Hyperadrenocorticism in ferrets (Proceedings)
Adrenal disease is one of the most common and serious disorders facing pet ferrets in the United States today, and is emerging as a common disease entity in other parts of the world as well. Ongoing research provides more clues to the etiology of adrenal disease, and is helps to direct therapeutic choices as well. Some insight into short and long-term prevention strategies is now available.
Ferrets belong to the Mustelidae family, in the group of medium-sized carnivores that includes skunks, mink, otters and badgers. Ferrets are sexually mature at 6-9 months, and are seasonal breeders, breeding twice yearly. Ferrets are induced ovulators. Mating produces a surge of luteinizing hormone (LH), which is followed by ovulation and pregnancy. Hormonal feedback from the gonads ends the breeding season.1
Peak sex hormone levels that occur at puberty and during the breeding season "set the gonadostat" at the hypothalamus and pituitary gland. This sensitivity to fluctuating hormone levels controls the intact ferret's hormonal feedback system.Recent work has determined that ferret adrenal tissue has LH receptors as well, allowing it to produce sex steroids, even in the absence of gonadal tissue.
In the spayed or castrated ferret, sex hormones still cycle annually, but to a lesser degree. Blood levels of sex hormones in all ferrets, intact or otherwise rise at the onset of breeding season, and peaks in late December or January in males, and January to March in the female.2
The difference between intact and early spay/neuter ferrets is that in intact ferrets, seasonal gonadal production of sex steroids is followed by breeding, then LH surge followed by downregulation of the hormone pathway. In early spay/neuter ferrets, the adrenal gland produces sex steroids, and breeding does not occur to shut the system down. In some cases, sex hormones are produced all year long at levels similar to those in normal intact ferrets during the breeding season.
Therefore, removal of the gonads apparently interrupts the normal feedback system present in the intact ferret. While the exact mechanism remains uncertain, elevated blood levels of LH and GnRH upregulate sex hormone production from the adrenal gland. The adrenal gland apparently responds by becoming hyperplastic, and ultimately neoplasia. A number of things are unclear about the mechanism of the development of adrenal disease in ferrets, including why GnRH analogues such as Luprolide acetate (Lupron, TAP Pharmaceuticals, Inc. Deerfield, IL USA) depress the production of sex steroids in the ferret.2
As an interesting side note, Johnson-Delaney and Oliver observed that 1-2 weeks of elevated ambient temperature (greater than 80 F) can also cause both intact and neutered ferrets to spontaneously cycle out of season (unpublished data).
Dr. Michelle Hawkins is currently pursuing a theory that development of adrenal disease in ferrets may have a genetic component. In humans, the appearance of neoplasia within two or more endocrine organs is almost always genetic in origin and is termed multiple endocrine neoplasia syndrome (MENS). Affected tissues often progress from hyperplasia to neoplasia, and organs most commonly involved include the parathyroid gland, pancreas, pituitary gland, adrenal gland, thyroid and thymic tissues.3
History and Physical Examination Findings
History and physical examination findings include varying degrees of bilaterally symmetrical alopecia, thinning of the skin, pruritus, increased aggression, dysuria, enlarged prostate in the male and enlarged vulva in the female ferret. Enlarged prostate is linked to dysuria and prostatitis. In theory, increased estrogen levels may contribute to bone marrow aplasia and anemia in ferrets, but the author has been unable to confirm or document this.
Work up of ferrets with suspected adrenal disease includes complete blood count (CBC) and chemistry panel, including measurement of fasting blood glucose, radiographs and possibly ultrasound. Ferrets with anemia should undergo evaluation of the bone marrow, especially in those with splenomegaly which may indicate extra-medullary hematopoiesis and a much more severe clinical picture.
Measurement of adrenal hormones is useful in ferrets where the diagnosis of adrenal disease is uncertain, but it should be kept in mind that hormone levels in ferrets with adrenal disease fluctuate.
Diagnosis is through clinical symptoms, measurement of adrenal hormones, ultrasound and exploratory laparotomy.