Methimazole is commonly used for the medical management of hyperthyroidism in cats. With some cats, giving an oral medication can be challenging and alternatives have been sought. A promising avenue is the transdermal application of methimazole in a pleuronic lecithin organogel. The gel allows penetration through the skin of the patient. The use of methimazole formulated in PLO gel has previously been reported and it has been demonstrated that chronic administration can control hyperthyroidism in cats.1 The dosage required to achieve control varies, however, with 2.5 mg administered BID, 67 percent of cats with follow-up at four weeks were well controlled.
A group of researchers from the Vetsuisse Faculty at the University of Zurich looked at short and long-term follow-up in a group of cats treated with transdermal methimazole.2 The study encompassed 20 newly diagnosed hyperthyroid cats. Initial dose was 2.5 mg BID. All cats were rechecked between one and four weeks after starting therapy. Eight cats were also reevaluated at five to eight weeks, nine to 20 weeks and after a median of 42.5 weeks (range 21 to 118 weeks). This study also attempted to look at the effect of the gel on T4 concentrations over a 10-hour period (sampling every two hours after administration). This was carried out in six cats on the first day of treatment and one week after starting therapy. In three cats, this was also done three weeks after starting therapy.
Treatment was effective in controlling clinical signs. Side effects were rare and included GI signs in two cats and ear irritation in one cat. Significant decreases in T4 were noted at the first recheck and at every time point afterward. Some cats were still in the hyperthyroid range except at the last recheck where the highest T4 concentration was 46.3 nmol/L (reference range generally goes to 45).
In order to achieve this, methimazole dosage had to be increased to 3.5 to 8.7 mg per application in nine cats. There were no significant changes noted in T4 concentration during the 10 hours it was sampled.
The authors concluded that methimazole in PLO gel is effective at treating hyperthyroidism long-term. The lack of detectable effect on T4 over the 10-hour period after administering the gel suggests that once-a-day dosing may be adequate, although this information has yet to be confirmed.
Published data to date shows that transdermal methimazole can be an effective medication to control hyperthyroidism. It appears to take longer to achieve control than with oral medications and a higher dosage of methimazole may be needed. Long-term management is possible and appears to be well-tolerated by cats. Adverse side effects can occur and are similar to those seen with oral administration, though some studies suggest that GI signs are less likely to be present.
Whenever hyperthyroidism is treated, there is concern that significant renal disease could be unmasked. Certainly careful evaluation is needed when treating a cat with obvious renal failure and hyperthyroidism, as treatment of the hyperthyroid state will result in worsening azotemia. This decrease in renal function is a result of hyperthyroidism, causing an abnormally elevated glomerular filtration rate.3
A group of researchers from the Royal Veterinary College in London examined whether the development of azotemia after treatment for hyperthyroidism affects survival.4 The study was retrospective and looked at cats treated between 1995 and 2004. A total of 116 cats were included that were not azotemic prior to therapy and that were successfully treated with oral medications or thyroidectomy.
Group 1 (27 cats) developed azotemia within six months of successful therapy, Group 2 (89 cats) did not. Cats were not included in the evaluation if they were lost to follow-up or still alive at the completion of the study (four in Group 1, 25 in Group 2). Median survival time after treatment was 595 days in Group 1 (range 62 to 2016) and 584 days in Group 2 (range 29 to 2044).
This study shows that mild azotemia that can occur after treatment of hyperthyroidism does not affect outcome. The same, of course, cannot be said for those cats that are azotemic prior to therapy. It would appear that there is no indication to discontinue therapy for hyperthyroidism if mild azotemia develops with therapy. The survival time after therapy is relatively long in most cats considering that hyperthyroid cats represent geriatric pets.
In humans, it is known that prior to overt hyperthyroidism there is a variably long sub-clinical phase. During this phase thyroid hormones are normal but TSH concentration is below normal (negative feedback loop with thyroid hormones). Researchers from the Royal Veterinary College in London undertook a study to look at the relationship between TSH concentration and the histopathology of feline thyroid glands.5
Thyroid glands were collected from cats with normal TSH, low TSH, healthy young cats and cats with confirmed hyperthyroidism. The glands were assessed for the amount of adenomatous change noted as well as how many adenomatous nodules were present. The study showed that cats with low TSH experienced more adenomatous change than healthy young cats or cats with normal TSH. There were also fewer nodules in the young cats than in those with low TSH. The adenomatous changes were less pronounced in the low TSH group than in those cats with confirmed hyperthyroidism.
This study suggests that there may be a period of time prior to overt hyperthyroidism where hormonal changes are already occurring. A low TSH concentration points toward this possibility.
Based on Abstracts presented at the 16th ECVIM-CA Congress in Amsterdam, Holland (2006).
References:
1. Sartor LL, Trepanier LA, Kroll M, et al. Efficacy and safety of transdermal methimazole in the treatment of cats with hyperthyroidism. J Vet Intern Med 18: 651-655: 2004.
2. Boretti FS, Sieber-Ruckstuhl NS, Tschour F, et al. Short and long-term follow-up of hyperthyroid cats treated with transdermal methimazole. J Vet Intern Med 20;1523-1524: 2006.
3. Becker TJ, Graves TK, Kruger JM, et al. Effects of methimazole on renal function in cats with hyperthyroidism. J Am Anim Hosp Assoc 36; 215-223: 2000.
4. Wakeling J, Rob C, Elliott J, Syme H. Survival of hyperthyroid cats is not affected by post-treatment azotemia. J Vet Intern Med 20;1523: 2006.
5. Kirkby R, Scase T, Wakeling JE, et al. Adenomatous hyperplasia of the thyroid gland is related to TSH concentrations in cats. J Vet Intern Med 20;1522-1523: 2006