Would Methimazole Be More Effective Given 3 Times Daily?

I have a hyperthyroid cat being treated with methimazole who is difficult to control. Are there any studies comparing the effectiveness of methimazole given 3 times daily (8 hours) versus twice daily?

I know that the plasma half-life of the drug is relatively short so it makes sense to me that giving the medication more frequently should be more effective.

My Response:

It is clear that twice daily administration of methimazole to cats with hyperthyroidism works much better than only once daily administration (1). No studies have been done in hyperthyroid cats to evaluate the effect of methimazole three times daily.

Pharmacokinetics studies of methimazole in cats document that the drug has a relatively short elimination half-life in the circulation— the average serum half-life of methimazole is only 6-7 hours (2,3). Therefore, one might think that giving the drug 3 or even 4 times a day might be more effective in normalizing the high serum T4 and T3 concentrations in cats with hyperthyroidism. However, most cat owners would not be thrilled about medicating their cat at 6- to 8-hour intervals, and fortunately, administrating methimazole more than twice a day should not ever be necessary.

After absorption, methimazole circulates in the plasma and gets taken up by the cat's thyroid tumor where the drug acts to block thyroid hormone secretion. Because methimazole is concentrated in the thyroid after administration, the intrathyroidal residence time of the drug is considerably longer than serum half-life. In studies of human patients, an intrathyroidal residence time of 24 hours or longer has been documented (4-6). Therefore, the "duration of action" of methimazole within the thyroid tumor becomes much more valuable than does the serum half-life in determining dosing schedules.

Bottom Line

The serum elimination half-life of the methimazole is relatively short in cats, but the residence time of the drug within the thyroid gland is much longer.

Although giving methimazole 3 times a day is not contraindicated, it's probably not going to help any more than simply giving a higher dose twice a day because the residence time appears to be longer than 12 hours in all hyperthyroid cats.

Methimazole is available as the human preparation, Tapazole, as well as the veterinary formulation, Felimazole.

References:

1. Trepanier LA, Hoffman SB, Kroll M, et al. Efficacy and safety of once versus twice daily administration of methimazole in cats with hyperthyroidism. J Am Vet Med Assoc 2003;222:954-958.    
2. Trepanier LA, Peterson ME, Aucoin DP. Pharmacokinetics of methimazole in normal cats and cats with hyperthyroidism. Res Vet Sci 1991;50:69-74. 
3. Trepanier LA, Peterson ME, Aucoin DP. Pharmacokinetics of intravenous and oral methimazole following single- and multiple-dose administration in normal cats. J Vet Pharmacol Ther 1991;14:367-373. 
4. Okuno A, Yano K, Inyaku F, et al. Pharmacokinetics of methimazole in children and adolescents with Graves' disease. Studies on plasma and intrathyroidal concentrations. Acta Endocrinol (Copenh) 1987;115:112-118. 
5. Jansson R, Dahlberg PA, Johansson H, et al. Intrathyroidal concentrations of methimazole in patients with Graves' disease. J Clin Endocrinol Metab 1983;57:129-132. 
6. Huang G. Relation between the dosage of methimazole and its intrathyroidal concentrations. Zhonghua Yi Xue Za Zhi 1991;71:301-303, 322. 

Complications of Thyroidectomy in Cats: Persistent Hyperthyroidism & Relapse

Most hyperthyroid cats are readily cured quite easily with the use of surgical thyroidectomy (1-6).
Occasionally, however, cats treated with thyroidectomy remain persistently hyperthyroid (7). Others improve temporarily to become euthyroid, only to experience a relapse of hyperthyroidism days to months after surgery. Such problematic hyperthyroid cats can be frustrating to manage, especially as their disease becomes more severe and they develop complications of advanced and poorly controlled hyperthyroidism (1,2,7).

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 (6,8). 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.

Persistent Hyperthyroidism After Thyroidectomy

Occasionally, cats undergoing thyroidectomy will remain hyperthyroid or develop relapse very shortly after surgery. If unilateral thyroidectomy was performed, it is likely that the other thyroid lobe is also adenomatous and was missed at surgery. Thyroid imaging can be very helpful in identifying all adenomatous thyroid tissue (1,9), no matter where its location (see Figure 1).

Figure 1: Bilateral thyroid adenoma in a cat with hyperthyroidism. Notice that gravity has pulled the larger thyroid tumor ventrally, through the thoracic inlet into the chest cavity. At surgery, this large thyroid tumor could easily be missed, resulting in persistent hyperthyroidism.

Alternatively, especially in those cats undergoing bilateral thyroidectomy, ectopic thyroid tissue, intrathoracic thyroid tissue, or thyroid carcinoma must be suspected (1,2,7). In these cats, use of thyroid scintigraphy (Figure 2) is again the best way to identify the location of the remaining hyperfunctioning thyroid tumor tissue and to help diagnose thyroid carcinoma (1,9).

Figure 2: Thyroid carcinoma in a cat with hyperthyroidism (thyroid scan on left). Notice the 3 thyroid masses, with the larger two being located within the chest cavity. The horizontal yellow line indicates the area of the thoracic inlet (top opening of the chest cavity). At surgery, these large thoracic tumor could easily be missed, resulting in persistent hyperthyroidism.

Recurrent Hyperthyroidism After Thyroidectomy

Unilateral Thyroidectomy
Only 30% of all hyperthyroid cats have unilateral disease. In these cats, removal of the one affected thyroid tumor will result in complete cure of the hyperthyroid state. Although it is possible for "new" adenomatous changes to develop in the remaining thyroid lobe sometime in the future, this is uncommon and would take many months to years to occur (8).

Although 70% of hyperthyroid have bilateral disease, some of these cats have asymmetrical thyroid enlargement, with one thyroid lobe being very large and the other being only minimally enlarged. In these cats, unilateral thyroidectomy generally restores euthyroidism, at least for a few weeks, and it may take a up to 6 months for the remaining lobe to grow to a size for hyperthyroidism to recur (8). However, unless preoperative thyroid scintigraphy is performed to verify that unilateral disease is indeed present (Figure 3), the owner must be aware of the possibility that hyperthyroidism could persist or recur after unilateral thyroidectomy is performed.

Figure 3: Bilateral asymmetric thyroid adenomas in a cat with hyperthyroidism. At surgery, it could be easy to mistake the slightly enlarged thyroid tumor (on the left) as being normal size. 

If hyperthyroidism recurs following unilateral thyroidectomy, reoperation to remove the remaining thyroid lobe can be performed, but care must be taken to preserve parathyroid function or hypoparathyroidism will develop after the second thyroid tumor is removed.

Bilateral Thyroidectomy
Because most hyperthyroid cats have involvement of both thyroid lobes, bilateral thy­roidectomy is generally indicated if long-term cure is the goal. The two major techniques for bilateral thyroidectomy include the intracapsular and extracapsular methods (3-6,10,11).

The major problem with the intracapsular technique for thyroidecto­my, as noted in my previous post on surgical techniques for thyroidectomy, is that it can be difficult to remove the entire thyroid capsule (and therefore all abnormal thyroid tissue) while con­currently preserving parathyroid function. Small remnants of thyroid tissue that remain attached to the capsule may regenerate and produce recur­rent hyperthyroidism (10,11). With the extracapsular tech­nique, the incidence of relapse is much less than because the entire thyroid capsule is removed at time of surgery.

When recurrent hyperthyroid does occur after bilateral thyroidectomy, it generally takes many months to years for the serum T4 to increase or clinical signs of hyperthyroidism to redevelop (10,11).

Prognosis and Long-Term Follow-up

The prognosis for hyperthyroid cats after thyroidectomy is good. Treated cats show improved behavior and significant weight gain.

Relapse of hyperthyroidism can occur but is uncommon if all involved tissue is removed at time of the original surgery. The lowest rates have been associated with the extracapsular technique.  Postoperative hypocalcemia is more common after reoperation, so alternative treatment methods (e.g., methimazole or radioiodine) should be considered in cats that experience relapse of the hyperthyroidism.

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, Broome MR. Thyroid scintigraphic findings in 917 cats with hyperthyroidism. J Vet Intern Med 2012; 26:754.
10. 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. 
11. Swalec KM, Birchard SJ. Recurrence of hyperthyroidism after thyroidectomy in cats. J Am Anim Hosp Assoc 1990;26:433-437.

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. 

Complications of Thyroidectomy in Cats: Postoperative Hypocalcemia

Surgical thyroidectomy is a highly effective treatment for hyperthyroidism in cats. While thyroidectomy is most often successful, it can be associated with significant morbidity and mortality (1-6).

Many potential complications are associated with thyroidectomy, including hypoparathyroidism, Horner's syndrome, laryngeal paralysis, and persistent or recurrent hyperthyroidism. The most serious complication is hypocalcemia, which develops after the parathyroid glands are injured, devascularized, or inadvertently removed in the course of bilateral thyroidectomy. Since only one parathyroid gland is required for maintenance of normocalcemia, hypoparathyroidism develops only in cats treated with bilateral thyroidectomy (4-6).

Pathogenesis of hypoparathyroidism (calcium crisis) after thyroidectomy
Hypocalcemia is the most serious complication associated with thyroidectomy. This adverse effect develops almost exclusively in hyperthyroid cats with bilateral thyroid disease who must have both thyroid lobes removed (bilateral or total thyroidectomy).

Under normal circumstances, the circulating calcium concentration is tightly regulated to remain within a narrow normal range, as calcium is required both for adequate muscle and nerve function. When circulating calcium falls, the parathyroid glands secrete parathyroid hormone (PTH), which leads to an increase in serum calcium concentration back to normal (7). PTH acts on several organs to increase calcium levels, including the intestinal tract, kidney, and bone.

A discussed in my recent blog post on thyroid and parathyroid anatomy, the 4 parathyroid glands are located within or around the cat’s thyroid gland (the prefix para is from Greek, meaning “at or to one side of, beside, side by side”). However, only the external parathyroid glands will be visible at time of thyroidectomy, whereas the internal parathyroid gland will be embedded within the tumor itself (Figure 1).

Figure 1: Identifying and preserving the external parathyroid gland in a hyperthyroid cat.
(Note: this cat has concurrent kidney disease, which led to secondary enlargement of the parathyroid gland, making it easier to find).

If the parathyroid glands are removed or damaged, the loss of parathyroid hormone secretion leads to a condition called hypoparathyroidism (the prefix hypo is again from Greek, meaning “under”). This leads to a low circulating calcium concentration which can progress to a hypocalcemia crisis due to hypoparathyroidism (7-10).

Clinical signs of hypoparathyroidism (calcium crisis) in cats
Hypocalcemia causes the major clinical manifestations of hypoparathyroidism by increasing the excitability of both the central and peripheral nervous systems (7-10).

Early signs of hypocalcemia due to iatrogenic hypoparathyroidism include anxiety, appetite loss, depression and weakness, twitching, muscle tremors, and facial itch (4-10). Later in the course of hypoparathyroidism, these signs can progress to tetany, collapse, and seizures—hence, the importance of monitoring serum calcium levels during the postoperative period.

Monitoring for hypoparathyroidism after thyroidectomy
After bilateral thyroidectomy, the serum calcium concentration should be monitored on a daily basis until it has stabilized within the normal range. In most cats with iatrogenic hypoparathyroidism, clinical signs associated with hypocalcemia will develop within 1 to 3 days of surgery, but it may take as long as 5 days in some cats (4-10).

Although mild hypocalcemia (6.5-7.5 mg/dl) is a common finding during this immediate postoperative period, laboratory evidence of hypocalcemia alone does not require treatment. However, if accompanying signs of muscle tremors, tetany, or convulsions develop, therapy with vitamin D and calcium is indicated (7-12).

Treating hypoparathyroidism 
If symptomatic hypocalcemia develops, the cat needs to be treated with large doses of calcium and vitamin D. Calcium is initially administered as an intravenous infusion, followed by daily oral administration. Large doses of oral vitamin D also need to be given daily to increase the intestinal absorption of calcium (7-12).  Supplementation with calcium and vitamin D may be needed for only a few days or for the rest of the cat’s life, depending on the extent of damage to the parathyroid glands.

Although hypoparathyroidism may be permanent in some cats, spontaneous recovery of parathyroid function usually occurs days to months after surgery. Therefore, in most cats with surgically-induced hypoparathyroidism, oral calcium and vitamin D supplementation can eventually be tapered and withdrawn (typically, after a few weeks of treatment).

In most cases, such transient hypoparathyroidism probably results from reversible parathyroid damage and ischemia incurred during surgery. Alternatively, accessory parathyroid tissue may secrete PTH and compensate for the damaged parathyroid glands to maintain normocalcemia, or accommodation of calcium-regulating mechanisms in the absence of PTH may occur (7,13).

Incidence of postoperative hypoparathyroidism
Several studies have evaluated the incidence of hypoparathyroidism after thyroidectomy in cats. In an early study (14), 4 out of 53 cats (7.5%) that had a total thyroidectomy performed with an intracapsular technique developed hypoparathyroidism.

A much higher rate was found in another study that compared the complication between different surgical techniques (15). In that study, extracapsular dissection resulted in an 82% incidence of hypocalcemia, whereas intracapsular dissection resulted in a 36% incidence of hypocalcemia. Staged bilateral thyroidectomy, in which two thyroidectomy procedures were performed a few weeks apart, resulted in an 11% incidence of hypocalcemia (15). However, another study found lower (and similar) rates of hypocalcemia between techniques—23% with a modified extracapsular technique and 33% with a modified intracapsular technique (16).

In the most recent study of thyroidectomy in cats, performed using the modified intracapsular dissection technique, a very low incidence of hypoparathyroidism was reported (17). In that study, only 5 (5.8%) of 86 cats developed postoperative hypocalcemia and none required permanent treatment with calcium and vitamin D.

Bottom Line

No matter which surgical technique is chosen, hypoparathyroidism will develop in a significant proportion of cats treated with bilateral thyroidectomy. However, the very low occurrence of postoperative hypocalcemia in some, but not all, studies suggests that surgeon experience may be the most important factor in determining the outcome for hyperthyroid cats undergoing thyroidectomy.

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. Baral RM. Disorders of calcium metabolism In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders, 2012;625-642.
8. Peterson ME. Hypoparathyroidism, in Kirk RW (ed): Current Veterinary Therapy IX. Philadelphia, WB Saunders. 1986; 1039-1045.
9. Peterson ME. Hypoparathyroidism and other causes of hypocalcemia in cats, in Kirk RW (ed): Current Veterinary Therapy XI. Philadelphia, WB Saunders. 1992; 376-379.
10. Skelly BJ. Hypoparathyroidism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Quedgeley, Gloucester: British Small Animal Veterinary Association. 2012;56-62.
11. Chew D, Nagode L. Treatment of hypoparathyroidism, in Bonagura JD (ed): Kirk’s Current Veterinary Therapy XIII. Philadelphia, WB Saunders. 2000; 340-345. 
12. Henderson AK, Mahony O. Hypoparathyroidism: treatment. Compend Contin Educ Vet 2005; April:280-287.  
13. Flanders JA, Neth S, Erb HN, et al. Functional analysis of ectopic parathyroid activity in cats. Am J Vet Res. 1991 Aug;52(8):1336-40.  
14. Birchard SJ, Peterson ME, Jacobson A. Surgical treatment of feline hyperthyroidism: Results of 85 cases. Journal of the American Animal Hospital Association 1984;20:705-709. 
15. Flanders JA, Harvey HJ, Erb HN. Feline thyroidectomy. A comparison of postoperative hypocalcemia associated with three different surgical techniques. Veterinary Surgery 1987;16:362–366. 
16. 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. 
17. Naan EC, Kirpensteijn J, Kooistra HS, et al. Results of thyroidectomy in 101 cats with hyperthyroidism. Vet Surg 2006;35:287-293.