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DOI: 10.1177/1098612X13512627

2014 16: 491 originally published online 14 November 2013Journal of Feline Medicine and SurgeryMarieke van der Kooij, Iveta Becvárová, Hein P Meyer, Erik Teske and Hans S Kooistra

Effects of an iodine-restricted food on client-owned cats with hyperthyroidism

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IntroductionFeline hyperthyroidism, a multisystemic, potentially life-threatening disease, was first described in the late 1970s and early 1980s.1,2 The disease has been recognised with increasing incidence and is now one of the most common endocrine disorders in middle-aged and elderly cats.3,4 The aetiology of feline hyperthyroidism is not completely understood and may be multifactorial. Several potential risk factors have been described, including genetic, environmental and nutritional factors. However, none of the studies has isolated a single domi-nant factor that could be responsible for the develop-ment of hyperthyroidism.5

Hyperthyroidism in cats requires prompt veterinary attention. Currently, there are three effective options for the treatment of feline hyperthyroidism, all with the objective of normalising circulating thyroid hormone concentration: (i) pharmacological therapy with either methimazole or carbimazole; (ii) thyroidectomy; and (iii)

radioiodine therapy.4 All treatment modalities have their advantages and disadvantages, and the best treatment option for an individual cat depends on the age, charac-ter and medical condition of the cat (including concur-rent illnesses), financial situation of the owner and availability of therapy.6

Recently, a new reversible option in the management of feline hyperthyroidism has been introduced, consist-ing of an iodine-restricted food. Iodine is an essential

Effects of an iodine-restricted food on client-owned cats with hyperthyroidism

Marieke van der Kooij1, Iveta Becvárová2, Hein P Meyer2, Erik Teske1 and Hans S Kooistra1

AbstractThe objective of this prospective, multicentre, non-controlled, open-label study was to evaluate the effects of an iodine-restricted food on circulating total thyroxine (TT4) concentrations and clinical parameters in client-owned cats with hyperthyroidism. Two hundred and twenty-five cats were enrolled in the study and adapted to the iodine-restricted food. Data from physical examinations, questionnaires completed by veterinarians and owners, and circulating concentrations of TT4, urea and creatinine were recorded at weeks 0, 4 and 8. The study group included 136 female and 89 male cats (median age 15 years, range 4–21 years). Group 1 (n = 113) had been on previous anti-thyroid medication, while group 2 (n = 112) consisted of newly diagnosed cats. No differences were found between the two groups at any time point. Circulating TT4 concentrations had decreased (P <0.0001) at week 4 and did not change significantly from week 4 to week 8. Circulating TT4 concentration was within the reference range in 56/88 cats at week 4 and in 51/68 cats at week 8. Clinical parameters (vomiting, polyuria, polydipsia, hyperactivity, polyphagia, weight loss, hair coat quality, and quality of life) had improved (P <0.0001) by week 4. Circulating creatinine concentration decreased (P = 0.001) from week 0 to week 4. Side effects associated with feeding the iodine-restricted food were not observed. In conclusion, in client-owned cats with hyperthyroidism an iodine-restricted food is a valuable management option to normalise circulating TT4 concentrations, and improve clinical signs of hyperthyroidism within 4 weeks. This applies to newly diagnosed cats, as well as to previously diagnosed cats receiving anti-thyroid drugs.

Accepted: 14 October 2013

1 Department of Clinical Sciences of Companion Animals, Utrecht University, the Netherlands

2Hill’s Pet Nutrition, Prague, Czech Republic

Corresponding author:Marieke van der Kooij DVM, Department of Clinical Sciences of Companion Animals, Utrecht University, Yalelaan 108, 3584 CM, Utrecht, the Netherlands Email: m.vanderkooij@uu.nl

512627 JFM16610.1177/1098612X13512627Journal of Feline Medicine and Surgeryvan der Kooij et al2013

Original Article

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492 Journal of Feline Medicine and Surgery 16(6)

nutritional element and is required in only very small amounts. Iodine is an important component of thyroid hormones and the vast majority is located in a protein-bound form in the thyroid glands.7

In an abstract presented at the American College of Veterinary Internal Medicine (ACVIM) Forum, Melendez et al8 reported the effect of iodine restriction in the nutritional management of cats with naturally occurring hyperthyroidism by feeding foods with dif-ferent iodine concentrations (0.47 ppm dry matter, 0.28 ppm dry matter and 0.17 ppm dry matter). They con-cluded that restriction of dietary iodine is an effective method for decreasing circulating total thyroxine (TT4) concentration in hyperthyroid cats.8 In another ACVIM abstract, it was reported that the maximum iodine con-centration required in food to control hyperthyroidism is 0.39 ppm.9

An iodine-restricted food may thus be an alternative modality to the regular treatment options in the man-agement of feline hyperthyroidism. However, the effect of an iodine-restricted food has not yet been evaluated in client-owned cats. The first aim of this study was therefore to evaluate the effect of an iodine-restricted food on the circulating TT4 concentration in client-owned cats with naturally occurring hyperthyroidism. The second aim was to evaluate the clinical effects of the food, including various clinical parameters and renal function. It was hypothesised that dietary iodine restric-tion in hyperthyroid cats would reduce circulating TT4 concentrations and lead to improvement in clinical signs.

Materials and methodsStudy designThis study was conducted as a prospective, multicentre, non-controlled, open-label study, evaluating the effect of a commercially available, iodine-restricted food (Hill’s Prescription Diet y/d Feline) in client-owned hyperthy-roid cats from 10 January 2012 until 5 July 2012. The study was conducted in 139 veterinary clinics in 10 European countries (Denmark, France, Germany, Italy, the Netherlands, Norway, Spain, Sweden, Switzerland, UK) by an independent research company (CM Research) on behalf of Hill’s Pet Nutrition. Hill’s Pet Nutrition did not have access to the data of the owners and clinics that participated in the study, and European data protection laws were strictly adhered to.

Three hundred and eighty-seven client-owned cats suspected of hyperthyroidism were recruited by clinics which were invited to participate in the study. Each clinic could register up to 10 cats via an online survey. The owners agreed to participate voluntarily through an online participant survey and consent form.

Cats were included in the study if they had clinical signs compatible with hyperthyroidism and

a circulating TT4 concentration above the reference interval prior to enrolment (day 0). Cats were excluded from the study if the circulating TT4 concentration at day 0 was not increased and if no past increased circu-lating TT4 concentrations with compatible clinical signs of hyperthyroidism were known. The cats could either be previously diagnosed with hyperthyroidism and treated with anti-thyroid drugs (group 1), or newly diagnosed with hyperthyroidism (group 2). Two hun-dred and twenty-five cats met the inclusion criteria and entered the study.

FoodAn iodine-restricted food was given to the cat owners by the veterinarians. The food is commercially availa-ble as Hill’s prescription Diet y/d Feline and is availa-ble in canned form and dry form. All food distributed originated from one batch. The nutrient content on a dry matter basis and the content per 100 kcal metabolis-able energy (ME) of the food are shown in Table 1. The average iodine concentration of the canned food was 0.14 ppm dry matter and for the dry food it was 0.19 ppm dry matter. The iodine concentration of the food was based on previous titration studies by Melendez and Yu.9

The recommended feeding amount in kcal ME per day to meet the daily energy requirement (DER) when completely transitioned to the iodine-restricted food was determined based on the following calculation: DER = (70 ! target BW0.75) ! 1.2. As iodine intake from other food sources may compromise the effectiveness of iodine-restricted nutrition, the owners were given clear instructions by their veterinarians to feed the iodine-restricted food exclusively, with water ad libitum.

Study detailsThe owners were instructed by their veterinarian to gradually transition their cat from the original food to the iodine-restricted food (Hill’s Prescription Diet y/d Feline) over a 1-week period. The cats entered the study (day 0) when they were consuming the iodine-restricted food exclusively.

The owners of the previously diagnosed cats treated with anti-thyroid drugs (group 1) were instructed by their veterinarians to have reduced the total dose of the anti-thyroid drugs by 50% at day 0. After 2 weeks on the iodine-restricted food, the anti-thyroid drugs were discontinued.

At day 0, the signalment and lifestyle of the cats were noted. A physical examination was performed by the veterinarian at day 0, and then at week 4 and week 8. At each visit, body condition score (BCS) and heart rate were recorded. A five-point scale was used to monitor BCS in which 1 = very thin, 2 = thin, 3 = ideal, 4 = over-weight and 5 = obese.10

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Venous blood samples were collected, and circulating TT4, urea and creatinine concentrations were measured at each visit. As several laboratories were involved using different analytical methods and reference intervals, the laboratory values were expressed as the ratio between the actual value and the upper reference limit for each laboratory, that is, a ratio >1 indicates a value above the upper limit of the reference interval.

Both owners and veterinarians were requested to com-plete online questionnaires evaluating the clinical signs at each visit. All parameters of the questionnaire were scored subjectively. Table 2 shows the details of each clinical parameter that was scored by the owner or veterinarian at weeks 0, 4 or 8, including the applied scale. At week 4, reasons for incomplete data were evaluated by an open question. At week 8, there was a free comment section for the veterinarians for entering any remarks.

Statistical analysisData are presented as consolidated data for all 225 patients, as well as being separated into two groups: pre-viously diagnosed hyperthyroid cats that had been treated with anti-thyroid drugs (group 1) and newly diagnosed hyperthyroid cats (group 2). Normality was tested by the one-sample Kolmogorov–Smirnov test. None of the data was normally distributed.

For evaluation of the differences between groups 1 and 2 for the nominal data (gender, neuter status, life-style) and ordinal data (BCS, questionnaire scores of weight loss, polyphagia, hyperactivity, polyuria, poly-dipsia, poor hair coat, vomiting and quality of life) the Pearson 2 test was used. A Mann–Whitney U-test was used to compare the differences between groups 1 and 2 for the continuous data (age, heart rate, TT4 ratio, urea ratio, creatinine ratio).

Table 1 Average nutritional contents on dry matter basis (DMB), caloric basis (per 100 kcal metabolisable energy [ME]) and ingredients of the iodine-restricted food (Hill’s Prescription Diet y/d Feline)

Canned food* Dry food†

DMB Per 100 kcal ME DMB Per 100 kcal ME

Protein 34.1% 7.6 g 34.0% 7.6 gFat 25.9% 5.8 g 24.9% 5.5 gCarbohydrate 31.4% 7.0 g 34.0% 7.6 gCrude fibre 3.1% 0.7 g 1.1% 0.2 gMoisture – 54.5 g – 1.4 gCalcium 0.86% 192 mg 0.85% 189 mgPhosphorus 0.59% 131 mg 0.61% 135 mgSodium 0.24% 54 mg 0.26% 57 mgPotassium 0.86% 192 mg 0.90% 201 mgMagnesium 0.07% 15 mg 0.07% 17 mgIodine 0.14 ppm 3 µg 0.19 ppm 4 µgME kcal/100 g 449 450

*Ingredients of canned formula: liver, pork, maize, rice, animal fat, vitamins, digest, cellulose, minerals, trace elements, fish oil, L-carnitine†Ingredients of dry formula: maize gluten meal, maize, animal fat, dried whole egg, flax seed, L-lysine, digest, minerals, fish oil, dl-methionine, L-carnitine, rice, taurine, vitamins, trace elements

Table 2 Questionnaire details

Scored by owner (O) or veterinarian (V)

Scored in week 0, 4 or 8

Scale Scale interpretation

Vomiting O 0, 4, 8 0–5 0 = not present, 5 = severePolyuria O 0, 4, 8 0–5 0 = not present, 5 = severePolydipsia O 0, 4, 8 0–5 0 = not present, 5 = severeHyperactivity O 0, 4, 8 0–5 0 = not present, 5 = severePolyphagia O 0, 4, 8 0–5 0 = not present, 5 = severePoor hair coat V 0, 4, 8 0–5 0 = not present, 5 = severeWeight loss V 0, 4, 8 0–5 0 = not present, 5 = severeQuality of life V 0, 4, 8 1–5 1 = very poor, 5 = excellentPalatability O 4, 8 1–5 1 = very poor, 5 = excellentCompliance V 4, 8 1–4 1 = poor compliance, 4 = full compliance

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The within-group differences in outcome between the three time points (weeks 0, 4 and 8) were tested by the Friedman test for repeated measurements. If significant, a post hoc analysis using the Wilcoxon signed-rank test was conducted with Bonferroni correction. Difference in TT4 ratio for the different lifestyle groups was tested with the two-tailed Mann–Whitney test.

Because of multiple testing, P !0.001 was considered significant. All data are presented as mean and SD except for the laboratory results and age, which are represented as median and range.

The difference between the number of males and females was tested by the Wilcoxon signed-rank test. Differences in palatability and owner compliance between cats with TT4 ratio <1 and cats with a TT4 ratio >1 at weeks 4 and 8 were evaluated by the Pearson 2test. P !0.05 was considered significant. Poor owner compli-ance was defined as a score of 1 or 2 out of 4, and poor palatability was defined as a score of 1 or 2 out of 5.

All statistical analyses were performed by the statisti-cal software package SPSS 20.0.

ResultsTwo hundred and twenty-five hyperthyroid cats were enrolled in the study, of which 113 were previously diag-nosed and had been treated with anti-thyroid drugs (group 1), and 112 were newly diagnosed (group 2). In 216 cats, circulating TT4 concentration was above the upper limit of the reference interval at the time of enrolment. Five previ-ously diagnosed cats had a circulating TT4 concentration within the reference interval, and the circulating TT4 con-centration of four previously diagnosed cats was unknown on the day of enrolment. The circulating TT4 concentration of these nine cats was above the reference interval at the time of diagnosis, and the cats exhibited clinical signs com-patible with hyperthyroidism; therefore, they met the inclusion criteria and were included in the study.

The median age, gender, neuter status and lifestyle of group 1, group 2 and the total group are presented in Table 3. Females (136/225 cats) were significantly (P <0.001) over-represented. The parameters did not dif-fer significantly between group 1 and group 2.

Many of the data were incomplete. In Tables 4 and 5 the number of cats that completed each parameter is shown. Thirty-nine veterinarians entered reasons for incomplete data at week 4. The most common reasons were poor acceptance of the food and/or poor owner compliance (n = 28). Other reasons included death of unrelated cause (n = 7), weight loss (n = 2), red gums (n = 1) and loss of contact with the owner (n = 1). In the free comment section of the questionnaire at week 8, poor palatability and/or poor owner compliance was reported in 24 cases.

None of the measured parameters (physical examina-tion findings, biochemical parameters or questionnaire results) differed significantly between groups 1 and 2, neither at day 0 nor at week 4 or week 8.

The results of the repeated measurements of the phys-ical examination parameters (BCS, heart rate), biochemi-cal parameters (TT4 ratio, urea ratio, creatinine ratio) and parameters of the questionnaires are presented in Tables 4 and 5. The results of TT4 ratios are also visual-ised in a box-and-whisker plot (Figure 1). The Friedman test revealed a significant decrease in median TT4 ratio (P <0.0001) and a significant improvement of all clinical parameters of the questionnaire between weeks 0, 4 and 8 (P <0.0001). Post hoc analysis using the Wilcoxon signed-rank test with Bonferroni correction showed a significant difference for all parameters and TT4 ratio between weeks 0 and 4 (P <0.0001) and between weeks 0 and 8 (P <0.0001). There were no significant differences for any of these parameters between week 4 and week 8. All significant differences were found for the total group, as well as for group 1 and group 2 separately.

Table 3 Gender, neuter status, lifestyle and median age of the total group, group 1 (previously diagnosed cats that had been treated with anti-thyroid medication) and group 2 (newly diagnosed cats)

Totaln

% Group 1n

% Group 2n

%

n 225 50.2 113 50.2 112 49.8Gender Male 89 39.6 46 40.1 43 38.4 Female 136 60.4 67 59.3 69 61.6Neuter status Intact 5 2.2 2 1.8 3 2.7 Neutered 219 97.3 111 98.2 108 94.4 Unknown 1 0.4 0 0 1 0.9Lifestyle Indoor 137 60.9 69 61.1 68 60.7 Outdoor 69 30.7 37 32.7 32 28.6 Unknown 19 8.4 7 6.19 12 10.7Median age, years (range)

15 (4–21) 15 (4–21) 16 (6–21)

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Circulating TT4 concentration was measured in 88 cats at week 4 (Table 5). Of these 88 cats, 56 had a normal-ised circulating TT4 concentration and 32 cats continued to have a circulating TT4 concentration above the refer-ence interval. In 11 of these 32 cats, a poor palatability and/or poor owner compliance was reported, whereas this was reported in only nine of the 56 cats with a normal circulating TT4 concentration (P = 0.049). Circulating TT4 concentration was measured in 68 cats at week 8 (Table 5). Of these 68 cats, 60 had also been sampled at week 4. The remaining eight cats were sampled at weeks 0 and 8, but not at week 4. Of the 68 cats, 51 had a normalised circulating TT4 concentration and 17 cats continued to

have a circulating TT4 concentration above the reference interval. In nine of these 17 cats, a poor palatability and/or poor owner compliance was reported, whereas this was reported in only nine of the 51 cats with normal cir-culating TT4 concentration (P = 0.004). In one previously diagnosed cat the circulating TT4 concentration decreased below the reference interval at week 8, but the cat did not have signs of hypothyroidism.

No difference was found between lifestyle and effect on circulating TT4 concentration at week 4 (P = 0.93) or week 8 (P = 0.92).

Both circulating creatinine and urea concentrations remained within reference interval during the study

Table 4 Mean and SD of different clinical parameters at weeks 0, 4 and 8

Parameter Scored by owner (O) or veterinarian (V)

Week 0 Week 4 Week 8

Mean SD n Mean SD n Mean SD n

Vomiting* O 2.09a 1.67 140 1.24b 1.36 80 1.12b 1.45 52Polydipsia* O 2.37a 1.75 139 1.31b 1.43 80 1.13b 1.40 52Polyuria* O 2.17a 1.68 138 1.01b 1.40 80 0.92b 1.37 52Hyperactivity* O 1.91a 1.75 139 0.75b 1.01 80 0.67b 1.08 52Polyphagia* O 2.70a 1.80 139 1.45b 1.55 80 1.17b 1.42 52Weight loss† V 2.78a 1.64 220 0.97b 1.54 90 0.72b 1.33 72Poor coat† V 1.82a 1.50 216 1.13b 1.44 91 0.80b 1.15 70Quality of life‡ V 3.26a 0.81 223 3.70b 0.75 92 3.82b 0.79 73BCS (1–5) V 2.19a 0.85 225 2.32a 0.74 92 2.44a 0.65 73Heart rate (bpm)

V 182a 39 167 172a 33 62 173a 32 51

Palatability‡ O ND ND ND 3.71 1.36 78 3.79 1.27 52Compliance§ V ND ND ND 2.75 0.55 91 2.58 0.76 72

BCS = body condition score; bpm = beats per minute; ND = not determinedDifferent letters within a row indicate significant difference (P <0.001)*Score 0–5 (not present–severe)†Score 0–5 (not present–severe)‡Score 1–5 (very poor–excellent)§Score 1–4 (poor–full)

Table 5 Median and range of total thyroxine (TT4) ratio, creatinine ratio and urea ratio at weeks 0, 4 and 8

Week 0 Week 4 Week 8

Median(range)

n Median(range)

n Median(range)

n

TT4 ratio 1.67a

(0.19–8.56)221 0.91b

(0.09–5.23)88 0.69b

(0.11–9.43)68

Creatinine ratio 0.63a

(0.04–1.58)201 0.56b

(0.13–2.06)74 0.55a,b

(0.10–2.21)59

Urea ratio 0.84a

(0.07–3.64)193 0.76a

(0.19–2.60)61 0.81a

(0.14–2.26)50

Ratio = ratio between the actual value and the upper limit of the reference intervalDifferent letters within a row indicate significant difference (P <0.001)

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period. A significant decrease in creatinine ratio was found between weeks 0 and 4 (P = 0.001), but not between weeks 0 and 8 (P = 0.009) and weeks 4 and 8 (P = 0.66). No significant differences were found between the three time points regarding physical examination parameters and urea ratio (P = 0.64).

DiscussionResults of the present study show that in a large group of client-owned hyperthyroid cats fed exclusively an iodine-restricted food (Hill’s Prescription Diet y/d Feline), a significant reduction in circulating TT4 concen-tration and improvement of most clinical signs occured within 4 weeks, in both newly diagnosed cats and in cats that had already been treated with anti-thyroid drugs. Despite the significant decrease in TT4, circulating TT4 concentration was still elevated in 25% of the cats at week 8.

No significant differences in laboratory results and clinical were found between the newly diagnosed group and the previously diagnosed group, indicating that pre-vious treatment with anti-thyroid drugs did not influ-ence the response to the food. As mainly cats with an increased circulating TT4 concentration at week 0 were included, it is most likely that the cats that did not respond appropriately to anti-thyroid drugs were selected in the previously diagnosed group.

After the significant reduction in circulating TT4 concen-tration and improvement in clinical signs within the first 4 weeks, no further significant changes occurred between weeks 4 and 8. Poor owner compliance and/or poor palat-ability of the food was reported in most of the 17 cats in which circulating TT4 concentration was above the refer-ence interval in week 8, and these factors may well have been responsible for the less than desired result in these cats.

No clinical development of hypothyroidism occurred in this study. In only one case did the circulating TT4 concentration decrease below the reference interval at week 8, but this cat clinically improved and did not show any clinical signs of hypothyroidism. Based on this observation, as well as anecdotal information about development of mild hypothyroidism in cats receiving the food concurrently with anti-thyroid medication, the current advice is not to combine these two management options. In our study, it is possible that some cats devel-oped temporary subclinical hypothyroidism. However, circulating TT4 concentrations were not measured in the transition period and no clinical signs of hypothyroid-ism were reported.

An improvement of clinical signs indicated by the owner and veterinarian could, perhaps, partially be caused by a placebo effect. Because the study was designed as an open-label study, the subjective assess-ments could be open to bias in positive direction. However, in our study it was thought that most of the improvement could be attributed to normalisation of cir-culating TT4 concentration, as circulating TT4 concentra-tion and clinical signs improved concurrently. A double-blinded, placebo-controlled study to test for pla-cebo effects was considered unethical; hence, the study was designed as an open-label one.

The BCS remained stable during the study period. However, in the veterinarians’ questionnaire the param-eter ‘weight loss’ significantly improved. An unchanged BCS could indicate that hyperthyroidism in some cats was not well controlled by the iodine-restricted food as weight gain is suspected when circulating TT4 concen-tration normalises. Also, both BCS and the parameter ‘weight loss’ could be biased in a positive way in weeks 4 and 8, as these are subjective parameters. However, it might also be possible that the duration of the study was too short to see improvement in BCS. Furthermore, the BCS is a subjective method to assess body fat stores and, to a smaller extent, to evaluate muscle mass. Despite defined descriptors for BCS assessment, disagreement among scorers about the exact criteria is possible.11,12 The large number of independent scorers in our multicentre study could also have contributed to the increased vari-ability in assigned BCS. Unfortunately, the actual body weight of the cats was not available and further long-term studies are needed to quantify the effect of the iodine-restricted food on body weight.

Figure 1 Box plots of total thyroxine (TT4) ratio at weeks 0 (221 cats), 4 (88 cats) and 8 (68 cats). The box represents the interquartile range from the 25th to 75th percentile. The horizontal bar through the box indicates the median, and the whiskers represent the main body of data. = outliers defined as cases with values between 1.5 and three box lengths from the upper or lower edge of the box; * = extremes defined as cases with values more than three box lengths from the upper or lower edge of the box. The horizontal dotted line shows the upper limit of the reference interval (TT4 ratio of 1)

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Although the mean heart rate at week 8 was lower when compared with day 0, the decrease was not sig-nificant. It was expected that the heart rate would decrease as thyroid hormones have a direct positive chronotropic effect on heart rate.13 In addition, thyroid hormones cause an up-regulation of cardiac beta recep-tors and enhance the response to catecholamines. Thyroid hormones also have an indirect effect on heart rate by increasing the metabolic activity of almost all tissues, which increases the demand for blood flow. Thyroid hormones have a relaxant effect on the vascu-lar smooth muscles and dilate the resistant arterioles of the peripheral circulation causing a reduction in sys-temic vascular resistance.13–17 The food-induced reduc-tion in circulating TT4 concentration may have caused an increase in peripheral vascular resistance and, sub-sequently, partly reversed the decrease in heart rate due to the direct cardiac effect of the lower circulating TT4 concentration. Another explanation for the lack of a significant reduction in heart rate is that heart rate is a varying parameter that was not assessed in a stand-ardised protocol in our study. This could have resulted in fluctuations partially caused by the ‘white coat effect’.14 Furthermore, it may be that the iodine-restricted food did not restore complete euthyroidism in all cats.

Remarkably, the circulating creatinine concentration decreased significantly between weeks 0 and 4, whereas the circulating urea concentration remained stable dur-ing the trial, with median values within normal refer-ence intervals. It was expected that both creatinine and urea concentrations would rise with normalisation of the circulating TT4 concentration, as a reduction in thyroid hormone concentration may cause a decrease in glomer-ular filtration rate.13 A possible explanation for the decrease in circulating creatinine concentration is that the iodine-restricted food has a lower heat-processed meat content than regular cat food. That dietary protein intake significantly affects the circulating creatinine con-centration has been shown in humans.18 Furthermore, because the iodine-restricted food did not result in euthyroidism in all cats, a further decrease in muscle mass of these cats may have resulted in a lower circulat-ing creatinine concentration.

No difference was found between indoor vs outdoor cats. It was expected that the iodine-restricted food would be less effective in outdoor cats, as these cats might have access to other iodine-containing food sources outside or catch prey. The results of our study suggest that the potential ingestion of food or prey in outdoor cats was not sufficient to have a negative influ-ence on the effectiveness of the iodine-restricted food.

An advantage of the iodine-restricted food over anti-thyroid drugs is that the potential stress associ-ated with medical therapy is prevented. In addition,

side effects, frequently associated with anti-thyroid drugs, were not observed in cats fed the iodine-restricted food. In contrast to treatment with radioac-tive iodine, iodine-restricted food is widely available. Other advantages include the lack of anaesthetic risk and hospitalisation. Furthermore, as the iodine-restricted food is a reversible management option, the possibility to change to a different management method remains.

A few limitations of this study have to be mentioned. A major limitation of the present study is that the sam-ples were measured at different laboratories. Therefore, the laboratory values were expressed as the ratio between the actual value and the upper reference limit for each laboratory. However, it is unknown how the reference interval of each laboratory was established and if this was achieved correctly. Despite these limita-tions, it is important to note that the samples for each cat at weeks 0, 4 and 8 were measured by the same method. Consequently, changes in circulating concen-trations are very informative and more reliable than comparisons between cats. A second limitation is that both veterinarians and owners contributed on a volun-tary basis, resulting in many incomplete data. Because of data protection laws, it was not possible to contact the veterinarians and owners to retrieve missing data. The important reasons for incomplete data were poor palatability and owner compliance. As poor palatabil-ity often results in poor owner compliance, these two reasons were taken together. In addition, the canned and dry food did not contain exactly the same iodine concentration. It was not consistently documented if canned or dry food or both were used for individual cats. However, it was thought that this would not influ-ence the results of this study, but further studies are warranted to evaluate if there is a difference in effect between dry or canned iodine-restricted food. Another limitation is that the 2 month duration of the study was relatively short, and possible long-term side effects may have been missed. Further studies are needed to assess the long-term effect of iodine-restricted food in cats, although no side effects have been reported by Wedekind et al19 who fed six cats a diet with 0.15 ppm dry matter iodine and six cats a diet with 0.24 ppm dry matter iodine for a 1 year period.

ConclusionsIn client-owned hyperthyroid cats an iodine-restricted food (Hill’s Prescription Diet y/d Feline) can be a valu-able management option to normalise circulating TT4 concentration and improve clinical signs within 4 weeks, provided that the cat exclusively eats the iodine-restricted food and the owner is compliant. No short-term impairment of renal function or other side effects were detected.

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498 Journal of Feline Medicine and Surgery 16(6)

Acknowledgements We would like to thank all veterinar-ians and owners who participated in this study.

Funding This study was funded by Hill’s Pet Nutrition.

Con!ict of interest M van der Kooij received a study grant from Hill’s Pet Nutrition Europe to complete this study. No fur-ther conflicts of interest are reported.

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