Wednesday, June 26, 2013

Surgical Thyroidectomy: A Useful Treatment Option for Dogs with Thyroid Carcinoma?

Outcome following simultaneous bilateral thyroid lobectomy for treatment of thyroid gland carcinoma in dogs: 15 cases (1994–2010)

Joanne L. Tuohy, Deanna R. Worley, and Stephen J. Withrow
Tumors of the thyroid gland are the most common endocrine neoplasm of the dog. Thyroid carcinomas, while responsible for approximately 50–70% of all thyroid tumors diagnosed at postmortem examination, account for up to 90% of thyroid tumors detected during life (1-3). Therefore, all thyroid masses detected upon physical examination must be presumed to malignant until proven otherwise.

In dogs suffering from thyroid carcinoma, the likelihood for metastasis is high, with up to 38% of dogs having gross metastatic disease at the time of initial evaluation (4,5). The most common site for metastasis is the lungs, with other sites being the regional lymph nodes, jugular veins, and heart (1-3). Tumor size appears to be predictive of metastasis; in 1 study, dogs with tumor volumes < 21 cubic cm had a significantly lower risk of metastasis (2). The finding of vascular invasion by neoplastic cells is also suggestive of potential metastasis (5). Bilateral thyroid tumors are typically larger than unilateral tumors. In accord with that, one study reported that bilateral tumors were 16 times more likely to metastasize than unilateral thyroid tumors (6).

Treatment options for canine thyroid carcinoma include surgical resection, external radiation therapy, radioiodine therapy, and chemotherapy (7). The choice of treatment for a particular dog with a thyroid gland tumor depends on tumor size, vascularity, and invasiveness; whether the tumor is fixed or mobile upon palpation; and most importantly, whether gross metastatic disease is present (7-10). External beam radiation and radioiodine treatment are indicated for dogs deemed to have nonresectable tumors, such as fixed, deeply invasive, or bilateral tumors (3,6,7,11-14). Metastatic disease can be potentially treated with radioiodine or chemotherapy (7,15-18). Surgical thyroidectomy can be considered in thyroid tumors that are not large or invasive, with no evidence of metastasis (8-10).

To date, however, there are no published guidelines for surgical management of dogs with freely movable thyroid gland tumors. The purpose of the study reported by Tuohy et al (10) was to evaluate the outcome of resection of simultaneous discrete bilateral mobile thyroid gland carcinomas in dogs.  The hypothesis of this study was that dogs with bilateral, mobile thyroid gland carcinoma would be amenable to a single bilateral thyroidectomy procedure, even when parathyroid glandular tissue was not preserved and hypoparathyroidism would be likely. A second hypothesis of this study was that bilateral tumor development does not always necessitate a need for adjuvant chemotherapy in order to obtain prolonged survival.

Objective of this study—To evaluate the outcome of resection of simultaneous discrete bilateral mobile thyroid gland carcinomas in dogs.

Design— Retrospective case series.

Animals— 15 dogs with resected simultaneous discrete bilateral mobile thyroid gland carcinomas. The dogs ranged in age from 7.6 to 11.9 years, with 10 breeds affected.  Seven of the dogs were females, and 8 were castrated males.

Procedures— Medical records (from 1994-2010) were searched for dogs with the appropriate diagnosis and treatment. Information collected included signalment, clinical signs, diagnostic test results, tumor mobility (mobile tumor identified by movement ≥ 1 cm in all planes during palpation), complications, adjuvant treatments, and outcome.

Results— Prior to surgery, serum thyroxine (T4) concentrations were assessed in 10 of the 15 dogs. Four dogs had low serum T4 concentrations (<1.0 μg/dL), and 2 dogs had high serum T4 concentrations (7.4 and 4.5 μg/dL); these dogs had no associated clinical signs. Four dogs were euthyroid (2.0 and 1.6 μg/dL). None of the dogs were treated with supplemental L-T4 prior to thyroidectomy.

Preoperatively, 6 dogs underwent ultrasound examination of the cervical region, 2 had thyroid scintigraphy, and 3 had computed tomographic (CT) scans.

Mobile, discrete, bilateral thyroid gland carcinomas were removed in all dogs. Among the 15 dogs, complete parathyroidectomies were necessary in 9; parathyroid tissue was reimplanted in 4 and preserved in 2. Complications included hemorrhage and laryngeal nerve trauma, but without serious consequences. Thirteen dogs received calcitriol with or without supplemental calcium after surgery.

In the immediate postoperative period, hypocalcemia developed and was corrected in 11 dogs. At the last study followup, 7 dogs continued to receive calcitriol with or without supplemental calcium, and 8 dogs required long-term thyroid hormone treatment.

Serum total T4 concentrations, as assessed at the end of the immediate postoperative period, were low in 4 dogs, within reference range in 4 dogs, and slightly high in 2 dogs. Serum total T4 concentrations in 5 dogs were not determined. Eleven dogs received thyroid hormone treatment (ie, L-T4) whereas 3 dogs did not.

Six dogs received adjuvant chemotherapy. Local tumor recurrence or de novo distant metastasis was not detected at each dog’s last follow-up examination. Median survival time was 38.3 months. Three dogs were lost to follow-up, 8 survived (4.3 to 77 months after surgery), and 4 died of unrelated causes.

Thyroid hormone replacement therapy had a significant effect on overall survival time; median survival time was 38.3 months among  the 11 dogs that received L-T4 and 17.5 months among 3 dogs that did not receive L-T4 (Figure 1). Otherwise, there were no significant effects of chemotherapy or administration of supplemental calcitriol or calcium among the dogs.
Figure 1: Survival curve for dogs that were given L-T4 supplementation (dashed line; n = 11) and dogs that were not given L-T4 following surgery (solid line; 4)

Conclusions and Clinical Relevance— In dogs with thyroid gland carcinomas undergoing bilateral thyroid lobectomies, a successful outcome can be expected, even when parathyroid gland tissue cannot be preserved. The role of adjuvant chemotherapy in treatment outcome was not clearly defined.

My Bottom Line

This study by Tuohy et al (19) suggests that surgical resection is a viable treatment option for dogs with bilateral mobile thyroid gland carcinoma and that a good prognosis can be expected. Thyroid tumor mobility was the most important criterion for determining feasibility of successful resection in these dogs. The size of these tumors did not impact resection or patient survival, nor was preservation of parathyroid gland tissue critical.

Should adjunct chemotherapy or radiotherapy be given to dogs with thyroid carcinoma?
Vascular or lymphatic invasion (or both) by tumor cells was commonly detected during histologic examination of excised thyroid carcinomas (i.e., in 9 of the 15 dogs). This finding suggests that these affected dogs could benefit from adjuvant chemotherapy or external radiotherapy because such invasive tumors likely have a higher risk of metastasis.

None of the dogs in this study received adjuvant external radiotherapy or radioiodine therapy, so neither of these treatments could be evaluated. However, 6 dogs did undergo adjuvant chemotherapy (doxorubicin only or with carboplatin), but their survival time did not differ from the other dogs that did not receive any chemotherapy. This finding highlights the need for more definitive studies on the role of adjuvant chemotherapy in the treatment of thyroid gland carcinoma in dogs.

Postoperative thyroid hormone treatment for dogs with thyroid carcinoma?
After bilateral thyroidectomy, one would expect serum T4 and T3 levels to decrease into the subnormal  range within 1 to 2 days after surgery. If normal or high T4 values are found in the postoperative period (as reported in 6 dogs of this report), functional thyroid metastasis should be suspected and other follow-up tests of thyroid function (e.g., serum thyroid panel, thyroid uptake and scintigraphy) performed. Why 6 of the dogs of this study had normal to slightly high serum T4s in the "immediate" postoperative period is unclear since no additional follow-up information was reported. It is certainly possible — and even likely— that repeat thyroid testing done at a later date would have revealed low serum T4 values.

In human patients, administration of large doses of thyroid hormone is commonly used as an adjunct treatment after surgery, with the goal of inducing mild hyperthyroidism and completely suppressing circulating TSH to low or undetectable levels (20-22). Circulating TSH can serve as a growth factor to stimulate growth of residual tumor cells; therefore, suppression of TSH may prevent or slow the regrowth of carcinoma tissue in patients with residual neoplastic disease.

In this study, it was interesting that thyroid hormone supplementation appeared to improve survival time in the 11 dogs treated (see Figure 1). Unfortunately, it is not known if TSH suppression was achieved in these dogs since the dose(s) of L-T4 given to these dogs was not provided, and follow-up post-pill serum thyroid hormone or TSH values were not reported. However, two things are very clear— it can be difficult to produce iatrogenic hyperthyroidism in dogs with L-T4 supplementation and that high doses would be needed to completely suppress TSH secretion (23,24).

In the end, it's really impossible to know if the L-T4 therapy really had any true suppressive effect on thyroid carcinoma regrowth or on the dog's survival.  That all said, it remains an interesting observation, and high-dose thyroid hormone suppressive therapy certainly deserves to be investigated as an adjuvant  treatment for dogs with thyroid carcinoma.

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