Complications of Thyroidectomy in Cats: Postoperative Hypothyroidism

Iatrogenic hypothyroidism in a cat. Note the matted hair coat.

Most hyperthyroid cats are readily cured quite easily with the use of surgical thyroidectomy (1-6). Most cats that are cured with surgery, however, will develop iatrogenic hypothyroidism, which may be temporary or permanent depending on the extent of surgery (i.e, unilateral vs. bilateral thyroidectomy).

After successful surgical thyroidectomy in a cat with hyperthyroidism, the serum thyroid hormone concentrations (both T4 and T3) should fall to low-normal or low concentrations by 24 hours postoperatively (8-10). I recommend checking a serum T4 concentration before the cat is discharged from the hospital (within 1-2 days of surgery) to ensure that the procedure has been successful in removing all adenomatous thyroid tissue.

If the serum T4 concentration remains high or has only fallen into the high-normal range, it is very likely that remaining adenomatous tissue remains and that the cat will require additional treatment (I'll be covering persistent hyperthyroidism in my next post). If, on the other hand, the serum T4 value is subnormal, treatment for hypothyroidism must be considered.

Hypothyroidism After Unilateral Thyroidectomy

In cats that have unilateral thyroid disease, only one thyroid lobe is generally removed (i.e., unilateral thyroidectomy is performed). Because the remaining "normal" thyroid lobe in these cats has been suppressed and is not functioning normally, serum thyroid hormone concentrations are expected to fall to subnormal levels for 1 to 2 months. This transient hypothyroid state is followed by a return to euthyroidism by 3 months postoperatively, as the remaining thyroid lobe recovers and starts to function once again (8).

After treatment of a hyperthyroid cat with unilateral thyroidectomy, thyroid hormone supplementation is not generally recommended during this period of transient hypothyroidism.  The main reason for this recommendation is that thyroid hormone replacement will postpone —and may even prevent— full recovery of normal thyroid function.

The major exception to this rule pertains to cats that have or develop concurrent kidney disease. It is now clear that hypothyroidism (even transient or temporary) can lower renal blood flow and the glomerular filtration rate (GFR), which can lead to worsening of concurrent chronic renal disease (11-14). Treating the hypothyroidism can raise the renal blood flow and GFR to an acceptable level, thus helping to protect kidney function in these cats (15-17).

Hypothyroidism After Bilateral Thyroidectomy

Almost all cats that undergo bilateral or "total" thyroidectomy will become hypothyroid and will benefit from thyroid hormone replacement therapy. Remember that after one performs a total thyroidectomy and removes both adenomatous thyroid lobes, we expect to find undetectable thyroid hormone values. If the serum T4 concentration remains high or only falls to the reference range limits, it is very likely that remaining adenomatous tissue remains and that the cat will require additional treatment (7).

Initial thyroid hormone replacement dose
After bilateral thyroidectomy has been performed, L-thyroxine or L-T4 (0.1 mg, once or twice daily) should be started as soon as we document that the postoperative serum T4 concentration is low to undetectable (8-10). While the use of divided dosing will result in less fluctuation of the circulating T4 concentrations compared to administration of the same total dose as a single daily bolus, the biological action of thyroid hormones (within the tissues and cells) far exceeds that of their serum half-life. This explains why many cats will do well on once-daily L-T4 supplementation.

Either L-T4 pills (e.g, Soloxine, Virbac; Thyro-Tabs, Vetamix) or liquid suspension (e.g., Leventa solution, Merke Animal Health) can be used successfully in cats. When thyroid hormone supplementation is given to cats, the dose should be given at the same time(s) each day.

The supplement can be given either with food or on an empty stomach, but one should be consistent in how it is dosed to avoid marked fluctuations in the absorption of L-T4. Absorption of the L-T4  is likely better when administered on an empty stomach, as has been reported in both humans and dogs (18,19). However, studies comparing absorption of L-T4 in the fed vs. fasting state have not yet been reported in cats.  Nevertheless, we can expect that a higher daily dose of L-T4 might be needed if the thyroid hormone supplement is given at the time of feeding (e.g., if the medication is placed in the food).

Monitoring L-T4 supplementation
The ideal replacement dosage is based on the results of a serum thyroid panel, which includes at minimum the determination of serum T4 and TSH concentrations (20-22). This serum thyroid panel is collected 4 hours after the cat's morning dose of L-T4 is administered (23). If serum T4 is low to low-normal and serum TSH concentration is high, the dose of L-T4 should be increased or given twice daily, or both.  If the serum T4 is high-normal to high, especially if the cat is showing signs of hyperthyroidism (i.e., weight loss despite a good appetite), the dose of L-T4 should be reduced.

Once the proper daily replacement dose is determined for the individual cat, the T4 supplementation can be safely continued indefinitely. However, in some cats, the low serum concentrations of T4 and T3 may spontaneously increase into the normal reference range after a few weeks to months (6,8,24,25). Small pieces of adenomatous thyroid tissue left attached to the thyroid capsule (in the area of the parathyroid gland) can regrow enough to secrete normal amounts of thyroid hormone. Thyroid hormone administration can then be discontinued.

To evaluate whether or not L-T4 replacement therapy can be discontinued, we must stop the thyroid supplement for at least 2 days and repeat a serum thyroid hormone panel. If normal values are maintained after being off L-T4 for 48 hours, the thyroid hormone supplementation can  be discontinued.

Monitoring Cats After Thyroidectomy

In all hyperthyroid cats treated with thyroidectomy, thyroid function testing should be monitored  at 6- to 12-month intervals for the rest of the cat's life. In some cats, relapse of hyperthyroidism can develop, especially after many months. Such hyperthyroid cats can be difficult to manage, especially is reoperation is contemplated.

In my next post, I'll be covering both persistent and recurrent hyperthyroidism and how to diagnose and treat these difficult cases.

References:

1. Mooney CT, Peterson ME. Feline hyperthyroidism In: Mooney CT,Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association. 2012;92-110.
2. Baral RM, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders, 2012;571-592.
3. Panciera DL, Peterson ME, Birchard, SJ: Diseases of the thyroid gland. In: Birchard SJ, Sherding RG (eds): Manual of Small Animal Practice (Third Edition), Philadelphia, Saunders Elsevier, pp 327-342, 2006.
4. Flanders JA. Surgical therapy of the thyroid. Veterinary Clinics of North America. Small Animal Practice 1994;24:607–621. 
5. Padgett S. Feline thyroid surgery. Veterinary Clinics of North America. Small Animal Practice 2002;32:851–859. 
6. Birchard, SJ. Thyroidectomy in the cat. Clinical Techniques in Small Animal Practice 2006;21:29-33. 
7. Peterson ME. Treatment of severe, unresponsive, or recurrent hyperthyroidism in cats. Proceedings of the 2011 American College of Veterinary Internal Medicine (ACVIM) Forum. 2011; 104-106. 
8. Peterson ME, Randolph JF, Mooney CT: Endocrine diseases, In: Sherding RG (ed): The Cat: Diagnosis and Clinical Management. (2nd Ed) New York, Churchill Livingstone, 1994; 1404-1506.
9. Peterson ME: Feline hypothyroidism, In: Kirk RW (ed): Current Veterinary Therapy X. Philadelphia, WB Saunders Co., pp 1000-1001, 1989.
10. Daminet S. Feline hypothyroidism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Small Animal Endocrinology. 4th ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012:111-115.
11. Langston CE, Reine NJ. Hyperthyroidism and the kidney. Clin Tech Small Anim Pract 2006;21:17-21.
12. Syme HM. Cardiovascular and renal manifestations of hyperthyroidism. Vet Clin North Am 2007; 37:723-743.
13. van Hoek I, Lefebvre HP, Peremans K, et al. Short- and long-term follow-up of glomerular and tubular renal markers of kidney function in hyperthyroid cats after treatment with radioiodine. Domest Anim Endocrinol 2009;36:45-56.
14. Williams TL, Elliott J, Syme HM. Association of iatrogenic hypothyroidism with azotemia and reduced survival time in cats treated for hyperthyroidism. J Vet Intern Med 2010;24:1086-1092.
15. Gommeren K, van Hoek I, Lefebvre HP, et al. Effect of thyroxine supplementation on glomerular filtration rate in hypothyroid dogs. J Vet Intern Med 2009;23:844-849.
16. Panciera DL, Lefebvre HP. Effect of experimental hypothyroidism on glomerular filtration rate and plasma creatinine concentrations in dogs.  J Vet Intern Med 2009;23:1045-1050.
17. Broome MR. Feline hyperthyroidism - avoiding further renal injury. Proceedings of the Southern California Veterinary Medical Association, 2012.
18. Wenzel KW, Kirschsieper HE. Aspects of the absorption of oral L-thyroxine in normal man. Metabolism 1977;26:1-8.  
19. Le Traon G, Burgaud S, Horspool LJ. Pharmacokinetics of total thyroxine in dogs after administration of an oral solution of levothyroxine sodium. J Vet Pharmacol Ther 2008;31:95-101. 
20. Wakeling J, Moore K, Elliott J, et al. Diagnosis of hyperthyroidism in cats with mild chronic kidney disease. J Small Anim Prac 2008;49:287-294.
21. Wakeling J. Use of thyroid stimulating hormone (TSH) in cats. Can Vet J 2010;51:33-34.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797347/
22. Peterson ME. Diagnostic testing for thyroid disease in cats: Hypothyroidism. Comp Cont Educ Pract 2012; in press.
23. Le Traon G, Burgaud S, Horspool L. Pharmacokinetics of L-thyroxine after oral administration to healthy cats. Proceedings of the 19th ECVIM-CA Congress (European College of  Veterinary Internal Medicine - Companion Animals). 2009;209.
24. Welches CD, Scavelli TD, Matthiesen DT, Peterson ME. Occurrence of problems after three techniques of bilateral thyroidectomy in cats. Veterinary Surgery 1989;18:392-396. 
25. Swalec KM, Birchard SJ. Recurrence of hyperthyroidism after thyroidectomy in cats. J Am Anim Hosp Assoc 1990;26:433-437. 

Hypothyroidism: A Rare Disorder in Cats?

Hypothyroidism is the condition where the thyroid gland does not produce enough of the thyroid hormones T3 and T4. When levels of these hormones are low, it slows metabolism.

Causes of hypothyroidism in cats
In contrast to dogs, where hypothyroidism is one of the most commonly diagnosed hormonal disorders, naturally-occurring hypothyroidism is extremely rare in cats. When it does occur, it is most common in young cats that are born with the disorder.

In older cats, hypothyroidism is usually caused as a complication of treatment for hyperthyroidism. Hypothyroidism may develop after surgically removing a thyroid tumor, destroying it with radioiodine, or by administering antithyroid drugs as a treatment for hyperthyroidism.

Clinical features seen in cats with hypothyroidism
Because deficient thyroid hormone affects the function of all organ systems, the signs of hypothyroidism vary. In cats, signs include lethargy, loss of appetite, hair loss, low body temperature, and occasionally decreased heart rate.

Obesity may develop, especially in older cats that become hypothyroid after treatment of hyperthyroidism. In cats that are born with hypothyroidism (or that develop it at a young age), signs include dwarfism, severe lethargy, mental dullness, constipation, and decreased heart rate.

Diagnosing feline hypothyroidism
To accurately diagnose hypothyroidism, one must first closely evaluate the cat’s clinical signs and routine laboratory tests to rule out other diseases that affect thyroid hormone testing.

The veterinarian must confirm the diagnosis using one more specific thyroid function tests. Like dogs with suspected hypothyroidism, these tests may include serum total T4, free T4, or TSH levels.

In some cases, a TSH stimulation test or thyroid imaging (scintigraphy) is necessary for diagnosis.

Treating cats with hypothyroidism
Hypothyroidism is easily treatable; it only requires synthetic thyroid hormone supplements (L-thyroxine or L-T4). The success of treatment can be measured by the amount of improvement in clinical signs. Your veterinarian will have to monitor the thyroid hormone level to determine whether the thyroid hormone supplement dose is correct. Once the dose has been stabilized, thyroid hormone levels are usually checked once or twice a year.

Treatment is generally life-long, but the prognosis is excellent.

How Do We Treat Dogs With Hypothyroidism?

There is no cure for hypothyroidism, but it is a disease that is easily managed.

The foundation of treatment of dogs with hypothyroidism is thyroid hormone replacement therapy. In other words, we simply replace the missing hormone to restore the dog’s metabolic function back to normal.

However, it’s important that the dog receives the proper thyroid hormone supplement that is given at the appropriate dosage and at the correct intervals to best resolve all of the clinical signs of hypothyroidism.

Thyroid hormone replacement therapy: Which product do we use?

Treatment for hypothyroidism involves lifelong oral medication with levothyroxine (L-T4), a relatively inexpensive synthetic thyroid hormone supplement. These treatments have to be given by mouth, and the supplements are available both as tablets and a liquid formulation. It is important to give the medication at the same time every day (preferably twice daily), and it’s been shown that absorption is better if given on an empty stomach.

Why give L-T4 as the thyroid hormone replacement? As discussed in our last post, thyroxine (abbreviated T4, because it contains 4 iodine molecules) is the hormone produced by the thyroid gland. It is converted primarily in the liver and kidney by an enzyme (deiodinase enzyme) that removes one of the iodine molecules, thereby forming the T3 hormone, which enters the cells. Its function is to regulate the body’s metabolism.  So by giving L-T4, this will be automatically metabolized to all of the other forms of thyroid hormone made in a dog’s body.

Administering thyroid hormone replacement therapy
How and when you administer your dog's thyroid medication will have a tremendous impact on the success of the treatment.

First of all, it is extremely important that the thyroid hormone treatment not be given with food. It is best to administer thyroid medication at least 1 hour before the dog’s meal or at least 3 hours after eating. Many veterinarians are not aware of the fact that absorption of thyroid hormone from the gut is much better when the hormone is given on an empty stomach.

Thyroxine is best given twice per day, in the morning and evening, spaced about 12 hours apart. Dividing the medication into two doses ensures that the dog receives a steady state of thyroid hormone throughout the day, rather than experiencing very high levels shortly after administration and low levels later in the day when only a morning dose is given.

Although most L-T4 medication comes in pill form, there is a liquid available (Leventa; see figure above) that the company suggests just one dose per day. However, I still recommend that the liquid medication be given twice daily for the best results. If your dog is taking liquid L-T4, be sure to discuss the dosing with your veterinarian.

Monitoring the hypothyroid dog’s L-T4 dosage
Regular follow-up blood tests are vital to ensure your dog receives the accurate amount of hormone replacement therapy. Generally blood tests are rechecked approximately 4 to 8 weeks after starting medication and again as needed while the dog’s metabolism adjusts to the therapy. After that, once yearly checks are adequate to ensure that the thyroid hormone level remains in the normal range.

When taken as directed, thyroxine is extremely safe. However, it is important to make sure your dog is receiving the proper dosage based on the variables discussed above, since excessive thyroxine intake can lead to thyrotoxicosis (thyroxine overdose), a condition that needs to be promptly addressed by your veterinarian. Common signs of L-T4 overdosage include excessive thirst and urination, panting, restlessness, and pacing. If this occurs, the L-T4 needs to be stopped for a day or two and the daily dosage lowered accordingly.

Prognosis for canine hypothyroidism
With proper treatment, the long-term prognosis is excellent. However, complete resolution of clinical features of hypothyroidism may take several weeks to months in some dogs.