Dr Lizzie Youens BSc(Hons) BVSc MRCVS

The last patient of the morning is a 16-year-old cat, with a history of weight loss despite a ravenous appetite. She is polydipsic and the owner describes some erratic behaviors. Clinical examination reveals an unkempt coat, a body condition score of 3/9, a palpable thyroid nodule, and a grade I/VI systolic heart murmur with a heart rate of 200bpm. A fundic exam was performed, with no abnormalities seen. The rest of the exam is unremarkable.

Do the above details point to a certain diagnosis? Hyperthyroidism would be shooting straight to the top of my list of differential diagnoses. Learn more about tools you can utilize when monitoring hyperthyroid cats undergoing medical management. 

Feline hyperthyroidism: the basics

Feline hyperthyroidism (FHT) is the most common endocrine disease in older cats with a prevalence of around 10% in cats over 10 years of age.¹ 

Ninety-seven percent of cases are due to the development of a functional adenoma or adenomatous hyperplasia of the thyroid tissue. The remainder of cases are due to  thyroid carcinoma, most commonly adenocarcinoma.²

Current epidemiologic studies looking at risk factors for feline hyperthyroidism are in agreement that a single factor cannot explain the underlying aetiology of hyperthyroidism.²

Interestingly, a retrospective epidemiological cross‐sectional study, long‐haired non‐purebred cats were at increased risk of hyperthyroidism compared with shorthaired non‐purebred cats and purebred cats.³

There is no single symptom which is pathognomonic for FHT, but classic signs include weight loss, polyphagia, polyuria, polydipsia, agitation, and increased activity, tachycardia, tachypnea, vomiting, diarrhea, poor hair coat, and thinning skin.⁴

Making the diagnosis 

A definitive diagnosis is made via the demonstration of persistently elevated thyroid hormone (T4) occurring alongside clinical signs. Ninety percent  of cats with hyperthyroidism have an elevated total T4³, and 85% have mild to moderate increase in alanine aminotransferase (ALT).⁸ In cases where T4 measures beyond the reference interval, the diagnosis is clear.  

Suspect cases with poorly managed or undiagnosed comorbidities, such as CKD, can return as euthyroid. When hyperthyroidism is highly suspected additional thyroid function measurements, such as free T4 and thyroid-stimulating hormone (TSH), will be helpful.  

Studies have found that fT4 is above the Ri in 95% of cats with CKD and occult hyperthyroidism showing that they could be helpful in chalenging cases. Measurement of TSH concentration can also help as a high concentration rules out hyperthyroidism. Interpreting low TSH alone as a diagnosis for hyperthyroidism should be avoided as this can be found in euthyroid cats as well. 

Using the three measurements together results in an accurate diagnosis in over 98% of cases.⁵ It is important to recognize that if measuring free T4 that mutliple methods, immulite and equalibrium dialysis, exisit for measurement but have different reference intervals and therefore cannot be compared to eachother. Equalibrium dialysis (ED) is considered the gold standard.²  Veterinary diagnostic laboratories such as Moichor often offer a panel combining these thyroid tests to encourage immediate and accurate diagnoses.

Medical management of hyperthyroidism

There are currently a variety of  treatment options for FHT including radioactive iodine therapy, surgical removal of the thyroid glands, treatment with anti-thyroid drugs, or a low iodine diet. In cases of radio-iodine therapy and surgery, a cure should be achieved, but with medication, treatment will require lifelong application and regular monitoring.

For the purpose of this article, we shall focus on medical management using the drug methimazole, a common treatment modality. Methimazole blocks thyroid peroxidase, and thereby inhibits synthesis of the thyroid hormones.

The challenges of monitoring FHT

There are some challenges with monitoring cats with FHT on anti-thyroid drugs such as methimazole. The main treatment aim is to maintain the patient’s total T4 within normal range and resolve the clinical symptoms. Does this sound straightforward? Well, there are some trials involved in achieving this goal, including dealing with common comorbidities.]

Oral or Topical?

Non-compliance is a huge issue in the medical field. Not only are some medication schedules difficult to follow, but many feline patients are not cooperative with twice daily medication administration. As a result, alternative routes of medication administration have been evaluated. Both oral and topical routes for methimazole administration are used in practice. Although both routes have been proven to result in therapeutic blood levels, long term studies using transdermal application show that thyroid level control was not as consistent when compared to oral methimazole.^17,18 Despite this, for the cat who is pill adverse, this is a fair alternative route.  

What do we monitor?

There are a range of parameters to monitor to assess a hyperthyroid cat. They include the following:

·  Clinical Improvement – weight and body condition score, hair coat, heart rate, respiratory rate

·  Total T4

·  CBC (complete blood count)

·  Renal parameters

·  Hepatic parameters

·  Blood pressure

·  Free T4 and TSH

·  Specific testing for concurrent disease

It’s a long list! So why do we need all of these monitoring assessments, and how often should we be seeing these patients?

Monitoring: TT4 levels 

The starting dose for methimazole is 1.25-2.5mg/cat, given twice daily. Most hyperthyroid cats become euthyroid after 2-3 weeks on treatment⁶, so it is recommended to re-test T4 at this point. When retesting, it is important to use the same methodology and lab to ensure that conclusions from data trends are as accurate as possible. The aim is to retain T4 levels within the reference range.⁴ A physical examination should always be performed concurrently: checking weight, heart rate, and coat condition for signs of improvement.  

·  If the cat is still hyperthyroid, increase dose by 1.25-2.5mg/day and re-test in 2-3 weeks

·  If doses reach levels over 10mg/cat/day, compliance may need to be questioned, and co-morbidities examined

·  If the T4 drops below reference range, decrease dose by 1.25-2.5mg/day and re-test in 2 weeks, alongside renal parameters.⁴

Once euthyroid, a clinical response should be seen within 2-6 weeks. The outcome is usually good with a high level of response to methimazole treatment.⁹

 However, regular and continuous monitoring is required. Methimazole doses are expected to increase over time since methimazole does not destroy thyroid tissue nor counter its growth and the size and number of thyroid nodules producing active hormones will often grow. T4 monitoring is therefore recommended every 4-6 months in cats who are euthyroid on their current methimazole dose. In cases where patients are not euthyroid, repeat T4 levels are advised 2-3 weeks after every dose change.

Monitoring: concurrent disease 

As hyperthyroidism is primarily a disease of older cats, it is common for these patients to have co-morbidities.² 

Blood pressure

Hypertension has been shown in around 10-23% of hyperthyroid cats at time of diagnosis.¹¹ Additionally, around a quarter of cats who are not hypertensive at the time of an FHT diagnosis develop hypertension once euthyroid.¹¹ It is therefore recommended that systolic blood pressure is checked at time of diagnosis and at every monitoring appointment. For cats who are suspected to have stress-induced hypertension at time of veterinary attention, a fundic exam to check for hypertensive retinopathy is recommended.

Heart disease

Concurrent cardiac disease is again common in hyperthyroid cats and is often a sequale of unmanaged hypertension. Unless the patient is in active heart failure, it is recommended to achieve euthyroidism before evaluating the heart, as correction of T4 levels and hypertension can correct cardiac parameters in some cases.⁴ If N-terminal probrain naturietic peptide (NT-proBNP) remains high three months after the patient has been euthyroid, a cardiac work-up is recommended.

Chronic Kidney Disease (CKD)

It is estimated that between 15-51% of cats with hyperthyroidism also have some degree of renal disease.¹²

FHT can mask the presence of CKD, as the high thyroxine levels increase renal blood flow and glomerular filtration rate. Serum creatinine levels also become unreliable due to the effect on FHT on the reduction of muscle mass.

Due to the need for 75% of renal function to be compromised prior to creatinine and BUN elevation, SDMA has been investigated as an early marker for renal disease in FHT patients. Based on current studies it has not been found to be consistently predictive of the development of azotemia after treatment for FHT.¹⁶  

CKD also has an effect on treatment and monitoring protocols. It was long thought that maintaining TT4 levels slightly above reference range had a positive “protective” effect on renal function, but it is now accepted that even mild elevations in T4 can exacerbate glomerular damage.¹² Similarly, low levels of T4 were not thought to be harmful as long as the patient was clinically well, but it is now well understood that iatrogenic hypothyroidism can worsen renal disease and lead to increased morbidity and mortality.¹³

It is recommended to always treat FHT, despite co-morbidities and the potential to ‘un-mask’ CKD.⁴ The guidelines differ according to the level of renal disease, and so it is important to stage the patient using the International Renal Interest Society (IRIS) guidelines before treatment commences.

Cats who are non-azotemic at time of diagnosis should be started on normal doses of methimazole. Those cats who become azotemic after starting treatment have markedly lower survival times.¹³ These cats should be closely monitored using serial creatinine, T4, and TSH levels. 

Patients who are azotemic at time of diagnosis with FHT are common. The diseases should both be treated, concurrently. Cats in IRIS stage 1 or 2 should be treated for thyroid disease as normal. Those with stage 4-5 renal failure need more careful treatment with lower doses of methimazole and active management of the CKD.⁴

Monitoring: adverse effects of methimazole

Methimazole has various side effects, but most are mild and self-limiting. The adverse effects are not related to dose.¹⁴ Mild adverse complaints include gastrointestinal upset, lethargy, and facial pruritus. Most effects appear within the first 6 weeks of therapy.¹²

However, rarely, more serious concerns are raised. Severe hepatopathy has been noted on methimazole treatment as well as blood dyscrasias: leukopenia, anemia and thrombocytopenia. A CBC and hepatic parameters should always be included in the first monitoring appointment for this reason. 

Monitoring cats on methimazole treatment: a summary 

Regular monitoring of hyperthyroid cats is essential to achieve therapeutic purpose, avoid hypothyroidism, assess for serious adverse effects, and to detect co-morbidities. This monitoring can be achieved by a combination of physical exam and laboratory testing and must remain regular and comprehensive. 

·  Physical examination should occur at every appointment

·  TT4 should be tested initially to confirm diagnosis, then every 2-3 weeks until euthyroid, and then every 4-6 months

·  FreeT4/TSH – used to confirm diagnosis and to aid in the monitoring for iatrogenic hypothyroidism

·  NT pro-BNP – used if signs of cardiac disease, signposts to further investigation if still high 3 months after euthyroidism is achieved

·  BP – tested at every monitoring appointment and treated accordingly

·  CBC – part of primary work-up, then used after commencement of medication and after dose changes to monitor for adverse reactions

·  Hepatic parameters - part of primary work-up, then used after commencement of medication and after dose changes to monitor for adverse reactions

·  Renal parameters – part of initial work up, then monitored as needed depending if azotemia noted.

 Some diagnostic labs combine TT4 measurements into part of a bundle, which allows for ease of sampling and testing if multiple parameters require monitoring, for example Moichor’s Extended Wellness Bundle.

And what about our patient?

Remember the 16-year-old cat from our opening paragraph? Well, she was hyperthyroid with a massively increased TT4 at 156nmol/l. Given her age, her owner opted for treatment with methimazole twice daily. After a few dose adjustments, she stabilized well on 7.5mg of methimazole daily, split over two doses. Prognosis is variable for FHT, as mortality is often more influenced by co-morbidities than the hyperthyroidism itself¹³ if the patient is well controlled. Cats without concurrent CKD have a median survival time of 5.3 years.¹⁵ 

References

1. Peterson ME. Hyperthyroidism in cats: what’s causing this epidemic of thyroid disease and can we prevent it? J Feline Med Surg 2012; 14: 804–818

2.   Yu L, Lacorcia L, Johnstone T. Hyperthyroid cats and their kidneys: a literature review. Aust Vet J. 2022 Sep;100(9):415-432. doi: 10.1111/avj.13179. Epub 2022 Jun 16. PMID: 35711100; PMCID: PMC9543258.

3. Crossley VJ, Debnath A, Chang YM et al. Breed, coat color, and hair length as risk factors for hyperthyroidism in cats. J Vet Intern Med 2017;31:1028–1034. 10.1111/jvim.14737.

4. Carney HC, Ward CR, Bailey SJ, et al. 2016 AAFP guidelines for the management of feline hyperthyroidism. J Feline Med Surg. 2016;18(5):400-416

5. Wehner A, Koehler I, Ramspott S, Hartmann K. Relationship between total thyroxine, thyroid palpation and a clinical index in hyperthyroid and healthy cats and cats with other diseases. J Feline Med Surg. 2019;21(8):741-749

6. Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction, 3rd ed. Elsevier; 2014

7. Peterson ME, Guterl JN, Nichols R, Rishniw M. Evaluation of serum thyroid-stimulating hormone concentration as a diagnostic test for hyperthyroidism in cats. J Vet Intern Med. 2015;29(5):1327-1334

8. Scott-Moncrief JC. Feline hyperthyroidism. In: Feldman EC, Nelson RW, Reusch CE, et al. (eds). Canine and feline endocrinology and reproduction. 4th ed. St Louis, MO: Elsevier, 2015: 136–195

9. Baral RM, Peterson ME: Hyperthyroidism. In: Little SE (ed). The cat: clinical medicine and management. St Louis, MO: Elsevier Saunders, 2012, pp 571–583

10. Morrow LD, Adams VJ, Syme HM. Hypertension in hyperthyroid cats: prevalence, incidence, and predictors of its development. J Vet Intern Med 2009; 23: 699

11. Syme HM and Elliott J. The prevalence of hypertension in hyperthyroid cats at diagnosis and following treatment [abstract]. J Vet Intern Med 2003; 17: 754

12.  Williams T, Peak K, Brodbelt D, et al. Survival and the development of azotemia after treatment of hyperthyroid cats. J Vet Intern Med 2010; 24: 863–869

13.  Daminet S, Kooistra H, Fracassi F, et al. Best practice for pharmacological management of hyperthryoid cats with antithyroid drugs. J Small Anim Pract 2014; 55: 4–13

14.  Peterson ME, Kintzer PP, Hurvitz AI. Methimazole treatment of 262 cats with hyperthyroidism. J Vet Intern Med 1988; 2: 150–157

15.  Milner RJ, Channell CD, Levy JK, et al. Survival times for cats with hyperthyroidism treated with iodine 131, methimazole, or both: 167 cases (1996–2003). J Am Vet Med Assoc 2006; 228: 559–563

16.  Geddes, R. & Aguiar, J. (2022) ‘Feline comorbidities: balancing hyperthyroidism and concurrent kidney disease.’ J Fel Med Surg 24(7) 641-650

17.Lécuyer M, Prini S, Dunn ME, Doucet MY. Clinical efficacy and safety of transdermal methimazole in the treatment of feline hyperthyroidism. Can Vet J. 2006 Feb;47(2):131-5. doi: 10.4141/cjas67-019. PMID: 16579038; PMCID: PMC1345727.

18. Boretti, Felicitas S., et al. "Transdermal application of methimazole in hyperthyroid cats: a long-term follow-up study." Journal of feline medicine and surgery 16.6 (2014): 453-459