Evidence-based practice guidelines for the treatment of patients who have hyperthyroidism and other forms of thyrotoxicosis were recently developed by a task force of expert clinicians jointly appointed by the American Thyroid Association (ATA) and the American Association of Clinical Endocrinologists (AACE).
The guidelines — consisting of 100 recommendations, the supporting evidence, and a rating of the quality of the evidence and the strength of each recommendation — were published simultaneously in the journals of the two associations (Bahn, et al. Thyroid. 2011;21:593-654 and Bahn, et al. Endocr Pract. 2011;17;456-520). The guidelines are also available on the websites of the two associations.
Rebecca S. Bahn, M.D., of the Division of Endocrinology at Mayo Clinic in Rochester, Minn., and chair of the Guidelines Task Force, says: "Clinical topics addressed in the guidelines include:
"The guidelines were constructed to be useful to the practicing physician. To this end, 14 detailed tables are included in the text. In addition, many technical details are discussed relative to:
"The overall content is indexed for ease of access, and a listing of the recommendations without text is included as an appendix."
Marius N. Stan, M.D., of the Division of Endocrinology at Mayo Clinic in Rochester and a member of the Guidelines Task Force, explains: "The ATA/AACE hyperthyroidism recommendations center on the patient and her or his individual needs and preferences. This focus is manifest in the guidelines pertaining to Graves' disease, in that no general recommendation is given to use one particular treatment option (RAI, thyroidectomy, or an anti-thyroid medication) over the others.
"Rather, the guidelines state that patients with overt Graves' hyperthyroidism 'should be treated' with one of these three modalities. In addition, the treating physician and the patient 'should discuss each of the treatment options, including the logistics, benefits, expected speed of recovery, drawbacks, potential side effects and cost. This sets the stage for the physician to make recommendations based on best clinical judgment and allows the final decision to incorporate the personal values and preferences of the patient.'
"This recommendation is followed by a detailed section describing the medical factors that favor each modality, the contraindications to each, and the factors that may impact patient preference of one over another."
Anti-thyroid drug use
An area where the guidelines are more proscriptive is concerning which particular anti-thyroid drug to use. Dr. Bahn comments: "In the past, both methimazole (MMI) and propylthiouracil (PTU) were thought to be appropriate as first line therapy for Graves' disease. However, recent evidence has come to light that PTU can cause fulminant hepatic necrosis that may be fatal.
"Liver transplantation has been necessary in some patients taking PTU. For this reason, the guidelines state that 'MMI should be used in virtually every patient who chooses anti-thyroid drug therapy for Graves' disease, except during the first trimester of pregnancy, when PTU is preferred; in the treatment of thyroid storm; and in patients with minor reactions to MMI who refuse RAI or surgery.'
"Because the onset of PTU-induced hepatotoxicity is rare and the hepatotoxicity may be acute and rapidly progressive, routine monitoring of liver function in all patients taking this medication has not been found to prevent severe hepatotoxicity."
Dr. Bahn continues: "Both MMI and PTU can produce transient cholestatic abnormalities, with the latter causing increases in serum alanine aminotransferase and aspartate aminotransferase in up to one-third of patients. Hyperthyroidism can itself cause mildly abnormal liver function test results.
"Therefore, 'a liver profile including bilirubin and transaminases should be measured prior to initiating either drug,' and 'liver function and hepatocellular integrity should be assessed in patients taking PTU who experience pruritic rash, jaundice, light-colored stool or dark urine, joint pain, abdominal pain or bloating, anorexia, nausea, or fatigue.'
"Similarly, because routine monitoring of white blood cell counts is not likely to identify cases of agranulocytosis associated with either medication, routine monitoring of white blood cell counts is not recommended. However, because patients are typically symptomatic, 'a differential white blood cell count should be obtained during febrile illness and at the onset of pharyngitis in all patients taking anti-thyroid medication.'
This approach is, of course, predicated on the recommendation that patients be informed of the adverse effects of anti-thyroid drugs and be alerted to stop the medication immediately and call their physician should they note symptoms suggestive of either hepatic injury or agranulocytosis."
Specific recommendations are given in the guidelines regarding the prevention of GO and the treatment of hyperthyroidism in patients with established GO. Dr. Stan explains: "Because smoking is a significant risk factor for GO, the guidelines emphasize that 'smokers with Graves' disease should be advised to stop smoking and be referred to a structured smoking cessation program.'
"In patients who have no clinically apparent GO and do not smoke, 'RAI, MMI or thyroidectomy are equally acceptable therapeutic options.' In contrast, 'patients with mild active GO who choose RAI should be considered for concurrent treatment with corticosteroids,' depending on the risk-benefit ratio relative to the patient's overall health.
"This recommendation is based on several studies showing that RAI therapy is a risk factor for progressive disease in patients with established mild active GO — a risk that can be essentially negated by the concurrent use of oral corticosteroids. If the patient with mild active GO is a smoker, however, 'RAI should not be given without concurrent corticosteroids.'
"Finally, the guidelines assert that 'patients with active moderate-to-severe or sight-threatening GO should not be treated with RAI but should instead either receive MMI or undergo surgery.' "