Thyroid storm: does this syndrome really exist in cats?

Dear Editors, – I am writing to comment on the recently published 2016 AAFP Guidelines for the Management of Feline Hyperthyroidism. ¹ Specifically, I wish to comment on the following statements made in the Guidelines concerning ‘thyroid storm’ in cats with hyperthyroidism:

‘Thyroid storm is a rare, but life-threatening, complication of FHT. It results from a rapid increase in serum thyroid hormone. Causes include damage to the thyroid gland during ¹³¹I therapy or vigorous thyroid gland palpation, abrupt withdrawal of antithyroid medication, anesthesia, exacerbation of NTD or a stressful event. If you anticipate the occurrence of a possible event, using a beta-adrenergic antagonist, such as atenolol at 6.25 mg/cat q24h, as a prophylactic treatment at least 24 h prior to the event will effectively prevent clinical signs.’

For this statement, only a single reference comprising a non-refereed review article (Ward 2007 ² ) was cited. Even in that review paper, however, it states that ‘Thyroid storm is not as well defined a syndrome in feline medicine.’ I completely agree with that statement and would even argue that, although we certainly see cats that exhibit signs of severe and chronic hyperthyroidism that may be exacerbated by stress or acute withdrawal of chronic methimazole therapy, I do not believe that cats truly develop thyroid storm, as defined in human medicine. Even if it does occur, the idea that radioiodine may induce feline thyroid storm has never been documented, and I have never seen a cat that developed ‘storm’ after such radioiodine, although I have been routinely treating cats with radioiodine for over 36 years.^3–5

So what exactly is thyroid storm, at least as defined in human hyperthyroid patients? Thyroid storm is a term applied to a clinical syndrome marked by exaggerated manifestations of thyrotoxicosis and, because of its high mortality, represents the most serious complication of hyperthyroidism. ⁶

In human hyperthyroid patients, it is not possible to distinguish those with thyroid storm from those with uncomplicated thyrotoxicosis on the basis of routine laboratory or thyroid function tests. ⁷ Rather, the diagnosis is a clinical one based on the identification of signs that point to decompensation of a number of organ systems. Manifestations characteristic of thyroid storm include high fever/hyperthermia (a near universal finding)^6,8–10 and central nervous system (CNS) signs varying from marked agitation, delirium, mania and confusion to stupor, obtundation and even coma (CNS signs are second only to fever as a major sign of storm).^6–8,10,11 In thyroid storm, the typical cardiovascular findings of mild-to-moderate tachycardia associated with uncomplicated hyperthyroidism may be supplanted by severe, accelerated tachycardia, often with arrhythmias or congestive heart failure.^6,9 Other multiorgan dysfunction common in thyroid storm includes gastrointestinal dysfunction (severe nausea, profuse vomiting, severe diarrhea) and, in severe cases, hepatic failure with jaundice.^6–9,12 The earliest possible diagnosis and subsequent implementation of therapy are required to avoid a fatal outcome. Even with early diagnosis and treatment, survival is not guaranteed, with reported mortality rates ranging from 10–75% in hospitalized patients.^6,8,12

Thyroid storm is frequently precipitated by physical stress, such as infection or other underlying illness, non-compliance with antithyroid medications, surgery or trauma.^6–8 Thyroid storm following the administration of radioactive iodine has been reported only rarely and is somewhat controversial.^13–16 Currently, infection remains the most common cause of thyroid storm in the in-patient setting.^8,9

Patients in thyroid storm are critically ill, and they are generally hospitalized in an intensive care unit. A prompt, aggressive multipronged approach to management of thyroid storm is needed to achieve a successful outcome.^6–9,15,17 First, the increased thyroid production and release of thyroxine (T4) and triiodothyronine (T3) must be inhibited by the use of antithyroid drugs, such as methimazole. Secondly, the effects of the remaining excessive circulating concentrations of free T4 and T3 must be attenuated by use of beta-adrenergic blockers. The third arm of therapy is directed against the underlying systemic decompensation (fever, congestive heart failure, shock, etc). And, finally, it is important to address any underlying precipitating illness such as infection, or storm may recur after initial control. Because of the strikingly bleak prognosis associated with untreated storm, no component of this multipronged approach to therapy can be neglected.

Although one might believe it prudent to err on the side of overdiagnosis of thyroid storm to assure appropriate treatment, aggressive therapy is not without possible adverse consequences. ¹⁰ As in cats, high doses of antithyroid drugs may increase adverse drug reactions (eg, hepatotoxicity, agranulocytosis), ¹⁸ and beta-blockers may cause further cardiovascular decompensation in patients with occult underlying failure. ¹⁹ Hence, unnecessary treatment for suspected thyroid storm is not without potential harm.

In hyperthyroid cats treated with radioiodine, we have not seen increases in serum T4 or T3, as has sometimes been documented in human patients.^16,20 The thyroid ¹³¹I kinetics and response to radioiodine is much faster in cats than in man,^20–22 so side effects or response in human patients (generally with Graves’ disease) cannot be easily compared with those of cats with unilateral or bilateral adenomatous thyroid nodules. ²³

So can radioiodine treatment induce thyroid storm in cats? To help specifically answer this question, we carefully reviewed the medical records of all 1179 hyperthyroid cats treated with radioiodine at our clinic over the past 4 years. All of these cats were originally diagnosed and referred by their regular veterinarian and about half had been treated with methimazole. With our ¹³¹I protocol, cats are taken off methimazole at least 7 days prior to the date of our evaluation. In 11 (1%) cats with severe, long-standing hyperthyroidism (poorly controlled despite increasing doses of methimazole), however, we continued the methimazole up to 3 days prior to ¹³¹I treatment. At the time of our evaluation at our clinic, we draw blood for a complete thyroid profile (serum total and free T4, total T3 and thyroid-stimulating hormone [TSH]) and perform thyroid scintigraphy to confirm the diagnosis.^24,25 All cats are then treated with radioiodine on the same day. Although several of our 1179 cats showed signs of severe thyrotoxicosis, especially those with long-standing and severe hyperthyroidism, no cat was considered to be suffering from thyroid storm based on the lack of marked hyperthermia or CNS decompensation, and none received any specific treatment for thyroid storm.

During their stay at our facility, all cats are monitored by a licensed veterinary technician four to six times daily. A log is kept and included in the medical record of each cat’s attitude (eg, alert and active vs depressed), appetite, and signs of vomiting, diarrhea, polyuria or polydipsia (water intake is measured daily). We also have webcams installed in each cat cage, allowing both hospital staff and owners to monitor the cats as needed, 24 h a day. Approximately 24 h after treatment, we check each cat’s vital signs and repeat the physical examination. We also monitor the radiation counts emitted from the cat’s thyroid tumor on a daily basis until the counts are low enough for release back to the owner (generally 3–6 days).

Upon review of these 1179 hospitalized cats treated with radioiodine, no cat developed signs of thyroid storm and all cats were discharged back to their owners without signs of thyroid storm. Again, none of these cats received any specific emergency treatment that would be needed to prevent death if they did indeed develop true thyroid storm.

Based on my data and clinical experience, I do not believe that cats develop what can or should be termed thyroid storm. Even if it does occur, the idea that radioiodine may induce feline thyroid storm has never been reported, and certainly has not been observed in any of my treated cats. The idea that I ‘missed’ the diagnosis of thyroid storm in some of my ¹³¹I-treated cats is next to impossible, since survival without any treatment would not be expected.^6,8,12

Mark E Peterson DVM, Dip ACVIMAnimal Endocrine Clinic, 21 West 100th Street, New York, NY 10021, USA