Current issues of ACP Journal Club are published in Annals of Internal Medicine


Relapse frequently occurred in Graves disease after treatment

ACP J Club. 1991 Nov-Dec;115:91. doi:10.7326/ACPJC-1991-115-3-091

Source Citation

Berglund J, Christensen SB, Dymling JF, Hallengren B. The incidence of recurrence and hypothyroidism following treatment with antithyroid drugs, surgery, or radioiodine in all patients with thyrotoxicosis in Malmö during the period 1970-1974. J Intern Med. 1991 May; 229:435-42. [PubMed ID: 1710255]



To determine the incidence of late recurrence and hypothyroidism in patients with thyrotoxicosis treated with antithyroid drugs, surgery, or radioiodine.


Inception cohort with follow-up of 1 to 192 months.


Population-based study in Malmö, Sweden.


Patients were identified at the time of diagnosis of thyrotoxicosis between 1970 and 1974. 79% were followed for more than 5 years. Median follow-up for euthyroid patients was similar to that for all patients combined. (Data provided by authors). 333 patients from Malmö who were treated for thyrotoxicosis were evaluated; 24 (7%) were not available for follow-up.

Assessment of prognostic factors

The diagnosis of thyrotoxicosis was based on clinical examination, serum protein-bound iodine values, a triiodothyronine uptake test, and a thyroid radioiodine uptake measurement. 212 patients had Graves disease, 62 had toxic multinodular goiter, and 35 had solitary toxic adenoma.

Main outcome measures

Recurrent disease consisted of a second diagnosis of thyrotoxicosis. Hypothyroidism was diagnosed based on clinical examination and either a low serum protein-bound iodine value and triiodothyronine test (before 1975) or an elevated serum thyrotropin level with a low serum thyroxine concentration (after 1975). (The follow-up schedule was not described.)

Main results

36 of 83 patients (43%) with Graves disease who were treated with antithyroid drugs had a recurrence after a median time of 21 months; 1 patient developed hypothyroidism after 36 months. 2 of 23 patients (9%) with Graves disease who had surgery had a recurrence, and 6 patients (27%) became hypothyroid. There were no recurrences among 10 patients with solitary toxic adenoma or among 12 patients with toxic multinodular goiter who had surgery, but 1 of the 12 patients became hypothyroid after 3 months. Of the 106 patients with Graves disease who received radioiodine treatment, 5 (5%) had a recurrence and 59 (56%) became hypothyroid after a median of 36 months. The median total dose of radioiodine was higher (15 000 rad) for patients who became hypothyroid than for those who did not (8000 rad) (P< 0.05). There were no recurrences among 48 patients with toxic multinodular goiter or among 25 patients with solitary toxic adenoma treated with radioiodine, but there were 9 (19%) and 6 (24%) instances of hypothyroidism in the 2 groups, respectively.


Thyrotoxicosis recurred frequently in patients with Graves disease who were treated with antithyroid drugs. Late hypothyroidism occurred frequently in all patients with Graves disease and in those with solitary toxic adenoma or toxic multinodular goiter treated with radioiodine.

Source of funding: Not stated.

Address for article reprint: Dr. J. Berglund, Department of Surgery, Malmö General Hospital, Malmö, Sweden.


The choice of treatment for hyperthyroidism is influenced by the cause of the disease and its severity. When caused by autonomous thyroid hormone-producing nodules, hyperthyroidism is usually treated with surgery or radioiodine; antithyroid drugs may be used to render the patient euthyroid before such therapy, but is rarely the long-term treatment of choice. When caused by Graves disease, long-term antithyroid drugs may be given in an effort to induce an immunologic remission; radioiodine or surgery is an alternative, and the actual choice of therapy is somewhat arbitrary. Because there are no randomized trials that compared the 3 different types of therapy for hyperthyroidism, information regarding their relative effectiveness and consequences is lacking.

This cohort study of hyperthyroid patients provides information that confirms some current views and challenges others. First, the high incidence of hypothyroidism after radioiodine therapy of single toxic nodules is unexpected, suggesting that radioiodine may damage areas of the thyroid that are not concentrating iodine. Conversely, in patients with radioiodine-treated Graves disease, the high incidence of hypothyroidism and its relation to radioiodine dose are well known. Second, the high recurrence rate of Graves disease after stopping antithyroid drugs is not surprising, given that a genetic predisposition to autoimmune Graves disease is unlikely to be removed by current regimens. Unfortunately, because patients achieving immunologic remission before a recurrence were not distinguished from nonremitters (i.e., dependent on drugs for euthyroidism), the extent to which this number reflects the underlying risk of a predisposed population, or the refractoriness of the disease, is unclear.

These data confirm that radioiodine-treated hyperthyroid patients and all patients with Graves disease require continued follow-up. The risk for recurrence in drug-treated Graves disease supports the view that radioiodine or surgery is best chosen for noncompliant patients or for those with other medical problems.

Hertzel C. Gerstein, MD, MSc
McMaster UniversityHamilton, Ontario, Canada