Sunday, September 30, 2012

Iopanoic Acid for Treatment of Cats with Hyperthyroidism

Chemical structure of iopanoic acid

Efficacy of Iopanoic Acid for Treatment of Spontaneous Hyperthyroidism in Cats

Alexander E. Gallagher and David L. Panciera

Antithyroid drugs, such as methimazole and carbimazole, are the mainstay of medical therapy for feline hyperthyroidism. Occasionally, an alternative medical therapy may be needed for a hyperthyroid cat because of adverse reactions to the standard antithyroid drugs.

In human patients with hyperthyroidism, a number of iodine-containing, oral cholecystographic agents (e.g., calcium ipodate and iopanoic acid) act to decrease T4 production and also acutely inhibit peripheral T4 to T3 conversion (1-5). These drugs have been reported to be effective in both the short- and long-term management of patients with hyperthyroidism.

In hyperthyroid cats, we have previously demonstrated that administration of calcium ipodate was associated with clinical improvement and normalization of serum total T3 concentrations in over 60% of cases (6). However, in our study, waning of the thyroid-lowering effect generally occurred within 3 months of therapy. Therefore, calcium ipodate was recommended only as an alternative medical treatment for short-term use (e.g., as a preparation for surgery).

The manufacturer discontinued calcium ipodate over a decade ago, so it is no longer available for use in either humans or cats. However, a related compound—iopanoic acid— has replaced ipodate for use in human patients (4,5). Iopanoic acid has a rapid onset of action and primarily acts by inhibiting deiodination of T4 to T3 (similar to the action of ipodate).

Iopanoic acid has only been evaluated in clinically normal cats, which were made hyperthyroid by administering high doses of levothyroxine (7). In that study, iopanoic acid was effective in lowering the cat's serum T3 concentrations. However, the efficacy of iopanoic acid on relief of clinical signs of the cats’ iatrogenic hyperthyroidism was not apparent, possibly due to the experimental model used.

The purpose of the present study by Gallagher and Panciera (8) was to evaluate the effects of iopanoic acid in cats with spontaneous hyperthyroidism.

Eleven cats with naturally-occurring hyperthyroidism were included in the study. Median age of the cats was 13 years; there were 6 females and 5 males.

Cats were administered 50 mg of iopanoic acid orally twice daily for up to 12 weeks. If after 4 weeks of treatment the serum T3 concentration remained above the reference interval or signs of hyperthyroidism were still present, the dose of iopanoic acid was increased to 100 mg twice daily. After the first 8 cats completed the study, the starting dosage of iopanoic acid was increased to 100 mg twice daily because of the lack of clinical efficacy at the lower dose.

All cats were evaluated before treatment and at 2, 4, and 12 weeks of treatment. Blood was collected at each recheck for a complete blood count, serum biochemistry analysis, and assay of serum concentrations of both T3 and T4.

Cats that had stable body weight during the first 4 weeks of treatment were classified as partial responders. Cats that lost weight during this period were classified as non-responders.

Clinically, there was improvement in individual cats. Body weight was stable through 4 weeks of treatment in 5 cats and increased at 12 weeks in 1 of these cats (6 total partial responders). However, the mean body weight of all 11 cats decreased despite iopanoic acid treatment.  Likewise, the mean heart rates did not decrease during treatment.

Compared to pretreatment concentrations, the mean T3 concentrations were significantly decreased at all time periods after iopanoic acid. Of the 11 hyperthyroid cats, 6 had high serum T3 values prior to therapy. During treatment, all 11 cats had T3 concentrations within the reference interval at all time points.

All cats had increased T4 concentrations prior to therapy. However, the mean T4 concentration was significantly higher than pretreatment values at both weeks 4 and 12.

Conclusions and clinical relevance
Iopanoic acid appears ineffective for long-term control of feline hyperthyroidism at the doses used in this study. However, the stability of disease in some cats during the first 2 to 4 weeks of therapy suggests that iopanoic acid may be suitable for short-term management when methimazole is not tolerated.

My Bottom Line: Using iopanoic acid to treat hyperthyroid cats

In this study of spontaneously hyperthyroid cats, administration of iopanoic acid (50 to 100 mg, BID) decreased mean serum T3 concentrations by more than 50%. These changes in serum T3 levels are due primarily to the inhibitory effect of iopanoic acid on the activity of type I and II deiodinases, the enzymes responsible for catalyzing the deiodination of T4 to T3 (5).

However, the serum T4 concentrations tended to increase despite treatment and the clinical signs of hyperthyroidism did not consistently improve (8). This is in contrast to the cats treated with calcium ipodate, where most cats showed noticeable clinical improvement, at least for a few weeks (6).  Therefore, iopanoic acid cannot be recommended as an alternative treatment for cats with hyperthyroidism, at least for cats with severe disease or for long-term control of the disease.

The drug may be suitable for short-term management (i.e., in preparation for surgical thyroidectomy) in cats with early or mild hyperthyroidism, particularly when the cat cannot tolerate methimazole. However, iopanoic acid should never be used in preparation for radioiodine therapy, since its high iodine content would lower the uptake of I-131 by the thyroid tumor and likely result in radioiodine treatment failure.

  1. Wu SY, Chopra IJ, Solomon DH, et al. Changes in circulating iodothyronines in euthyroid and hyperthyroid subjects given ipodate (Oragrafin), an agent for oral cholecystography. J Clin Endocrinol Metab 1978; 46:691–697. 
  2. Wu SY, Shyh TP, Chopra IJ, et al. Comparison of sodium ipodate (Oragrafin) and propylthiouracil in early treatment of hyperthyroidism. J Clin Endocrinol Metab 1982;54:630–634.  
  3. Shen DC, Wu SY, Chopra IJ, et al. Long term treatment of Graves hyperthyroidism with sodium ipodate. J Clin Endocrinol Metab 1985; 61:723–727.  
  4. Wang Y, Tsou C, Lin W, et al. Long-term treatment of Graves’ disease with iopanoic acid (Telepaque). J Clin Endocrinol Metab 1987;65:679–682.  
  5. Braga M, Cooper DS. Clinical review 129: Oral cholecystographic agents and the thyroid. J Clin Endocrinol Metab. 2001;86:1853-1860. 
  6. Murray LA, Peterson ME. Ipodate treatment of hyperthyroidism in cats. J Am Vet Med Assoc 1997;211:63-67.  
  7. Gallagher AE, Panciera DL. Effects and safety of iopanoic acid in cats administered levothyroxine. J Feline Med Surg 2009;11:69-75. 
  8. Gallagher AE, Panciera DL. Efficacy of iopanoic acid for treatment of spontaneous hyperthyroidism in cats. J Feline Med Surg 2011;13:441-447. 

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