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Iodinated radiocontrast agents in the treatment of hyperthyroidism

Iodinated radiocontrast agents in the treatment of hyperthyroidism
Author:
Douglas S Ross, MD
Section Editor:
David S Cooper, MD
Deputy Editor:
Jean E Mulder, MD
Literature review current through: Jan 2024.
This topic last updated: Nov 01, 2023.

INTRODUCTION — As of this writing, neither US Food and Drug Administration (FDA)-approved preparations of iopanoic acid nor ipodate are available in the United States. It is unclear when, or even whether, they will ever again be marketed in the United States. It may be possible to obtain iopanoic acid from compounding pharmacies [1]; the raw chemical is available from numerous suppliers worldwide.

Ipodate and iopanoic acid, two iodine-containing drugs marketed as oral cholecystographic agents, have been used in the treatment of hyperthyroidism. These drugs are the most potent inhibitors of 5'-monodeiodinase, thereby impairing the extrathyroidal conversion of thyroxine (T4) to the more potent triiodothyronine (T3). The release of iodine in pharmacologic quantities from these agents has the additional benefits of blocking thyroid hormone release and interfering with its synthesis in some patients. (See "Iodine in the treatment of hyperthyroidism".)

This topic will review the uses and limitations of iodinated radiocontrast agents in the treatment of hyperthyroidism. The clinical manifestations, diagnosis, and treatment of hyperthyroidism are reviewed separately. (See "Overview of the clinical manifestations of hyperthyroidism in adults" and "Diagnosis of hyperthyroidism" and "Graves' hyperthyroidism in nonpregnant adults: Overview of treatment" and "Surgical management of hyperthyroidism" and "Thyroid storm".)

MAJOR USES — Iodinated radiocontrast agents (if available) can be used in conjunction with methimazole for the treatment of severe hyperthyroidism or "thyroid storm." In patients with Graves' hyperthyroidism who are allergic to thionamides and who choose surgery, the combination of an iodinated radiocontrast agent, a beta blocker, and a glucocorticoid can be used to normalize thyroid tests prior to surgery.

Ipodate and iopanoic acid impair the extrathyroidal conversion of thyroxine (T4) to the more potent triiodothyronine (T3) and block the release of thyroid hormone from the thyroid gland. Iodinated radiocontrast agents are more potent than propylthiouracil in blocking the conversion of T4 to T3, and they result in a rapid reduction in serum T4 and T3 concentrations (figure 1) [2,3]. In one study, the combination of methimazole and ipodate in hyperthyroid patients with Graves' disease was more effective than methimazole alone or methimazole plus potassium iodide, and the serum T3 concentration may fall to normal within five days [4].

Patients with Graves' hyperthyroidism who require rapid preparation for surgery or who are allergic to thionamides and who choose surgery also can benefit from an iodinated radiocontrast agent. These patients can be rendered euthyroid within five days with the triad of the radiocontrast agent, a beta blocker, and a glucocorticoid [5,6]. As noted above, long-term use of these agents may result in resistant hyperthyroidism and should therefore be avoided [7]. Iopanoic acid has also helped to lower T3 levels and hyperthyroid symptoms preoperatively in patients with amiodarone-associated hyperthyroidism [8].

These agents may also be effective during the hyperthyroid phase that can occur with subacute thyroiditis, a disorder in which thionamides are of no benefit since thyroid hormone is leaking from an inflamed gland. As an example, serum T3 levels fell rapidly after ipodate administration (500 mg daily or every other day) and patients noted symptomatic improvement within several days [9,10]. Ipodate was continued for 15 to 60 days until both T3 and T4 levels normalized.

Ipodate or iopanoic acid also may be useful in both adults and children with an acute levothyroxine overdose [11-13].

Iopanoic acid, 500 mg daily for seven days, rapidly ameliorates Graves' hyperthyroidism. Sufficient recovery of the radioiodine uptake to allow radioiodine treatment occurs after one or two weeks after stopping iopanoic acid in 86 and 94 percent of patients, respectively [14].

LIMITATIONS TO USE — Ipodate and iopanoic acid should not be used as monotherapy in patients with Graves' hyperthyroidism, toxic adenoma, or toxic multinodular goiter, since the iodine may provide substrate for de novo hormone synthesis by the autonomous thyroid tissue, leading to more severe hyperthyroidism [7]. In addition, although they have been used as monotherapy for the treatment of hyperthyroidism caused by Graves' disease [15], they are not as effective as methimazole or propylthiouracil in controlling the hyperthyroidism, and the relapse rate after discontinuation is higher with poor response to subsequent methimazole treatment [16]. They can be used in this setting only if thyroid hormone synthesis is first blocked by the administration of a thionamide. (See "Treatment of toxic adenoma and toxic multinodular goiter".)

As noted above, neither iopanoate nor ipodate are available in the United States. It is unclear when, or even whether, they will ever again be marketed in the United States.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hyperthyroidism".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Hyperthyroidism (overactive thyroid) (The Basics)")

Beyond the Basics topics (see "Patient education: Hyperthyroidism (overactive thyroid) (Beyond the Basics)" and "Patient education: Antithyroid drugs (Beyond the Basics)")

SUMMARY

Mechanism of action – Ipodate and iopanoic acid impair the extrathyroidal conversion of thyroxine (T4) to the more potent triiodothyronine (T3) and block the release of thyroid hormone from the thyroid gland. (See 'Introduction' above.)

Major uses – In countries where these agents are available, they can be used in conjunction with methimazole for the treatment of severe hyperthyroidism or "thyroid storm." In patients with Graves' hyperthyroidism who are allergic to thionamides and who choose surgery, the combination of an iodinated radiocontrast agent, a beta blocker, and a glucocorticoid can be used to normalize thyroid tests prior to surgery. (See 'Major uses' above.)

Limitations to use – They should not be used as monotherapy in patients with Graves' hyperthyroidism, toxic adenoma, or toxic multinodular goiter, since the iodine may provide substrate for de novo hormone synthesis by the autonomous thyroid tissue, leading to more severe hyperthyroidism. (See 'Limitations to use' above.)

  1. Way JS, Shen Y, Martinez DS. Iopanoic Acid to Treat Acute Psychiatric Crisis Associated With Thyrotoxicosis: Three Case Reports and Review of the Literature. J Clin Psychopharmacol 2015; 35:743.
  2. Wu SY, Shyh TP, Chopra IJ, et al. Comparison sodium ipodate (oragrafin) and propylthiouracil in early treatment of hyperthyroidism. J Clin Endocrinol Metab 1982; 54:630.
  3. Robuschi G, Manfredi A, Salvi M, et al. Effect of sodium ipodate and iodide on free T4 and free T3 concentrations in patients with Graves' disease. J Endocrinol Invest 1986; 9:287.
  4. Roti E, Robuschi G, Gardini E, et al. Comparison of methimazole, methimazole and sodium ipodate, and methimazole and saturated solution of potassium iodide in the early treatment of hyperthyroid Graves' disease. Clin Endocrinol (Oxf) 1988; 28:305.
  5. Baeza A, Aguayo J, Barria M, Pineda G. Rapid preoperative preparation in hyperthyroidism. Clin Endocrinol (Oxf) 1991; 35:439.
  6. Panzer C, Beazley R, Braverman L. Rapid preoperative preparation for severe hyperthyroid Graves' disease. J Clin Endocrinol Metab 2004; 89:2142.
  7. Caldwell G, Errington M, Toft AD. Resistant hyperthyroidism induced by sodium iopodate used as treatment for Graves' disease. Acta Endocrinol (Copenh) 1989; 120:215.
  8. Bogazzi F, Miccoli P, Berti P, et al. Preparation with iopanoic acid rapidly controls thyrotoxicosis in patients with amiodarone-induced thyrotoxicosis before thyroidectomy. Surgery 2002; 132:1114.
  9. Chopra IJ, van Herle AJ, Korenman SG, et al. Use of sodium ipodate in management of hyperthyroidism in subacute thyroiditis. J Clin Endocrinol Metab 1995; 80:2178.
  10. Arem R, Munipalli B. Ipodate therapy in patients with severe destruction-induced thyrotoxicosis. Arch Intern Med 1996; 156:1752.
  11. Berkner PD, Starkman H, Person N. Acute L-thyroxine overdose; therapy with sodium ipodate: evaluation of clinical and physiologic parameters. J Emerg Med 1991; 9:129.
  12. Brown RS, Cohen JH 3rd, Braverman LE. Successful treatment of massive acute thyroid hormone poisoning with iopanoic acid. J Pediatr 1998; 132:903.
  13. Braga M, Cooper DS. Clinical review 129: Oral cholecystographic agents and the thyroid. J Clin Endocrinol Metab 2001; 86:1853.
  14. Bal CS, Kumar A, Chandra P. Effect of iopanoic acid on radioiodine therapy of hyperthyroidism: long-term outcome of a randomized controlled trial. J Clin Endocrinol Metab 2005; 90:6536.
  15. Shen DC, Wu SY, Chopra IJ, et al. Long term treatment of Graves' hyperthyroidism with sodium ipodate. J Clin Endocrinol Metab 1985; 61:723.
  16. Martino E, Balzano S, Bartalena L, et al. Therapy of Graves' disease with sodium ipodate is associated with a high recurrence rate of hyperthyroidism. J Endocrinol Invest 1991; 14:847.
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