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Abstract

Practical relevance:

Since first being reported in the late 1970s, there has been a dramatic increase in the prevalence of hyperthyroidism in cats. It is now recognized worldwide as the most common feline endocrine disorder.

Patient group:

Hyperthyroidism is an important cause of morbidity in cats older than 10 years of age. It is estimated that over 10% of all senior cats will develop the disorder.

Clinical challenges:

Despite its frequency, the underlying cause(s) of this common disease is/are not known, and no one has suggested a means to prevent the disorder. Because of the multiple risk factors that have been described for feline hyperthyroidism, it is likely that more than one factor is involved in its pathogenesis. Continuous, lifelong exposure to environmental thyroid disruptor chemicals or goitrogens in food or water, acting together in an additive or synergistic manner, may first lead to euthyroid goiter and then to autonomous adenomatous hyperplasia, thyroid adenoma and hyperthyroidism.

Evidence base:

This review draws on published research studies to summarize the available evidence about the risk factors for feline hyperthyroidism. Based on the known goitrogens that may be present in the cat’s food, drinking water or environment, it proposes measures that cat owners can implement that might prevent, or reduce the prevalence of, thyroid tumors and hyperthyroidism in their cats.

Feline hyperthyroidism – a relative newcomer

Hyperthyroidism is a multisystemic disorder resulting from excessive circulating concentrations of thyroxine (T₄) and triiodothyronine (T₃).^1–5 It develops in middle- to old-aged cats (Figure 1), with no obvious breed or sex predilection found in most epidemiologic studies.

Figure 1

Over the past 30 years, the hyperthyroid cat has become a familiar sight in veterinary clinics around the world

Feline hyperthyroidism appears to be a relatively ‘new’ disorder, first being described in 1979.⁶ Before that time, enlargement of the thyroid gland had been found at necropsy in a few cats and nodules were observed histopathologically, but these abnormalities were relatively rare and were not associated with clinical signs relating to hyperthyroidism.^7,8

Since first being described in 1979, the prevalence of hyperthyroidism has steadily, but dramatically, increased.

Over the past 33 years, the prevalence of thyroidal pathologic abnormalities has steadily, but dramatically, increased. The associated state of hyperthyroidism is now accepted as being the most common feline endocrine disorder and an important cause of morbidity in middle-aged cats in the United States, Canada, United Kingdom, Continental Europe, Australia, New Zealand and Japan.^4,5 Despite its frequency, the underlying cause(s) of this disorder is/are not known, so it is not clear how to prevent it.

Epidemiology of this common worldwide disorder

There is little detailed epidemiologic data concerning the true prevalence of hyperthyroidism in cats. Different studies have used different measures of disease rates, but it does appear that the prevalence shows some geographical variation.

In one 2005 study, an annualized incidence rate of 11.92% was recognized in cats older than 9 years of age at a UK primary accession practice, compared with 1.53% in Spanish practices.⁹ The hospital prevalence among cats over 8 years of age in an urban population in Germany was noted as 11.4% in 2006.¹⁰ In Japan, in 2002, a prevalence of 8.9% was reported in cats older than 9 years¹¹ and, in Hong Kong, in 2009, a prevalence of 3.93% was recorded in cats over 10 years of age.¹²

Despite these high disease rates, hyperthyroidism was first described as recently as 1979 in New York and 1980 in Boston.^6,13 Since these initial descriptions, several studies have documented marked increases in prevalence in the cat population across the world with time; for example, from 0.3% in 1979 to 4.5% in 1985 in North America;¹⁴ from 0.1% in 1978–1982 to 2% in 1993–1997, also in North America;¹⁵ and from 0.2% in 1987–1994 to 2.6% in 1998 in Germany.¹⁶

Thyroid pathologic changes

Until the late 1970s, few references pertaining to pathologic abnormalities of the feline thyroid gland existed.^7,8 In my own review of approximately 7000 cats that had necropsies performed at The Animal Medical Center during the 14-year period from 1970 to 1984,¹⁷ an average of only 1.9 cats per year were found to have gross evidence of thyroid enlargement (caused by adenomatous hyperplasia, adenoma or carcinoma) in the period before 1977, when we diagnosed the first cat with hyperthyroidism.⁶ Based on these pathologic studies, it does seem that feline hyperthyroidism, if it did exist at all in cats before 1970, was extremely rare.

Despite the fact that the underlying cause(s) of feline hyperthyroidism have not been clearly elucidated, the thyroid pathologic findings associated with hyperthyroidism have been well characterized. Functional thyroid adenomatous hyperplasia (or adenoma) involving one or both thyroid lobes (Figure 2) is the most common pathologic abnormality associated with hyperthyroidism in cats.^7–9 Over 95% of cats have benign, adenomatous changes of the thyroid gland at the time of diagnosis. In approximately 70% of hyperthyroid cats, both thyroid lobes are enlarged, with the remaining cats having involvement of only one lobe.^1,3–5 On histologic examination, these enlarged thyroid lobes contain one or more well-discernible foci of hyperplastic tissue, sometimes forming nodules ranging in diameter from <1 mm to 3 cm.^2,18,19

Figure 2

Palpation of the thryoid to reveal a thyroid nodule in a cat with suspected hyperthyroidism

Thyroid carcinoma is a less common cause of hyperthyroidism in cats, with a prevalence of less than 5%.^20–23 Recently, investigators have reported that some hyperthyroid cats may have areas of adenoma adjacent to areas of carcinoma within the same thyroid lobe on biopsy.²¹ In addition, my own studies have shown that the prevalence of thyroid carcinoma in hyperthyroid cats receiving long-term methimazole treatment increases considerably over time,²² rising to approximately 20% in cats treated for over 4 years.^23,24 This suggests that, at least in some cats with long-standing hyperthyroidism, there may be transformation of thyroid adenomatous hyperplasia/adenoma to thyroid carcinoma.²¹ If that is the case, the pathogenesis of thyroid adenoma and thyroid carcinoma may be identical in nature, rather than these representing two separate tumor processes.

The feline thyroid gland normally contains a subpopulation of follicular cells that have a high growth potential.^18,19,25 In the thyroid gland eventually destined to develop adenomatous changes, this subpopulation of thyrocytes starts to replicate in an autonomous fashion. Once these rapidly dividing cells are present in sufficient numbers, they continue to grow in the absence of extrathyroidal stimulation (eg, from thyroid-stimulating hormone, TSH). Therefore, these thyroid adenomatous/hyperplastic cells show autonomy of thyroid growth as well as the ability to function and secrete thyroid hormone autonomously.^18,19,25

Once overt hyperthyroidism develops, the adenomatous hyperplastic thyroid tissue or nodules found in these cats function and secrete thyroid hormone in an autonomous fashion. In other words, these are true thyroid neoplasms, which exhibit growth and function similar to other hyperfunctional endocrine tumors.^3,8,19,25

Why do feline thyroid tumors develop in the first place?

Several epidemiologic studies have attempted to identify potential risk factors for feline hyperthyroidism, but a single dominant factor has not yet been isolated. The most likely candidate risk factors fall into two broad categories:

Nutritional deficiencies or excesses in cat food, leading to metabolic thyroid dysfunction;

Thyroid-disrupting compounds present in the environment, drinking water or diet that interfere with thyroid hormone control pathways and lead to thyroid gland pathology and dysfunction.

Nutritional deficiencies or excesses

The feeding of commercially prepared cat foods is one leading candidate as a major risk factor for development of thyroid pathology and hyperthyroidism in cats.

In support of this statement, all epidemiologic studies reported to date have identified that feeding an increased proportion of canned cat food in the diet is a risk factor for developing hyperthyroidism.^{14,15,26–31} One of these studies suggested that particular flavors of canned food (fish, liver and giblets) may be involved,²⁷ and another incriminated cans with plastic linings in easy-open (pop-top) lids,¹⁵ which may contain the thyroid disruptor chemical bisphenol A (BPA, see later). Soy isoflavones, well-known goitrogens, are also present in most dry cat foods.^32,33 Finally, iodine excess or deficiency certainly may play a role in the increased risk associated with eating more commercially prepared cat food.^3,28,34

Soy isoflavones

Polyphenolic soy isoflavones, namely genistein and daidzein, are commonly used as dietary supplements and as a low-cost source of protein, despite the negative effects of soy isoflavones on the pituitary–thyroid axis having been well described in both human subjects and experimental animals. Studies in rats revealed a clear cause–effect relationship between soy consumption and goitrogenesis.^35,36 Hypothyroidism and goiter have also been well characterized in infants fed non-iodized soy-based formula.^37–39

Experimental evidence for goiter formation in cats fed high amounts of soy isoflavones has not been reported. However, soy isoflavones, in particular genistein and daidzein, were identified in 60–75% of the cat foods tested in two studies.^32,33 Virtually all dry and semi-moist foods containing soy protein have high isoflavone content, adequate to interfere with thyroid function and decrease the synthesis of thyroid hormones. Although a higher percentage of dry diets contain measurable isoflavones, these compounds are also found in about 60% of moist cat diets.³³

There are at least two different levels at which soy isoflavones can interact with the thyroid hormone system to lead to goiter and hypothyroidism.^39–41 Firstly, soy isoflavones inhibit the activity of thyroid peroxidase,^40–42 a key enzyme in the synthesis of thyroid hormones, which liberates iodine for addition onto thyroglobulin for production of T₄ and T₃ (Figure 3 and Table 1). They also inhibit 5’-deiodinase activity, the enzyme that converts total T₄ into the biologically active T₃.⁴² By blocking the production of thyroid hormones, pituitary TSH secretion would be increased, leading to thyroid hyperplasia and possibly goiter (Figure 4). With increased numbers of hyperplastic cells, serum T₄ and T₃ concentrations may normalize.

Figure 3:

Thyroid hormone regulation, action and metabolism

Table 1

Effects and mechanism of action of iodine deficiency and thyroid hormone disruptors

	Mechanism	Effects	Site(s) of action
Iodine deficiency	Iodine needed as substrate for thyroid hormone synthesis	Decreased synthesis of T₄ and T₃, high TSH	Thyroid gland
Soy isoflavones Herbicides Methimazole	Inhibition of thyroid peroxidase in thyroid follicles	Decreased synthesis of T₄ and T₃, high TSH	Thyroid gland
PCBs Flame retardants Phthalates	Competitive binding to thyroid hormone binding protein	Decreased thyroid hormone delivery to brain	Bloodstream
PBDEs	Altered transport across cell membrane	Increased biliary elimination of thyroid hormones	Liver
FD&C red dye #3 PCBs Selenium deficiency	Inhibition of deiodinase activity	Decreased peripheral T₃ synthesis	Peripheral tissues (kidney and liver)
BPA PBDEs PCBs	Thyroid receptor antagonist	Altered binding of T₃ to thyroid hormone receptor, with altered activation of thyroid hormone-dependent gene transcription	Brain, pituitary gland, peripheral tissues
Pesticides PCBs	Inhibition of TSH receptor	Decreased production of T₄ and T₃	Pituitary gland

PCBs = polychorinated biphenyls, PBDEs = polybrominated diphenyl ethers, BPA = bisphenol A, TSH = thyroid-stimulating hormone

Figure 4:

Target sites for iodine deficiency and thyroid chemical disruption

Only a single short-term feeding study has evaluated the effects of dietary soy intake on thyroid function in the cat.⁴³ In that study, young, clinically normal cats were randomly assigned to receive either a soy or soy-free diet for 3 months each in a crossover design. Compared with the cats eating the soy-free diet, cats fed the soy diet had slightly (but significantly) higher serum T₄ and free T₄ concentrations. Serum T₃ values were unchanged, but the T₃/free T₄ ratio was significantly lower in cats that received the soy diet. These results indicate that short-term feeding of soy to normal cats has a measurable, although modest, effect on thyroid hormone homeostasis in cats. An increase in T₄ concentration relative to T₃ concentration may result from inhibition of 5’-deiodinase, as described above. Despite maintaining these normal thyroid hormone values, detectable urinary concentrations of the isoflavone, genistein, were found in 10/18 cats in the study, suggesting that cats may have clinically significant body burdens of this goitrogen.⁴³

So do cats handle soy isoflavones differently than humans or rats? Obviously, further long-term feeding studies with soy need to be undertaken, especially in older cats prone to developing hyperthyroidism. Of interest are studies in rats that demonstrate that feeding large amounts of soy isoflavones has little demonstrable effect on thyroid function, despite significant inactivation of the thyroid peroxidase enzyme. However, in the presence of iodine deficiency, feeding soy will readily inhibit thyroid hormone secretion and induce goiter and even thyroid carcinomatous changes.^35,36,41,44 In other words, iodine deficiency greatly increases soy’s antithyroid effects, whereas iodine supplementation is protective. Stated another way, soy can cause goiter, but only in animals or humans consuming diets that are only relatively deficient in iodine, or in those who are otherwise predisposed to developing goiter because of exposure to other goitrogenic agents.

This suggests that cats, like man and rats, certainly might develop goiter and hypothyroidism on high amounts of soy when concurrently being fed a low iodine diet or being exposed to other goitrogens through their food, water or environment. Given the trend to lower iodine levels in cat food over the past two decades (see later),³⁴ could marginal iodine deficiency combined with the feeding of soy isoflavones be contributing to the rising trend in hyperthyroid cases that we have been seeing?

Dietary iodine

Iodine is a trace element that is naturally present in some foods, added to others, and available as a dietary supplement.⁴⁵ Iodine is an essential component of the thyroid hormones; T₄ contains four iodine atoms per molecule, whereas T₃ contains three. Iodine may perform other physiologic functions in the body as well. For example, iodine has antioxidant and anti-inflammatory properties and can enhance immune function (ie, shows antibacterial, antiviral and antifungal effects) in humans.^45,46 Iodine may also help prevent some cancers (especially breast, gastric and thyroid cancer) and supplementation might have a beneficial effect in human patients suffering from mammary dysplasia and fibrocystic breast disease.^45,47

Because of the clear association between diet and hyperthyroidism, several studies have attempted to implicate iodine in the cause or progression of feline hyperthyroidism. The iodine content of cat food is extremely variable, both among cat food manufacturers as well as among cat foods produced by the same manufacturer. However, a tendency towards lower amounts of added iodine has occurred over the past 30 years, as the recommended dietary iodine requirements in cats have changed (see box).³⁴

Could iodine deficiency be contributing?

Iodine deficiency is a known cause of thyroid hyperplasia and goiter in man and animals, including cats.^{46,47,55–58} Iodine is a key element in the synthesis of thyroid hormones.^46,57 As a consequence, inadequate iodine intake leads to low circulating thyroid hormone concentrations, which spurs the pituitary gland to increase its secretion of TSH (Figure 3). Persistently high circulating TSH concentrations will lead to thyroid hyperplasia and possibly goiter (Figure 4).^55,56 It is possible that, with enough time and continued stimulation, the hyperplastic thyrocytes become autonomous, leading to adenomatous hyperplasia and then to thyroid adenoma. As these tumors continue to grow and function independently of TSH control, hyperthyroidism would ensue, leading to suppression of pituitary TSH secretion (Figure 4). In some cats, transformation of adenomatous hyperplasia/adenoma to thyroid carcinoma may occur.^21,24

So, based on the trend towards lower iodine levels in cat food over the past two decades, could iodine deficiency be contributing to the surge in hyperthyroid cases that we are seeing? In support of that reasoning, a recent case control study reported that cats consuming commercial foods which were relatively deficient in iodine were more than four times as likely to develop hyperthyroidism compared with cats that ate iodine-supplemented foods.²⁸

In another study supporting the possible role of iodine deficiency in the pathogenesis of this disease, hyperthyroid cats showed a subnormal urinary iodine excretion. Following successful treatment for hyperthyroidism, urinary iodine excretion in these cats increased into the normal range.⁵⁹ If the low urinary iodine concentrations in these hyperthyroid cats reflected low iodine intake while the disease was developing, inadequate iodine intake may be a risk factor for hyperthyroidism.

What about potential combined effects?

It is difficult to envisage how deficiency, excess or wide fluctuations in iodine intake would be solely responsible for the thyroid adenomatous changes and the development of hyperthyroidism in cats. However, most, if not all, hyperthyroid cats are also exposed to other goitrogens (eg, soy isoflavones) or thyroid disruptors in the water, diet or environment (eg, BPA) throughout their lifetime. In addition, concurrent deficiencies of other micronutrients such as iron, selenium, vitamin A and zinc can exacerbate the goitrogenic effects of mild iodine deficiency.^60,61

Thus, iodine deficiency may act together with these other nutrient deficiencies or goitrogens (or both) in a synergistic or cooperative manner to affect multiple sites of thyroid hormone metabolism or action (Figures 3 and 4). Over many months to years, this could lead to the adenomatous thyroid changes characteristic of hyperthyroidism.

Dietary selenium

Selenium is an essential trace mineral that is incorporated into proteins to make selenoproteins, which are important antioxidant enzymes and play a role in immune and thyroid function.⁶² Like iodine, the content of selenium in foods depends on the mineral content of the soil where plants are grown or animals are raised. Animals that eat grains or plants that were grown in selenium-rich soil have higher levels of selenium in their muscle.

Like iodine, selenium plays an important role in the regulation of thyroid metabolism in many species, including the cat. Selenium is incorporated as selenocysteine in thyroid deiodinase, the enzyme that converts T₄ to T₃ peripherally.^62,63 Hence, a deficiency of selenium may impair thyroid function and promote hypothyroidism. In accord with that, humans living in countries where the soil is poor in selenium show an increased prevalence of both hypothyroidism and thyroid nodule formation.⁶⁴

In cats fed a low selenium diet, plasma total T₄ concentrations increased significantly, whereas total T₃ decreased.⁶⁵ These results suggest that the type I deiodinase enzyme in cats is a selenoprotein, similar to the situation in humans.⁶⁵

In another study,⁶⁶ whole blood and plasma selenium concentrations in cats living in regions with a high incidence of hyperthyroidism as well as regions in which the disease is less commonly reported were analyzed. The investigators found no difference in selenium concentrations among the cats in the differing regions. However, all cats had plasma concentrations of selenium that were approximately five times higher than values reported in either rats or humans.⁶⁶ The reason for the high levels of selenium in these cats is unclear, but it is known that most cat foods contain relatively high amounts of selenium, which may contribute to the high circulating levels in this species.^48,67

Like iodine, however, selenium status alone does not correlate with the development of hyperthyroidism in cats, but it may again play an additive and/or synergistic role in the development of this disease, especially in cats that are deficient in this trace mineral. Additional studies need to be undertaken to better define the role of selenium in the development of hyperthyroidism in cats.

Thyroid-disrupting compounds in the environment, drinking water or diet

Thyroid disruptors can target many of the sites of thyroid hormone regulation or metabolism (Figures 3 and 4).^68–70 The complex system of iodine uptake and thyroid hormone production, as well as plasma thyroid hormone transport, T₄ to T₃ conversion, cellular thyroid hormone uptake, cell receptor activation or hormone degradation can all be affected by thyroid disruptors (Table 1).

Bisphenol A

BPA is a key building block of the epoxy resins commonly used for lining the interior of metal cans.^71–73 This thin epoxy coating helps prevent corrosion of the can and makes it possible for food products to maintain their quality and taste, while extending shelf life. BPA is also commonly added to hard polycarbonate plastics (eg, baby bottles, water bottles and food storage containers) in order to give shape and durability (impact resistance). Annually, billions of pounds of BPA are produced and over 100 tons are released into the atmosphere worldwide.⁷³ BPA has been found in food, drinks, indoor and outdoor air, floor dust and soil.^71,72

BPA is a chemical of concern because it is an endocrine disruptor and has been associated with various adverse health effects, including thyroid dysfunction.^68–70,74 Some of the toxic effects of BPA on thyroid function may derive from its structural similarity to thyroid hormones (Figure 5).

Figure 5

Chemical structure of bisphenol A (BPA), thyroxine (T₄) and triiodothyronine (T₃)

Exposure to BPA is thought to occur primarily through ingestion.⁷¹ It is well established that residual BPA monomer migrates into can contents during processing and storage,^75,76 and evidence of BPA contamination of canned foods for human use has been widely reported.^72,75–77 Similarly, in two studies evaluating pet foods, most of the dog and cat foods were found to contain measurable levels of BPA;^77,78 in one of the studies, it was confirmed that the BPA in the food had originated from the can coating.⁷⁸

One large study of control and hyperthyroid cats demonstrated an association between hyperthyroidism and cats fed food from ‘pop-top’ cans.²⁹ Results of that study suggested that, overall, consumption of pop-top canned food at various times throughout a cat’s life was associated with greater risk of developing hyperthyroidism. In female cats, increased risk was associated with consumption of food packaged in pop-top cans or in combinations of pop-top and non-pop-top cans. In male cats, increased risk was associated with consumption of food packaged in pop-top cans alone. Although these investigators suggested that the lids of pop-top cans are more likely to be lined with BPA-containing epoxy resins, it appears that most cans (even those requiring a can opener) are coated with BPA.^72,75–78 Taken together, it would seem that feeding canned cat food may pose a greater risk than feeding food from pouches or sachets.

Blood or tissue levels of BPA have not yet been measured in cats, but lifelong, daily exposure to even the relatively low levels of this chemical found in commercial canned cat foods could result in potentially harmful effects.^79,80 There is ample evidence in both experimental animal models and humans that low-dose exposure to BPA has negative health consequences (eg, diabetes mellitus, heart disease, liver toxicity, thyroid dysfunction, infertility and other reproductive problems).^71,81–84

In rats, ingested BPA is eliminated primarily via hepatic glucuronidation,⁸⁵ a process that is known to be greatly reduced in cats as compared with other species.^86,87 The domestic cat is exquisitely sensitive to the adverse effects of many drugs and toxins that require glucuronidation before elimination.^86,87 If ingested BPA is eliminated via glucuronidation, as in other species, the slower clearance rate could lead to higher-than-expected blood and tissue levels of BPA in cats.¹⁵

Chronic exposure to BPA may affect thyroid signaling through a number of potential mechanisms.^73,80,88,89 BPA has been shown to directly bind to the thyroid hormone receptor as well as acting to disrupt thyroid hormone action within cells by competitively displacing T₃ from the receptor, thus suppressing activation of transcription of thyroid hormone-regulated genes. By acting as a thyroid hormone receptor antagonist, BPA might work at the pituitary level to increase circulating TSH concentrations (Figure 3 and Table 1). Again, this could lead to thyroid hyperplasia and goiter formation in susceptible cats (Figure 4). In addition, like other goitrogenic agents, the effects of BPA may be potentiated by the presence of concurrent iodine deficiency.

Polybrominated diphenyl ethers

Polybrominated diphenyl ethers (PBDEs) are synthetic brominated compounds that are used as flame retardants in a variety of consumer products such as electronics, furniture and textiles, as well as construction materials.^{68–70,90,91} The chemical structure and properties of PBDEs are similar to those of polychlorinated biphenyls (PCBs), which were banned in the United States in the late 1970s.^90,91

Like PCBs in the past, PBDEs have become ubiquitous persistent organic pollutants; they bioaccumulate in the environment, biomagnify up the food chain, and have been detected in significant amounts in animals as well as humans.^90–94 Over the past 30 years, PBDEs have become major global contaminants, and have been detected in human adipose tissue, serum and breast milk samples collected in Asia, Europe, North America, Oceania and the Arctic.^90–94 Exposure occurs principally through the diet (PBDEs are present in food, milk and water) and the indoor environment (in particular dust).⁹⁵

Like PCBs, some of the toxic effects of PBDEs may derive from their structural similarity to thyroid hormones (Figure 6).^90,91 In both man and experimental animals, PBDEs clearly disrupt thyroid hormone metabolism. Studies performed in rats and mice report that exposure to PBDEs lowers free and total T₄ concentrations in a dose-dependent manner; PBDE exposure generally did not affect circulating TSH concentrations in these animals.^96–98 In contrast, epidemiologic studies in humans suggest that higher exposure to PBDEs reduces serum TSH values and may increase serum T₄ concentrations.^95,99–101

Figure 6

Chemical structure of PBDEs, PCBs and thyroxine (T₄). The similarity of PBDEs and PCBs to thyroid hormones may underlie the chemicals’ toxicity. All of the compounds consist of two six-carbon rings decorated with halogens. Bromine attaches to the carbon rings of PBDEs, chlorine to those of PCBs, and iodine to those of thyroid hormone. In PBDEs, an atom of oxygen bridges the rings, whereas the rings of PCBs and thyroid hormones are linked by carbon–carbon bonds

Given, therefore, that PBDEs are known thyroid disruptors, these chemicals may play a role in the pathogenesis of thyroid tumors and hyperthyroidism in cats. In support of this hypothesis is the fact that major PBDE production began just before hyperthyroidism was first reported in 1979.^6,90,91 In one US study designed to determine whether body burdens of PBDEs in hyperthyroid cats were greater than those of non-hyperthyroid cats, serum samples were collected from 11 hyperthyroid and 12 euthyroid house cats for PBDE measurement.¹⁰² A spectrum of PBDE congeners was detected in all cats, with overall PBDE levels in cats being 20- to 100-fold greater than median levels in US adults. However, due to high variability within each group, no association was detected between hyperthyroid cats and serum PBDE levels.¹⁰²

In a follow-up study,¹⁰³ investigators measured PBDEs, PCBs and organochlorinated pesticides (OCPs) in serum samples from 26 California household cats (16 hyperthyroid and 10 euthyroid cats). Results indicated that both groups of cats had extremely high serum PBDE levels, with values that were approximately 50 times higher than levels in human residents living in California. PBDE congener patterns in these cats resembled patterns found in house dust, similar to findings in human patients.^95,103 These results suggested that house dust, rather than diet, is the most likely route of exposure to PBDEs in the cats.

In a study of 138 pet cats in Sweden, investigators found that both euthyroid and hyperthyroid cats had high serum PBDEs, at concentrations about 50 times higher than in the general Swedish human population.¹⁰⁴ Like the US cats, no association between PBDE levels and hyperthyroid status of the Swedish cats was found. The overall distribution of PBDEs in cat serum was again similar to the patterns found in dust samples. However, Swedish and American cats did have slightly different PBDE congener patterns, probably due to the fact that some of the frequently identified PBDEs in the US cats had been banned by the EU in 2004.¹⁰⁴

In a second Swedish study of 30 hyperthyroid cats, which was designed to identify the most prominent PBDE metabolites in cat serum, investigators found that cats appear to metabolize PBDEs differently to other species thus far studied.¹⁰⁵ In humans and rats, transformation of PBDEs to hydroxylated metabolites (OH-PBDEs) is a major route of elimination; in contrast, hyperthyroid cats had low serum levels of hydroxylated PBDE metabolites, suggesting that cats metabolize PBDEs much slower and/or differently.

In a very recent study from the University of Illinois, investigators measured serum PBDE in 62 client-owned cats (21 euthyroid and 41 hyperthyroid house cats), as well as 10 feral cats.¹⁰⁶ Although no difference in serum PBDE concentrations was detected between the two groups of house cats, serum PBDE concentrations in the feral cats were significantly lower than in either of the groups of client-owned cats, suggesting that the home environment was the source of their exposure.¹⁰⁶

The same investigators next evaluated dust samples for PBDE and found significantly higher PBDEs in dust from homes of hyperthyroid cats, compared with homes of euthyroid cats. A significant correlation was also found between dust PBDE levels and serum total T₄ concentration in the cats.¹⁰⁶ Estimates of PBDE exposure calculated from canned cat food and dust data strongly suggest that domestic cats are primarily exposed through ingestion of household dust,¹⁰⁰ similar to previous findings.^102,103

Overall, these studies show that cats can be highly exposed to PBDEs, presumably through ingestion of household dust during their normal grooming behavior.^{102–104,106} These findings also provide compelling evidence for the possible role of PBDEs in the development of thyroid tumors and hyperthyroidism in cats.

Additional investigation into the role of PBDEs in the development of hyperthyroidism in cats is certainly warranted. If PBDEs play a role in hyperplasia leading to thyroid autonomy, they apparently do not do so by markedly increasing TSH.¹⁰⁶ However, as PBDEs have been demonstrated to bind to thyroid hormone receptors,^91,107 it is plausible that they may act on the pituitary thyroid nuclear receptors and/or at an earlier, potentially developmental, time point (Figure 3 and Table 1).

Environmental pesticides or herbicides

Exposure to environmental chemicals (eg, pesticides, herbicides) is known to induce thyroid abnormalities in other species (Table 1),^68–70 and chemicals applied directly to a cat (topical flea control products) or to the cat’s environment have been associated with increased risk of developing hyperthyroidism.^3,14,25,26 None of these studies, however, was able to identify a specific flea product or component associated with the risk.

Other goitrogens or thyroid disruptors

In addition to the above, there are many other goitrogenic materials (eg, perchlorates, PCBs, resorcinol, dioxins, fluoride, FD&C red dye #3) that cats may be exposed to through their diet, drinking water or the environment that could contribute to the development of thyroid adenomatous hyperplasia and hyperthyroidism.^{68–70,108,109} In support of this, endocrine disruptors such as heavy metals (eg, mercury) and chlorinated hydrocarbons (eg, polyvinyl chloride, PVC) have been reported as contaminants in commercial canned cat foods.^48,110–112

Such agents generally cause goiter by acting directly on the thyroid gland to reduce thyroid hormone synthesis; the resultant low circulating T₄ concentrations lead to increased pituitary TSH secretion, which, in turn, leads to thyroidal enlargement (Figure 4).^{68–70,108,109} Other goitrogens, however, act indirectly to alter the regulatory mechanisms of the thyroid gland or the peripheral metabolism and excretion of thyroid hormones.

What can be done in terms of prevention?

With the numerous nutritional and environmental factors likely involved in the pathogenesis of hyperthyroidism in cats, is there anything that can be done to help prevent the development of this disease in older cats?

Based on the goitrogens that we know may be present in the cat’s food, drinking water or environment, we can certainly suggest some measures that may minimize the risk; these are summarized in the box on page 813 and discussed below. Even if these measures do not prevent the development of hyperthyroidism, they are unlikely to be detrimental and may even improve the cat’s health.

Diet fed to the cat

Firstly, since all epidemiologic studies reported to date have identified commercial cat foods as a risk factor for feline hyperthyroidism, the diet fed should be evaluated for the presence of goitrogens (Figure 7).^{14,15,25–31} Avoiding cat food products containing soy isoflavones, a well-known goitrogen,^39–42 seems reasonable inasmuch as cats have no requirement for this ingredient and would be highly unlikely ever to ingest soy in the wild.¹¹³ Limiting the amount of fish-flavored foods fed could also be important, as fish can contain high levels of iodine and may be contaminated with PCBs, PBDEs, dioxins and DDT (dichlorodiphenyltrichloroethane), as well as mercury and other heavy metals.^114,115

Figure 7

With regard to the cat’s diet, it is not only the food itself, but also the means of storage and the type of food bowl used that need to be considered

If canned cat food is fed, selecting commercial foods that do not incorporate an epoxy coating containing BPA within the can is ideal, although these are likely to be the exception.^77,78,116 For those pet food companies that do limit their use of BPA, the smaller cans (3 oz; 85 g) appear to be less likely to be lined with BPA than larger cans (5.5 oz; 156 g).¹¹⁶ It also appears that the vast majority, if not all, of the largest cat food cans (13 oz; 369 g) do contain a BPA lining. The reason for the continued need for BPA in larger-sized cans may be related to the fact that smaller cans do not need to be as ‘flexible’ as larger sizes for the pop-top lid to easily open.

Given that the issue of BPA lining of cat food cans may vary from product to product, even within the same pet food company, and is subject to change at any time, the owner or veterinarian will need to contact the individual pet food manufacturer to inquire specifically if their cans (and what size) are BPA-free. Alternatively, wet foods for cats supplied in foil pouch form by some manufacturers may be selected in preference over canned foods lined with BPA.⁷⁷

As iodine excess or deficiency certainly might contribute to an increased risk of hyperthyroidism, diets that contain low or high amounts of iodine should be avoided.^34,54,55 Large fluctuations in the amounts of daily iodine fed to cats are also not recommended, as these could potentially contribute to the development of hyperthyroidism.^52–54 My recommendation is to feed a diet containing between 0.50 and 2.0 ppm I (on a mg/kg of diet dry matter basis), which would provide the average-sized cat (eg, 4.5 kg) with an iodine intake of 25–100 ?g per day. This ensures that the minimum iodine requirement is met, based on the latest recommendations from the Association of American Feed Control Officials (0.35 ppm I),¹¹⁷ as well as recent research on iodine requirements in normal cats (0.46 ppm I).¹¹⁸ The recommendation also ensures that the daily iodine intake remains well below levels suggested to produce toxic or adverse effects in the cat (ie, 5.8–9.2 ppm I).¹¹⁸

Home cooking for the cat is another option which some owners might prefer to ensure consistent and appropriate levels of iodine and other minerals and avoid contamination with industrial chemicals such as BPA and PBDE. If this option is chosen, consultation with a veterinary nutritionist is strongly recommended to avoid nutritional deficiencies or imbalances.^119,120

Irrespective of the diet fed, heating (microwaving) food in plastic containers, or storing fatty foods in plastic containers or plastic wrap, should be avoided. Food should be only reheated in ceramic or glass to reduce exposure to endocrine-disrupting chemicals (eg, BPA) that may leach from plastic containers into food.^71,75

Water safety measures

Source water samples can be analyzed to determine the overall general water quality characteristics and to check for the presence of microbial contaminants, inorganic or organic chemical contaminants (eg, PCBs, dioxins, BPA and other phthalates, isoflavenoids), herbicides and other pesticides (eg, atrazine), and chemical disinfection byproducts (eg, volatile organic compounds, haloacetic acid). Based on the findings of the analysis, water purification can be used to remove undesirable chemicals, biological contaminants and gases from contaminated water.^121,122

Use of a high quality water filter for the home tap or use of well water can decrease exposure to numerous known or suspected carcinogens and endocrine-disrupting chemicals. Unless the home water source is known to be contaminated, it is preferable to use filtered tap water instead of commercially bottled water. Although bottled water is typically from a spring or has gone through reverse osmosis before it is bottled, some brands are simply bottled tap water that may or may not have gone through any additional filtering.

Cat litter

Use of cat litter has been reported as a risk factor for hyperthyroidism,^3,26 but a direct cause–effect relationship has not been established. This epidemiologic finding may simply relate to the fact that cats that use more litter spend much or all of their time indoors, whereas cats that do not use litter are primarily outdoor cats. When cats are left outside unsupervised, their freedom to roam comes at a cost because they have an increased risk of being injured, becoming ill, or even dying.^123–125 Therefore, because indoor cats generally live longer than outdoor cats, they would be more likely to develop hyperthyroidism as they grow older to reach middle- to old age.

There are several different types of cat litter, some of which contain chemicals (eg, deodorizers) that could theoretically increase the risk of developing hyperthyroidism. The most commonly used litters include the clay-based and the silica gel types, although plant-derived biodegradable litters are becoming more popular.¹²⁶

Clay litters are composed of a combination of aluminum silicates and minerals, and these litters are frequently blended with sodium bentonite, a swelling clay which is an extremely effective clumping agent.¹²⁶ A dust-controlling agent is then added to the ground clay to help prevent the silica dust in the litter from becoming airborne. If the clay litter is dusty, the cats and other members of the household may inhale the silica dust, which may result in respiratory problems.^126–128 Cats, additionally, may be further exposed through their fastidious cleaning habits, which would generally remove any traces of litter or dust that may be on their coat.¹²⁹

Silica gel litter, often referred to as crystal litter, is a porous granular form of sodium silicate.^126,128 The silica gel used to make these crystals is chemically similar to that used in desiccants. The crystals themselves are dotted with tiny pores, allowing them to absorb cat urine, then slowly allowing the water to evaporate off. Although this type of litter appears to be relatively safe, ingestion of the silica gel by cats, dogs or infants may be harmful.

Biodegradable plant-derived or organic litters can be made from corn, wheat, wood pulp and recycled newspaper,^126,128 and are less likely to contain chemicals than clay and silica gel litters. Some brands of biodegradable cat litter can be safely flushed down the toilet, unlike normal cat litter.

Even if a change to a biodegradable cat litter does not prevent or delay the onset of hyperthyroidism, use of these more natural litters should be better for the cats and humans in the household (eg, less dust and associated respiratory problems). In addition, natural litters are better for the environment. The components of clay-based litters must be strip-mined, creating a huge environmental impact. Once used, clay litter essentially never biodegrades, so its disposal too has a sizeable environmental impact by contributing to landfill.^126,128

Environmental control

Because PBDEs are in wide use as fire retardants, these toxic chemicals are likely to be present in dozens of products in the homes of most cats. They are most commonly found in polyurethane foam products and electronics. The box above suggests some steps that can be taken to lessen contact with PBDE-containing items in the home.

Footnotes

Key Points

Funding

The author received no specific grant from any funding agency in the public, commercial or not-for-profit sectors for the preparation of this article.

Conflict of interest

The author does not have any potential conflicts of interest to declare.

References

Peterson

Kintzer

Cavanagh

Fox

Ferguson

Johnson

, et al. Feline hyperthyroidism: pretreatment clinical and laboratory evaluation of 131 cases. J Am Vet Med Assoc 1981; 183: 103–110.

Hoenig

Goldschmidt

Ferguson

Koch

Eymontt

. Toxic nodular goitre in the cat. J Small Anim Pract 1982; 23: 1–12.

Peterson

Ward

. Etiopathologic findings of hyperthyroidism in cats. Vet Clin North Am Small Anim Pract 2007; 37: 633–645.

Mooney

Peterson

. Feline hyperthyroidism. In: Mooney

Peterson

(eds). Manual of canine and feline endocrinology. 4th ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012, pp 92–110.

Baral

Peterson

. Thyroid gland disorders. In: Little

(ed). The cat: clinical medicine and management. Philadelphia: Elsevier Saunders, 2012, pp 571–592.

Peterson

Johnson

Andrews

. Spontaneous hyperthyroidism in the cat. Proceedings of the American College of Veterinary Internal Medicine; Seattle, WA. ACVIM, 1979, p 108.

Lucke

. A histological study of thyroid abnormalities in the domestic cat. J Small Anim Pract 1964; 5: 351–358.

Leav

Schiller

Rijnberk

Legg

der Kinderen

. Adenomas and carcinomas of the canine and feline thyroid. Am J Pathol 1976; 83: 61–122.

Wakeling

Melian

Font

, et al. Evidence for differing incidences of feline hyperthyroidism in London UK and Spain. In: Congress Proceedings 15th ECVIM-CA, Glasgow, Scotland, Poster 43; 2005, p 220.

10.

Sassnau

. Epidemiological investigation on the prevalence of feline hyperthyroidism in an urban population in Germany. Tierarztl Prax Ausg K Kleintiere Heimtiere 2006; 34: 450–457.

11.

Miyamoto

Miyata

Kurobane

Kamijima

Tani

Sasai

, et al. Prevalence of feline hyperthyroidism in Osaka and the Chugoku Region. J Jpn Vet Med Assoc 2002; 55: 289–292.

12.

De Wet

Mooney

Thompson

Schoeman

. Prevalence of and risk factors for feline hyperthyroidism in Hong Kong. J Feline Med Surg 2009; 11: 315–321.

13.

Holzworth

Theran

Carpenter

Harpster

Todoroff

. Hyperthyroidism in the cat: ten cases. J Am Vet Med Assoc 1980; 176: 345–353.

14.

Scarlett

Moise

Rayl

. Feline hyperthyroidism: a descriptive and case control study. Prev Vet Med 1988; 7: 295–310.

15.

Edinboro

Scott-Moncrieff

Janovitz

Thacker

Glickman

. Epidemiologic study of relationships between consumption of commercial canned food and risk of hyperthyroidism in cats. J Am Vet Med Assoc 2004; 224: 879–886.

16.

Kraft

Buchler

. Hyperthyroidism: incidence in the cat. Tierarztl Prax Ausg K Klientiere Heimtiere 1999; 27: 386–388.

17.

Peterson

Randolph

Mooney

. Endocrine diseases. In: Sherding

(ed). The cat: diseases and clinical management. 2nd ed. New York: Churchill Livingstone, 1994, pp 1403–1506.

18.

Peter

Gerber

Studer

Becker

Peterson

. Autonomy of growth and of iodine metabolism in hyperthyroid feline goiters transplanted onto nude mice. J Clin Invest 1987; 80: 491–498.

19.

Gerber

Peter

Ferguson

Peterson

. Etiopathology of feline toxic nodular goiter. Vet Clin North Am Small Anim Pract 1994; 24: 541–565.

20.

Turrel

Feldman

Nelson

Cain

. Thyroid carcinoma causing hyperthyroidism in cats: 14 cases (1981–1986). J Am Vet Med Assoc 1988; 193: 359–364.

21.

Hibbert

Gruffydd-Jones

Barrett

Day

Harvey

. Feline thyroid carcinoma: diagnosis and response to high-dose radioactive iodine treatment. J Feline Med Surg 2009; 11: 116–124.

22.

Peterson

. Treatment of severe, unresponsive, or recurrent hyperthyroidism in cats. Proceedings of the 2011 ACVIM Forum; 2011 June 15–19; Denver, CO. American College of Veterinary Internal Medicine, pp 104–106.

23.

Peterson

Broome

. Thyroid scintigraphic findings in 917 cats with hyperthyroidism. J Vet Intern Med 2012; 26: 754.

24.

Peterson

Broome

. Hyperthyroid cats on long-term medical treatment show a progressive increase in the prevalence of large thyroid tumors, intrathoracic thyroid masses, and suspected thyroid carcinoma. Proceedings of the 22nd Congress of the European College of Veterinary Internal Medicine – Companion Animals, 2012, p 224.

25.

Peter

Gerber

Studer

Peterson

Becker

Groscurth

. Autonomous growth and function of cultured thyroid follicles from cats with spontaneous hyperthyroidism. Thyroid 1991; 1: 331–338.

26.

Kass

Peterson

Levy

James

Becker

Cowgill

. Evaluation of environmental, nutritional, and host factors in cats with hyperthyroidism. J Vet Intern Med 1999; 13: 323–329.

27.

Martin

Rossing

Ryland

DiGiacomo

Freitag

. Evaluation of dietary and environmental risk factors for hyperthyroidism in cats. J Am Vet Med Assoc 2000; 217: 853–856.

28.

Edinboro

Scott-Moncrieff

Glickman

. Review of iodine recommendations for commercial cat foods and potential impacts of proposed changes. Thyroid 2004; 14: 722.

29.

Edinboro

Scott-Moncrieff

Glickman

. Environmental risk factors for feline hyperthyroidism: pet cats as potential sentinels for public health [abstract]. Thyroid 2004; 14: 759.

30.

Olczak

Jones

Pfeiffer

Squires

Morris

Markwell

. Multivariate analysis of risk factors for feline hyperthyroidism in New Zealand. N Z Vet J 2005; 53: 53–58.

31.

Wakeling

Everard

Brodbelt

Elliott

Syme

. Risk factors for feline hyperthyroidism in the UK. J Small Anim Pract 2009; 50: 406–414.

32.

Court

Freeman

. Identification and concentration of soy isoflavones in commercial cat foods. Am J Vet Res 2002; 63: 181–185.

33.

Bell

Rutherfurd

Hendriks

. The isoflavone content of commercially-available feline diets in New Zealand. N Z Vet J 2006; 54: 103–108.

34.

Edinboro

Scott-Moncrieff

Glickman

. Feline hyperthyroidism: potential relationship with iodine supplement requirements of commercial cat foods. J Feline Med Surg 2010; 12: 672–679.

35.

Kimura

Suwa

Ito

Sato

. Development of malignant goiter by defatted soybean with iodine-free diet in rats. Gann 1976; 67: 763–765.

36.

Ikeda

Nishikawa

Son

Nakamura

Miyauchi

Imazawa

, et al. Synergistic effects of high-dose soybean intake with iodine deficiency, but not sulfadimethoxine or phenobarbital, on rat thyroid proliferation. Jpn J Cancer Res 2001; 92: 390–395.

37.

Shepard

Pyne

Kirschvink

McLean

. Soybean goiter: report of three cases. N Engl J Med 1960; 262: 1099–1103.

38.

Kay

Kimura

Nishing

Itokawa

. Soyabean, goitre, and prevention. J Trop Pediatr 1988; 34: 110–113.

39.

Köhrle

. Flavonoids as a risk factor for goiter and hypothyroidism. In: Péter

Wiersinga

Hostalek

(eds). The thyroid and environment. Proceedings of the Merck European Thyroid Symposium. Stuttgart/New York: Schattauer; 2000, pp 41–63.

40.

Divi

Chang

Doerge

. Anti-thyroid isoflavones from soybean: isolation, characterization, and mechanisms of action. Biochem Pharmacol 1997; 54: 1087–1096.

41.

Doerge

Sheehan

. Goitrogenic and estrogenic activity of soy isoflavones. Environ Health Perspect 2002; 110 (suppl 3): 349–353.

42.

de Souza Dos Santos

Goncalves

Vaisman

Ferreira

de Carvalho

. Impact of flavonoids on thyroid function. Food Chem Toxicol 2011; 49: 2495–2502.

43.

White

Freeman

Mahony

Graham

Hao

Court

. Effect of dietary soy on serum thyroid hormone concentrations in healthy adult cats. Am J Vet Res 2004; 65: 586–591.

44.

Ikeda

Nishikawa

Imazawa

Kimura

Hirose

. Dramatic synergism between excess soybean intake and iodine deficiency on the development of rat thyroid hyperplasia. Carcinogenesis 2000; 21: 707–713.

45.

National Research Council. Iodine. In: Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press, 2001, pp 258–289.

46.

Soriguer

Gutierre-Repiso

Rubio-Martin

Linares

Cardona

López-Ojeda

, et al. Iodine intakes of 100–300 µg/d do not modify thyroid function and have modest anti-inflammatory effects. Br J Nutr 2011; 25: 1–8.

47.

Patrick

. Iodine: deficiency and therapeutic considerations. Altern Med Rev 2008; 13: 116–127.

48.

Mumma

Rashid

Shane

Scarlett-Kranz

Hotchkiss

Eckerlin

, et al. Toxic and protective constituents in pet foods. Am J Vet Res 1986; 47: 1633–1637.

49.

Dzanis

. The Association of American Feed Control Officials dog and cat food nutrient profiles: substantiation of nutritional adequacy of complete and balanced pet foods in the United States. J Nutr 1994; 124 (suppl): 2535S–2539S.

50.

Johnson

Ford

Tarttelin

Feek

. Iodine content of commercially-prepared cat foods. N Z Vet J 1992; 40: 18–20.

51.

Ranz

Tetrick

Opitz

Kienzle

Rambeck

. Estimation of iodine status of cats. J Nutr 2002; 132 (suppl 2): 1751S–1753S.

52.

Tarttelin

Johnson

Cooke

Ford

Feek

. Serum free thyroxine levels respond inversely to changes in levels of dietary iodine in the domestic cat. N Z Vet J 1992; 40: 66–68.

53.

Tarttelin

Ford

. Dietary iodine level and thyroid function in the cat. J Nutr 1994; 124: 2577S–2578S.

54.

Kyle

Tarttelin

Cooke

Ford

. Serum free thyroxine levels in cats maintained on diets relatively high or low in iodine. N Z Vet J 1994; 42: 101–103.

55.

Scott

Greaves

Scott

. Nutrition of the cat. 4 Calcium and iodine deficiency on a meat diet. Br J Nutr 1961; 15: 35–51.

56.

Roberts

Scott

. Nutrition of the cat. 5 The influence of calcium and iodine supplements to a meat diet on the retention of nitrogen, calcium, and phosphorus. Br J Nutr 1961; 15: 73–82.

57.

Delange

Ermans

. Iodine deficiency. In: Braverman

Utiger

(eds). Werner and Ingbar’s the thyroid: a fundamental and clinical text. 8th ed. Philadelphia: Lippincott-Raven, 1996, pp 296–316.

58.

Zimmermann

. Iodine deficiency. Endocr Rev 2009; 30: 376–408.

59.

Wakeling

Elliott

Petrie

Brodbelt

Syme

. Urinary iodide concentration in hyperthyroid cats. Am J Vet Res 2009; 70: 741–749.

60.

Hess

. The impact of common micronutrient deficiencies on iodine and thyroid metabolism: the evidence from human studies. Best Pract Res Clin Endocrinol Metab 2010; 24: 117–132.

61.

Scott

. Effect of calcium and vitamin A deficiency on the thyroid gland. Proc R Soc Med 1969; 62: 240.

62.

Fairweather-Tait

Bao

Broadley

Collings

Ford

Hesketh

, et al. Selenium in human health and disease. Antioxid Redox Signal 2011; 14: 1337–1383.

63.

Duntas

. Selenium and the thyroid: a close-knit connection. J Clin Endocrinol Metab 2010; 95: 5180–5188.

64.

Rasmussen

Schomburg

Kohrle

Pedersen

Hollenbach

Hög

, et al. Selenium status, thyroid volume, and multiple nodule formation in an area with mild iodine deficiency. Eur J Endocrinol 2011; 164: 585–590.

65.

Howard

Wedekind

Morris

Rogers

. A low-selenium diet increases thyroxine and decreases 3,5,3’triiodothyronine in the plasma of kittens. J Anim Physiol Anim Nutr (Berl) 2002; 86: 36-41.

66.

Foster

Thoday

Arthur

Nicol

Beatty

Svendsen

, et al. Selenium status of cats in four regions of the world and comparison with reported incidence of hyperthyroidism in cats in those regions. Am J Vet Res 2001; 62: 934–937.

67.

Simcock

Rutherford

Wester

Hendriks

. Total selenium concentrations in canine and feline foods commercially available in New Zealand. N Z Vet J 2005; 53: 1–5.

68.

Boas

Main

Feldt-Rasmussen

. Environmental chemicals and thyroid function: an update. Curr Opin Endocrinol Diabetes Obes 2009; 16: 385–391.

69.

Patrick

. Thyroid disruption: mechanism and clinical implications in human health. Altern Med Rev 2009; 14: 326–346.

70.

Diamanti-Kandarakis

Bourguignon

Giudice

Hauser

Prins

Soto

, et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev 2009; 30: 293–342.

71.

Tsai

. Human health risk on environmental exposure to bisphenol-A: a review. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2006; 24: 225–255.

72.

Noonan

Ackerman

Begley

. Concentration of bisphenol A in highly consumed canned foods on the US market. J Agric Food Chem 2011; 59: 7178–7185.

73.

Vandenberg

Maffini

Sonnenschein

Rubin

Soto

. Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr Rev 2009; 30: 75–95.

74.

Meeker

Ferguson

. Relationship between urinary phthalate and bisphenol A concentrations and serum thyroid measures in US adults and adolescents from the National Health and Nutrition Examination Survey (NHANES) 2007–2008. Environ Health Perspect 2011; 119: 1396–1402.

75.

Goodson

Robin

Summerfield

Cooper

. Migration of bisphenol A from can coatings – effects of damage, storage conditions and heating. Food Addit Contam 2004; 21: 1015–1026.

76.

Cabado

Aldea

Porro

Ojea

Lago

Sobrado

, et al. Migration of BADGE (bisphenol A diglycidyl-ether) and BFDGE (bisphenol F diglycidyl-ether) in canned seafood. Food Chem Toxicol 2008; 46: 1674–1680.

77.

Schecter

Malik

Haffner

Smith

Harris

Paepke

, et al. Bisphenol A (BPA) in US food. Environ Sci Technol 2010; 44: 9425–9430.

78.

Kang

Kondo

. Determination of bisphenol A in canned pet foods. Res Vet Sci 2002; 73: 177–182.

79.

vom Saal

Hughes

. An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment. Environ Health Perspect 2005; 113: 926–933.

80.

Welshons

Nagel

vom Saal

. Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. Endocrinol 2006; 147(6 suppl): S56–69.

81.

Richter

Birnbaum

Farabollini

Newbold

Rubin

Talsness

, et al. In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol 2007; 24: 199–224.

82.

Lang

Galloway

Scarlett

. Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. J Am Med Assoc 2008; 300: 1303–1310.

83.

Meeker

Calafat

Hauser

. Urinary bisphenol A concentrations in relation to serum thyroid and reproductive hormone levels in men from an infertility clinic. Environ Sci Technol 2010; 44: 1458–1463.

84.

Schug

Janesick

Blumberg

Heindel

. Endocrine disrupting chemicals and disease susceptibility. J Steroid Biochem Mol Biol 2011; 127: 204–215.

85.

Pottenger

Domoradzki

Markham

Hansen

Cagen

Waechter

. The relative bioavailability and metabolism of bisphenol A in rats is dependent upon the route of administration. Toxicol Sci 2000; 54: 3–18.

86.

Chiu

Huskey

. Species differences in N-glucuronidation. Drug Metab Dispos 1998; 26: 838–847.

87.

Nebbia

. Factors affecting chemical toxicity. In: Gupta

(ed). Veterinary toxicity: basic and clinical principles. 2nd ed. London. Academic Press, 2007, pp 48–61.

88.

Moriyama

Tagami

Akamizu

Usui

Saijo

Kanamoto

, et al. Thyroid hormone action is disrupted by bisphenol A as an antagonist. J Clin Endocrinol Metab 2002; 87: 5185–5190.

89.

Kitamura

Jinno

Ohta

Kuroki

Fujimoto

. Thyroid hormonal activity of the flame retardants tetrabromobisphenol A and tetrachlorobisphenol A. Biochem Biophys Res Commun 2002; 293: 554–559.

90.

Costa

Giordano

Tagliaferri

Caglieri

Mutti

. Polybrominated diphenyl ether (PBDE) flame retardants: environmental contamination, human body burden and potential adverse health effects. Acta Biomed 2008; 79: 172–183.

91.

Talsness

. Overview of toxicological aspects of polybrominated diphenyl ethers: a flame-retardant additive in several consumer products. Environ Res 2008; 108: 158–167.

92.

Hale

Alaee

Manchester-Neesvig

Stapleton

Ikonomou

. Polybrominated diphenyl ether flame retardants in the North American environment. Environ Int 2003; 29: 771–779.

93.

Law

Allchin

deBoer

Covaci

Herzke

Lepom

, et al. Levels and trends of brominated flame retardants in the European environment. Chemosphere 2006; 64: 187–208.

94.

Wang

Jiang

Lam

PKS

. Polybrominated diphenyl ether in the East Asian environment: a critical review. Environ Int 2007; 33: 963–973.

95.

Meeker

Johnson

Camann

Hauser

. Polybrominated diphenyl ether (PBDE) concentrations in house dust are related to hormone levels in men. Sci Total Environ 2009; 407: 3425–3429.

96.

Hallgren

Darnerud

. Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and chlorinated paraffins (CPs) in rats – testing interactions and mechanisms for thyroid hormone effects. Toxicology 2002; 177: 227–243.

97.

Zhou

Ross

DeVito

Crofton

. Effects of short-term in vivo exposure to polybrominated diphenyl ethers on thyroid hormones and hepatic enzyme activities in weanling rats. Toxicol Sci 2001; 61: 76–82.

98.

Hallgren

Sinjari

Hakansson

Darnerud

. Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice. Arch Toxicol 2001; 75: 200–208.

99.

Chevrier

Harley

Bradman

Gharbi

Sjödin

Eskenazi

. Polybrominated diphenyl ether (PBDE) flame retardants and thyroid hormone during pregnancy. Environ Health Perspect 2010; 118: 1444–1449.

100.

Bloom

Spliethoff

Vena

Shaver

Addink

Eadon

. Environmental exposure to PBDEs and thyroid function among New York anglers. Environ Toxicol Pharmacol 2008; 25: 386–392.

101.

Dallaire

Dewailly

Pereg

Dery

Ayotte

. Thyroid function and plasma concentrations of polyhalogenated compounds in Inuit adults. Environ Health Perspect 2009; 117: 1380–1386.

102.

Dye

Venier

Zhu

Ward

Hites

Birnbaum

. Elevated PBDE levels in pet cats: sentinels for humans? Environ Sci Technol 2007; 15: 6350–6356.

103.

Guo

Park

Wang

Gardner

Baek

Petreas

, et al. High polybrominated diphenyl ether levels in California house cats: house dust a primary source? Environ Toxicol Chem 2012; 31: 301–306.

104.

Kupryianchyk

Hovander

Jones

Lindqvist

Eriksson

Bergman

. Hyperthyroidism, a new disease in cats — is it caused by exposure to environmental organic pollutants? Organohalogen Compd 2009; 71: 2720–2725.

105.

Norrgran

Jones

Lindquist

Bergman

. Decabromobiphenyl, polybrominated diphenyl ethers, and brominated phenolic compounds in serum of cats diagnosed with the endocrine disease feline hyperthyroidism. Arch Environ Contam Toxicol 2012; 63: 161–168.

106.

Mensching

Slater

Scott

Ferguson

Beasley

. The feline thyroid gland: a model for endocrine disruption by polybrominated diphenyl ethers (PBDEs)? J Toxicol Environ Health A 2012; 75: 201–212.

107.

Marsh

Bergman

Bladh

Glillner

Jackobsson

. Synthesis of p-hydroxybromodiphnyl ethers and binding to the thyroid hormone receptor. Organohalogen Compd 1998; 37: 305–308.

108.

Gaitan

. Goitrogens in food and water. Annu Rev Nutr 1990; 10: 21–39.

109.

National Research Council. Effects on the endocrine system. In: Fluoride in drinking water: a scientific review of EPA’s standards. Washington, DC: The National Academies Press, 2006, pp 224–267.

110.

Boyer

Jr Andrews

deLahunta

Bache

Gutenman

Lisk

. Accumulation of mercury and selenium in tissues of kittens fed commercial cat food. Cornell Vet 1978; 68: 365–374.

111.

Sakai

Ito

Aoki

Aimi

Nitaya

. Hair mercury concentrations in cats and dogs in central Japan. Br Vet J 1995; 151: 215–219.

112.

Furr

Bache

Gutenmann

Pakkala

Lisk

. Element and chlorinated hydrocarbon content of commercial pet foods. Cornell Vet 1976; 66: 513–527.

113.

Hamper

Bartges

Kirk

LusbyAL Murphy

Raditic

. The unique nutritional requirements of the cat: a strict carnivore. In: Little

(ed). The cat: clinical medicine and management. St Louis: Elsevier Saunders, 2012, pp 236–242.

114.

Clarkson

. Environmental contaminants in the food chain. Am J Clin Nutr 1995; 61: 682S–686S.

115.

Frederiksen

Vorkamp

Thomsen

Knudsen

. Human internal and external exposure to PBDEs — a review of levels and sources. Int J Hyg Environ Health 2009; 212: 109–134.

116.

Thixton

. Which pet foods have BPA free cans? TruthaboutPetFood.com. http://www.truthaboutpetfood.com/articles/which-pet-foods-have-bpa-free-cans.html (17 January, 2010).

117.

AAFCO. 2010 Official Publication, Association of American Feed Control Officials, Oxford, IN.

118.

Wedekind

Blumer

Huntington

Spate

Morris

. The feline iodine requirement is lower than the 2006 NRC recommended allowance. J Anim Physiol Anim Nutr (Berl) 2009; 9: 527–539.

119.

Remillard

. Homemade diets: attributes, pitfalls, and a call for action. Top Companion Anim Med 2008; 23: 137–142.

120.

Freeman

Becvarova

Cave

MacKay

Nguyen

Ramaet

, et al. WSAVA nutritional assessment guidelines. J Feline Med Surg 2011; 13: 516–525.

121.

World Health Organization. Guidelines for drinking-water quality. Vol 1, Recommendations. 3rd ed. 2006.

122.

Richardson

. Water analysis: emerging contaminants and current issues. Anal Chem 2009; 81: 4645–4677.

123.

Lacheretz

Moreau

Cathelain

. Causes of death and life expectancy in carnivorous pets (I). Revue Méd Vét 2002; 153: 819–822.

124.

Moreau

Cathelain

Lacheretz

. Comparative study of causes of death and life expectancy in carnivorous pets (II). Revue Méd Vét 2003; 154: 127–132.

125.

Levy

Lorentzen

Shields

, et al. Long-term outcome of cats with natural FeLV and FIV infection. In: 8th International Feline Retrovirus Research Symposium. Washington, DC, 2006.

126.

Shojaim

. How cat litter is made. Cat Fancy Magazine October 1994, pp 12–19.

127.

Noone

Borchelt

Rice

Bressler

Morales

Lee

. Detection of silica particles in lung wash fluid from cats with and without respiratory disease. J Am Holistic Vet Med Assoc 2001; 20: 13–20.

128.

Frischmann

. Managing pet waste responsibly. In: Pets and the planet: a practical guide to sustainable pet care. Wiley Publishing, Hoboken, New Jersey, 2009, pp 103–126.

129.

Eckstein

Hart

. The organization and control of grooming in cats. Appl Anim Behav Sci 2000; 68: 131–140.

Hyperthyroidism in Cats

Abstract

Practical relevance:

Patient group:

Clinical challenges:

Evidence base:

Feline hyperthyroidism – a relative newcomer

Epidemiology of this common worldwide disorder

Thyroid pathologic changes

Why do feline thyroid tumors develop in the first place?

Nutritional deficiencies or excesses

Soy isoflavones

Dietary iodine

Could iodine deficiency be contributing?

What about potential combined effects?

Dietary selenium

Thyroid-disrupting compounds in the environment, drinking water or diet

Bisphenol A

Polybrominated diphenyl ethers

Environmental pesticides or herbicides

Other goitrogens or thyroid disruptors

What can be done in terms of prevention?

Diet fed to the cat

Water safety measures

Cat litter

Environmental control

Footnotes

Key Points

Funding

Conflict of interest

References