Discussion

Cystic endometrial hyperplasia is a common lesion of the female reproductive tract and has been reported in a number of domestic species, such as dogs and cats,² guinea pigs,³ and rabbits,⁴ as well several nondomestic species, such as captive elephants⁵ and canids⁶ and felids⁷ kept in zoos. Cystic endometrial hyperplasia is of importance, as it is thought to impair fertility^5,6 in some species and is a common antecedent to pyometra in dogs^2,8,9 and cats.² To the authors' knowledge, this is the first detailed report of natural development of CEH with associated endometritis in a chinchilla.

Cystic endometrial hyperplasia involves progressive endometrial thickenings characterized by an increase in size and number of the endometrial glands as well as cystic dilation of glands.¹⁰ This is a hormone-dependent change that likely represents an exaggeration of the normal proliferative response of the endometrial tissue to ovarian hormones. The exaggerated endometrial response is believed to be caused by chronic or repeated progesterone stimulation following estrogen priming after repeated estrous cycles without pregnancy.^2,10 For this reason, in several species, CEH is more often recognized in middle-aged to older animals that are nulliparous.^4,5,9 This particular chinchilla was nulliparous and, by 4 years of age, would have undergone multiple estrous cycles, as the mean age of sexual maturity in this species is 8.5 months.¹¹ It is possible that a similar hormonal mechanism of repeated nonproductive estrous cycles was responsible for endometrial hyperplasia in this case.

It is also known that abnormal blood concentrations of estrogens and progestins from either endogenous or exogenous sources can hasten the development of CEH in many species. Endogenous sources of hormones include estrogen-secreting ovarian cysts or tumors.¹² In guinea pigs, the incidence of cystic rete ovarii is 76% in females between 18 months and 5 years of age. If these cysts are functional, several concurrent lesions, including CEH, can be seen.^3,13 In this particular chinchilla, both ovaries were examined grossly and microscopically and lesions were not observed, suggesting that ovarian disease was not the cause of the endometrial changes in this patient.

Several examples of exogenous sources of hormones causing endometrial hyperplasia have been noted in the veterinary literature, including administration of estrogens and progestins in dogs,² cats,² and canids⁶ and felids⁷ kept in zoos. Feedstuffs are another potential source of estrogens, and estrogenic compounds in clover pastures and estrogenic mycotoxins have been reported to cause CEH in ewes¹⁴ and sows,¹² respectively. A study¹⁵ examined the effects of zeranol or zearalanol on the endometrium in chinchillas. That study¹⁵ demonstrated that zeranol has estrogenic effects on the uterus, and these changes included an increase in uterine diameter, endometrial vascular congestion and edema, and proliferation of endometrial glands. Zearalanol is a metabolite of zearalenone; both represent mycotoxins produced by Fusarium spp and are known contaminates of grains and hay.^16,17 For the chinchilla of the present report, the diet was predominately composed of hay, which raised the question as to whether estrogenic mycotoxins may have been present in the diet. Although the possibility of estrogenic compounds in the feed cannot be completely eliminated, a review of feeding management with the owner did not reveal any history of moldy hay.

In the chinchilla of the present report, there were cystic endometrial changes as well as evidence of chronic suppurative endometritis. The association between CEH and inflammation is established in the veterinary literature and is best exemplified in bitches and queens, in which it is known as the CEH-pyometra complex.^2,8–10 It is generally assumed that the pathogenesis of the CEH-pyometra complex begins with the development of endometrial hyperplasia, causing secretions to accumulate within the uterus followed by the establishment of a bacterial infection. However, an alternative pathogenesis has also been considered, which suggests that the initial event is the establishment of a low-grade, subclinical bacterial infection. This low-grade infection causes the endometrium to proliferate, resulting in changes in the uterine environment with an accumulation of secretions; this in turn allows for massive bacterial proliferation and the development of pyometra.⁹ The authors of the present report can only speculate about the role of bacterial infection in this chinchilla, as bacteriologic culture of the uterine tissue was not performed. However, the link between CEH and bacterial infection should be further investigated in chinchillas; in future studies of suspected CEH in chinchillas, uterine tissue should be submitted for histologic examination and bacteriologic culture. It is also interesting to speculate whether pyometra would have developed in this patient in the absence of surgical intervention.

Hemorrhage in association with CEH and pyometra has been reported for many species. In rabbits with CEH, the most common clinical sign encountered is bleeding in the form of hematuria or bloody vaginal discharge.^4,18 Hematuria and serosanguineous vaginal discharge are also common clinical signs associated with uterine adenocarcinoma in rabbits.¹⁸ In the chinchilla of the present report, a neoplastic process was ruled out on the basis of gross examination and histologic examination of the reproductive tract. Hemorrhagic discharge has also been observed in dogs with CEH-pyometra syndrome, with 1 report¹⁰ of severe hematometra and frank hemorrhage from the vulva.

Interestingly, in the chinchilla of the present report, the primary clinical sign was bleeding from an unknown source that was initially thought to originate from either the urinary or reproductive tract. The reproductive tract is believed to have been the source of hemorrhage given the resolution of clinical signs after OHE. This theory is supported by the histopathologic findings, which include foci of chronic hemorrhage within the endometrium and RBCs within the lumen. Although the reproductive tract is strongly suspected to have been the source of hemorrhage in this chinchilla, the possibility of urinary tract disease was not completely ruled out. In retrospect, additional diagnostic tests such as abdominal ultrasonography and evaluation of the urine sediment by a clinical pathologist would have been helpful in definitively ruling out a urinary tract infection leading to hematuria. Additionally, a CBC should have been performed to establish whether the hemorrhage was associated with anemia, as this finding may have altered the therapeutic course and prognosis for this patient. Therefore, we recommend that in future cases where hematuria or hemorrhagic vaginal discharge are suspected in this species, a complete diagnostic evaluation including a CBC, serum biochemical analysis, urinalysis, bacteriologic culture of urine, radiography, and ultrasonography of the urinary tract should be performed prior to making a diagnosis and initiating treatment.

To the authors' knowledge, this clinical report is the first of CEH and associated endometritis in an adult female chinchilla, which clinically manifested as hemorrhagic discharge believed to be of reproductive origin that resolved following OHE. Cystic endometrial hyperplasia and endometritis should be considered as a differential diagnosis in a sexually intact female chinchilla with bleeding from an unknown source, suspected hematuria, or bloody vaginal discharge. On the basis of published literature, CEH appears to be rare to uncommon in this species. However, the true incidence of CEH in chinchillas may be underestimated for several reasons, including the absence of clinical signs in uncomplicated cases of CEH and reluctance to pursue costly diagnostic procedures in exotic companion animal species.