Management of Graves Disease: Shift Is Occurring
This article provides useful clinical information regarding present treatment approaches for patients with Graves disease and compares geographical differences in its assessment and management. It is interesting to compare these responses with the recent guidelines that have been published. Of course, guidelines are only recommendations, and in this area, they are based to a large extent on expert opinion because there are only few randomized controlled prospective studies. Nonetheless, these guidelines were formulated by both the American Thyroid Association and the American Association of Clinical Endocrinologists, and they were derived as rigorously as possible. These guidelines were published at approximately the same time in their respective society journals. They give recommendations on clinically important issues related to Graves disease. The authors reviewed the literature on this wide topic and then formulated recommendations, noting the strengths of the recommendations and quality of evidence. The committee members are certainly experienced and experts in the area. As such, these recommendations are very valuable to the clinician.
Of course, it also takes time for guidelines to be disseminated and incorporated into clinical practice. The survey that was analyzed in the Burch study requested responses from its participants between April and July 2011. The data were presented at the American Thyroid Association meeting in October 2011, and the full data were published in December 2012. The guidelines were published in mid-2011; therefore, the survey should not be taken as a record of compliance to the guidelines but as an initial starting point with which future surveys can compare changes in clinical practice.
The article by Burch and colleagues indicates a decreased use of radioactive iodine as initial therapy in uncomplicated Graves disease. When an antithyroid agent is used, it is most frequently methimazole or carbimazole. The increased use of methimazole and the infrequent use of propylthiouracil is consistent with the published guidelines as well as a multidisciplinary conference that noted the relatively higher complication rate of propylthiouracil, especially in regard to hepatic problems. Indeed, the number of prescriptions given for methimazole has risen dramatically in the United States, whereas prescriptions for propylthiouracil have decreased. The guidelines published in 2011, note that "patients with overt Graves hyperthyroidism should be treated with any of the following modalities: 131-I therapy, antithyroid medication, or thyroidectomy." Therefore, the choice of therapy should be individualized on the basis of discussion between the treating physician and the patient. It is difficult to find an explanation for the varying recommendations geographically for uncomplicated Graves disease.
Guidelines note that radioactive iodine uptake should be performed when the clinical presentation of thyrotoxicosis is not diagnostic of Graves disease. In the presence of thyroid nodularity, a thyroid scan should also be added. In regard to laboratory studies, a baseline CBC with white blood cell count differential and a liver profile with bilirubin and transaminase levels are recommended before initiating antithyroid drug therapy. For all patients taking antithyroid medication, a differential white blood cell count should be performed during febrile illness. Routine monitoring of white blood cell counts is not recommended. If a patient who is taking propylthiouracil experiences pruritic rash, jaundice, light-colored stool or dark urine, joint pain, abdominal pain or bloating, anorexia, nausea, or fatigue, then liver function and hepatocellular integrity should be tested. If methimazole is being used as primary therapy, it should be administered for 12-18 months and then tapered or discontinued if the TSH level is normal at that time. The survey results showed significant discrepancies between the guideline recommendations and clinical practice.
It is now recognized that radioactive therapy might worsen ophthalmopathy, especially when the ophthalmopathy is moderate or severe. Therefore, it is not surprising that many respondents would not recommend radioactive iodine therapy in this circumstance. If radioactive iodine is to be used, the patient should be treated with corticosteroids, which have been demonstrated to decrease the progression of orbitopathy that is associated with radioactive iodine.
Recent guidelines and conferences have also recommended that patients with Graves disease who are contemplating pregnancy and taking antithyroid agents be given propylthiouracil while attempting to conceive and during the first trimester of pregnancy because methimazole has been associated with various fetal complications, including aplasia cutis. The guidelines note that methimazole should be used in almost every patient who chooses antithyroid therapy. However, propylthiouracil is preferred in pregnancy, in the treatment of thyroid storm, and in patients with reactions to methimazole who refuse radioactive iodine or surgery. The American Thyroid Association's pregnancy guidelines indicate that patients who are on methimazole should be switched to propylthiouracil if pregnancy is confirmed in the first trimester. Switching to methimazole can be considered after the first trimester.
The study by Burch and colleagues has served a useful purpose in documenting clinical practices for treating patients with Graves disease. A strength of the study is the large number of respondents who returned the survey; the total number of respondents was larger than for any previous study. Weaknesses of the study relate to the relatively small percentage of members of each society that returned the survey. Of course, it is not known how the remaining clinicians would have responded. Approximately 10%, 13%, and 6% of active members of The Endocrine Society, American Thyroid Association, and the American Association of Clinical Endocrinologists responded, respectively. Also, the majority of the respondents were from the United States and relatively fewer (about 40%) were from other geographical areas. Further, it is difficult to mimic precisely what an individual physician would recommend in the real clinical world compared with completing a survey questionnaire because many additional factors must be taken into account in the real world. In summary, this geographic assessment indicates how clinicians assess and treat patients with Graves disease and can be used as a baseline barometer of the impact of guideline recommendations. It may also serve to stimulate further prospective randomized trials in this area.
Abstract
Viewpoint
This article provides useful clinical information regarding present treatment approaches for patients with Graves disease and compares geographical differences in its assessment and management. It is interesting to compare these responses with the recent guidelines that have been published. Of course, guidelines are only recommendations, and in this area, they are based to a large extent on expert opinion because there are only few randomized controlled prospective studies. Nonetheless, these guidelines were formulated by both the American Thyroid Association and the American Association of Clinical Endocrinologists, and they were derived as rigorously as possible. These guidelines were published at approximately the same time in their respective society journals. They give recommendations on clinically important issues related to Graves disease. The authors reviewed the literature on this wide topic and then formulated recommendations, noting the strengths of the recommendations and quality of evidence. The committee members are certainly experienced and experts in the area. As such, these recommendations are very valuable to the clinician.
Of course, it also takes time for guidelines to be disseminated and incorporated into clinical practice. The survey that was analyzed in the Burch study requested responses from its participants between April and July 2011. The data were presented at the American Thyroid Association meeting in October 2011, and the full data were published in December 2012. The guidelines were published in mid-2011; therefore, the survey should not be taken as a record of compliance to the guidelines but as an initial starting point with which future surveys can compare changes in clinical practice.
The article by Burch and colleagues indicates a decreased use of radioactive iodine as initial therapy in uncomplicated Graves disease. When an antithyroid agent is used, it is most frequently methimazole or carbimazole. The increased use of methimazole and the infrequent use of propylthiouracil is consistent with the published guidelines as well as a multidisciplinary conference that noted the relatively higher complication rate of propylthiouracil, especially in regard to hepatic problems. Indeed, the number of prescriptions given for methimazole has risen dramatically in the United States, whereas prescriptions for propylthiouracil have decreased. The guidelines published in 2011, note that "patients with overt Graves hyperthyroidism should be treated with any of the following modalities: 131-I therapy, antithyroid medication, or thyroidectomy." Therefore, the choice of therapy should be individualized on the basis of discussion between the treating physician and the patient. It is difficult to find an explanation for the varying recommendations geographically for uncomplicated Graves disease.
Guidelines note that radioactive iodine uptake should be performed when the clinical presentation of thyrotoxicosis is not diagnostic of Graves disease. In the presence of thyroid nodularity, a thyroid scan should also be added. In regard to laboratory studies, a baseline CBC with white blood cell count differential and a liver profile with bilirubin and transaminase levels are recommended before initiating antithyroid drug therapy. For all patients taking antithyroid medication, a differential white blood cell count should be performed during febrile illness. Routine monitoring of white blood cell counts is not recommended. If a patient who is taking propylthiouracil experiences pruritic rash, jaundice, light-colored stool or dark urine, joint pain, abdominal pain or bloating, anorexia, nausea, or fatigue, then liver function and hepatocellular integrity should be tested. If methimazole is being used as primary therapy, it should be administered for 12-18 months and then tapered or discontinued if the TSH level is normal at that time. The survey results showed significant discrepancies between the guideline recommendations and clinical practice.
It is now recognized that radioactive therapy might worsen ophthalmopathy, especially when the ophthalmopathy is moderate or severe. Therefore, it is not surprising that many respondents would not recommend radioactive iodine therapy in this circumstance. If radioactive iodine is to be used, the patient should be treated with corticosteroids, which have been demonstrated to decrease the progression of orbitopathy that is associated with radioactive iodine.
Recent guidelines and conferences have also recommended that patients with Graves disease who are contemplating pregnancy and taking antithyroid agents be given propylthiouracil while attempting to conceive and during the first trimester of pregnancy because methimazole has been associated with various fetal complications, including aplasia cutis. The guidelines note that methimazole should be used in almost every patient who chooses antithyroid therapy. However, propylthiouracil is preferred in pregnancy, in the treatment of thyroid storm, and in patients with reactions to methimazole who refuse radioactive iodine or surgery. The American Thyroid Association's pregnancy guidelines indicate that patients who are on methimazole should be switched to propylthiouracil if pregnancy is confirmed in the first trimester. Switching to methimazole can be considered after the first trimester.
The study by Burch and colleagues has served a useful purpose in documenting clinical practices for treating patients with Graves disease. A strength of the study is the large number of respondents who returned the survey; the total number of respondents was larger than for any previous study. Weaknesses of the study relate to the relatively small percentage of members of each society that returned the survey. Of course, it is not known how the remaining clinicians would have responded. Approximately 10%, 13%, and 6% of active members of The Endocrine Society, American Thyroid Association, and the American Association of Clinical Endocrinologists responded, respectively. Also, the majority of the respondents were from the United States and relatively fewer (about 40%) were from other geographical areas. Further, it is difficult to mimic precisely what an individual physician would recommend in the real clinical world compared with completing a survey questionnaire because many additional factors must be taken into account in the real world. In summary, this geographic assessment indicates how clinicians assess and treat patients with Graves disease and can be used as a baseline barometer of the impact of guideline recommendations. It may also serve to stimulate further prospective randomized trials in this area.
Abstract
Source...