Antithyroid drugs, including methimazole and carbimazole, are medications

that treat an overactive thyroid (hyperthyroidism) by blocking the thyroid

gland's ability to make thyroid hormone. Carbimazole is a "pro-drug" since,
after its absorption, it is converted to "active" methimazole in the body;
therefore, these drugs can be considered equivalent (1).

Over the 25 years since we first reported the use of methimazole for
treatment of cats with hyperthyroidism (2), I have had repeated questions
from veterinarians and cat owners about the use of once or twice-daily dosing
regimes. In addition, I've had many questions regarding the best time to
monitor a hyperthyroid cat's serum thyroid concentrations during
methimazole treatment.

The purpose of this post is to review how these drugs actually work to lower
serum T4 and T3 values. In addition, I'll provide an overview of my current
protocols for dosing and monitoring hyperthyroid cats treated with these
drugs.

How Do Antithyroid Drugs Work? What's the Mechanism of Action?

After administration, the thyroid gland takes up and concentrates
methimazole from the circulation. Once within the thyroid, methimazole
works by inhibiting the production of T4 and T3 from the hyperthyroid cat's
thyroid tumor.

More specifically, methimazole blocks thyroid hormone synthesis by inhibiting

thyroid peroxidase, an enzyme involved in the oxidation of iodide to iodine,
incorporation of iodine into thyroglobulin, and coupling of tyrosine residues to
form T4 and T3 (2-7). Methimazole does not block the release of preformed
thyroid hormone, so there is generally a delay of 2 to 4 weeks before serum
T4 concentrations return to normal after initializing therapy.

It is important to remember that antithyroid drugs, such as methimazole, do

not destroy the thyroid tumor, decrease it's size, or slow the progressive
thyroid tumor growth that is characteristic for this disorder. Because the
thyroid tumor continues to grow larger over time despite methimazole
therapy, the need for higher doses should be anticipated during long term

treatment in many cats (6-8).

How Long Does a Dose of Methimazole "Last" After Its Given?

After oral administration, studies show that methimazole has a relatively
short half-life in the circulationonly 2.3 hours and 4.7 hours in hyperthyroid
and normal cats, respectively (9,10). But we must remember that this drug
does not work to lower T4 by remaining in the circulation. Rather, this
antithyroid drug is taken up by the thyroid gland, the site where it acts to
inhibit the production of thyroid hormones. In accord with that, normal cats
show sustained suppression of serum thyroid hormone concentrations for up
to 24 hours after a single dose of methimazole (11), proving that this drug
inhibits T4 production far beyond its known half-life in the circulation.

Unfortunately, once-daily dosing with methimazole will not be adequate in

most cats with hyperthyroidism. In one study of 40 hyperthyroid cats (12),
once-daily dosing was much less effective than use of twice-daily
administration (the total daily dose given was the same in both groups of
cats). In that study, only 54% of cats become euthyroid (i.e., normal thyroid
state) after 2 weeks with once daily treatment, whereas 87% of cats became
euthyroid with twice-daily administration (12). Therefore, I strongly
recommend twice daily dosing of methimazole to help ensure better control
of the cat's hyperthyroid state.

If once-daily treatment is insufficient and twice-daily treatment causes

compliance issues, a sustained carbimazole formulation (Vidalta, MSD Animal
Health) can be tried at 10 to 15 mg, once a daily (13). However, this drug is
not approved for use in the USA and is currently only available in Europe.

For more information about carbimazole and Vidalta, see my last post on
Antithyroid Drug Treatment for Hyperthyroidism: Brand Name, Generic, or
Compounded Drug?

Initial Methimazole Dose

The initial methimazole doses used vary depending on the cats pretreatment
serum T4 value and the size of the thyroid tumor. In general, however, most
cats are started on 1.25 mg to 2.5 mg of methimazole, administered twice

daily (4-7). This dose is adjusted according to T4 measurements (see below),

as well as the cat's clinical response.

In cats that fail to respond and remain hyperthyroid, the daily doses are
slowly titrated upwards to lower serum T4 concentrations into the desired
range. For more information about making dose adjustments, see my blog
post on: Treating Cats with Hyperthyroidism: Antithyroid Drugs.

Best Time to Collect Blood (Post-Pill) for Monitoring Cats on Methimazole?

Although one might expect that protocols for monitoring cats on methimazole
would be standardized among veterinarians, this is not the case. Some have
stated that the time of serum T4 sampling in relation to the administration of
the antithyroid drug is not important, even in cats on once-daily methimazole
(11).

However, I strongly disagree with that recommendation. We know that the

suppressive effect of methimazole on thyroid secretion is highly variable
among hyperthyroid cats, depending on the severity of their disease and size
of their thyroid tumor. In addition, we also know that twice daily dosing is
more effective and that once daily therapy is less likely to be successful in
treatment (12).

The protocol that I use for my hyperthyroid cats is to have the methimazole
dosed twice a day (morning and night) and then collect the post-treatment
serum T4 sample sometime during the day. Ideally, it would make the most
sense to me to take the sample around 6 hours post-pill (half-way between
the two methimazole administration times), but the "exact" timing does not
appear to critical.

However, I would recommend that one be consistent in the timing of the

post-pill test sample. In other words, do not have your cat tested once in the
morning (an hour after the methimaole was given) and then compare those
results to another testing time when the sample was collected late in the
afternoon (11 hours after the methimazole was administered). In other words,
we should try to monitor the post-methimazole serum thyroid hormone
values at the same time each hospital visit.

What's the Ideal Serum T4 Concentration for Cats on Methimazole?

It is important to keep the serum T4 concentration within the mid-normal
range and not have even mildly high or high-normal values on methimazole.
For example, if the T4 reference range is listed as 0.8-4.0 g/dl (10-50
nmol/L), my goal is maintain the T4 values between 1.5-2.5 g/dl (20-32
nmol/L). Recent research indicates that hyperthyroidism may contribute to
the development or progression of chronic renal disease in cats (14-16).
Leaving a hyperthyroid cat untreated (or poorly regulated with methimazole
or carbimazole) may therefore be detrimental to long-term kidney function
and is never recommended.

During long-term treatment, it is also important to avoid inducing

hypothyroidism, which may be deleterious to the cats kidney function
(25,26). If hypothyroidism is suspected, a complete thyroid panel is
recommended, including determination of the serum concentrations of total
T4, free T4, T3, and TSH (see my previous blog posts on diagnostic testing for
more information about these tests). The findings of low serum free T4 with
high TSH concentrations is diagnostic for iatrogenic hypothyroidism; in those
cats, the daily dose of methimazole should be decreased.