In human medicine measurement of thyroid stimulating hormone (TSH) is considered the single best test for accurate assessment of thyroid function. There are two important reasons for this. Firstly, there is a log-linear relationship between TSH and free T4 such that a small change in free T4 results in a much greater change in TSH. Secondly and of significant relevance for diagnosing hyperthyroidism, the current assays are capable of measuring TSH values up to 30 times lower than the lower limit of the reference interval. However, TSH is species specific and no dedicated feline assay is yet available. The greater homology of feline with canine (95%) rather than human (78%) TSH has prompted widespread use of the canine assay in cats. Whilst of some value in investigating thyroid disease in cats, the limitations of this assay must be acknowledged.

The most commonly used canine TSH assay is chemiluminescent (Canine TSH®, Siemens) and it is suggested that this assay is capable of measuring only approximately 35% of recombinant feline TSH by contrast to 75% of similarly derived recombinant canine TSH.¹ As a consequence, the upper limit of the reference interval is much lower (approximately 0.3 ng/mL) in cats compared to dogs (approximately 0.6 mg/mL). More importantly, the canine assay is already known to be incapable of distinguishing normal from low values with the lower reference limit simply defined as <0.03 ng/mL. Clearly this has major implications for the cat where suppressed (i.e., low) values are expected in hyperthyroidism. In order to circumvent this problem, results for cats are usually quoted as being detectable (≥0.03 ng/mL) or undetectable (<0.03 ng/mL). Greater imprecision is expected at these limits and could potentially result in the same sample giving different values on the same or different assay runs.

Almost all hyperthyroid cats have undetectable TSH concentrations and diagnostic sensitivity approaches 98%.² A small number of hyperthyroid cats have detectable values including some that are not near the lower limit of the reference interval. The reasons for this are unclear. In some cases, prior antithyroid medication may play a role. Many healthy cats and those with non-thyroidal illness may also have undetectable values and diagnostic specificity is only approximately 70%. This is not surprising given the limitations of the assay and the fact that TSH suppression is likely a feature of non-thyroidal illness in cats as it is in humans. With such assay performance, TSH is not recommended as a sole diagnostic test for feline hyperthyroidism. Rather it may be used to provide support for hyperthyroidism in certain circumstances. Demonstrating undetectable TSH in a cat with appropriate clinical signs with high reference interval total T4 supports a diagnosis of hyperthyroidism. Demonstrating detectable TSH concentrations is more likely to reflect euthyroidism, particularly if there are limited clinical signs.

Measurement of TSH may also be helpful in depicting which cats may become overtly hyperthyroid within months. Cats with undetectable TSH values are more likely to become hyperthyroid than those with undetectable values.³

Despite the limitations of using TSH to diagnose hyperthyroidism, it appears to perform particularly well in diagnosing iatrogenic subclinical and overt hypothyroidism in cats after treatment for hyperthyroidism.^4-6 In such instances measurement of TSH appears to be the most sensitive and specific diagnostic test for hypothyroidism. Diagnosis of hypothyroidism is particularly important given its known relationship with kidney disease and its adverse effect on survival.⁷

References

1.  Ferguson DC, Caffall Z, Hoenig M. Obesity increases free thyroxine proportionally to nonesterified fatty acid concentrations in adult neutered female cats. J Endocrinol. 2007;194:267–273.

2.  Peterson ME, Guterl JN, Nichols R, et al. Evaluation of serum thyroid- stimulating hormone concentration as a diagnostic test for hyperthyroidism in cats. J Vet Intern Med. 2015;29:1327–1334.

3.  Wakeling J, Elliott J, Syme H. Evaluation of predictors for the diagnosis of hyperthyroidism in cats. J Vet Intern Med. 2011;25:1057–1065.

4.  Peterson ME, Nichols R, Rishniw M. Serum thyroxine and thyroid-stimulating hormone concentration in hyperthyroid cats that develop azotaemia after radioiodine therapy. J Small Anim Pract. 2017;doi:10.1111/jsap.12695.

5.  Aldridge C, Behrend EN, Martin LG, et al. Evaluation of thyroid-stimulating hormone, total thyroxine, and free thyroxine concentrations in hyperthyroid cats receiving methimazole treatment. J Vet Intern Med. 2015;29:862–868.

6.  Lucy JM, Peterson ME, Randolph JF, et al. Efficacy of low-dose (2 millicurie) versus standard-dose (4 millicurie) radioiodine treatment for cats with mild-moderate hyperthyroidism. J Vet Intern Med. 2017;31:326–334.

7.  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.