Professional Documents
Culture Documents
e2014
Original Article
Abstract
Feline hyperthyroidism is commonly diagnosed in general practice. This study assessed the opinions and
experiences of UK general practitioners (GPs) regarding the management of feline hyperthyroidism. This
included an evaluation of preferred treatment modalities and the monitoring of medically treated cats in relation
to thyroxine (T4) level, co-morbid disease and adverse drug reactions. Six hundred and three GPs completed
an online questionnaire comprising 34 questions. Oral medication was the most commonly preferred treatment
option (65.7% of respondents), followed by thyroidectomy (27.5%) and then radioiodine (5.5%). When cost of
treatment was eliminated as a consideration factor, significantly more respondents selected radioiodine (40.5%,
P <0.001). Concerning target total T4 levels during medical management, 48.4% aimed for the lower half of the
reference interval (RI), 32.3% anywhere within RI, 13.1% within the top half of RI and 0.5% above the RI; 3.4%
evaluated efficacy by physical assessment only. In the presence of chronic kidney disease (CKD) respondents
were significantly more likely to target total T4 levels within the upper half of the RI (40.3%) or above it (9.8%) when
compared with targets for routine cases (P <0.001). Assessment for unmasking of CKD after initiating treatment
or for hypertension was not consistently performed. Variability in monitoring strategies may result in CKD and
hypertension remaining undetected, inadequate suppression of T4 levels in cats with concurrent CKD and delayed
recognition of potentially significant haematological abnormalities.
Accepted: 7 December 2013
Introduction
Feline hyperthyroidism was first reported in 1979 and,
since that time, has increased in prevalence to become
one of the most commonly diagnosed endocrinopathies.1
The diagnosis of hyperthyroidism is routinely made in
general practice, with at least 91% of cases being confirmed on the basis of elevated total thyroxine (T4) levels.2 There are currently four treatment modalities
available, including anti-thyroid medications, surgical
thyroidectomy, radioiodine therapy and, more recently,
iodine-restricted dietary therapy.3,4 Choice of treatment
modality is believed to be strongly influenced by the
individual general practitioner (GP) and is likely influenced by their experience, prior education and awareness of current literature, and specialist opinion.
Treatment options for hyperthyroidism can be separated into those that are potentially curative (radioiodine,
surgical thyroidectomy) and those that require life-long
intervention and monitoring (anti-thyroid medication,
iodine-restricted diet). Most cats will receive anti-thyroid
medication at some stage, either for short-term
Downloaded from jfm.sagepub.com at The Royal Veterinary College on January 20, 2015
Higgs et al
789
Results
Six hundred and three questionnaires were completed.
The majority of respondents were female (n = 345;
57.2%). The year of graduation of the respondents ranged
from 1960 to 2012 (median 1996); 78 (12.9%) graduated
outside of the UK and Ireland. The median estimated
percentage of the working day spent with feline patients
was 40% (range 0.25100%).
In the 6 months leading up to the questionnaire the
number of new cases of hyperthyroidism that had been
diagnosed was between one and five for 215 respondents
(35.7%), six and 10 for 213 (35.3%), 11 and 20 for 140 (23.2%),
more than 20 for 28 (4.6%) and zero for seven (1.1%).
Downloaded from jfm.sagepub.com at The Royal Veterinary College on January 20, 2015
790
Considering respondents personal preference for
long-term management of hyperthyroidism, 396
(65.7%) chose oral anti-thyroid medication, 166 (27.5%)
chose thyroidectomy and 33 (5.5%) chose radioiodine.
Eight (1.3%) were either unsure or chose other options,
including homoeopathy. As the data were collected
shortly after the launch of the iodine-restricted diet,
respondents were asked to give the answer that
reflected their preference in the time before the diet
launch. When cost of treatment was eliminated as a
consideration factor, significantly more respondents
selected radioiodine (244, 40.5%), with 202 (33.4%)
choosing oral medication and 151 (25.0%) selecting
thyroidectomy as their preferred management option
(P <0.001). Respondents were asked whether they
agreed with the statement radioiodine is the gold
standard treatment for hyperthyroidism; 58.9% agreed
or strongly agreed, 19.4% disagreed or strongly disagreed, and 21.7% were not sure.
Respondents were asked to rate the importance of
factors that might influence their choice of treatment
for long-term management of hyperthyroidism in a
cat. More than 95% of respondents rated owner compliance with medication, ease of drug administration
and the presence of co-morbid disease as very important or important factors in formulating a management
plan. Table 1 summarises how respondents rated all
factors.
When asked which oral anti-thyroid medications they
preferred to use in a newly diagnosed hyperthyroid cat,
sustained-release carbimazole was favoured by 311 of
the respondents (51.6%), methimazole by 244 (40.5%)
and 39 (6.5%) had no specific preference. The unlicensed,
human form of carbimazole (Neomercazole; Roche
Products) was chosen by 9 (1.5%) respondents.
Table 1 Importance of factors in the formulation of a long-term plan for management of hyperthyroidism in a cat, as
rated by 603 UK general practitioners in an online questionnaire (2012)
Factor
591 (98.0)
6 (1)
6 (1)
589 (97.7)
582 (96.5)
488 (80.9)
474 (78.6)
460 (76.3)
402 (66.7)
394 (65.3)
290 (48.1)
184 (30.5)
119 (19.7)
8 (1.3)
14 (2.3)
59 (9.8)
75 (12.4)
97 (16.1)
174 (28.9)
135 (22.4)
227 (37.6)
309 (51.2)
394 (65.3)
6 (1)
7 (1.2)
56 (9.3)
54 (9.0)
46 (7.6)
27 (4.5)
74 (12.3)
86 (14.3)
110 (18.2)
90 (14.9)
Downloaded from jfm.sagepub.com at The Royal Veterinary College on January 20, 2015
Not sure
(number of respondents
[% of total respondents])
Higgs et al
791
Table 2 Frequency of measurement of monitoring parameters in a recently diagnosed hyperthyroid cat as stated by
603 UK general practitioners in an online questionnaire (2012)
Parameter
Body weight
Serum total T4
Renal biochemistry*
Hepatic biochemistry
PCV
Complete blood count
Blood pressure
Urinalysis (in-house)
Urinalysis (external)
34 weeks
26 months
Not specified
529
(87.7)
521
(86.4)
430
(71.3)
348
(57.7)
247
(41.0)
285
(47.3)
251
(41.6)
231
(38.3)
52
(8.6)
302
(50.1)
283
(46.9)
192
(31.8)
130
(21.6)
87
(14.4)
88
(14.6)
109
(18.1)
76
(12.6)
23
(3.8)
321
(53.2)
155
(25.7)
90
(14.9)
60
(10.0)
46
(7.6)
38
(6.3)
91
(15.1)
53
(8.8)
4
(0.7)
55
(9.1)
93
(15.4)
151
(25.0)
246
(40.8)
329
(54.6)
307
(50.9)
296
(49.1)
356
(59.0)
492
(81.6)
220
(36.5)
310
(51.4)
245
(40.6)
169
(28.0)
122
(20.2)
129
(21.4)
144
(23.9)
124
(20.6)
35
(5.8)
7
(1.2)
45
(7.5)
117
(19.4)
128
(21.2)
106
(17.6)
129
(21.4)
72
(11.9)
70
(11.6)
72
(11.9)
Discussion
Hyperthyroidism is the most frequently diagnosed
endocrinopathy in cats and is commonly diagnosed in
general practice.1 There is limited information regarding the standard approach used by UK GPs in managing
and monitoring this disease. This study demonstrates
that there is a strong overall preference for the use of
oral anti-thyroid medications among UK GPs for the
long-term management of feline hyperthyroidism; reasons for specific brand preferences were not investigated. When cost was eliminated from the
decision-making process, significantly more respondents chose radioiodine as their treatment of choice
(40.0% vs 5.5%). Over 75% of respondents stated that
the cost of treatment and the cost of monitoring were
important or very important factors in the choice of
treatment modality.
The effect of cost for cat owners may be less significant than practitioners believe; 51.3% of owners of
hyperthyroid cats surveyed in one study stated that
cost had no impact on their decision over which treatment to choose.9 A second survey of owners reported
Downloaded from jfm.sagepub.com at The Royal Veterinary College on January 20, 2015
792
Table 3 Adverse reactions to anti-thyroid medications seen by 404/603 UK general practitioners within the 12 months
prior to the completion of an online questionnaire (2012)
Adverse drug reaction seen in the last
12 month period
Number of respondents
Vomiting
Anorexia
Facial pruritus
Azotaemia
Anaemia
Leukopenia
Hepatic damage
Neutropenia
Thrombocytopenia
Lymphadenomegaly
Death (sudden)
279
190
181
92
48
44
39
34
34
19
4
69.0
47.0
44.8
22.7
11.8
10.9
9.6
8.4
8.4
4.7
0.9
Downloaded from jfm.sagepub.com at The Royal Veterinary College on January 20, 2015
Higgs et al
793
Previous publications have implied that the development of azotaemia following treatment for hyperthyroidism is an unwanted adverse effect of euthyroid
ism;12,19,2326 indeed, it is listed under the adverse effects
sections of one of the datasheets (sustained release carbimazole [Vidalta; MSD Animal Health]). This is now
understood to represent an unmasking of co-existing
kidney disease by restoration of GFR.12,19,24 Adams etal20
demonstrated a reduction in GFR following treatment
for hyperthyroidism; however, the degree of change in
GFR did not affect the outcome. More recent studies
have also found that the prognosis for survival in cats
developing azotaemia after treatment is unaffected
unless the cat becomes iatrogenically hypothyroid.14,21
Conversely, persistent hyperthyroidism maybe detrimental to renal function by inappropriate activation of
the reninangiotensinaldosterone system (RAAS).5,7,23
While this increases GFR, the activation of RAAS and
secondary systemic and renal afferent arterial hypertension may contribute to the progression or development
of CKD and progressive cardiac remodelling, ultimately
increasing morbidity and decreasing survival. These
recent studies suggest that the concept of maintaining an
azotaemic cat in a mildly hyperthyroid state to promote
GFR and kidney function is outdated, although the
results of this questionnaire suggest that this dogma is
still followed by some practitioners.
Only 50.9% of our respondents indicated that they
routinely (at least annually) measured blood pressure as
part of their monitoring protocol for feline hyperthyroidism. Fourteen to 22% of hyperthyroid cats are
reported to be hypertensive at diagnosis and a further
24% are described to develop hypertension de novo following the treatment for hyperthyroidism.6,7 The low
number of practitioners monitoring blood pressure may
reflect limited access to blood pressure monitoring
equipment or could be because blood pressure monitoring is not advised on the datasheet for either licensed
medication. From the questionnaire data we postulate
that a considerable proportion of hypertensive cats may
be undiagnosed before or after treatment. This may contribute to morbidity with progression of cardiac remodelling and CKD, and potentially may lead to
development of ocular and central nervous system complications.2729 Furthermore, hypertension has also been
shown to be a negative predictor of survival in hyperthyroid cats.21
Adverse reactions were suspected by 67% of respondents in the 12 months leading up to completing the questionnaire, although data were not collected on the
frequency of each type of adverse reaction. However, the
data suggest that adverse reactions remain common, in
particular vomiting and anorexia. This supports previous studies in which gastrointestinal problems were the
most frequently reported adverse effects.30,31
Downloaded from jfm.sagepub.com at The Royal Veterinary College on January 20, 2015
794
dependent upon each case seen; in particular, when asking regarding target total T4 levels in the presence of
CKD, we did not specify the International Renal Interest
Society stage or stability of CKD.
The true prevalence of adverse reactions could not be
determined from the questionnaire as the question format did not evaluate the frequency of reactions per case.
We also acknowledge that these responses are reliant on
accurate recall by respondents and this may create additional inaccuracy in these data. Finally, the effect of dietary therapy and transdermal methimazole on GPs
favoured management is unknown; the iodine-restricted
diet (Hills y/d) had been available for only short period
at the time of questionnaire and was not included in general management questions.
Conclusions
There is a preference for the use of anti-thyroid medications in the management of feline hyperthyroidism in
UK general practice over potentially curative treatment
options. This preference appears to be strongly influenced by cost considerations. Although most GPs do
perform some sort of regular monitoring of hyperthyroid cats receiving oral medications, common co-morbid
diseases, including hypertension and renal disease, may
be undiagnosed and unmanaged in some cases.
Recent information regarding the management of
azotaemic cats with hyperthyroidism relating to optimising total T4 levels and detection of hypertension
does not appear to be widely implemented in general
practice. Azotaemia may still be considered by some
practitioners as an adverse reaction to medication or
treatment in general rather than evidence that uncontrolled hyperthyroidism may be masking CKD.
Finally, the protocol for monitoring for adverse effects
varies significantly between practitioners; however, this
study demonstrates that adverse effects may be more
common than indicated by data held by the VMD.
10
11
12
13
Acknowledgements
We would like to thank all those who completed this questionnaire, the editors of The Veterinary Record, VetSurgeon.org and
the International Society of Feline Medicine for advertising this
questionnaire, as well as The Langford Trust and Langford
Veterinary Services for supporting the study.
14
15
of interest to declare.
16
17
References
1 Edinboro CH, Scott-Moncrieff JC, Janovitz E, etal. Epidemiologic study of relationships between consumption of
18
Downloaded from jfm.sagepub.com at The Royal Veterinary College on January 20, 2015
Higgs et al
19
20
21
22
23
24
25
26
795
27
28
29
30
31
32
33
Downloaded from jfm.sagepub.com at The Royal Veterinary College on January 20, 2015