Boretti, Felicitas S

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Zurich Open Repository andArchiveUniversity of ZurichUniversity LibraryStrickhofstrasse 39CH-8057 Zurichwww.zora.uzh.chYear: 2022Feline hyperthyroidism: treatment, all but I-131Boretti, Felicitas SPosted at the Zurich Open Repository and Archive, University of ZurichZORA URL: https://doi.org/10.5167/uzh-226014Conference or Workshop ItemPublished VersionOriginally published at:Boretti, Felicitas S (2022). Feline hyperthyroidism: treatment, all but I-131. In: ESVE Summer School of VeterinaryEndocrinology, Bologna, 3 July 2022 - 9 July 2022, ESVE. 1 Feline hyperthyroidism: treatment (all, but I-131) ESVE summer school Bologna July 2022 Felicitas Boretti, DipACVIM, DipECVIM-CA Clinic for Small Animal Internal Medicine, Zurich, Switzerland   Treatment /management options include: Reversible: medical treatment with anti-thyroid medication or nutritional management with an iodine-restricted diet  Irreversible/curative: radio-iodine treatment, surgical thyroidectomy, less common ultrasound-guided heat or ethanol ablation of the thyroid gland.  Ideally, medical options should be tried and tested before considering an irreversible form of treatment. The final decision for treatment should be made together with the owner considering among others, the cat's age, tolerance of medications, owner's finances and ability to be compliant with medications, presence of concurrent disease, availability, and willingness of the owner to pursue I131.   Anti-Thyroid drugs The thioureylene methimazole and its pro-drug carbimazole are the drug of choice for the treatment of feline HT. They inhibit thyroperoxidases in the thyroid follicular cells thereby leading to a reversible decrease in the synthesis of thyroid hormones (T4 and T3).  The recommended starting dose of methimazole is 2.5 mg/cat PO twice daily, a sustained-release formulation of carbimazole is available in some European countries and is started at 10 or 15 mg, PO, once daily.  Transdermal medication If owners are unable to pill the cat or if gastro-intestinal side effects occur, a change to a transdermal methimazole formulation can be tried. Currently, there are no registered products, and the cream must be produced by compounding pharmacies. Dosage usually is the same as with the oral product. It is important to instruct the owners to wear gloves to administer the drug to avoid “self-therapy”.   Treatment monitoring The first reassessment is recommended after 2-4 weeks of therapy, depending on the clinical condition of the cat and the presence of concurrent disease (e.g., cardiac failure) and pre-treatment blood parameters (e.g., urea, creatinine). If euthyroidism is not achieved after 4 weeks, dosage adjustments are usually made in 1.25–2.5 mg/day increments. Owner compliance must be assessed before increasing the dose. Serum T4 concentration should be maintained within the middle of the reference interval. For long-term treatment, it is very important to avoid iatrogenic hypothyroidism (see below). Findings of low serum T4 with high TSH concentrations are diagnostic for iatrogenic hypothyroidism, and therefore the daily dose of methimazole should be decreased.   Adverse effects of medical therapy  Adverse reactions associated with anti-thyroid drugs usually occur within the first 3 months of starting therapy, including nausea, vomiting, lethargy, diarrhea, and facial excoriation.  Life-threatening adverse reactions, which can rarely occur, include agranulocytosis, thrombocytopenia, and hepatopathy. If treatment is stopped, clinical signs are reversible. If only mild leukopenia, eosinophilia, and lymphocytosis are noted, they should be closely monitored, as they usually resolve despite continuing treatment.  Disadvantages of medical therapy are:  Compliance, treatment intolerance, efforts, and costs associated with lifelong treatment/monitoring. Another major disadvantage of medical therapy is that the disease tends to advance despite the medication (no cytotoxic effect of methimazole/carbimazole). There is evidence that the prevalence of large thyroid tumors, multifocal disease, intrathoracic thyroid masses, and suspected malignant disease increase with disease duration in medically treated cats.    2 Limited-Iodine / iodine-restricted Diet  Iodine is essential in the production of thyroid hormones and limited nutritional availability of iodine leads to reduced thyroid hormone concentrations. Within 4 to 8 weeks of strictly feeding the commercially available diet (Hill`s prescription diet y/d Feline thyroid health), approximately 90% of HT cats become euthyroid, after 12 weeks almost all cats have T4 concentrations within the reference interval. So far, iatrogenic hypothyroidism could not be shown even after prolonged feeding of the diet. A major disadvantage however is that all other food, treats or table scraps must be strictly avoided because they will counteract the effects of the diet and re-increase the T4 concentration. This can be problematic in the long-term management of the disease. Also, the composition of y/d (rather low protein and high carbohydrate content) may not be optimal in the long run for cats. But, against earlier concerns, the diet can be used in a muti-cat household, where healthy cats have access to the diet. In a recent study, it could be shown that feeding a limited-iodine diet for 2 years to healthy adult cats did not lead to iatrogenic hypothyroidism or goiter.  Surgical thyroidectomy  Depending on the experience of the surgeon, thyroidectomy can be a good treatment option especially if radio-Iodine treatment is not available. The risk of anesthesia in untreated HT cats is high and to decrease peri- and postoperative mortality, cats should be medically treated and stabilized before the surgery.  Surgical complications include post-op laryngeal paralysis/voice change, Horner's syndrome, and iatrogenic hypoparathyroidism (hypocalcemia) if bilateral surgery is performed. Calcium levels should be monitored 3–7 days postoperatively and hypocalcemia treated if clinical symptoms occur or if concentrations of ionized Calcium are in the very low range. Recovery of the parathyroid gland function is possible (dependent on the surgical technic) but can take days to months. Temporary or permanent hypothyroidism (bilateral thyroidectomy) is also possible and has to be monitored at regular intervals. Cats can recover and become euthyroid, however, if clinical signs of hypothyroidism develop or azotemia worsens, levothyroxine supplementation should be started. Owners also have to be advised that even after bilateral thyroidectomy, cats can become hyperthyroid.   Table 1: Comparison of options for managing cats with hyperthyroidism  Treatment option Advantage Disadvantage    Anti-thyroid drugs Reversible Easily available Initial costs low and spread over time  No hospitalization  Not curative Daily administration  Compliance difficult Side effects possible   Limited-iodine diet  Reversible Easily available Costs spread over time  No hospitalization  Not curative Only single food required  Compliance difficult  Thyroidectomy  Curative  Anesthesia and hospitalization required  High initial costs  Risk of postoperative hypocalcemia and other surgical complications  Not effective for ectopic tissue Recurrence possible Radio-iodine  See lecture of Prof. Dr. M. Peterson: “Feline hyperthyroidism: radioactive iodine treatment”  3  Post-treatment renal disease  Chronic kidney disease (CKD) may be masked during the hyperthyroid state and due to the decrease in the glomerular filtration rate during therapy, overt CKD can develop (independent of the treatment modality). The prevalence of CKD varies between 15 and 60%. Unfortunately, to date, there is no clinical test that can reliably predict which cats have concurrent CKD that will become overt after treatment of the hyperthyroid state.  Recently, the determination of SDMA has been evaluated in several studies as a possible predictor for pre-existing CKD in hyperthyroid cats. There is general agreement that sensitivity is only poor (about 15-30%), which means that finding a normal SDMA cannot exclude CKD. Specificity seems very good with values reaching 98%. However, it could be shown that when GFR was determined concurrently, there was no significant relationship between SDMA and GFR before and 1 month after radioiodine treatment. Further, in another study, there was an unexpected decrease in SDMA after treatment in almost 30% of the cats. It is assumed that extra-renal factors might interfere with the specificity of SDMA. Therefore, SDMA should be used cautiously for the prediction of CKD. (Please also refer to the lecture of Prof. Dr. S. Daminet: “Impact of thyroid disease on our dogs and cats' kidney”)  During therapy, care must be taken to avoid iatrogenic hypothyroidism as it may contribute to the development of azotemia and these cats may have a shorter survival time compared to azotemic but euthyroid cats. An increased TSH is a sensitive marker for the diagnosis of iatrogenic hypothyroidism. However, TSH seems to correlate with time since the start of the treatment and it can take at least 3 months of treatment before an increase in TSH is observed. Overt hypothyroidism, which is defined as a T4 below and a TSH above the reference interval seems to be more problematic than subclinical hypothyroidism (T4 within and only TSH above the reference interval) concerning the development of azotemia and survival time.    The prognosis of hyperthyroid cats which are non-azotemic before starting the therapy is good.     References:  Available from the author upon request. 

Feline hyperthyroidism: treatment, all but I-131

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Feline hyperthyroidism: treatment, all but I-131

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