of light cycles may prevent the onset of oestrus in jills (14 hours light: 10 hours dark).
Packed Cell Volume as a Prognostic Indicator in Female Ferrets with Persistent Oestrus:

Normal Endocrine Hormone Levels in Ferrets

Packed Cell
Volume (%)
Prognosis Treatment Options
>25 Good Ovariohysterectomy or HCG/GnRH
injection
15 25 Guarded HCG/GnRH injection, supportive care
(see below), then consider surgery.
May require blood transfusion if PCV
decreases further.
<15 Poor HCG/GnRH injection, IV fluids,
vitamin B, iron, prophylactic
antibiotics, blood transfusion(s), then
consider surgery.

Healthy female ferrets can be spayed when in season.

Insulinoma

These tumours occur commonly in middle-aged ferrets in the United States. Incidence in the United Kingdom has not been reported. Occasional cases have been reported in the Netherlands (0.5%). The beta islet cells of the pancreas are affected resulting in an increase in insulin production and clinical signs associated with hypoglycaemia. In affected animals the feedback mechanism to counteract this decrease in blood glucose levels by the release of glucagon, cortisol, adrenaline and growth hormone is inhibited.

Clinical signs associated with this neoplasm may be acute in onset or chronic (manifesting over weeks or months). In acute cases clinical signs include collapse, recumbency, depression, hypersalivation and a 'glassy-eyed' appearance. More chronic cases manifest as gradual weakness, particularly of the hind limbs, lethargy, ataxia, with or without weight loss and reduced appetite. Diagnosis is based on history, clinical signs, low blood glucose levels (care should be taken when recording a fasting level) and a high or normal blood insulin level. Blood glucose levels lower than 3.89mmol/L are suggestive, with comatosed cases having levels between 1.11 2.22mmol/L (see table below). Biochemistry may show elevation of alanine aminotransferase and aspartate aminotransferase levels and haematology may show leucocytosis, monocytosis and neutrophilia. Other diagnostic tests include radiography (although this is often unremarkable) and abdominal ultrasonography with visualisation of the pancreas.

Treatment may be surgical or medical in nature, although neither is likely to be curative. Lifespan post diagnosis and treatment averages between 6 24 months. Surgical treatment is indicated in younger ferrets or those with concurrent adrenal disease. Surgery is often not curative, but is aimed at prolonging life span post diagnosis. Longer survival times have been associated with surgical therapy as opposed to medical. A nodulectomy or partial pancreatectomy is carried out. Metastases are common, predominately involving the local lymph nodes, spleen and liver. Prior to surgery ferrets are fasted only for a short period (3 to 10 hours) and intravenous maintenance fluid therapy commenced with 5% dextrose solution. Blood glucose levels should be monitored before, during and after the operation and for several days following surgery. Recurrence of hypoglycaemic episodes is common (on average 2 6 months after surgery) and so cases should be monitored regularly. It should be noted that this is usually a progressive disease and is frequently fatal, progressing to islet cell carcinoma and metastatic spread.

Medical therapy consists of oral prednisolone or diazoxide together or singly. Mild cases should be started on 0.5 2mg/kg prednisolone by mouth twice daily, with regular monitoring of blood glucose levels and gradual increases in dose until clinical signs are reduced. In cases which are non-responsive to prednisolone, diazoxide can be given at 5 10mg/kg by mouth twice daily. Side effects include anorexia and vomiting. This drug is a benzothiadiazine derivative which inhibits insulin release, increases gluconeogenesis and glycogenolysis and decreases the uptake of glucose by cells. Ferrets should be fed regularly with high protein, high fat diets (dried food, cooked meat). Foods with high sugar or carbohydrate levels should be avoided. Snacks should be fed after periods of sleep when the ferret becomes more active to coincide with when blood glucose levels are low and hypoglycaemia is more likely to occur.

(First published in NFWS News - #84 May 2009)