Q & A: Persistent Hyperthyroidism in a Cat Treated with Hill's y/d

My patient is a 12-year old male spayed Siamese cat who has been hyperthyroid for 3 years. Over this time, his thyroid nodules have gradually increased in size and his methimazole dosage has increased from 2.5 mg once a day to 15.5 mg twice a day. Despite this large dose of methimazole, his serum T4 value remained in the high-normal to slightly hyperthyroid range.

After looking over the blood work and dosage and talking to the owner, we decided to try the new Hill's y/d diet. The cat has been on y/d food for over 3 months and her last serum T4 level was high-normal at 3.8 μg/dl. I usually prefer the values to be within the lower end of the reference range, so this seems to high for this cat.

Should I continue the y/d food and recheck or consider adding back the methimazole again? Why isn't this cat responding to either the methimazole or y/d diet?

My Response:

First of all, we must never forget that all cats with hyperthyroidism have a hyperfunctional thyroid tumor (1-6). These tumors are almost always benign at time of diagnosis, but they will usually continue to grow progressively larger when treated medically with either methimazole or carbimazole.

Although we don't know how the growth of these feline thyroid tumors will response to an iodine deficient diet, such as Hill's y/d, I would predict that the tumor will continue in its progressive growth pattern (1).

The fact that neither the methimazole or Hill's y/d is controlling the hyperthyroidism as well as you would expect is probably related to the fact that, after 3 years, the volume of this cat's thyroid tumor tissue is quite large. You could continue the y/d diet and reinstate a small dose of methimazole to the cat's treatment regimen, but you would need to monitor the cat's thyroid function very carefully over the next few weeks to ensure that hypothyroidism does not develop on the concomitant therapy.

Even if you can control the hyperthyroidism now, your cat could live a long time (she is a Siamese, after all). As she ages, the thyroid tumor will continue to grow and may transform into a thyroid carcinoma (7,8). In my studies, less than 2% of recently diagnosed hyperthyroid cats had thyroid carcinoma, whereas up to 20% of cats treated medically for longer than 4 years had evidence of thyroid carcinoma on thyroid imaging (7).

If this was my patient, I'd either do surgery or radioiodine to cure the cat's hyperthyroidism rather than trying to manage it with Hill's y/d or methimazole for the rest of her life. She is already suffering from a severe case of hyperthyroidism, which will only worsen with time. In the long run, a definitive treatment would be the wisest (and most cost effective) means of treating this relatively young cat.

And again, she is a Siamese and most cats of that breed, when properly managed, seem to live almost forever!

References:

1. Peterson ME, Ward CR. Etiopathologic findings of hyperthyroidism in cats. Veterinary Clinics of North America Small Animal Practice 2007;37:633-645. 
2. Baral R, Peterson ME. Thyroid gland disorders. In: Little, S.E. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders 2012; 571-592. 
3. Peterson ME: Hyperthyroidism, In: Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat (Fifth Edition). Philadelphia, WB Saunders Co. 2000; pp 1400-1419.
4. Peterson ME: Hyperthyroidism in cats. In: Melian C (ed): Manual de Endocrinología en Pequeños Animales (Manual of Small Animal Endocrinology). Multimedica, Barcelona, Spain, 2008, pp 127-168.
5. Mooney CT, Peterson ME: Feline hyperthyroidism, In: Mooney C.T., Peterson M.E. (eds), Manual of Canine and Feline Endocrinology (Fourth Ed), Quedgeley, Gloucester, British Small Animal Veterinary Association, 2012; in press. 
6. Peterson ME: Hyperthyroidism in cats, In: Rand, J (ed), Clinical Endocrinology of Companion Animals. New York, Wiley-Blackwell, 2012; in press.
7. Peterson ME, Broome MR. Thyroid scintigraphic findings in 917 cats with hyperthyroidism. Journal of Veterinary Internal Medicine 2012; in press.
8. Hibbert A, Gruffydd-Jones T, Barrett EL, et al. Feline thyroid carcinoma: diagnosis and response to high-dose radioactive iodine treatment. Journal of Feline Medicine and Surgery 2009;11:116-124. 

Q & A: Confirming Hyperthyroidism in a Borderline Cat

Jessie, is a 13-year old female DSH cat that presented to our clinic for annual exam and vaccines. The owner reports that Jessie has been doing fairly well, but that the cat has been drinking more water over the last 4 months. The cat has also been progressively losing weight over the past year, dropping from 4.2 kg to 3.6 kg.

My physical examination was unremarkable, except for evidence of mild muscle wasting. Because of the signs of weight loss and polyuria, we ran a complete blood count and serum chemistry profile, but all of the results (including the serum creatinine, BUN, glucose, and calcium) were within reference range limits.

We also did a serum T4, which showed a high-normal value of 51 nmol/L (reference range, 13-51 nmol/L). Because of the high-normal serum total T4 concentration, I added on a free T4 by dialysis, which came back high at 81 pmol/L (reference range, 10-50 pmol/L).

Based on those thyroid results, I made a diagnosis of hyperthyroidism and started the cat on methimazole (Felimazole, Dechra) at a dosage of 2.5 mg, PO, once daily. After 2 weeks, we rechecked the kidney values (which remained normal) and a free T4 concentration (which was higher than the pretreatment value at 88 pmol/L).

So my main questions include the following:

• Why is the free T4 by ED is still high? 
• Should I only be assessing the free T4 along with a total T4 concentration?  I know that this is important when first trying to diagnose hyperthyroidism, but was wondering if I should be measuring both total and free T4 values on rechecks as well.
• Could the timing of the blood collection make a difference considering she is on SID dosing? She reports that she gives the cat her medication at about midnight and her sample would have been collected at 5:20 PM (so about 17 hours post-pill).

I am going to likely increase the methimazole dose to 2.5 mg BID. I have also gotten the owner to measure the exact water intake over a 24-hour period.

Thanks. Any help would be much appreciated.

My Response:

My first question is: do you think that cat really is hyperthyroid? I know that the cat has lost weight, but you have examined the cat 2 to 3 times and I don't see any mention of a thyroid nodule. Is there tachycardia or any other clinical signs? Is there improvement in the clinical signs after methimazole?

Determination of free T4 concentrations can be helpful in diagnosis of cats with early or mild hyperthyroidism (1), but the test is pretty worthless in monitoring initial methimazole or I-131 treatment. In addition, falsely high free T4 values have been reported in up to 12% of cats with nonthyroidal illness (1,2).

It does bother me that this cat has lost so much weight and is showing signs of polyuria and polydipsia with these mild thyroid values. Could this cat have nonthyroidal illness and not be hyperthyroid at all?

What I do in borderline cats like this is to do one of the following, especially when a thyroid nodule canot be palpated (2-6):

1. Repeat the serum total T4 in a week or two using a different technique (either RIA or Chemiluminescence - ie, Immulite methods). Many labs now use an automatic immunoassay technique, which can sometimes be misleading. But remember, the T4 will fluctuate over time, and some "normal" cats just have higher T4 values than the average normal cat. If you get a high total T4 value, we have the answer. Note that falsely high total T4 values do not occur unless there is lab error. 
2. Repeat the FT4 at the same time as the repeat TT4 test. You have already done this step in this cat, but you didn't repeat the T4 and the cat is on methimazole. Again, a high value with a normal TT4 and no thyroid nodule really doesn't tell you that the cat is hyperthyroid for sure! 
3. If this in not helpful (i.e., the total T4 not high), then I do either a T3 suppression test or thyroid scintigraphy. 
4. Finally, we can just wait and monitor. Over time — generally 3 months — the thyroid tumor (if present) will grow and the T4 will be clearly high. If there is nonthyroidal illness, this will usually become obvious with enough time. 

So in this case, I'd start by asking yourself if the cat is truly hyperthyroid and even needs to be treated. If your answer is yes, the cat is hyperthyroid, then I would increase the dose, and monitor only with a total T4 value. SID dosing is acceptable, but BID dosing is best (7). The timing of the post-pill T4 is not important as long as the medication is given at least once a day (7,9).

Bottom Line: If you are not sure that the cat is hyperthyroid, treating with an antithyroid drug, at least in my opinion, is not a wise choice given that side effects (some serious) can occur. I understand that we all want to look at the "numbers." But when the thyroid numbers are wrong (as they can be), we can never forget that we first must look a the patient.

In other words, we don't treat abnormal lab values — we treat the cat.

References:

1. Peterson ME, Melian C, Nichols R. Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease. Journal of the American Veterinary Medical Association 2001;218:529-536.
2. Mooney CT, Little CJ, Macrae AW. Effect of illness not associated with the thyroid gland on serum total and free thyroxine concentrations in cats. Journal of the American Veterinary Medical Association 1996;208:2004-2008.
3. Baral R, Peterson ME. Thyroid gland disorders. In: Little, S.E. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders 2012;571-592.
4. Mooney CT, Peterson ME: Feline hyperthyroidism, In: Mooney C.T., Peterson M.E. (eds), Manual of Canine and Feline Endocrinology (Fourth Ed), Quedgeley, Gloucester, British Small Animal Veterinary Association, 2012; in press.
5. Peterson ME: Hyperthyroidism in cats, In: Rand, J (ed), Clinical Endocrinology of Companion Animals. New York, Wiley-Blackwell, 2012; in press.
6. Peterson ME. Diagnostic tests for hyperthyroidism in cats. Clinical Techniques in Small Animal Practice 2006;21:2-9.
7. Peterson ME, Kintzer PP, Hurvitz AI. Methimazole treatment of 262 cats with hyperthyroidism. Journal of Veterinary Internal Medicine 1988;2:150–157. 
8. Trepanier LA, Hoffman SB, Knoll M, et al. Efficacy and safety of once versus twice daily administration of methimazole in cats with hyperthyroidism. Journal of the American Veterinary Medical Association 2003;222:954–958. 
9. Rutland BE, Nachreiner RF, Kruger JM. Optimal testing for thyroid hormone concentration after treatment with methimazole in healthy and hyperthyroid cats. Journal of Veterinary Internal Medicine 2009;23:1025-1030.

Hyperthyroidism & Renal Disease: Is a "Tapazole Trial" Really Necessary?

Hyperthyroidism and chronic kidney disease (CKD) are both common disorders in older cats. Therefore, it should not be surprising that both disorders frequently develop together in the same cat. The prevalence of concurrent renal disease in cats with hyperthyroidism is estimated to be approximately 30–35% (1,2).

Hyperthyroidism & the Kidney: A Love-Hate Relationship

Hyperthyroidism tends to "artificially" increase the renal blood flow (RBF) as well as the glomerular filtration rate (GFR) (1–4). When the GFR is increased in a hyperthyroid cat with underlying CKD, it can mask renal insufficiency; serum concentrations of urea nitrogen and creatinine may be normal despite mild to moderate kidney disease (1–7). Decreased muscle mass and muscle wasting, a common feature of hyperthyroidism, also contribute to the lowered serum creatinine concentration in these cats (since creatinine is derived from muscle tissue) (1,2).

Treating hyperthyroidism restores the high serum T4 concentration to normal and, in cats without CKD, also returns the high GFR back to normal values. In cats with CKD, however, the GFR will fall to the low-normal or subnormal levels expected with moderate renal dysfunction. Therefore, this decrease in GFR can result in the apparent worsening of the serum kidney function tests or the development of renal disease.

It is important to remember, however, that treating the hyperthyroidism itself does not cause the CKD in these cats. The renal disease was already present before treatment but was masked by the hyperdynamic state of the hyperthyroidism.

Physiological Interactions Between Thyroid Hormones & Renal Function

Hyperthyroidism decreases peripheral vascular resistance by dilating the arterioles of the peripheral circulation. Because of this decrease in systemic vascular resistance, the effective circulating volume decreases, stimulating the renin-angiotensin-aldosterone system. This leads to renal sodium retention with a resultant increase in blood volume. Cardiac output may increase dramatically in cats with hyperthyroidism. In addition to the decrease in systemic vascular resistance, an increase in heart rate, increases in left ventricular contractility and ejection fraction, and increase in blood volume all contribute to this increase in cardiac output (1,2).

These systemic hemodynamic factors (i.e., the increased cardiac output) combined with intrarenal vasodilation lead to increases in renal blood flow (RBF), glomerular hydrostatic pressure, and glomerular filtration rate (GFR). Thyroid hormones also influence renal tubular function including electrolyte handling.

With time, hyperthyroidism can lead to renal changes including glomerular hypertension, glomerulosclerosis, proteinuria, and hyperplasia and hypertrophy of the renal tubules (1,2).

Hyperthyroidism Itself May Contribute to Chronic Kidney Disease

Recent research provides three lines of evidence that untreated hyperthyroidism itself contributes to the development or progression of CKD in cats.

• First of all, a number of recent reports indicate that many untreated hyperthyroid cats develop proteinuria, which resolves within 4 weeks of successful treatment (8,9). This proteinuria, which reverses after treatment, could be a reflection of glomerular hypertension and hyperfiltration, changes in tubular protein handling, or a change in the structure of the glomerular barrier (1). Whatever the cause of the proteinuria, no treatment is generally needed other than treatment of the hyperthyroid state itself.
• Secondly, cats with untreated hyperthyroidism have high levels of retinol binding protein (RBP), a urinary marker for tubular dysfunction or damage (10,11). This high urinary RBP excretion may reflect tubular damage or dysfunction resulting from the thyroid-induced hypertrophy and hyperplasia of the tubular cells. After treatment, these high urinary RBP levels fall in cats without azotemia but may remain slightly high in cats with pre-existing CKD. This too suggests that hyperthyroidism can cause reversible renal dysfunction; however, the renal tubular changes may become irreversible with time as CKD progresses.
• Thirdly, many cats with untreated hyperthyroidism have high values for urinary N-acetyl-ß-D-glucosaminidase (NAG), a lysosomal glycosidase found primarily in epithelial cells of the proximal convoluted tubule (12). Like RBP, NAG is a specific marker of active proximal tubular damage. After treatment, these high urinary NAG levels decrease, again suggesting that these renal changes can be reversed, at least in cats without pre-existing CKD.

Overall, these studies all suggest that that leaving a hyperthyroid cat untreated (or poorly regulated with methimazole) may be detrimental to long-term kidney function. Treating and curing hyperthyroidism may help to both reverse renal damage and preserve remaining kidney function.

Clinical Implications in Hyperthyroid Cats

Decision-making with regard to treating cats with hyperthyroidism and CKD can be difficult. Clinicians can be confronted with two different scenarios concerning hyperthyroid cats with concurrent CKD.

1. First of all, about 10% of hyperthyroid cats have known pre-existing CKD at time of diagnosis. These cats have obvious clinical and biochemical evidence of mild to moderate kidney disease, and do not present a diagnostic dilemma. However, hyperthyroid cats with pre-existing azotemia are more difficult to treat successfully, at least on a long-term basis. They have a worse prognosis than do cats that are not azotemic prior to treatment for hyperthyroidism.
2. In the second scenario, cats are initially not azotemic but develop high serum concentrations of urea nitrogen or creatinine only after they have been treated for hyperthyroidism. These cats, which represent 20% to 25% of all hyperthyroid cats, are much more of a diagnostic dilemma because one may not even suspect that they have concurrent renal disease.

1. Pre-existing Azotemia in a Newly Diagnosed Hyperthyroid Cat
In hyperthyroid cats with overt CKD, we can predict that the GFR will fall once the euthyroidism is restored. Therefore, it is generally advised to try medical management prior to a more definitive treatment in cats with concurrent hyperthyroidism and pre-existing CKD. A low starting dose (i.e., 1.25 mg orally once daily) of methimazole with gradual dose escalation is prudent when starting a cat with CKD and hyperthyroidism on medical therapy. Cats should be monitored every 2 weeks with a CBC, biochemical profile, urinalysis, and serum T4 concentration.

Because the initial decline in GFR stabilizes after a month of successful resolution of the hyperthyroidism, one can decide at that time whether or not the cat's renal function is stable or worsening.

Hyperthyroid cat with overt CKD
and hypokalemia

Concurrent management of CKD is also extremely important these cats. If the renal function remains stable after a euthyroid state is established, a more definitive treatment, such as 131-I, should be strongly considered. If, on the other hand, renal function declines dramatically after antithyroid drug treatment, especially if accompanied by marked clinical deterioration of the cat's renal failure (to IRIS Stage 3 or 4), it may be best to maintain the cat on a reversible anti-thyroid therapy, decrease the dose, or stop it all together if need be.

In some of these cats with severe CKD, maintenance of a mild hyperthyroid state may give the best short-term clinical result. However, this course of action is far from ideal, and these cats have a very guarded to poor prognosis. Except in these extreme circumstances, the validity of maintaining a cat in a mildly hyperthyroid state is questionable given that uncontrolled hyperthyroidism, in itself, appears to be damaging to renal function (1,8,10–12)

2. Non-Azotemic Before Treatment of Hyperthyroidism; Development of Post-Treatment Azotemia
Hyperthyroidism is known to increase GFR, decrease circulating creatinine concentrations, and mask underlying renal disease. About 20% to 25% of hyperthyroid cats without known CKD develop azotemia after successful treatment of hyperthyroidism, irrespective of therapeutic modality (methimazole/carbimazole, surgical thyroidectomy, or radioiodine) (1).

Predicting which hyperthyroid cats will develop overt azotemia after treatment of hyperthyroidism can be difficult to impossible. The determination of GFR is clearly the best predictor of post-treatment CKD, with a low to low-normal GFR indicating that a hyperthyroid cat is at increased risk for post-treatment azotemia. However, techniques for assessment of GFR are not widely used in practice, and even GFR determinations are not a 100% perfect predictor of CKD. Routine pre-treatment parameters such as serum urea or creatinine concentrations, and urine specific gravity are certainly useful, but they cannot consistently predict impending azotemia (13).

Should Methimazole Trials be Performed in all Hyperthyroid Cats?

For years, it has been accepted practice to perform a methimazole trial in cats in which hyperthyroidism has been newly diagnosed to evaluate the impact of a euthyroid state on renal function.  Again, determining which untreated hyperthyroid cats have clinically significant underlying CKD can sometimes be difficult. Use of methimazole or carbimazole can provide a "preview" of how the cat will be after curing hyperthyroidism. Thus, many veterinarians attempt trial therapy with methimazole or carbimazole to help test what renal function might remain after treating the hyperthyroidism. If no marked deterioration occurs, then a more permanent therapeutic option for hyperthyroidism may be recommended.

Except for advanced (IRIS Stage 3–4) CKD, the necessity of this approach in cats without pretreatment azotemia is questionable, given that treatment for the hyperthyroidism is strongly recommended whatever the outcome. In support of this reasoning, the survival of cats that do develop azotemia is not shorter than those that do not develop azotemia after treatment of hyperthyroidism. In one study, the median survival time of cats that developed azotemia (595 days) was similar to that in cats that remained non-azotemic (584 days) after treatment (14).

Preventing Hypothyroidism after Treatment for Hyperthyroidism

Whatever treatment option for hyperthyroidism is considered, it is important to avoid hypothyroidism as it may have its own detrimental effects on GFR. Hypothyroidism in both humans and dogs has been showed to reduce GFR (15,16), and it is likely that similar changes occur in cats that develop iatrogenic hypothyroidism.

In a recent study by Williams et al (17), cats with iatrogenic hypothyroidism were more likely to develop azotemia in the 6 months after treatment than cats that remained euthyroid. Hypothyroid cats with azotemia also had shorter survival times than nonazotemic cats, whereas no difference in survival between euthyroid cats with or without azotemia could be detected. This suggests that the development iatrogenic hypothyroidism contributes to the development of azotemia, at least in cats with mild underlying CKD (IRIS Stage I or II) (17,18). More importantly, the hypothyroidism may shorten survival after treatment of hyperthyroidism.

If a cat with post-treatment azotemia develops a low T4 concentration, a serum TSH level should be measured to help exclude hypothyroidism (19). The finding of a high serum TSH concentration confirms hypothyroidism. A specific assay for feline TSH is not yet available. However, the commercially available canine TSH assay cross-reacts with feline TSH enough to enable its use as a diagnostic test for hypothyroid cats (19,20).

If iatrogenic hypothyroidism is diagnosed, treatment with L-thyroxine (0.1 mg once to twice daily) is indicated (20,21). The dosage should be adjusted based on post-pill serum T4 and cTSH determinations. Most cats treated will show improvement in their azotemia as the hypothyroidism resolves and euthyroidism is restored (18).

Long-Term Renal Function in Cats that Develop Azotemia after Treatment

In most cats that develop post-treatment azotemia, the CKD is not that severe or life threatening. It is also unusual to see a jump of more than one IRIS stage after treatment (22). In other words, hyperthyroid cats with IRIS Stage I–II CKD may develop overt azotemia after treatment, but one would not expect those cats' CKD to advance to more than IRIS Stage II–III after treatment (Figure 1).

Figure 1. Box plots of serum creatine concentrations in 45 hyperthyroid cats
before and after treatment. Prior to treatment 34 of the 45 cats were not azotemic, whereas 11 cats (Green Box) had IRIS stage 2 CKD.
After treatment, 12 of the 34 nonazotemic cats progressed to stage 2 CKD (Red Box).  All 11 cats with prior azotemia remained azotemic, but the the median value was not significantly different (Green Box).
Click image above to enlarge figure.

In addition, the decline in GFR after successful treatment of a cat's hyperthyroidism is not very progressive. Rather, the fall in GFR is detectable within 1 month but then remains stable at this level for months thereafter (1,6). The rise in serum urea nitrogen and creatinine values in cats with CKD follow the decrease in GFR, so that azotemia, when it does occur, would be expect to develop within 1 month of treatment but remain relatively stable over many months (6,22).

The Bottom Line

For years, conventional wisdom has been to perform a methimazole trial in cats in which hyperthyroidism has been newly diagnosed to evaluate the impact of a euthyroid state on renal function. In most cats without overt CKD, use of a methimazole trial prior to definitive therapy is not needed.

Remember that hyperthyroidism itself has long-term deleterious effects on renal function, and survival of cats that do develop azotemia after treatment for hyperthyroidism is no shorter than for those whose renal function remains stable. For those cats that do develop azotemia after their hyperthyroid state is corrected, the renal disease is not generally severe or life-threatening and usually stabilizes within the first month of therapy.

References

1. Syme HM. Cardiovascular and renal manifestations of hyperthyroidism. Veterinary Clinics of North America: Small Animal Practice 2007;37:723-743. 
2. Langston CE, Reine NJ. Hyperthyroidism and the kidney. Clinical Techniques in Small Animal Practice 2006;21:17-21. 
3. Graves TK, Olivier NB, Nachreiner RF, et al. Changes in renal function associated with treatment of hyperthyroidism in cats. American Journal of Veterinary Research 1994;55;1745-1749. 
4. Adams WH, Daniel GB, Legendre AM. Investigation of the effects of hyperthyroidism on renal function in the cat. Canadian Journal of Veterinary Research 1997;61:53-56. 
5. Becker TJ, Graves TK, Kruger JM, et al. Effects of methimazole on renal function in cats with hyperthyroidism. Journal of the American Animal Hospital Association 2000;36:215-223. 
6. Boag AK, Neiger R, Slater L, et al. Changes in the glomerular filtration rate of 27 cats with hyperthyroidism after treatment with radioactive iodine. Veterinary Record 2007;161:711-715. 
7. DiBartola SP, Broome MR, Stein BS, et al. Effect of treatment of hyperthyroidism on renal function in cats. Journal of the American Veterinary Medical Association 1996;208:875-878. 
8. 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. Domestic Animal Endocrinology 2009;36:45-56. 
9. Williams TL, Peak KJ, Brodbelt D, et al. Survival and the development of azotemia after treatment of hyperthyroid cats. Journal of Veterinary Internal Medicine 2010;24:863-869. 
10. van Hoek I, Daminet S, Notebaert S, et al. Immunoassay of urinary retinol binding protein as a putative renal marker in cats. Journal of Immunological Methods 2008;329:208-213. 
11. van Hoek I, Meyer E, Duchateau L, et al. Retinol-binding protein in serum and urine of hyperthyroid cats before and after treatment with radioiodine. Journal of Veterinary Internal Medicine 2009;23:1031-1037. 
12. Lapointe C, Bélanger MC, Dunn M, et al. N-acetyl-beta-D-glucosaminidase index as an early biomarker for chronic kidney disease in cats with hyperthyroidism. Journal of Veterinary Internal Medicine 2008;22:1103-1110. 
13. Riensche MR, Graves TK, Schaeffer DJ. An investigation of predictors of renal insufficiency following treatment of hyperthyroidism in cats. Journal of Feline Medicine and Surgery 2008;12:160-166. 
14. Wakeling J, Rob C, Elliott J, et al. Survival of hyperthyroid cats is not affected by post-treatment azotemia. Journal of Veterinary Internal Medicine 2006;20:1523.
15. Iglesias P, Diez JJ. Thyroid dysfunction and kidney disease. European Journal of Endocrinology 2009;160:503-515. 
16. Gommeren K, van Hoek I, Lefebvre HP, et al. Effect of thyroxine supplementation on glomerular filtration rate in hypothyroid dogs. Journal of Veterinary Internal Medicine 2009;23:844-849. 
17. Williams T, Elliott J, Syme H. Association of iatrogenic hypothyroidism with azotemia and reduced survival time in cats treated for hyperthyroidism. Journal of Veterinary Internal Medicine 2010;24:1086-1092. 
18. Wakeling J. Use of thyroid stimulating hormone (TSH) in cats. Canadian Veterinary Journal 2010;51:33-34. 
19. Greco DS. Diagnosis of congenital and adult-onset hypothyroidism in cats. Clinical Techniques in Small Animal Practice 2006;21:40-44. 
20. Peterson ME: Feline hypothyroidism, In: Kirk RW (ed): Current Veterinary Therapy X. Philadelphia, WB Saunders Co., pp 1000-1001, 1989
21. Harley LS, Peterson ME, Langston CE, Nichols RL: IRIS stages of chronic kidney disease before and after treatment with radioiodine in cats with hyperthyroidism. Journal of Veterinary Internal Medicine 25: 678-679, 2011.

Q & A: Hyperthyroid Cat Not Controlled on High-Dose Methimazole

Tommie is a 14-year old MC DSH cat that presented 6 months ago for vomiting and weight loss. Hyperthyroidism was diagnosed based on a high serum T4 value (11.5 μg/dl; reference range, 0.8-4.0 μg/dl). Results of a CBC, serum chemistry panel, and urinalysis were normal.

I started him on 2.5mg methimazole twice daily. On recheck his serum T4 values was still high at 10.3 μg/dl so I increased the dosage to 5 mg twice daily. After 4 months on this dose, his serum T4 has decreased but remains slightly high at 6.5 μg/dl

I am afraid of increasing his dose any higher than 10 mg per day. All of the other cats I've treated have responded to this or even lower daily doses of methimazole. Any thoughts about the dosage in this cat?

My Response:

The dose of methimazole needed to control hyperthyroid cats is based on what it takes to lower the serum T4 concentration into the reference range, so there is not an upper limit to what methimazole dosage can be used. I've gone as high as 30 mg per day in some cats, although the incidence of side effects tends to be higher as you raise the dose. So in this patient, I would raise the dose to around 7.5 mg twice a day (total dose, 15 mg/day).

A few things that must be considered in this and all hyperthyroid cats that are treated chronically with methimazole is the following:

• Methimazole and other antithyroid drugs work by being taken up by the thyroid tumor where the drugs inhibit thyroid hormone production and secretion. With time, the thyroid tumor will grow larger and larger. Therefore, most hyperthyroid cats will require higher dosages to inhibit thyroid hormone secretion as their goiter becomes larger and the thyroid volume increases.
• In some of these cats, especially those treated for many months to years, the thyroid adenoma can transform into thyroid carcinoma while on these antithyroid drugs.

So, getting back to your cat, are you planning on using the methimazole long-term? At the moment, his daily dose is still quite low, but you are already having trouble regulating him. You might want to discuss the use of surgical thyroidectomy or radioiodine with the owner if you haven't already. Both of these are definitive treatment that are better choices for long-term prognosis, at least in my opinion.

Q & A: Trouble Regulating Hyperthyroid Cat with Methimazole

This week, I received an email from a veterinarian asking me a question that I frequently get asked. I thought I’d share his question and my response with all of you.

Dear Dr. Peterson,

I have a 12-year-old F/S DSH cat that I diagnosed as being hyperthyroid in June of 2008 because the cat had lost 2.2 lbs. over the year and had a serum T4 level of 4.3 μg/dl (reference range, 0.8 -4.0 μg/dl). The cat was initially placed on methimazole (Tapazole) at the dosage of 2.5 mg, SID. The serum T4 level subsequently dropped to 2.8 μg/dl and the cat maintained her weight.

A year later, however, things started to get interesting. The cat lost another 1.3 lbs. and the serum T4 concentration was back up to 4.3. I increased the methimazole dose to 2.5 mg, BID. When the cat was rechecked in 1 month, her weight was stable, but the serum T4 was still high at 5.4 μg/dl. Over the next 3 months, the cat continued to lose weight and the T4 remained high at 6.1 μg/dl, despite an increase the methimazole dose to 5 mg PO BID. A month later, the T4 value was still high so the dose was again increased to 7.5 mg, BID.

The owner was POSITIVE that the cat was getting the pills.  To make sure that wasn’t the problem, I had the owner switch the cat from oral to transdermal methimazole compounded by a local pharmacy.  A month later, the cat had lost another 0.4 lbs. and the T4 value had increased 7.2!

This cat is driving me crazy! I am at a loss as to why this cat cannot be stabilized with oral or transdermal methimazole. Any ideas or suggestions?

My response:

This scenario isn't really that uncommon in cats treated with methimazole on a long-term basis. 

Hyperthyroid cats, as you know, have adenomatous hyperplasia of their thyroid gland. This adenomatous hyperplasia eventually will transform into one or more thyroid adenomas, which continues to grow larger and larger with time. The methimazole does NOT stop this process, since the drug just works to block thyroid hormone secretion. After 1 to 2 or more years, many of these cats will have fairly large palpable goiters and can be difficult to regulate, even with high daily doses of oral or transdermal methimazole.

In some of these cats, the thyroid adenoma also may transform into a thyroid carcinoma as the disease progresses. Again, methimazole does nothing to the tumor pathology and cannot stop this from happening.

So, what do you do? Well, even if you could regulate this cat with 7.5 mg BID now, what are you going to do next year or the year after that when the dose has to go up further? This cat is a relatively young cat, and I believe that the cat should be treated with definitively therapy (surgery or radioiodine) in order to remove the cat's thyroid tumor(s).

This all brings up another important point. We should always tell the cat owner that hyperthyroidism is caused by a thyroid tumor, and that this tumor will grow and grow with time. If methimazole is used as initially treatment, they should be told that the drug may eventually stop working and that other treatments may be needed. Both surgery and radioiodine can be more difficult in cats with large goiters, so early definitive therapy is always best. 

In cats that are young to middle-aged, it does not make much sense to me to try to use methimazole on a long-term basis, unless we don't believe that cat will live for another couple of years or the owner refuses definitive therapy.