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Radioiodine therapy for hyperthyroidism – Should “one size fit all”?

Lucy JM, Peterson ME, et al.  Efficacy of low-dose (2 millicurie) versus standard-dose (4 millicurie) radioiodine treatment for cats with mild-to-moderate hyperthyroidism.  J Vet Intern Med 2017; 31:326-34.

Treatment of feline hyperthyroidism with a radioactive isotope of iodine (I-131; radioiodine) is the safest, easiest, and most effective way of eliminating this disease.  Medical therapy with methimazole or a markedly iodine-restricted diet only suppresses hyperthyroidism and does not cure it, and over time cats treated in this way may escape control and ultimately develop thyroid carcinomas. Surgical thyroidectomy is a potentially curative option but is not without risks, and if there is functional ectopic thyroid tissue that is not detected or nonresectable, the patient will not attain euthyroidism.

The goal of radioiodine therapy is to ablate all abnormal adenomatous thyroid tissue while leaving normal thyroid tissue intact, so that the cat does not become iatrogenically hypothyroid.  Neither hyper- nor hypothyroidism is beneficial to the body, and a particular concern is the adverse effect that hypothyroidism can have on renal function and ultimately on the cat’s post-treatment survival time.

A number of methods have been proposed to determine the optimal dose of radioiodine to use in treating hyperthyroid cats with the least harm to healthy thyroid function. The standard-dose protocol, in which 4-5 millicuries is given to all patients without consideration of the severity of the hyperthyroidism or the size of the thyroid tumor, has been widely used. Other protocols tailor the radioiodine dose to the specific patient, and 3-5 millicuries are administered depending on the severity of the hyperthyroidism and the size of the thyroid tumor.  Conceivably, even lower doses of radioiodine may be effective in treating hyperthyroid cats, but then a concern about the potential for treatment failure may arise.  Among those cats receiving the standard-dose protocol, persistent post-treatment hyperthyroidism is uncommon, occurring in less than 5% of treated cats.

In this prospective, nonrandomized, cohort study of 189 client-owned cats with mild-to-moderate hyperthyroidism, these researchers hypothesized that low-dose radioiodine (2 mCi [millicuries]) would be effective in curing this disease, with a low prevalence of persistent hyperthyroidism, and a lower prevalence of post-treatment iatrogenic hypothyroidism than cats receiving the standard dose (4 mCi) of radioiodine.  Mild-to-moderate hyperthyroidism was defined as a serum thyroxine (T4) > 4.0 µg/dL and < 13.0 µg/dL.  The low-dose radioiodine was given to 150/189 patients, and the other 39 cats received standard-dose (4 mCi) radioiodine.  All cats enrolled in the study received physical examinations, serum biochemical panels, complete blood counts, serum T4 and TSH (thyroid stimulating hormone) assays, and quantitative thyroid scintigraphy prior to treatment.

Following radioiodine treatment, the cats were evaluated with serum T4, TSH, and creatinine concentrations at 1, 3, and 6 months.  Overt hypothyroidism in these patients was defined as low T4 and high TSH, while subclinical hypothyroidism was considered to exist in those with a normal T4 and high TSH.  Cats that received standard dose radioiodine were significantly less likely to be euthyroid at both 3 and 6 months compared to those who received the low dose protocol; at 6 months post-treatment, 36% of the cats receiving standard dose radioiodine were euthyroid, in contrast to 75% of those receiving the low dose protocol.

None of the cats receiving standard-dose radioiodine remained persistently hyperthyroid. Of the 150 patients who were treated with the low-dose protocol, 5 (3.3%) remained persistently hyperthyroid at 6 months post-treatment.  This was not considered a statistically significant difference between treatment groups.

At 6 months post-treatment, overt hypothyroidism was found in 6/39 (18%) of the cats receiving standard-dose I-131, while only 1% (1/150) of the cats who received the low-dose treatment was overtly hypothyroid.  Subclinical hypothyroidism was diagnosed in 18/39 (46%) of the patients 6 months after treatment with standard-dose radioiodine, while only 31/150 (21%) of the cats who received the low-dose treatment were subclinically hypothyroid 6 months later.

Azotemia was defined as creatinine > 2 mg/dL.  Both the standard-dose and low-dose groups demonstrated increases in serum creatinine at 3 and 6 months after treatment.  Of the 150 cats who received the low-dose protocol, 44/150 (29%) were azotemic at 6 months post-treatment.  Almost half of the cats who received standard-dose treatment (18/39; 44%) were azotemic 6 months later. The cats treated with standard-dose I-131 had significantly higher serum creatinine concentrations at 1, 3, and 6 months post-treatment compared to those who received low-dose treatment.

Low-dose (2 mCi) radioiodine treatment of cats with mild-to-moderate hyperthyroidism was therefore significantly less likely to cause iatrogenic hypothyroidism than standard-dose treatment.  Moreover, persistent post-treatment hyperthyroidism in cats receiving low-dose I-131 was uncommon and the rate of occurrence of this problem was essentially the same (<5% of treated cats) as has been published for cats receiving standard-dose radioiodine.

Treatment of feline hyperthyroidism results in a reduction of glomerular filtration rate (GFR) by the kidneys.  Occult chronic renal disease in cats can therefore be unmasked when the hyperthyroidism is treated, and pre-treatment azotemia in cats who already have clinicopathologic evidence of chronic kidney disease may be exacerbated by therapy for hyperthyroidism.  Iatrogenic hypothyroidism following I-131 treatment is suspected to play a role in progression of chronic kidney disease and reduced survival times of cats so affected.  In the study cats, 29% receiving the low-dose I-131 protocol and 46% receiving the standard-dose protocol became azotemic 6 months post-treatment.  While this difference was not considered statistically significant, those animals treated with standard-dose radioiodine developed higher serum creatinine levels and higher percentage increases in creatinine compared to pre-treatment concentrations than those receiving the low-dose protocol.

Supplementation of cats with overt post-treatment hypothyroidism with exogenous levothyroxine (L-T4) is recommended to promote a euthyroid state and hopefully increase GFR and improve kidney function. Based on evaluation of serum TSH levels in cats receiving L-T4 supplementation, the total daily L-T4 dose the authors recommend in these patients is 0.1-0.2 mg divided twice daily, rather than a single daily low dose of 0.075 mg/day.  This dosing protocol should maintain the peak, post-pill serum T4 levels in the high-normal range (2.5-3.5 µg/dL), restoring euthyroidism and reducing serum creatinine levels.

Further studies are required to determine if hyperthyroid cats who become hypothyroid post-radioiodine treatment, like iatrogenically hypothyroid humans who have received I-131 therapy, can undergo a progression from subclinical to overt hypothyroidism over time, or if over months to years, they can eventually attain a euthyroid state without L-T4 treatment.  Based on the results of the current study, low-dose radioiodine therapy for cats with mild-to-moderate hyperthyroidism appears safe, effective and less likely to promote the development of azotemia and iatrogenic hypothyroidism than the standard-dose protocol.  In addition, with low-dose radioiodine therapy, there is less radiation exposure experienced by the cats and veterinary personnel, reduced I-131 costs, and decreased quarantine time. [PJS]

See also:
Vaske HH, Schermerhorn T, Grauer GF.  Effects of feline hyperthyroidism on kidney function: A review.  J Feline Med Surg 2016;18:55-59.

Peterson ME, Guterl JN, et al.  Evaluation of serum thyroid-stimulating hormone concentration as a diagnostic test for hyperthyroidism in cats.  J Vet Intern Med 2015;29:1327-34.