Q & A: Diagnosis of Ovarian Remnant Syndrome in Cats

My patient is a 2-year old, female spayed DSH cat who presented with a 10-day history of vocalizing, rolling, and allowing a male altered cat in the household to mount her, especially at night. The cat has gone through two other similar episodes about 1 and 3 months ago, each lasting about 1 to 2 weeks in duration. The cat is otherwise completely healthy, and her behavior is totally normal between each of the episodes.

This certainly sound like the cat is coming into heat. I did the ovariohysterectomy on the cat myself when she was 10-months old, and the surgery was uneventful. I suspect that the cat either has an ovarian remnant or ectopic ovarian tissue.

My question is this — what's the best way to diagnosis this condition? I don't want to explore the cat without some evidence that the cat indeed does have ovarian tissue.

My Response:

Diagnosis of ovarian remnant syndrome is based on a combination of history and clinical signs, vaginal cytology, and hormonal testing (1-4).

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 (5).

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[3].

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 hrs. 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.

Serum luteinizing hormone (LH) concentrations: The hormonal serum test that is most useful in this situation is a basal luteinizing hormone (LH) determination (6). 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 (6). 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.

GnRH stimulation testing: 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 (7). Again, I would still perform vaginal cytology together with the test, since it is such a nice bioassay for the presence of estrogen.

I know that you are probably feeling guilty about this situation, but the presence of ovarian remnant(s) in a spayed cat is not always the result of "surgeon's error."  In most cats, it 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 (8). 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.

Follow-Up:

I did a vaginal smear with cytology, which showed a large population of increase in cornified vaginal epithelial cells consistent with estrus. I also performed the two serum LH tests within 24 hours of each other. The serum LH concentrations on both samples were undetectable, again consistent with presence of estrogen.

Time to go to surgery? If so, is it best to do the exploratory while the queen is exhibiting signs of heat? I assume the ovarian tissue would be easier to identify at that time, correct?

My Response:

Now that we know the cat has circulating estrogen, the next step is to exclude any exogenous exposure of the cat to human skin to which estrogen hormone replacement therapy (HRT) cream, spray, or gel has been applied (9). If your history rules out that possibility, then you should explore the cat  to look for an ovarian remnant.

And yes, having the cat in heat at the time of surgery should make it easier to find the ovarian remnant, so a few days delay after onset of the next estrus would be best. Alternatively, you can administer human chorionic gonadotropin (hCG), 44 IU/kg or 250 IU total dose, IM while the queen is in estrus to cause a LH surge and induce ovulation, and then look for the luteal tissue at exploratory (2).

References:

1. Muram D, Drouin P. Ovarian remnant syndrome. Canadian Medical Association Journal 1982;127:399-400.
2. Wallace MS. The ovarian remnant syndrome in the bitch and queen The Veterinary clinics of North America Small animal practice 1991;21:501-507. 
3. Miller DM. Ovarian remnant syndrome in dogs and cats: 46 cases (1988-1992). Journal of Veterinary Diagnostic Investigation 1995;7:572-574.
4. 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
5. Mills JN, Valli VE, Lumsden HH. Cyclical changes of vaginal cytology in the cat. Canadian Veterinary Journal 1979;20:95–101.  
6. 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. 
7. 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.
8. 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.
9. Parker-Pope T. When hormone creams expose others to risk. The New York Time. October 25, 2010.