Wednesday, October 30, 2013

Diagnostic Testing for Ovarian Remnant Syndrome in Dogs — Is There a Practical Test?


Layla is a 7-year old obese Golden retriever that had an ovariohysterectomy about 5 years ago. She continued to have heat cycles and her serum progesterone concentrations were high, consistent with a ovarian remnant. About a year after she was first spayed, an exploratory laporatomy was done and an ovarian remnant removed. At time of that exploratory, the surgeon also identified some suspicious tissue that was not removed due to its location right next to the colonic blood supply. The dog did have a couple more heat cycles, then nothing for the last 4 years— until now.

I saw her last week with signs of heat (e.g., vaginal bleeding, slightly swollen vulva). Her vaginoscopy showed no masses, just a lot of blood. She is otherwise clinically normal. Her vaginal cytology examination did not reveal any cornified epithelial cells but showed mostly parabasal and intermediate cells (more intermediates), lots of RBC, and a few WBC. We ran a serum progesterone level and it was low at 3.3 nmol/L.

Could this dog now be having a heat cycle, even though she hasn’t had any signs of estrus for the last 4 years? If so, what is the best way to confirm another ovarian remnant?
  • Is vaginal cytology useful?
  • I have read about serum luteinizing hormone (LH) levels— is that a good way to check for a remnant?  
  • Also how useful would an abdominal ultrasound be in finding the remnant?
I was still wondering how common (or if it is even possible) to go years without any signs of heat in a dog with an ovarian remnant?

My Response:

Diagnosing bitches with ovarian remnant syndrome can be straight-forward or be very challenging, depending on the phase of the reproductive cycle. Vaginal cytology may be useful in diagnosis of an ovarian remnant, but only if the dog presents during proestrus or actual estrus. In many cases, testing may need to be supplemented by one or more determinations of serum estrogen or progesterone concentrations, and even then, the measurement of these sex steroids can yield equivocal results (1-3).

In this dog, the lack of cornified cells on vaginal cytology and low serum progesterone concentrations are not consistent with estrus. Although these findings certainly do not confirm an ovarian remnant, they cannot totally rule out ovarian remnant syndrome either.

Abdominal ultrasonography can be helpful in suspected cases of ovarian remnant syndrome. However, its effectiveness depends on the expertise of the examiner and the size of the ovarian remnant (3,4). In my experience, use of abdominal ultrasound is generally a waste of time and money when trying to rule out an ovarian remnant in the bitch.

A nice screening test to check for the presence of circulating estrogen (which would be expected both in the intact bitch an dogs with an ovarian remnant) is to simply measure a baseline canine luteinizing hormone (LH) concentration (5). In spayed bitches, circulating LH concentrations increase as a result of the loss of negative feedback of ovarian hormones on the pituitary gland after ovariectomy (5-7). In one study, mean plasma LH concentrations were higher in the bitches with ovarian remnant syndrome (4.1 µg/L) than in the unspayed control dogs tested during anestrus (0.64 µg/L) (7). However, the mean LH values were not as high as in the spayed control dogs (20.2 µg/L), suggesting that the ovarian remnant still secretes enough hormone to partially suppress LH secretion. As might be expected, some overlap in plasma LH concentrations between the groups did occur, so the use of the LH test is not a perfect test for diagnosing ovarian remnant syndrome (7).

One big advantage of the plasma LH test is that it can be run at anytime (i.e., behavioral signs of estrus not necessary to run the LH test), as it is monitoring the negative feedback loop from the ovary to the pituitary gland. It is very important, however, to use the canine LH test and not a human LH test in order to obtain reliable results.

Because a single serum LH determination is not 100% reliable, dynamic stimulation testing with gonadotropin-releasing hormone (GnRH) has been advocated as a more definitive means for distinguishing between spayed bitches and those with an ovarian remnant (6,7). However, GnRH stimulation testing is costly and may require multiple visits and blood samplings in some dogs.

Another option is to submit a basal serum sample to Cornell University for an Anti-Mullerian hormone (AMH) test (8). The ovaries normally secrete AMH and appear to be the sole source of serum AMH in the intact bitch. Following ovariohysterectomy, the serum concentrations of AMH fall to very low levels. Therefore, measuring a serum AMH concentration can be a useful marker to access the presence of ovaries or an ovarian remnant in dogs (8). 

Bottom Line
Although ovarian remnant syndrome is possible in this dog, further hormone testing would certainly is required to make or exclude that diagnosis. However, I would consider it uncommon for a dog with an ovarian remnant to have gone 4 years without any signs of estrus.

So before you embark on a time-consuming and expensive regime of diagnostic tests, I'd recommend that you first question the owner carefully to be certain that there is no other potential sources of exogenous estrogen exposure that could be causing this dog's clinical signs.  Topical hormone replacement creams and sprays are widely used by many pet owners today. If the owner is using these creams and the dog occasionally licks the estrogen from the owner's skin, that could be responsible for the signs of estrus (9,10). Getting a complete history is sometimes the cheapest diagnostic test we have to rule out an ovarian remnant.

References:
  1. Feldman EC, Nelson RW. Ovarian cycle and vaginal cytology. In: Canine and Feline Endocrinology and Reproduction, ed. Feldman EC, Nelson RW, 3rd ed, Saunders, St. Louis. 2004;752.
  2. Feldman EC, Nelson RW. Infertility, associated breeding disorders, and disorders of sexual development. In: Canine and Feline Endocrinology and Reproduction, ed. Feldman EC, Nelson RW, 3rd ed, Saunders, St. Louis. 2004; 892–893. 
  3. Ball RL, Birchard SJ, May LR, et al. Ovarian remnant syndrome in dogs and cats: 21 cases (2000-2007). J Am Vet Med Assoc 2010;236:548-553. 
  4. Davidson AP, Baker TW. Reproductive ultrasound of the bitch and queen. Top Companion Anim Med 2009;24:55-63.
  5. Lofstedt RM, Vanleeuwen JA. Evaluation of a commercially available luteinizing hormone test for its ability to distinguish between ovariectomized and sexually intact bitches. J Am Vet Med Assoc 2002;220:1331-1335. 
  6. Beijerink NJ, Buijtels JJ, Okkens AC, et al. Basal and GnRH-induced secretion of FSH and LH in anestrous versus ovariectomized bitches. Theriogenology 2007;67:1039-1045. 
  7. Buijtels JJ, de Gier J, Kooistra HS, et al. The pituitary-ovarian axis in dogs with remnant ovarian tissue. Theriogenology 2011;75:742-751. 
  8. Place NJ, Hansen BS, Cheraskin JL, et al. Measurement of serum anti-Mullerian hormone concentration in female dogs and cats before and after ovariohysterectomy. J Vet Diagn Invest 2011;23:524-527. 
  9. Parker-Pope T. When hormone creams expose others to risks. New York Times, October 25, 2010. 
  10. Lau E. Hormone replacement skin products affect users' pets, confound veterinarians. The VIN News Service 2010. 

2 comments:

MB said...

My dog is now 1 year but her condition started about 2 months ago. She started losing her hair and her skin was darkening. We did notice her vulva was swollen and she was leaking a little urine. Our veterinarian did a blood test and ultra sound. They found nothing in the ultra sound but the blood test showed her estrogen level was 63 and they said normal would be under 15. She is a rescue dog and when we got her she was already spayed I think she was spayed about 8 week old. Do you think she could have ovarian tissue left in her. She is a wonderful dog and we will do anything for her. They said she is a lab/hound mix but she looks exactly like a Black Mouth Cur.

Dr. Mark E. Peterson said...

I don't know. Estrogen levels are not of any help in diagnosing this condition. Most dogs with a ovarian remnant show signs of heat, not hair loss or darking of skin. Ask for a referral if your vet doesn't know where to go next.