What's the Best Way to Confirm Ovarian Remnant Syndrome in Cats?

In the queen, the most common cause of behavioral and physical signs of estrus after ovariohysterectomy is remnant ovarian tissue that has regained folliculogenesis and production of estrogens (1). 

In most cats, the "ovarian remnant syndrome" certainly is caused by failure to completely remove both ovaries at ovariohysterectomy. It is possible to have a small piece of ovarian tissue inadvertently drop back into the abdominal cavity during the spaying procedure and subsequently revascularize, resulting in signs of estrus (2). However, this syndrome can be also associated with the presence of accessory ovarian tissue that can be extremely difficult to detect at the time of routine ovariohysterectomy.

Whether entrapped in a ligature or accidentally dropped into the peritoneal cavity, revascularization of remnants by the omental blood supply can occur (2). The ovarian tissue can remain hormonally functional and even ovulate.  Although this condition is generally called the ovarian remnant syndrome, there is much contention among veterinary surgeons that it is not a syndrome but a surgical error

Diagnosis of ovarian remnant syndrome can sometimes be challenging but is based on a combination of history and clinical signs, vaginal cytology, and hormonal testing (1,3-6).

Vaginal cytology

The first step in the workup of a cat in which ovarian remnant or ectopic ovarian tissue is suspected is to perform vaginal cytology during the time your cat is showing signs of estrus. The only thing that causes a cat's vaginal smear to contain a high number of cornified vaginal epithelial cells is the presence of estrogen. This finding on vaginal cytology is a great bioassay for the presence of high levels of estrogen in the circulation (6).

In general, the use of vaginal cytology as a bioassay for feline estrogen is more accurate than a single serum sample. Vaginal cytological changes in queens in estrus tends to be more subtle than those of dogs but usually include an increase in cornified vaginal epithelial cells and clearing of normal background mucous (6).

Serum estradiol concentrations

Why not simple measure serum estradiol, the main estrogen in the cat? In queens during estrus, estradiol levels rise sharply to more than 20 pg/ml before returning rapidly to basal concentrations in as few as 48 hours. Thus blood sampling for estradiol is generally not helpful because the timing of the sample may not coincide directly with the period of peak estrus activity.

Therefore, the finding of high serum estradiol concentrations (>20 pg/ml) in a cat showing sign of estrus is consistent with ovarian remnant syndrome, the diagnosis can never be excluded if lower levels of estradiol are measured (1).

Serum luteinizing hormone (LH) concentrations

The hormonal serum test that is most useful in this situation is a basal luteinizing hormone (LH) determination (7). For this LH testing, we generally use a commercially available LH assay from Synbiotics. Although originally designed as a canine ovulation timing aid, this LH test may be used to distinguish between ovariohysterectomized and sexually-intact queens (or bitches). One advantage of using the serum LH test over vaginal cytology is it can be run at any time, not just when the cat is showing signs of estrus. If you do LH test, the manufacturer recommends two tests at least 24 hours apart to rule out the LH surge.

In the intact queen, LH is maintained at basal concentrations through the negative feedback influence of ovarian estradiol secretion on the pituitary gonadotropins. Following ovariectomy, this control is lost and LH concentrations increase resulting in a positive test.

Therefore, if a high serum LH concentration is found, then it is unlikely that the cat has any ovarian tissue. On the other hand, if the serum LH is low (less than 1 ng/ml), that indicates there is estrogen present in the circulation suppressing pituitary LH secretion (7). The source of this circulating estrogen could be from either endogenous or exogenous sources. If it's of endogenous origin, that means that the cat does indeed have an ovarian remnant or ectopic ovarian tissue.

The only problem with the use of serum LH determination is that some cats ultimately found to have an ovarian remnant will have falsely high LH values. The reason for this discrepancy in the expected pituitary-ovarian feedback loop is unknown, but it is clear that the finding of a high LH value alone can never rule out an ovarian remnant with 100% certainty. So it's still best to use vaginal cytology in conjunction with the serum LH measurements.

Provocative testing with hCG or GnRH analogues

The most efficient diagnostic aid for ovarian remnant syndrome is a hormone challenge testing (1,3-5). The goal of these stimulation tests is to cause ovulation of a follicle by exogenous LH-like compounds, thus confirming the presence of functional ovarian tissue. 

For these protocols, it is important that the queen be in true estrus. The procedure for testing is as follows:

1. Collect blood needed to measure the basal concentration of serum progesterone (and estradiol if desired).
2. Inject the cat with human chorionic gonadotropin (hCG), 44 IU/kg BW or 250-500 IU total dose, IM.
3. Alternatively, inject the cat with gonadotropin-releasing hormone (GnRH), 2 μg/kg BW or 25 μg total dose, IM.
4. Collect a post-stimulation blood sample for serum progesterone 1-3 weeks later.

Documenting a high serum progesterone level (>2 ng/ml) after hGC or GnRH stimulations confirms a diagnosis of ovarian remnant syndrome (1).

GnRH stimulation testing for cats not currently in estrus

Finally, a recent study demonstrated that measurement of plasma estradiol 2 hours after stimulation with a gonadotropin-releasing hormone (GnRH)-analogue appeared to be a reliable method to diagnose the presence of ovarian tissue in the female cat not currently showing signs of estrus (8).  With this protocol, a serum estradiol concentration greater than 3 pg/ml is consistent with the presence of ovarian tissue.

References:

1. Little SE. Female reproduction. In: Little SE (ed). The Cat: Clinical Medicine and Management. Saunders Elseiver 2012; 1195-1227.
2. DeNardo GA, Becker K, Brown NO, et al. Ovarian remnant syndrome: revascularization of free-floating ovarian tissue in the feline abdominal cavity. Journal of the American Animal Hospital Association 2001;37:290-296.
3. Wallace MS. The ovarian remnant syndrome in the bitch and queen The Veterinary Clinics of North: America Small Animal Practice 1991;21:501-507. 
4. Miller DM. Ovarian remnant syndrome in dogs and cats: 46 cases (1988-1992). Journal of Veterinary Diagnostic Investigation 1995;7:572-574.
5. Ball RL, Birchard SJ, May LR, et al. Ovarian remnant syndrome in dogs and cats: 21 cases (2000-2007). Journal of the American Veterinary Medical Association 2010;236:548-553
6. Mills JN, Valli VE, Lumsden HH. Cyclical changes of vaginal cytology in the cat. Canadian Veterinary Journal 1979;20:95–101.  
7. Scebra LR, Griffin B. Evaluation of a commercially available luteinizing hormone test to distinguish between ovariectomized and sexually intact queens. Proc Am Coll Vet Intern Med Forum 2003. 
8. Axner E, Gustavsson T, Strom Holst B. Estradiol measurement after GnRH-stimulation as a method to diagnose the presence of ovaries in the female domestic cat. Theriogenology 2008;70:186-191.

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