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Compendium August 2013 (Vol 35, No 8)

Feline Focus: Diagnostic Testing for Feline Thyroid Disease: Hypothyroidism

by Mark Peterson, DVM, DACVIM

    Abstract

    Although naturally occurring hypothyroidism is very rare in cats, iatrogenic hypothyroidism is a recognized complication of treatment for hyperthyroidism. However, confirming the diagnosis of hypothyroidism in cats is not generally straightforward. The potential for false-negative and false-positive results exists with all thyroid function tests, especially in older cats that may have concurrent nonthyroidal illness. Therefore, all thyroid function test results must be interpreted in light of the cat’s history, clinical signs, and other laboratory findings. If a low to low-normal serum thyroxine (T4) value is found in a cat that has been treated for hyperthyroidism, repeating the total T4 analysis, determining free T4 and thyroid stimulating hormone (TSH) concentrations, or performing a TSH stimulation test or thyroid scintigraphy may be needed to confirm the diagnosis.

    In cats, as in other species, hypothyroidism is the clinical syndrome that results from the chronic deficient secretion of the two thyroid hormones: thyroxine (T4) and triiodothyronine (T3).1–4 Unlike dogs, in which primary hypothyroidism is common, naturally occurring hypothyroidism is extremely rare in adult cats, with only two documented cases reported.5,6 Most commonly, feline hypothyroidism is an iatrogenic complication associated with overtreatment of hyperthyroidism. Spontaneous hypothyroidism, when it does develop in cats, is seen most commonly as a congenital form in dwarf kittens.1–4

    Although many of the clinical features that develop in hypothyroid cats are similar to those seen in hypothyroid dogs, some major differences can make diagnosis more difficult in cats (TABLE 1).1–4 First, hypothyroid cats may develop a poor appetite, a sign not reported in dogs with hypothyroidism. Second, hypothyroid cats rarely develop severe hair loss or total alopecia, relatively common signs in dogs. The major clinical signs of hypothyroidism in adult cats are not specific but can include lethargy, decreased appetite, and weight gain (TABLE 1).1–4 Nonspecific cutaneous changes (e.g., nonpruritic seborrhea sicca, dull haircoat, excessive shedding or matting of hair) and obesity can develop, whereas hypothermia, and bradycardia are less common.1–4

    Iatrogenic hypothyroidism can develop during therapy with antithyroid drugs,7–9 after thyroidectomy,7,9,10 or following radioiodine therapy.7,11–14 Although early reports suggested that clinical signs associated with severe iatrogenic hypothyroidism in cats were uncommon and that most cats did not require treatment, it is now realized that milder degrees of iatrogenic hypothyroidism are relatively common and that these cats may benefit from thyroid replacement therapy. Many cats with mild or subclinical hypothyroidism fail to develop noticeable clinical features (TABLE 1).

    A major potential benefit of treating iatrogenic hypothyroidism in cats is helping maintain renal function. It is well known that untreated feline hyperthyroidism leads to a reversible increase in glomerular filtration rate (GFR) and that successful treatment of hyperthyroidism results in a decrease in GFR, which can result in the development of azotemia if underlying chronic kidney disease (CKD) is present.2,15 To make matters worse, if iatrogenic hypothyroidism develops in cats with underlying CKD, GFR may fall even further, leading to a further decline in renal function.2,16 A recent report concluded that cats that developed iatrogenic hypothyroidism after treatment with antithyroid drugs or surgical thyroidectomy were at higher risk for development of azotemia and had reduced survival times.9 Therefore, even if no severe clinical signs associated with hypothyroidism are present in these cats, treatment of hypothyroidism might help increase GFR, as it has been reported to do in hypothyroid dogs,17 thereby improving kidney function and survival. As a result, it may be important to avoid, or at least minimize, iatrogenic hypothyroidism when treating hyperthyroid cats, many of which are likely to have some degree of preexisting CKD.9,15

    This article reviews the common thyroid function tests currently recommended to diagnose hypothyroidism in cats. Because definitive diagnosis of this relatively common disorder is not always straightforward, this outline will concentrate on the diagnostic protocols used in the workup of cats suspected of having iatrogenic hypothyroidism.

    Diagnosing Cats With Hypothyroidism

    Correctly diagnosing feline hypothyroidism can be challenging, regardless of its etiology. Again, this syndrome rarely develops spontaneously.1–4 Because hypothyroidism in adult cats is almost always iatrogenic, diagnosing this disorder starts with a history of the cat being treated for hyperthyroidism. Thereafter, the presumptive diagnosis of hypothyroidism is based on a combination of clinical features (e.g., lethargy, weight gain despite normal or decreased appetite (TABLE 1), physical examination findings (e.g., poor haircoat, obesity), routine laboratory test findings (e.g., mild, nonregenerative anemia, azotemia), and low circulating thyroid hormone concentrations.1–4

    The diagnosis of hypothyroidism currently relies largely on assessment of basal thyroid hormone analyses (i.e., serum T4, T3, and free T4), as well as serum thyroid stimulating hormone (TSH) determinations. The greatest difficulty in interpreting these tests is the number of factors other than intrinsic thyroid function that can affect concentrations of thyroid hormones, including assay technique, nonthyroidal illness, and certain drugs (e.g., sulfonamides).1,18–20 In clinical practice, four major factors can make the diagnosis of iatrogenic hypothyroidism difficult to confirm in cats.

    1.    Concurrent diseases, common in older cats, can result in “euthyroid sick syndrome,” characterized by falsely low serum thyroid hormone concentrations.18–20 As in dogs,20 serum TSH concentrations may also be high in some of these cats,7 which may lead to an incorrect diagnosis of hypothyroidism.

    2.    Cats are expected to gain weight and decrease activity level after successful treatment of hyperthyroidism. Therefore, the clinical signs associated with iatrogenic hypothyroidism can overlap with those expected with a return to a euthyroid state.2–4,9

    3.    The classic routine laboratory abnormalities associated with hypothyroidism (anemia, hypercholesterolemia) are nonspecific and inconsistent, especially in adult cats with mild or subclinical hypothyroidism.1–4

    4.    Many cats develop a marked transient decrease in total T4 within the first month of therapy with iodine-131 or thyroidectomy. This transient hypothyroid state is followed by a return to euthyroidism over the next 3 to 6 months as the remaining normal thyroid tissue recovers and regains function.

    Specific Thyroid Function Tests Used in Cats

    Serum T4 Concentration

    By definition, cats with hypothyroidism have deficient thyroid hormone secretion. Therefore, finding a low serum T4 concentration is key in establishing a preliminary diagnosis of feline hypothyroidism. As in dogs, however, it is possible for a cat with mild or subclinical hypothyroidism to maintain a borderline serum T4 concentration in the low end of the reference interval (e.g., 0.8 to 1.5 μg/dL; 10 to 20 nmol/L).

    Again, while extremely important in establishing a diagnosis, a subnormal T4 concentration alone is never definitive for hypothyroidism for two reasons. First, the serum T4 concentration may be falsely or borderline low as a result of assay error. Practitioners should be aware of the assay techniques being used by their commercial or in-house laboratories. In general, serum T4 can now be measured by four different assay techniques: radioimmunoassay (RIA), long considered to be the gold standard; chemiluminescent enzyme immunoassay (CEIA; Immulite Total T4, Siemens Medical Solutions Diagnostics); homogenous enzyme immunoassay (DRI Thyroxine [T4] assay, Microgenics Corporation); and an ELISA test kit (SNAP Total T4, IDEXX Laboratories) for in-house use. Although the correlation of serum T4 concentrations between all of these assay methods is good, any of these techniques can provide serum T4 values that are falsely low (or high). Compared with the gold standard, RIA, CEIA is most reliable. Serum T4 results must always be interpreted in light of the cat’s history, clinical signs, and other laboratory findings. If a low serum T4 value is found in a cat that lacks clinical signs of hypothyroidism, especially if there is no history of treatment for hyperthyroidism or obvious nonthyroidal illness, the serum T4 test should be repeated using a different technique, with RIA or CEIA being the preferred assay techniques in such cases. (For more information on these assays, see the companion article, “Feline Focus: Diagnostic Testing for Feline Thyroid Disease: Hyperthyroidism.”)

    Second, the serum T4 concentration is often falsely low in cats with nonthyroidal illness, such as diabetes mellitus, hepatic disease, renal disease, and systemic neoplasia.18–20 In general, the severity of the illness correlates inversely with the serum T4 concentration (i.e., sicker cats have lower serum T4 concentrations).18,20 Because multiple diseases and other factors can falsely lower the serum T4 concentration in cats, nonthyroidal disease must always be ruled out before considering a diagnosis of hypothyroidism (FIGURE 1). Once assay error and nonthyroidal illness have been excluded, cats with suspected hypothyroidism and a low T4 concentration still require additional testing to establish a definitive diagnosis. Further thyroid function tests such as measurement of serum free T4 and canine TSH (cTSH) are recommended (FIGURE 1 and FIGURE 2). If difficulties are encountered in confirming (or excluding) a diagnosis of hypothyroidism using these standard tests, thyroid scintigraphy or TSH stimulation testing may be indicated to confirm the disease.

    Serum T3 Concentration

    In most cats with hypothyroidism, serum total T3 concentrations are low to subnormal, correlating fairly well with the low T4 values. By contrast, in dogs with hypothyroidism, serum T3 generally remains within the reference interval.21 The feline thyroid gland lacks the deiodinase enzyme (i.e., type 1 iodothyronine deiodinase) needed to convert T4 to T3.22 Therefore, cats may not secrete very much T3 directly from the thyroid gland, and circulating T3 appears to be primarily derived from peripheral deiodination of T4 in the liver and kidney. As thyroid function abates, it appears that some cats cannot compensate—as dogs and humans initially do—by increasing thyroid secretion of T3, so circulating concentrations fall. Like total T4, however, T3 concentrations can also be suppressed in euthyroid cats with nonthyroidal illnesses.1,2,20

    Serum Free T4 Concentration

    Free T4 is the non–protein-bound fraction of circulating T4 that can enter cells, producing the biologic effect of thyroid hormone and regulating the pituitary feedback mechanism. Free T4 accounts for less than 1% of circulating T4. Because only the free T4 is biologically active, measuring free T4 is considered a more sensitive test for diagnosing hypothyroidism. In addition, nonthyroidal illness influences free T4 less than it influences the total T4.2,19,20 Therefore, free T4 should be theoretically better at distinguishing a euthyroid cat with nonthyroidal disease from a hypothyroid cat.

    Although measuring free T4 concentration is generally a more accurate stand-alone test than total T4 concentration, free T4 is far from perfect for confirming feline hypothyroidism. First, the performance and accuracy of the current free T4 assays are variable, and false-positive test results are common. Second, moderate to severe nonthyroidal illness can also falsely lower the free T4 concentration, although to a lesser degree than seen with total T4.2,19,20 In contrast, when free T4 is measured by equilibrium dialysis, up to 20% of cats with nonthyroidal disease have a falsely high concentration.2,23 However, such a high free T4 result, even if falsely elevated, would completely exclude a diagnosis of hypothyroidism.

    As a thyroid function test, free T4 is always best interpreted with corresponding total T4 and TSH measurements (see “Serum Thyroid Hormone Panels,” below). A low total T4 value combined with a low free T4 concentration (and high TSH value) is consistent with hypothyroidism, whereas low T4 combined with normal or even high free T4 is found in normal and hyperthyroid cats with nonthyroidal illness (FIGURE 1 and FIGURE 2). As always, these thyroid test results must be combined with the cat’s clinical presentation and history to help make the correct diagnosis.

    Serum Thyroid Stimulating Hormone Concentration

    In human patients, measurement of serum TSH concentration is commonly used as the first-line test of thyroid function.24 The pituitary gland constantly monitors circulating levels of T4 and T3, and if it senses the slightest decrease in these concentrations, it increases the secretion of TSH. Therefore, finding a high serum TSH value in a human patient is considered diagnostic for hypothyroidism, even if serum T4 concentrations remain normal.24

    A specific assay for feline TSH is not yet available, but the commercially available cTSH assay cross-reacts with feline TSH enough to enable its use as a diagnostic test for hypothyroid cats. In one of the reported adult cats with spontaneous hypothyroidism, the serum TSH concentration was high when measured with the cTSH assay.6 Similarly, many cats with suspected iatrogenic hypothyroidism develop high serum TSH concentration as measured by the cTSH assay.7,9 Based on these results, the cTSH assay has been touted as a good diagnostic test for feline hypothyroidism.9,25 However, the measurement of TSH concentrations is relatively new, and no one has published results of a large case series documenting the true predictive value of serum cTSH as a diagnostic test for feline hypothyroidism.

    In a cat suspected of hypothyroidism, the finding of a high serum TSH value in combination with low serum concentrations of total or free T4 can generally be considered diagnostic for hypothyroidism (FIGURE 1 and FIGURE 2). This assay, however, is far from perfect. Similar to dogs, in which in which high TSH values are found in about 10% of cases with nonthyroidal illness,20,26 some cats with mild nonthyroidal illness—in particular, obese cats and cats with poorly controlled diabetes7—have high (false-positive) cTSH concentrations, even when they have mid- to high-normal T4 and free T4 concentrations. Similar findings have been reported in euthyroid, obese human patients.27

    In addition, it is common for high serum TSH to develop in cats treated for hyperthyroidism despite maintenance of completely normal concentrations of T4, free T4, or both (FIGURE 2, area B). Do these cats really have mild degrees of hypothyroidism? Should they be treated with levothyroxine despite their normal circulating thyroid hormone values? Or are these serum TSH values falsely high, simply representing a TSH laboratory artifact? At this time, the answers to these questions remain unknown.

    Finally, the high serum TSH concentrations in some cats with suspected iatrogenic hypothyroidism fail to decrease after adequate levothyroxine therapy. In some cats, serum TSH concentrations remain very high despite a rise in post-pill T4 concentrations to the upper end of the reference interval. Physiologically, the rise in T4 and T3 should signal the pituitary gland to shut off TSH secretion,24 so the failure of TSH to fall despite high circulating T4 and T3 calls into question the accuracy of the cTSH assay in these cats.

    Obviously, a better TSH assay for feline hyperthyroidism is needed—particularly, a feline-specific TSH assay. However, until better TSH assays for cats are available, caution is advised in overinterpreting values in cats.

    Serum Thyroid Hormone Panels

    Differentiating hypothyroid from euthyroid cats can be challenging and may require evaluation of more than a single thyroid function test. Thyroid panels, which include serum total T4, free T4, total T3, and cTSH, are now commonly offered by many commercial laboratories. Evaluation of these thyroid panels can be very helpful in improving diagnostic sensitivity for hypothyroidism (FIGURE 1 and FIGURE 2); however, these panels should be used for confirmation, rather than screening, as discordant results are very common. For example, as noted above, it is not uncommon to see high cTSH concentrations with completely normal T4 and free T4 values in cats that have been treated for hyperthyroidism (FIGURE 2). Most of these cats do not have clinical signs of hypothyroidism, and the clinical significance of the high TSH concentration in this subgroup is unclear. In general, if levels of at least three of the four main hormones are abnormal and consistent with hypothyroidism (low to low-normal T4, free T4, and T3; high TSH), the results can be considered diagnostic for hypothyroidism.

    Thyroid Stimulating Hormone Stimulation Test

    The TSH stimulation test provides important information for diagnosing hypothyroidism because it directly tests the thyroid’s secretory reserve. A recombinant human TSH (rhTSH) preparation (Thyrogen, Genzyme Corporation, Naarden, the Netherlands) has been validated for TSH stimulation testing in cats.28,29 The testing protocol involves collecting samples for serum T4 concentration before and 6 hours after IV administration of 25 to 200 μg of rhTSH. In normal cats, administering exogenous rhTSH produces a consistent rise in serum T4 concentration with at least a twofold rise in T4.28,29  Further studies are needed to validate the use of this test for diagnosing feline hypothyroidism, but hypothyroid cats tested to date showed little to no rise in serum T4 after TSH stimulation.29 The major disadvantage of this test is that rhTSH is extremely expensive, making it cost prohibitive for many owners.

    Thyroid Scintigraphy

    Thyroid scintigraphy is a nuclear medicine procedure that produces a visual display of functional thyroid tissue based on the selective uptake of various radionuclides by thyroid tissue.30,31 This test is considered the best imaging technique for cats (and dogs) suspected of having hypothyroidism because it can distinguish animals with hypothyroidism from those with a falsely low serum T4 concentration.32

    In cats with hypothyroidism secondary to treatment with thyroidectomy or radioiodine, thyroid scintigraphy typically reveals decreased or even absent radionuclide uptake (i.e., the thyroid gland is not visible on the scan; FIGURE 3).6,31 Cats with a falsely low serum thyroid hormone concentration secondary to illness or drug therapy have a normal thyroid image. This procedure is of no benefit in diagnosis of methimazole-induced hypothyroidism, however.8

    Unfortunately, few veterinarians have access to the equipment needed to obtain thyroid images or perform thyroid uptake determinations.

    Diagnostic Protocol for Cats With Suspected Iatrogenic Hypothyroidism

    After a cat has been treated for hyperthyroidism with radioiodine, surgical thyroidectomy, or methimazole, I recommend monitoring the cat with a complete physical examination, as well as routine laboratory testing (e.g., complete blood count, serum chemistry panel, complete urinalysis) and total T4 determinations at 1 and 3 months (FIGURE 1). If the serum T4 level falls to a subnormal or low-normal value and iatrogenic hypothyroidism is suspected, a complete thyroid profile (serum T4, free T4, T3, and TSH concentrations) is recommended to help establish the diagnosis (FIGURE 1 and FIGURE 2). The combination of low to low-normal serum concentrations of T4, free T4, and T3, together with a clearly high TSH value, can be considered diagnostic for hypothyroidism.

    No matter what treatment is chosen for hyperthyroidism, the ideal post-treatment serum T4 concentration is a value in the mid-normal range. For example, if the T4 reference interval is 0.8 to 4.0 μg/dL (10 to 50 nmol/L), my goal is to maintain the T4 value between 1.5 and 3.0 μg/dL (20 and 40 nmol/L). Recent research indicates that both mild hyper- and hypothyroidism are deleterious to kidney function and may worsen existing CKD.9,33

    As in dogs and people with hypothyroidism, the finding of a high serum TSH concentration, together with low serum total and free T4 values, is consistent with primary hypothyroidism (FIGURE 1 and FIGURE 2). Cats with nonthyroidal illness (such as CKD) commonly have low serum total and free T4 concentrations, but these cats generally maintain normal values for serum TSH, which helps exclude iatrogenic hypothyroidism. Many cats treated with radioiodine or unilateral thyroidectomy go through a period of transient hypothyroidism after treatment. Most of these cats have some remaining normal thyroid tissue that has been chronically suppressed by hyperthyroidism. With time, this normal thyroid tissue may start to function normally again to restore euthyroidism.

    For most cats, I recommend waiting at least 3 months after radioiodine therapy or thyroidectomy before embarking on a workup for permanent iatrogenic hypothyroidism, especially if the cat is not presenting with clinical features of hypothyroidism. However, clinicians should diagnose or exclude hypothyroidism as soon as possible in cats with renal disease because hypothyroidism, treatment for hyperthyroidism, and chronic renal disease all lower the GFR. The combined effect of these three factors can lead to severe renal azotemia or even renal failure. In hypothyroid cats with concurrent CKD, instituting T4 replacement therapy and increasing serum thyroid hormone concentrations back into the reference interval may help raise the GFR to an acceptable level and reduce azotemia.

    Conclusion

    Knowledge about hypothyroidism in cats has increased markedly over the last few years. Diagnosing iatrogenic hypothyroidism can be challenging in some cats because of the concomitant presence of another disease (e.g., CKD) or a transient decrease in total T4 within the first months of therapy for hyperthyroidism with surgery or radioiodine.

    However, there is much yet to learn: do cats that develop a high serum TSH concentration but maintain normal serum concentrations of T4 or free T4 have subclinical hypothyroidism? In other words, is the high circulating TSH concentration seen in these cats a compensatory mechanism that allows a cat with lower-than-normal amounts of residual thyroid tissue to maintain euthyroidism? Or is the high TSH a false-positive result? Although the answers to those questions remain to be determined, some obese and diabetic cats show false-positive (high) cTSH concentrations, despite maintaining serum T4 and free T4 concentrations within the middle of the reference interval (i.e., not low or low-normal). In further support of possible false-positive results, the high serum TSH concentrations in some cats with suspected iatrogenic hypothyroidism fail to decrease after adequate levothyroxine therapy, as would be expected based on the known negative feedback effects of thyroid hormones on pituitary TSH secretion.

    The bottom line is that all thyroid function test results must be interpreted in light of the cat’s history, clinical signs, and other routine laboratory findings, especially renal function test results. Therapeutic or monitoring decisions should never be based on the thyroid laboratory value(s) alone—always remember to look at the cat!

    Downloadable PDF

    References

    1. Daminet S. Feline hypothyroidism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. 4th ed. Quedgeley, Gloucester: British Small Animal Veterinary Association; 2012:111-115.

    2. Baral RM, Peterson ME. Thyroid gland disorders In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis, MO: Elsevier Saunders; 2012:571-592.

    3. Peterson ME. Feline hypothyroidism. In: Kirk RW, Bonagura JD, eds. Current Veterinary Therapy X. Philadelphia, PA: WB Saunders Co; 1989:1000-1001.

    4. Peterson ME, Randolph JF, Mooney CT. Endocrine diseases. In: Sherding RG, ed. The Cat: Diseases and Clinical Management. 2nd ed. New York, NY: Churchill Livingstone; 1994:1403.

    5. Rand JS, Levine J, Best SJ, et al: Spontaneous adult-onset hypothyroidism in a cat. J Vet Intern Med 1993;7:272-276.

    6. Blois SL, Abrams-Ogg AC, Mitchell C, et al. Use of thyroid scintigraphy and pituitary immunohistochemistry in the diagnosis of spontaneous hypothyroidism in a mature cat. J Feline Med Surg 2010;12:156-160.

    7. Graham P. Measurement of feline thyrotropin using a commercial canine-specific immunoradiometric assay. J Vet Intern Med 2000;14:342.

    8. Fischetti AJ, Drost WT, DiBartola SP, et al. Effects of methimazole on thyroid gland uptake of 99mTC-pertechnetate in 19 hyperthyroid cats. Vet Radiol Ultrasound 2005;46:267-272.

    9. Williams TL, Elliott J, Syme HM. Association of iatrogenic hypothyroidism with azotemia and reduced survival time in cats treated for hyperthyroidism. J Vet Intern Med 2010;24:1086-1092.

    10. Welches CD, Scavelli TD, Matthieson DT, et al. Occurrence of problems after three techniques of bilateral thyroidectomy in cats. Vet Surg 1989;18:392-396.

    11. Meric SM, Rubin SI. Serum thyroxine concentrations following fixed-dose radioactive iodine treatment in hyperthyroid cats: 62 cases (1986-1989). J Am Vet Med Assoc 1990;197:621-623.

    12. Jones BR, Cayzer J, Dillon EA, et al. Radio-iodine treatment of hyperthyroid cats. N Z Vet J 1991;39:71-74.

    13. Peterson ME, Becker DV. Radioiodine treatment of 524 cats with hyperthyroidism. J Am Vet Med Assoc 1995;207:1422-1430.

    14. Nykamp SG, Dykes NL, Zarfoss MK, et al. Association of the risk of development of hypothyroidism after iodine 131 treatment with the pretreatment pattern of sodium pertechnetate Tc-99m uptake in the thyroid gland in cats with hyperthyroidism: 165 cases (1990-2002). J Am Vet Med Assoc 2005;226:1671-1675.

    15. Langston CE, Reine NJ. Hyperthyroidism and the kidney. Clin Tech Small Anim Pract 2006;21:17-21.

    16. Panciera DL, Lefebvre HP. Effect of experimental hypothyroidism on glomerular filtration rate and plasma creatinine concentrations in dogs. J Vet Intern Med 2009;23:1045-1050.

    17. Gommeren K, van Hoek I, Lefebvre HP, et al. Effect of thyroxine supplementation on glomerular filtration rate in hypothyroid dogs. J Vet Intern Med 2009;23:844-849.

    18. Peterson ME, Gamble DA. Effect of nonthyroidal illness on serum thyroxine concentrations in cats: 494 cases (1988). J Am Vet Med Assoc 1990;197:1203-1208.

    19. Mooney CT, Little CJ, Macrae AW. Effect of illness not associated with the thyroid gland on serum total and free thyroxine concentrations in cats. J Am Vet Med Assoc 1996;208:2004-2008.

    20. Peterson ME, Melian C, Nichols R. Measurement of serum concentrations of free thyroxine, total thyroxine, and total triiodothyronine in cats with hyperthyroidism and cats with nonthyroidal disease. J Am Vet Med Assoc 2001;218:529-536.

    21. Peterson ME, Melián C, Nichols R. Measurement of serum total thyroxine, triiodothyronine, free thyroxine, and thyrotropin concentrations for diagnosis of hypothyroidism in dogs. J Am Vet Med Assoc 1997;211:1396-1402.

    22. Foster DJ, Thoday KL, Beckett GJ. Thyroid hormone deiodination in the domestic cat. J Mol Endocrinol 2000;24:119-126.

    23. Wakeling J, Moore K, Elliott J, et al. Diagnosis of hyperthyroidism in cats with mild chronic kidney disease. J Small Anim Pract 2008;49:287-294.

    24. Ross DS. Serum thyroid-stimulating hormone measurement for assessment of thyroid function and disease. Endocrinol Metab Clin North Am 2001;30:245–264.

    25. Wakeling J. Use of thyroid stimulating hormone (TSH) in cats. Can Vet J 2010;51:33-34.

    26. Kantrowitz LB, Peterson ME, Melian C, et al. Serum total thyroxine, total triiodothyronine, free thyroxine, and thyrotropin concentrations in dogs with nonthyroidal disease. J Am Vet Med Assoc 2001;219:765-769.

    27. Michalaki MA, Vagenakis AG, Leonardou AS, et al. Thyroid function in humans with morbid obesity. Thyroid 2006;16:73-78.

    28. Stegeman JR, Graham PA, Hauptman JG. Use of recombinant human thyroid-stimulating hormone for thyrotropin-stimulation testing of euthyroid cats. Am J Vet Res 2003;64:149-152.

    29. van Hoek IM, Vandermeulen E, Peremans K, et al. Thyroid stimulation with recombinant human thyrotropin in healthy cats, cats with non-thyroidal illness and in cats with low serum thyroxin and azotaemia after treatment of hyperthyroidism. J Feline Med Surg 2010;12:117-121.

    30. Daniel GB, Sharp DS, Nieckarz JA, et al. Quantitative thyroid scintigraphy as a predictor of serum thyroxin concentration in normal and hyperthyroid cats. Vet Radiol Ultrasound 2002;43:374-382.

    31. Broome MR. Thyroid scintigraphy in hyperthyroidism. Clin Tech Small Anim Pract 2006;21:10-16.

    32. Diaz Espineira MM, Mol JA, Peeters ME, et al. Assessment of thyroid function in dogs with low plasma thyroxine concentration. J Vet Intern Med 2007;21:25-32.

    33. van Hoek I, Lefebvre HP, Peremans K, et al. Short- and long-term follow-up of glomerular and tubular renal markers of kidney function in hyperthyroid cats after treatment with radioiodine. Domest Anim Endocrinol 2009;36:45-56.

    References »

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