October 2021

Feline Thyroid Disease: What’s the TSH?

By Dr. Stefanie DeMonaco, DVM, MS, DACVIM

In this VETgirl online veterinary continuing education blog sponsored by Zomedica, Dr. Stefanie DeMonaco, DVM, MS, DACVIM reviews what you need to know about cats with hyperthyroidism. When should you be measuring a TSH in addition to a tT4 in your hyperthyroid feline patients? Please note the opinions in this blog are the expressed opinion of the author and not directly endorsed by VETgirl.

The use of thyroid-stimulating hormone (TSH) in the diagnosis of feline thyroid disease has recently become more routine in clinical practice. Concurrent nonthyroidal illness (NTI) in hyperthyroid cats and those with mild hyperthyroidism can be problematic to diagnose when total T4 (tT4) concentration is within the reference interval. Concurrent TSH can be helpful in supporting the diagnosis. In addition to screening for hyperthyroidism, TSH has become part of the routine diagnosis of feline iatrogenic hypothyroidism that can occur after treatment for hyperthyroidism. The current use and best practices of TSH in cats with hyper- and hypothyroidism will be discussed.

Use of TSH to diagnose hyperthyroidism
Feline hyperthyroidism is the most common endocrinopathy in aged cats. Diagnosis is typically made by documenting an increased tT4 concentration in a cat with compatible clinical signs of hyperthyroidism. However, 10% of hyperthyroid cats will have a high-normal tT4 concentration due to early hyperthyroidism or NTI.1 This occurs because cats with early hyperthyroidism can have tT4 fluctuating in and out of the reference range, and NTI can lower tT4 into the reference range. In those cases, measuring TSH with free T4 (fT4) can aid in the diagnosis.

One of the limitations of using fT4 in cats with NTI is that 20% of cats will have a falsely elevated fT4,1 further confounding the diagnosis of hyperthyroidism. TSH is commonly used in humans and dogs for the diagnosis of thyroid disease, but until most recently, has not been routinely used in cats. The current assay that is widely available uses canine TSH assay (cTSH) to measure feline TSH. The limitation of this assay is the lowest detection limit (<0.03 ng/dL), as this does not differentiate low-normal concentrations from those below the reference interval. A closer look at cTSH in hyperthyroid and euthyroid cats highlights how the lower limit of detection obscures the diagnosis of hyperthyroidism. Serum cTSH was undetectable in most – if not all – hyperthyroid cats, but it was also undetectable in one-third of euthyroid cats.1 The overlap of undetectable cTSH concentrations between hyperthyroid and euthyroid cats is a limiting factor in the diagnosis of hyperthyroidism. The accuracy of cTSH improves when measured in combination with tT4 and fT4. A tT4 concentration within the upper-third of the reference range with high serum fT4 and undetectable TSH is suggestive of hyperthyroidism.

When considering cTSH for the diagnosis of thyroid disease, it is important to understand how NTI impacts the concentration in order to appropriately interpret the test. There are few studies that have evaluated cTSH in cats with nonthyroidal illness. In sick cats, TSH generally remains within the reference interval, but up to one-third of cats were found to have undetectable cTSH concentrations attributed to the effects of severe NTI.1 The degree of suppression of serum cTSH concentrations in cats with NTI appears to be impacted mostly by severity of illness where TSH decreases as severity of illness increases. The category of disease has minimal impact on cTSH, similar to tT4 and fT4. Again, the main limiting factor of cTSH is the lower detection limit. In cats with NTI and undetectable cTSH concentrations, it is uncertain whether cTSH could be low-normal or actually suppressed in these cats. Clearly, a TSH assay optimized for cats with the ability differentiate low-normal vs. those below the reference range has the potential to improve diagnosis of hyperthyroid cats.

A feline-optimized TSH (fTSH) assay has recently become available with a lowest limit of detection of 0.008 ng/mL and low-normal is 0.01 ng/mL.2 Current studies have shown that this assay readily differentiates between healthy and hyperthyroid cats. When evaluating serum fTSH in clinically healthy cats compared to hyperthyroid cats, the majority of healthy cats had a serum fTSH above the reference interval (> 0.01 ng/mL) whereas the majority of hyperthyroid cats had an fTSH concentration below the reference interval       (< 0.01 ng/mL). Current studies on how fTSH performs in the face of nonthyroidal illness as well as fTSH in cats with a various severity of hyperthyroidism are necessary.

Use of TSH to diagnose hypothyroidism
Iatrogenic hypothyroidism is the most common form of hypothyroidism in cats and occurs after treatment of hyperthyroidism with anti-thyroidal drugs, radioiodine therapy, and thyroidectomy. Based on current data, the prevalence of iatrogenic hypothyroidism in cats is approximately 10-25%.1 Cats do not display overt signs of hypothyroidism and it can be easily missed if serum TSH is not measured. Feline hypothyroidism is associated with decreased survival and kidney function, making an early and accurate diagnosis imperative. The screening test of choice for hypothyroidism in dogs is tT4; however, concurrent diseases (e.g., chronic kidney disease, or CKD, in cats) can falsely lower levels. The high prevalence of concurrent CKD in cats treated for hyperthyroidism could lead to overdiagnosis of hypothyroidism if tT4 is used alone. Luckily, serum cTSH performs well for the diagnosis of hypothyroidism and accurately differentiated azotemic iatrogenic hypothyroid cats from euthyroid azotemic cats. A diagnosis of hypothyroidism is supported by a low tT4 and an elevated TSH concentration. The current recommendation in monitoring cats post treatment of hyperthyroidism, particularly with I-131, is to routinely monitor both tT4 and TSH in order to catch the diagnosis of hypothyroidism as soon as possible and initiate treatment when necessary.

Currently, the best use of serum cTSH in cats is for the diagnosis of iatrogenic hypothyroidism as there are limitations for its use in feline hyperthyroidism. The new fTSH assay has the potential to improve diagnosis and outcome in hyperthyroid cats given its ability to differentiate euthyroid from hyperthyroid cats. Further studies evaluating fTSH in cats are necessary, particularly those with NTI.

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References:

  1. Peterson, Mark. (2013). More Than Just T4: Diagnostic testing for hyperthyroidism in cats. Journal of Feline Medicine & Surgery. 15. 765-77.
  2. Wood A, Ryder M, Harmon I. TRUFORMA™ Point-of-Care Canine and Feline Thyroid-Stimulating Hormone (TSH) assay. Zomedica website. https://zomedica.com/wp-content/uploads/2021/09/TRUFORMA-TSH-White-Paper.pdf

 

  2. Danielle Schafer says:

    Very helpful thank you, so do you suggest doing a TSH when you have a cat that has hyperthyroidism and newly diagnosed kidney disease ? Or do I treat both and then recheck the t4?

  3. Justine Lee says:

    Great question, Danielle. Once that you have your definitive diagnosis of hyperthyroidism, the job of evaluating TSH is done. So, at this point, monitoring the tT4 is all that is necessary. I would start with methimazole and support the kidneys – however necessary. If possible, check a blood pressure as well!

  4. Janae Saffold says:

    Curious to find out which labs are offering the feline TSH or if not yet universally available??

  5. Paris J. Revoir, DVM says:

    The only way currently to perform a feline optimized TSH is on the TRUFORMA platform, available from Zomedica. None of the commercial labs are offering this option, only canine TSH is available.

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