Antithyroid Drugs
http://www.100md.com
《新英格兰医药杂志》
To the Editor: In his review of antithyroid drugs (March 3 issue),1 Cooper does not mention the potential advantage of combined treatment with antithyroid drugs and thyroxine (referred to as the "block–replace regimen"). Even if such a regimen has not been demonstrated to be superior in terms of definitive cure, for many clinicians it is a simpler and faster way to achieve euthyroidism in most patients with Graves' disease than is treatment with methimazole alone. High doses of methimazole may be associated with more minor side effects, but in controlled studies the doses used ranged from 30 to 60 mg of carbimazole or methimazole per day,2 whereas most patients receiving the block–replace regimen have control with 20 mg. The higher cost of this treatment is probably offset by the decrease in the number of thyroid hormone assays required, because the patients' thyroid levels are normalized more quickly. In addition, the review did not mention some alternative and sometimes useful antithyroid drugs, such as iodide, lithium, glucocorticoids, and potassium perchlorate. These drugs can be used in patients with particular conditions such as amiodarone-induced hyperthyroidism or agranulocytosis due to the use of "classic" antithyroid drugs in preparation for surgery.
Bernard Goichot, M.D., Ph.D.
Stephane Vinzio, M.D.
H?pitaux Universitaires de Strasbourg
67098 Strasbourg, France
bernard.goichot@chru-strasbourg.fr
References
Cooper DS. Antithyroid drugs. N Engl J Med 2005;352:905-917.
Abraham P, Avenell A, Watson WA, Park CM, Bevan JS. Antithyroid drug regimen for treating Graves' hyperthyroidism. Cochrane Database Syst Rev 2004;2:CD003420-CD003420.
To the Editor: Cooper does not discuss certain thyrotoxic conditions in which the use of antithyroid drugs is, I believe, not justified. In thyrotoxic conditions such as amiodarone thyroiditis or the thyrotoxic phase of postpartum thyroiditis or in painless viral thyroiditis, in which there is no demonstrable trapping of iodine by the thyroid gland, there is no benefit to the use of antithyroid drugs. This point should have been specifically addressed by the author, given the growing frequency with which we are being confronted by these conditions and the controversy that still surrounds their treatment.
Ernesto Lubin, M.D.
Tel Aviv University
52246 Ramat Gan, Israel
lubin-fe@zahav.net.il
To the Editor: Cooper states that antithyroid drugs are the preferred primary treatment for Graves' disease in most children and adolescents. It is important to note that radioactive iodine is increasingly becoming the first-line therapy for pediatric patients with Graves' disease.1 Although there is concern regarding the theoretical risks of radioactive iodine in very young children, reports including nearly 40 years of follow-up indicate that radioactive iodine is safe and effective in the pediatric population.2 In addition, a higher incidence of side effects of antithyroid drugs has been noted in children than in adults3 — a fact that arouses concern about Cooper's recommendation (in Figure 4 of his article) that a second course of drug therapy be used after a relapse. At our center, we have successfully used fixed-dose radioactive iodine as primary, definitive treatment in most pediatric patients with Graves' disease.4 In addition to having a safer side-effect profile, radioactive iodine ablation results in permanent hypothyroidism, which is easily managed and requires fewer blood tests than does antithyroid-drug therapy, leading to increased satisfaction for patients and their families alike.
Todd D. Nebesio, M.D.
Erica A. Eugster, M.D.
Riley Hospital for Children
Indianapolis, IN 46202
tdnebesi@iupui.edu
References
Ward L, Huot C, Lambert R, Deal C, Collu R, Van Vliet G. Outcome of pediatric Graves' disease after treatment with antithyroid medication and radioiodine. Clin Invest Med 1999;22:132-139.
Read CH Jr, Tansey MJ, Menda Y. A 36-year retrospective analysis of the efficacy and safety of radioactive iodine in treating young Graves' patients. J Clin Endocrinol Metab 2004;89:4229-4233.
Rivkees SA, Sklar C, Freemark M. Clinical review 99: the management of Graves' disease in children, with special emphasis on radioiodine treatment. J Clin Endocrinol Metab 1998;83:3767-3776.
Nebesio TD, Siddiqui AR, Pescovitz OH, Eugster EA. Time course to hypothyroidism after fixed-dose radioablation therapy of Graves' disease in children. J Pediatr 2002;141:99-103.
To the Editor: The costs of antithyroid drug treatment in the United States are startling. In the Netherlands, the costs of a one-year supply of methimazole at daily doses of 15 mg and 30 mg are, respectively, 51.72 and 86.04, or approximately $67 and $112. Treatment with 300 mg of propylthiouracil per day would cost 85.40, or $111 per year. These prices include a fee for Dutch pharmacies' handling of prescriptions. If the prices mentioned in Dr. Cooper's article ($360, $720, and $408, respectively) are correct, I cannot but conclude that something is seriously wrong with the way the pharmaceutical industry in the United States determines the price level for these 50-year-old drugs.
Peter J.J. Admiraal, Ph.D.
Molenapotheek
1741GK Schagen, the Netherlands
Dr. Cooper replies: Drs. Goichot and Vinzio raise the issue of the so-called block–replace regimen in the management of hyperthyroidism. I do not have an objection to this method of treating hyperthyroidism, beyond the fact that two drugs are being used instead of one. Indeed, this regimen is often used in the pediatric population because of a possible greater ease of follow-up. It is unclear to me why Drs. Goichot and Vinzio say that patients become euthyroid faster with this regimen, except for the use of high doses of antithyroid drugs, which, as they note, are associated with a higher frequency of side effects. Their point about non-thionamide compounds that have antithyroid effects is well taken; my review focused solely on thionamide drugs.
I thank Dr. Lubin for pointing out that antithyroid drugs have no place in the management of hyperthyroidism caused by the various forms of thyroiditis.
Drs. Nebesio and Eugster state that radioactive iodine has become a more accepted initial therapy for "most" pediatric patients with Graves' disease, and cite small studies showing its safety after lengthy follow-up. They may well be correct, but there have been no large, long-term follow-up studies of young children — especially those under five years of age — who have received radioactive iodine. Unfortunately, such studies will probably never be performed. Moreover, the prospect of lifelong thyroxine therapy, when remission might be obtained with antithyroid drugs, is more than some parents are willing to accept, and there is often an emotional bias against radioactive iodine that is difficult to overcome. I concur that radioactive iodine should be strongly considered for any child with Graves' disease who has an antithyroid-drug allergy or whose compliance cannot be assured. Whether it should be the first-line therapy, however, will continue to be debated among thoughtful pediatric and adult endocrinologists.
Dr. Admiraal points out the high cost of drugs in the United States. His words speak for themselves.
David S. Cooper, M.D.
Sinai Hospital of Baltimore
Baltimore, MD 21215
dcooper@lifebridgehealth.org
Bernard Goichot, M.D., Ph.D.
Stephane Vinzio, M.D.
H?pitaux Universitaires de Strasbourg
67098 Strasbourg, France
bernard.goichot@chru-strasbourg.fr
References
Cooper DS. Antithyroid drugs. N Engl J Med 2005;352:905-917.
Abraham P, Avenell A, Watson WA, Park CM, Bevan JS. Antithyroid drug regimen for treating Graves' hyperthyroidism. Cochrane Database Syst Rev 2004;2:CD003420-CD003420.
To the Editor: Cooper does not discuss certain thyrotoxic conditions in which the use of antithyroid drugs is, I believe, not justified. In thyrotoxic conditions such as amiodarone thyroiditis or the thyrotoxic phase of postpartum thyroiditis or in painless viral thyroiditis, in which there is no demonstrable trapping of iodine by the thyroid gland, there is no benefit to the use of antithyroid drugs. This point should have been specifically addressed by the author, given the growing frequency with which we are being confronted by these conditions and the controversy that still surrounds their treatment.
Ernesto Lubin, M.D.
Tel Aviv University
52246 Ramat Gan, Israel
lubin-fe@zahav.net.il
To the Editor: Cooper states that antithyroid drugs are the preferred primary treatment for Graves' disease in most children and adolescents. It is important to note that radioactive iodine is increasingly becoming the first-line therapy for pediatric patients with Graves' disease.1 Although there is concern regarding the theoretical risks of radioactive iodine in very young children, reports including nearly 40 years of follow-up indicate that radioactive iodine is safe and effective in the pediatric population.2 In addition, a higher incidence of side effects of antithyroid drugs has been noted in children than in adults3 — a fact that arouses concern about Cooper's recommendation (in Figure 4 of his article) that a second course of drug therapy be used after a relapse. At our center, we have successfully used fixed-dose radioactive iodine as primary, definitive treatment in most pediatric patients with Graves' disease.4 In addition to having a safer side-effect profile, radioactive iodine ablation results in permanent hypothyroidism, which is easily managed and requires fewer blood tests than does antithyroid-drug therapy, leading to increased satisfaction for patients and their families alike.
Todd D. Nebesio, M.D.
Erica A. Eugster, M.D.
Riley Hospital for Children
Indianapolis, IN 46202
tdnebesi@iupui.edu
References
Ward L, Huot C, Lambert R, Deal C, Collu R, Van Vliet G. Outcome of pediatric Graves' disease after treatment with antithyroid medication and radioiodine. Clin Invest Med 1999;22:132-139.
Read CH Jr, Tansey MJ, Menda Y. A 36-year retrospective analysis of the efficacy and safety of radioactive iodine in treating young Graves' patients. J Clin Endocrinol Metab 2004;89:4229-4233.
Rivkees SA, Sklar C, Freemark M. Clinical review 99: the management of Graves' disease in children, with special emphasis on radioiodine treatment. J Clin Endocrinol Metab 1998;83:3767-3776.
Nebesio TD, Siddiqui AR, Pescovitz OH, Eugster EA. Time course to hypothyroidism after fixed-dose radioablation therapy of Graves' disease in children. J Pediatr 2002;141:99-103.
To the Editor: The costs of antithyroid drug treatment in the United States are startling. In the Netherlands, the costs of a one-year supply of methimazole at daily doses of 15 mg and 30 mg are, respectively, 51.72 and 86.04, or approximately $67 and $112. Treatment with 300 mg of propylthiouracil per day would cost 85.40, or $111 per year. These prices include a fee for Dutch pharmacies' handling of prescriptions. If the prices mentioned in Dr. Cooper's article ($360, $720, and $408, respectively) are correct, I cannot but conclude that something is seriously wrong with the way the pharmaceutical industry in the United States determines the price level for these 50-year-old drugs.
Peter J.J. Admiraal, Ph.D.
Molenapotheek
1741GK Schagen, the Netherlands
Dr. Cooper replies: Drs. Goichot and Vinzio raise the issue of the so-called block–replace regimen in the management of hyperthyroidism. I do not have an objection to this method of treating hyperthyroidism, beyond the fact that two drugs are being used instead of one. Indeed, this regimen is often used in the pediatric population because of a possible greater ease of follow-up. It is unclear to me why Drs. Goichot and Vinzio say that patients become euthyroid faster with this regimen, except for the use of high doses of antithyroid drugs, which, as they note, are associated with a higher frequency of side effects. Their point about non-thionamide compounds that have antithyroid effects is well taken; my review focused solely on thionamide drugs.
I thank Dr. Lubin for pointing out that antithyroid drugs have no place in the management of hyperthyroidism caused by the various forms of thyroiditis.
Drs. Nebesio and Eugster state that radioactive iodine has become a more accepted initial therapy for "most" pediatric patients with Graves' disease, and cite small studies showing its safety after lengthy follow-up. They may well be correct, but there have been no large, long-term follow-up studies of young children — especially those under five years of age — who have received radioactive iodine. Unfortunately, such studies will probably never be performed. Moreover, the prospect of lifelong thyroxine therapy, when remission might be obtained with antithyroid drugs, is more than some parents are willing to accept, and there is often an emotional bias against radioactive iodine that is difficult to overcome. I concur that radioactive iodine should be strongly considered for any child with Graves' disease who has an antithyroid-drug allergy or whose compliance cannot be assured. Whether it should be the first-line therapy, however, will continue to be debated among thoughtful pediatric and adult endocrinologists.
Dr. Admiraal points out the high cost of drugs in the United States. His words speak for themselves.
David S. Cooper, M.D.
Sinai Hospital of Baltimore
Baltimore, MD 21215
dcooper@lifebridgehealth.org