Three forms of primary therapy for Graves' disease are in common use today: (1) destruction of the thyroid by ¹³¹I; (2) blocking of hormone synthesis by antithyroid drugs; and (3) partial surgical ablation of the thyroid. Iodine alone as a definitive form of treatment has been used in the past, but is not used today because its benefits may be transient or incomplete and because more effective methods have become available. Iodine is primarily used now in conjunction with antithyroid drugs to prepare patients for surgical thyroidectomy when that plan of therapy has been chosen. Roentgen irradiation was also used in the past.³⁶

Selection of therapy depends on a multiplicity of considerations ^36.1. Availability of a competent surgeon, for example, undue emotional concern about the hazards of ¹³¹I irradiation, or the probability of adherence to a strict medical regimen might govern one's decision regarding one program of treatment as opposed to another. All three methods provide satisfactory outcomes in over 90% of patients ^36.2.  In the succeeding paragraphs, we will examine in some detail the resources open to the physician and attempt to weigh their merits under varied circumstances. Fig. 11-2

Figure 11-2. Comparison of outcome of treatment of thyrotoxicosis by 131I (left upper panel); 131I plus ATD + KI (right upper panel); surgery (left lower panel); and ATD (right lower panel); over ten years follow-up. Surgery produced the highest final percentage of euthyroidism without therapy, followed by ATD and 131I.

Antithyroid drug therapy offers the opportunity to avoid induced damage to the thyroid (and parathyroids or recurrent nerves), as well as radiation exposure and operation.  In a recent study patients with thyroids under 40 gm weight, with low TRAb levels, and age over 40, were most likely to enter remission (in up to 80%) ^36.3.  The difficulties are the requirement of adhering to a medical schedule for many months or years, frequent visits to the physician, occasional adverse reactions, and, most importantly, a disappointingly low permanent remission rate. Therapy with antithyroid drugs is used as the initial modality in people under age 18-20, in many adults through age 40, and in most pregnant women.

Iodine-131 therapy is quick, easy, relatively inexpensive, avoids surgery, and is without significant risk in adults and probably late teenagers. The larger doses required to give prompt and certain control generally induce hypothyroidism, and low doses are associated with a frequent requirement for retreatment or ancillary medical management over one to two years. We use ¹³¹I as the primary therapy in most persons over age 40 and in most adults above age 21, if antithyroid drugs fail to control the disease.

Surgery, which was the main therapy until 1950, has been to a major extent replaced by ¹³¹I treatment. As the high frequency of ¹³¹I-induced hypothyroidism became apparent, some revival of interest in thyroidectomy occurred. The major advantage of surgery is that definitive management is often obtained over an 8- to 12-week period, including preoperative medical control, and many adult patients are euthyroid after operation. Its well-known disadvantages include expense, surgery itself, and the risks of recurrent nerve and parathyroid damage, hypothyroidism, and recurrence. Nevertheless, if a skillful surgeon is available, surgical management may be used as the primary or secondary therapy in many young adults, as the secondary therapy in children poorly controlled on antithyroid drugs, in pregnant women requiring large doses of antithyroid drugs,  in patients with significant exophthalmos, and in patients with coincident suspicious thyroid nodules. Scholz et al found that early total thyroidectomy should be considered as the method of choice for treating older, chronically ill patients with thyrotoxic storm.  They studied a group of ten patients with thyrotoxic storm and severe cardiorespiratory and renal failure, with arrhythmias, coronary artery disease, chronic obstructive pulmonary disease, or acute inflammation.  They suggest early operation if high-dose thionamide treatment, iopanoic acid, and glucocorticoids fail to improve the patient’s condition within 12 – 24 hours (36.4).

Two recent surveys reporting trends in therapeutic choices made by thyroidologists have been published. ³⁷ In Europe, most physicians tended to treat children and adults first with antithyroid drugs, and adults secondarily with ¹³¹I or less frequently surgery. Surgery was selected as primary therapy for patients with large goiters. ¹³¹I was selected as the primary treatment in older patients. Most therapists attempted to restore euthyroidism by use of ¹³¹I or surgery. In the United States, ¹³¹I therapy is the initial modality of therapy selected by members of the American Thyroid Association for management of uncomplicated Graves' disease in an adult woman. ³⁸ Two-thirds of these clinicians attempt to give ¹³¹I in a dosage calculated to produce euthyroidism, and one-third plan for thyroid ablation.

NEW THERAPEUTIC APPROACHES-
Depletion of T cells or B cells by use of specific monoclonal antibodies has been used in several autoimmune diseases, as a method to suppress on going autoimmunity. The anti CD-20 monoclonal antibody rituximab was used to deplete B cells in 10 patients with newly diagnosed Graves’ disease, who were compared to 10 untreated patients.  Both groups received methimazole for approximately 3.5 months prior to the date of Rituximab administration, and for 22 days subsequently. Rituximab treatment appeared to induce sustained remission in patients with low TRAb levels, but did not affect antibody levels, and was not effective in patients with high TRAb levels. High cost, low efficacy, and possible side effects limit its usefulness.(El Fassi D, Nielsen CH, Bonnema SJ, Hasselbalch HC, Hegedus L B lymphocyte depletion with the monoclonal antibody rituximab in Graves' disease: a controlled pilot study.J Clin Endocrinol Metab. 2007 May;92(5):1769-72.)