Thursday, August 22, 2013

Cystic Thyroid Carcinoma in a Hyperthyroid Cat

Hyperthyroid cat with cystic thyroid tumor
My patient is a difficult hyperthyroid cat with a huge cystic thyroid mass, and I need your advice about how to best treat this cat.  This is a 14-year-old, F/S DSH that has been treated for 2 years with methimazole (5-7.5 mg per day). About 6 months ago, the referring veterinarian noticed that the cat had developed a small cystic thyroid mass in the mid-cervical region, but this cystic tumor has continued to rapidly expand and now extends from the mandible to below the thoracic inlet (Figure 1).

Figure 1: Large Cystic Thyroid Mass
The thyroid mass is easy to palpate, with one large right-sided mass palpable just caudal to the mandible (approximately 2 cm x 1 cm x 1cm) and a second, very extensive irregular mass extending from the larynx to the thoracic inlet (approximately 7 cm x 6 cm x 2 cm) (Figure 1). The cystic thyroid mass is soft and fluctuant in some regions.

Surgical resection was attempted but unsuccessful. Biopsy of the mass identified thyroid adenoma/adenomatous hyperplasia. However, a pulmonary nodule was also identified on a chest film so thyroid carcinoma is still suspected, especially given the large size of the mass.

Since surgery, the cat has continued to lose weight and has now developed a poor appetite. The cystic fluid continues to accumulate within the thyroid mass, and the cat has experienced  2 episodes of severe dyspnea and now has developed mild right-sided Horner's syndrome. The dyspnea was relieved by drainage of some of the cyst fluid. The cystic fluid was somewhat hemorrhagic (Figure 2), and the cat is now slightly anemic.

Figure 2: Cystic fluid removed
from thyroid mass
Routine blood work revealed mild azotemia, dilute urine specific gravity (1.018), and mild non-regenerative anemia (PCV, 23.6%). Cardiac and abdominal ultrasonography was noncontributory. The systolic blood pressure was normal at 140 mmHg.

The cat has been referred to me for radioiodine therapy to treat the cat's large cystic mass and poorly-controlled hyperthyroid state, and to determine whether any other causes could explain or be contributing to her weight loss and poor appetite.

My problem list for this cat includes the following:
  • Hyperthyroidism
  • Huge cystic thyroid tumor
  • Secondary dyspnea and Horner's syndrome due to the compressive effects of the cystic mass
  • Chronic kidney disease (IRIS Stage 2)  
  • Mild poorly-regenerative anaemia
  • Pulmonary nodule (my differentials include a thyroid metastatic lesion, primary pulmonary tumor, or metastatic lesion from an unrelated tumor).
Although the thyroid biopsy was read out as thyroid adenoma, the behavior of this cat's thyroid tumor is more suggestive of carcinoma.  Therefore, I am planning to treat her as a thyroid carcinoma with high-dose (30 mCi) radioiodine next week. I know that I'll have to drain the cystic fluid just prior to her I-131 treatment to minimize the respiratory complications. I plan to maintain her methimazole during treatment given the duration of her disease and size of the tumor.

Do you agree with my treatment protocol? Do these large cystic masses respond to treatment with radioiodine or do they behave differently? What is your experience with this sort of tumor?

This is the largest (hypersecretory) thyroid mass I have seen, and the owners are very realistic about the guarded prognosis and possible complications of treatment. But we really have nowhere else to go other than radioiodine (she was referred to me by a surgeon!).

My Response:

In cats with long-term hyperthyroidism, the development of cystic thyroid masses are not uncommon (1,2). Most of these cysts never become extremely large and the cats remain asymptomatic (i.e., no signs related to the compressive effects of the cystic tumor).

Cystic thyroid nodules have been associated with thyroid carcinoma in dogs, as well as thyroid adenomas or carcinomas in cats (1-5). It is also possible for cats to develop a nonfunctional cystic thyroid adenoma (6-9).

This cat will indeed be a challenge to manage and successfully cure. Here are my thoughts and responses to your questions:

Huge cystic mass extending from her mandible into mediastinum with a solitary pulmonary nodule
Many cats with advanced or chronic hyperthyroidism will develop a large thyroid tumor that can fall through the thoracic inlet into the anterior mediastinal area (10). Similarly, when cats develop thyroid carcinoma, local invasion of tumor tissue into the cranial thoracic area is very common. However, metastasis as a solitary pulmonary nodule would be very rare with thyroid carcinoma.

Therefore, if the pulmonary nodule in this cat is located in the lateral and/or caudal lung lobes, I would say that thyroid metastasis is quite unlikely.

Does the surgical biopsy rule out thyroid carcinoma in this cat?
Confirming thyroid carcinoma in some cats can be difficult. In one study of 8 cats with thyroid carcinoma (5), 2 cases had mixed adenomatous and carcinoma lesions on the same tissue section of their thyroid biopsies. This suggests that carcinoma can arise from a background of benign thyroid neoplasia, at least in some cats.

Therefore, the pathologic finding of thyroid adenoma (adenomatous hyperplasia) can never totally exclude concurrent carcinomatous tissue in a hyperthyroid cat.

The suggestion that thyroid adenoma can transform to thyroid carcinoma makes some sense, since most cats with carcinoma have severe, long-standing hyperthyroidism associated with a large tumor volume (10).  Given that this cat has a huge goiter and has been hyperthyroid for over 2 years, that would make thyroid carcinoma more likely. In any case, given that the thyroid cyst is so large in this cat, very large doses of 131-I would be required to destroy the tumor tissue, even if the cystic thyroid tumor is benign.

Draining the cystic fluid from the thyroid tumor
Of course, you must drain the cystic fluid in order to minimize and relieve the cat's dyspnea. But after you treat with I-131, you need to be prepared to do this in an ongoing fashion during the cats hospitalization.

In other words, the radioiodine will not have immediate effects and the cystic fluid will likely continue to accumulate for at least a few weeks after treatment.

Tumor behavior in hyperthyroid cats with large cystic masses
In this cat, I would expect a fair to good response after radioiodine treatment, with resolution of the hyperthyroidism and a marked decrease in size of the thyroid mass.

However, I have had a number of cats with large cystic masses ultimately require surgical resection to prevent recurrence of cystic fluid following cure of their hyperthyroidism (and return to euthyroid state). In these cats, the cystic fluid continues to accumulate, despite a decrease in the size of the adenomatous mass.

Many of these cystic masses which are deemed "unresectable" before radioiodine treatment will become much easier to remove with surgery after treatment.  Use of radioiodine renders the cyst relatively avascular, thereby making this surgical procedure much more successful.

References:
  1. Hofmeister E, Kippenes H, Mealey KL, et al. Functional cystic thyroid adenoma in a cat. J Am Vet Med Assoc 2001;219:190-193. 
  2. Phillips DE, Radlinsky MG, Fischer JR, et al. Cystic thyroid and parathyroid lesions in cats. J Am Anim Hosp Assoc 2003;39:349-354. 
  3. Wisner ER, Nyland TG. Ultrasonography of the thyroid and parathyroid glands. Vet Clin North Am Small Anim Pract 1998;28:973-991. 
  4. Turrel JM, Feldman EC, Nelson RW, et al. Thyroid carcinoma causing hyperthyroidism in cats: 14 cases (1981-1986). J Am Vet Med Assoc 1988;193:359-364. 
  5. Hibbert A, Gruffydd-Jones T, Barrett EL, et al. Feline thyroid carcinoma: diagnosis and response to high-dose radioactive iodine treatment. J Feline Med Surg 2009;11:116-124. 
  6. Liptak JM. Unilateral extracapsular thyroidectomy for a non-functional cystic thyroid adenoma. Aust Vet Practit 1996;26:174-177. 
  7. Lynn A, Dockins JM, Kuehn NF, et al. Caudal mediastinal thyroglossal duct cyst in a cat. J Small Anim Pract 2009;50:147-150. 
  8. Reed TP, Brisson BA, Schutt LK. Cystic ectopic lingual thyroid tissue in a male cat. J Am Vet Med Assoc 2011;239:981-984. 
  9. Nelson LL, Coelho JC, Mietelka K, et al. Pharyngeal pouch and cleft remnants in the dog and cat: a case series and review. J Am Anim Hosp Assoc 2012;48:105-112. 
  10.  Peterson ME, Broome MR. Hyperthyroid cats on long-term medical treatment show a progressive increase in the prevalence of large thyroid tumors, intrathoracic thyroid masses, and suspected thyroid carcinoma. Congress Proceedings, 22nd ECVIM-CA Congress (The European College of Veterinary Internal Medicine – Companion Animals) 2012;224.

4 comments:

Hannah's mom said...

I posted a question on your blog a couple of weeks ago about my 11-year old dachshund's hyperthyroidism, confirmed by two thyroid panels. I wanted to let you know the results of her thyroid scintigraphy, done at WSU. The good news is that the scan showed no tumors, no ectopic tissue, no evidence of underlying disease. The internists at WSU suspect that the recent change of diet to venison for her skin allergies is the culprit. This is not a raw diet. It is Royal Canin dry and canned venison and potato food, Real Meat brand venison treats and dried sweet potato treats. They think the Real Meat treats may be the cause or,that a batch of the Royal Canin may have had thyroid meat in it. The thyroid panel they did showed her total T4 back down to 4.1. So they recommended a change of diet and a thyroid recheck in 10 days. I hope this info is of some use to you.

Dr. Mark E. Peterson said...

Thank you very much for the follow-up. Dr. Michael Broome and I are currently writing a paper on diet-induced hyperthyroidism in dogs (we have 8 cases so far) -- I'd love to include your dog in this paper.

Could you email me the vet's name and your name (and your dog's name)? Then I'll contact them to ask if they would like to collaborate and be a part of our study. My email address is drpeterson@animalendocrine.com. I look forward to hearing from you.

admin said...

Dear Dr. Peterson,

I am a veterinarian. First of all let me thank you for your very informative writing work. It really helps vets and animals everywhere.
In the second paragraph of your response, you state that "Cystic thyroid nodules have been associated with thyroid carcinoma in dogs". Could you point me to some references? I've only found papers on feline neoplasia, nothing on dogs. I'm dealing with a canine bilateral cystic thyroid, with FNA cytology compatible with carcinoma (waiting for hormone blood levels and biopsy result).
Thank you so much.
Hugo Pereira, DVM

Dr. Mark E. Peterson said...

Dear Dr. Pereira,

Here's a classic paper that discusses cystic nodules in dogs with thyroid tumors:

Leav I, Schiller AL, Rijnberk A, et al. Adenomas and carcinomas of the canine and feline thyroid. The American Journal of Pathology 1976;83:61-122.

Good luck with your dog. The FNA is not generally that helpful, but the thyroid biopsy should tell you the answer!