Evaluation of Serum Thyroxine, Free Thyroxine, and Thyrotropin Concentrations for the Diagnosis of Feline Iatrogenic Hypothyroidism

Peterson ME, Nichols R, Rishniw M.

American College of Veterinary Internal Medicine 2017.

Radioiodine is generally considered the treatment of choice for feline hyperthyroidism but can cause iatrogenic hypothyroidism in up to 75% of cats. However, these hypothyroid cats rarely develop overt clinical signs of the disease (hair-coat changes), and there are no published guidelines for how to diagnose or manage iatrogenic hypothyroidism in cats. Treating hyperthyroidism can also unmask subclinical chronic kidney disease (CKD), with up to 49% of cats developing azotemia by 3–6 months of treatment. Cats with iatrogenic hypothyroidism are more likely to develop CKD than treated cats that remain euthyroid; iatrogenic hypothyroidism can also reduce survival time, especially in cats with concurrent azotemia. Therefore, it is important to diagnose hypothyroidism in these cats, since thyroid hormone replacement might preserve kidney function and improve survival.

In this study, we sought to determine which serum thyroid hormone or thyrotropin test best identifies iatrogenic hypothyroidism in cats that first develop azotemia after radioiodine treatment. Further, we sought to determine which test would best differentiate these azotemic, hypothyroid cats from azotemic sick euthyroid cats following radioiodine treatment, as well as from azotemic cats with CKD but no history of thyroid disease.

Five hundred and twenty-four hyperthyroid cats treated with radioiodine at the Animal Endocrine Clinic from June 2013 to June 2015 were evaluated for inclusion in this study. None of these cats had pre-existent azotemia (defined as serum creatinine >1.9 μg/dL), either when hyperthyroid or controlled with methimazole. Following radioiodine, 42 cats that developed post-treatment azotemia (creatinine >2.5 μg/dL) had serum concentrations of thyroxine (T4), free T4 by dialysis (fT4), and thyrotropin (TSH) measured at 3, 6, and 12 months. Iatrogenic hypothyroidism was confirmed (n=28) or excluded (n=14) in these 42 cats on the basis of thyroid scintigraphy. Fourteen cats with CKD and 166 clinically normal cats underwent similar serum thyroid testing and scintigraphy. Nineteen of the 28 cats with documented hypothyroidism had T4, fT4, and TSH reevaluated after 1–3 months of levothyroxine (L-T4) treatment to determine the influence of replacement therapy on these analytes.

Serum concentrations of T4 and fT4 were lower and TSH higher in hypothyroid cats than in all three groups of euthyroid cats (p<0.0001). Of the hypothyroid cats, T4 and fT4 concentrations were low in 15 (53.6%) and 7 (25%), respectively. Low serum T4 and fT4 concentrations were also measured in 7 (50%) and 2 (14.3%) of the cats with CKD. TSH concentrations were clearly high in all hypothyroid cats, whereas TSH remained within the reference interval in all three groups of euthyroid cats. After levothyroxine supplementation, serum T4 and fT4 increased and TSH concentrations decreased in all 19 cats treated, normalizing in 18. Serum creatinine also decreased significantly after L-T4 supplementation, with 4/19 (21.1%) cats becoming non-azotemic (creatinine ≤1.9 μg/dL).

Our results indicate that measurement of serum TSH concentration is a very sensitive and specific diagnostic test for iatrogenic hypothyroidism in cats that develop azotemic CKD after treatment. The finding of high serum TSH concentrations best identifies feline iatrogenic hypothyroidism and differentiates it from nonthyroidal illness syndrome in cats that develop azotemia following treatment. After L-T4 supplementation of cats with hypothyroidism, high serum TSH concentrations decreased to within the reference interval, indicating that serum TSH measurement can also aid in post-pill monitoring. L-T4 replacement in our hypothyroid cats also appeared to improve renal function, as indicated by the decrease in serum creatinine concentrations.