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REVIEW
Pharmacological management of feline hyperthyroidism offers a practical treatment option for many
hyperthyroid cats. Two drugs have been licensed for cats in the last decade: methimazole and its
pro-drug carbimazole. On the basis of current evidence and available tablet sizes, starting doses of
25 mg methimazole twice a day and 10 to 15 mg once a day for the sustained release formulation of
carbimazole are recommended. These doses should then be titrated to effect in order to obtain circulating total thyroxine (TT4) concentrations in the lower half of the reference interval. Treated cases
should be monitored for side-effects, especially during the first months of treatment. Some side-effects
may require discontinuation of treatment. At each monitoring visit, clinical condition and quality of life
should also be evaluated, with special attention to possible development of azotaemia, hypertension
and iatrogenic hypothyroidism. When euthyroidism has been achieved, monitoring visits are recommended after 1 month, 3 months and biannually thereafter. Cats with pre-existing azotaemia have
shorter survival times. However, development of mild azotaemia during the initial course of treatment,
unless associated with hypothyroidism, does not appear to decrease survival time. The long-term
effects of chronic medical management require further study.
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INTRODUCTION
PHARMACOLOGICAL MANAGEMENT
OF HYPERTHYROIDISM
Table 1. Grading of level of evidence for individual references (a) and of overall level of evidence for consensus
statements (b) (Adapted from Oxford Centre for Evidence-Based Medicine 2009, Elwood et al. 2010)
(a) Study type
1a
1b
1c
2a
2b
2c
3a
3b
4
5
Overall evidence grade (OEG)
A
B
C
D
*This principle is met when all patients died before the treatment became available, but some now survive on it; or when some patients died before the treatment became available, but none
now die on it
Table 2. Advantages and disadvantages of antithyroid drugs for treatment of hyperthyroid cats
Advantages
Disadvantages
Not curative
Not recommended in rare cases of functioning
thyroid carcinoma (Mooney 2001)
Poor or no response in a small proportion of cats
with thyroid adenoma (Peterson et al. 1988)
Comments
Benign adenomatous hyperplasia
(adenoma) is present in about 98% of
hyperthyroid cats (Mooney 2001)
Widely available
Cost-effective (short-term perspective) (Trepanier
2007)
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S. Daminet et al.
Carbimazole
Using human carbimazole tablets, a starting dose of 5 mg three
times a day showed a good level of achievement of biochemical euthyroidism (Mooney et al. 1992 [4], Bucknell 2000 [4]).
Feldman & Nelson (2004 [5]) recommend using 25 mg twice a
day for 7 days, then 5 mg twice a day for 3 weeks.
The sustained-release tablets for veterinary use (Vidalta;
MSD Animal Health) are registered with a starting dose of 15
mg once a day [or 10 mg once a day when TT4 concentration
is mildly increased (50 to 100 nmol/L)] (Summary of Product
Characteristics Anonymous, 2012c-d). In a clinical study, after
10 days of treatment at 15 mg once a day euthyroidism was
achieved in 70% of 40 cats (Frnais et al. 2009 [4]) with good
tolerability. On the basis of methimazole equimolar equivalence
and clinical experience, a dose of 10 mg once a day would be a
good starting dose in most cases [OEG D].
Dose adjustments
As most cats are euthyroid within 2 to 3 weeks of treatment with
antithyroid drugs (Felimazole Publicly Available Assessment
Report [4], Anonymous 2008, Frenais et al. 2009 [4]), the panel
recommends monitoring TT4 after that time period [OEG C].
If the cat is still hyperthyroid, methimazole dose adjustments
can be made in increments of 25 mg/day until euthyroidism is
achieved (Feldman & Nelson 2004 [5]). In a registration study
(NADA 141-292 [4], Anonymous 2009), after 20 weeks of
treatment, varying maintenance doses had been selected with the
majority of cats receiving 25 mg twice a day (34 of 58 cats) or
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Methimazole
The most severe but rare side-effects observed with methimazole
are hepatopathy and marked blood dyscrasias (severe leukopenia,
anaemia and/or thrombocytopenia). Gastrointestinal upset, pruritus and lethargy are frequently described with oral methimazole.
A possible irritating effect on gastric mucosa (and slightly bitter
taste of methimazole) may be causative. No relationship could be
demonstrated between the dose of methimazole (Peterson et al.
1988 [4]) or the dosing regimen (once a day versus twice a day)
(Trepanier et al. 2003 [1b]) and the occurrence, frequency or
severity of side-effects. Most side-effects appear within the first 4
to 6 weeks of therapy and are less common after 2 or 3 months of
treatment (Feldman & Nelson 2004 [5]).
TT4 monitoring
Circulating TT4 concentration should be measured 2 to 3 weeks
after induction of therapy or any treatment adjustment(s) until
euthyroidism is achieved, 3 months after stabilisation, and every
6 months thereafter [OEG D]. The panel supports the generally
accepted, although not evidence-based statement that clinicians
should aim for a TT4 concentration within the lower half of the
reference interval [OEG D]. Clinical improvement combined
with improvement of TT4 concentration (even if just within the
reference interval) is not sufficient to obtain adequate control
of the disease [OEG D]. Time of blood sampling for TT4 after
methimazole administration is not important (Rutland et al.
2009 [3b]).
Carbimazole
Carbimazole side-effects have been studied in a smaller number
of cats but demonstrate the same pattern (Table 4) as methimazole. Because carbimazole is the pro-drug of methimazole, there
is no value in switching from one drug to another if an adverse
drug reaction is suspected.
As both drugs are potential human teratogens, pet owners
should avoid exposure to the products when dosing cats and
strictly follow SPCs or label administration precautions.
Haematology
Haematological abnormalities are known adverse reactions to
antithyroid drugs. These can be mild and subclinical or more
severe (neutropenia, agranulocytosis, thrombocytopenia, haemolytic anaemia). Intensive (i.e. every other week) CBC monitoring is not recommended as severe haematological side-effects are
infrequent and unpredictable and such monitoring is not costeffective [OEG D].
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Biochemistry
Renal function should be assessed at each monitoring visit. It has
been demonstrated (in radioiodine treated cats) that glomerular
filtration rate (GFR) stabilises by approximately 1 month after
achievement of euthyroidism (Boag et al. 2007 [4], van Hoek
et al. 2008 [4], 2009 [4]) OEG [C].
S. Daminet et al.
Dose range
(total/day)
Route of
administration
Recommendation
Monitoring/
comments
Monitor liver
enzymes and
liver function
1 to 2
months later
5 to 15 mg
Oral
15 to 60 days (Peterson
et al. 1988)
5 mg
Transdermal
14 days
Bleeding diathesis
(epistaxis, oral
bleeding, prolonged
PIVKA* clotting
time)
5 to 15 mg
Oral
15 to 50 days (Peterson
et al. 1988)
5 to 20 mg
Oral
14 to 90 days (Peterson
et al. 1988)
10 mg
Transdermal
14 to 28 days
Agranulocytosis
(severe leukopenia
with a total granulocyte count <500/
L) and neutropenia
5 to 20 mg
Oral
26 to 95 days (Peterson
et al. 1988)
Within the first 4 weeks
(Trepanier et al. 2003,
Sartor et al. 2004)
5 mg
5 to 10 mg
Transdermal
Unknown
Oral
60 to 120 days
5 mg twice
a day
Transdermal
10 weeks
Unknown
Oral
Discontinue
treatment with
antithyroid drug
if anaemia is
severe, no rechallenge with
antithyroid drugs
Oral
7 to 60 days (Peterson
et al. 1988)
Continue
treatment
Lower dosage if
no improvement
Discontinue treatment temporally if still no
improvement
May require
permanent treatment discontinuation in some
cases
Myasthenia gravis
Anaemia (including
aplastic anaemia)
2.5 to 5 mg
In most cases
associated
with thrombocytopenia
Discontinue
treatment with
antithyroid drug
No re-challenge
with antithyroid
drugs
Perform CBC
two weeks
later
Perform CBC
2 weeks later
Non-life-threatening side-effects
Gastro-intestinal
upset or lethargy
25 to 15
mg
1 to 78 days (Peterson
et al. 1988)
5 mg
Transdermal
Generalised
peripheral
lymphadenopathy
10 mg
Oral
Discontinue
treatment with
antithyroid drug
Antinuclear antibodies
25 to 20
mg
Oral
Not routinely
measured
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Table 3. Continued
Side-effects
Dose range
(total/day)
Route of
administration
Recommendation
Mild haematological
abnormalities (leucopenia, eosinophilia,
lymphocytosis)
25 to 25
mg
Oral
10 to 15
mg
Oral
45 to 60 days (Peterson
et al. 1988)
Continue treatment if no
clinical or
haematological
signs of haemolytic anaemia
5 to 15 mg
Oral
6 to 40 days (Peterson
et al. 1988)
5 to 10 mg
Transdermal
Ideally, discontinuation of
treatment is
recommended
Monitoring/
comments
Route
5 to 25 mg
Oral
14 to 21 days (Mooney
et al. 1992)
Recommendation/Monitoring
5 mg twice
a day
14 days
Continue treatment
Lower dosage if no improvement
Discontinue treatment temporally
if still no improvement
May require permanent treatment
discontinuation in some cases
Peripheral lymphadenopathy
5 to 25 mg
Oral
5 to 25 mg
Oral
5 to 25 mg
Oral
5 to 25 mg
Oral
No treatment discontinuation
required
5 to 25 mg
Oral
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S. Daminet et al.
Pre-treatment
Every 6 months
(once 'stable')
History
Physical examination
Bodyweight and body condition score
Total T4
Complete blood count (CBC)
Full biochemistry profile
Liver profile
Renal profile
Urinalysis (USG, dipstick, sediment, culture)
Blood pressure (ideally) and/or ophthalmic examination
Recommended
Optional
If adverse event suspected or if inadequate resolution of clinical signs
*If not euthyroid then the dose of anti-thyroid drug should be adjusted and the TT4 checked every 3 weeks until the target value (TT4 concentration in lower half of reference interval) is reached
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S. Daminet et al.
CONCLUSION
Pharmacological treatment with methimazole or carbimazole allows efficient treatment in many hyperthyroid cats as a
life-long therapy or temporarily to stabilise a patient (before
anaesthesia/surgery or treatment with radioiodine). Close monitoring is important. Indeed, renal function before but also during
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Harley, L. S., Peterson, M. E., Langston, C. E., et al. (2011) IRIS stages of chronic
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