Correspondence

Subclinical Hyperthyroidism

N Engl J Med 2002; 346:67-68January 3, 2002

Article

To the Editor:

In his Clinical Practice article on subclinical hyperthyroidism (Aug. 16 issue),1 Toft states that “the choice should be made between a trial of antithyroid drugs and close clinical follow-up.” The well-accepted and benign use of beta-blockade pending definitive treatment is not mentioned. In addition, the high failure rates of both propylthiouracil and methimazole2 and their potential toxic effects (including potentially fatal agranulocytosis3 and hepatotoxic effects4) are not discussed. The use of radioiodine, which is widely recognized as safe and definitive therapy, is mentioned only briefly as an option for secondary treatment.

Lawrence Parker, M.D.
Veterans Affairs Medical Center, Long Beach, CA 90822

4 References

1. 1

   Toft AD. Subclinical hyperthyroidism. N Engl J Med 2001;345:512-516
   Full Text | Web of Science | Medline

2. 2

   Wartofsky L. Low remission after therapy for Graves disease: possible relation of dietary iodine with antithyroid therapy results. JAMA 1973;226:1083-1088
   CrossRef | Web of Science | Medline

3. 3

   Cooper DS, Goldminz D, Levin AA, et al. Agranulocytosis associated with antithyroid drugs: effects of patient age and drug dose. Ann Intern Med 1983;98:26-29
   Web of Science | Medline

4. 4

   Williams KV, Nayak S, Becker D, Reyes J, Burmeister LA. Fifty years of experience with propylthiouracil-associated hepatotoxicity: what have we learned? J Clin Endocrinol Metab 1997;82:1727-1733
   CrossRef | Web of Science | Medline

To the Editor:

Toft states that the presence of thyrotropin-receptor antibodies in serum is diagnostic of Graves' disease. However, the article cited in support of this statement1 indicated that 8 out of 54 patients with a diagnosis of Hashimoto's thyroiditis (15 percent) had a positive test result. Thus, it cannot be assumed that a positive test for thyrotropin-receptor antibodies confirms the diagnosis of Graves' disease. Distinguishing between a hyperthyroid phase of Hashimoto's thyroiditis and true Graves' disease may be important for determining the appropriate treatment.

Federico Relimpio, M.D., Ph.D.
Hospitales Universitarios Virgen del Rocío, 41001 Seville, Spain
relimpio@doymanet.es

1 References

1. 1

   Costagliola S, Morgenthaler NG, Hoermann R, et al. Second generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves' disease. J Clin Endocrinol Metab 1999;84:90-97
   CrossRef | Web of Science | Medline

Author/Editor Response

The author replies:

To the Editor: The issues raised by both Dr. Parker and Dr. Relimpio must be considered in context. I made the statement that “the choice [of treatment] should be made between a trial of antithyroid drugs and close clinical follow-up” as part of a discussion of situations in which the clinician is far from certain that the biochemical pattern consistent with subclinical hyperthyroidism is a consequence of thyroid disease. Few, if any, authorities would wish to treat such patients with iodine-131 in the first instance. Radioiodine therapy would, however, be indicated if a trial of antithyroid drugs resulted in objective evidence of benefit. Such evidence might include weight gain or conversion to sinus rhythm with restoration of serum thyrotropin to its normal level. A beta-adrenergic antagonist that alleviates, rather than abolishes, the clinical features of an excess of thyroid hormone and that has little or no effect on thyroid hormone concentrations is not useful for long-term management.

Although thyrotropin-receptor antibodies may be present in conditions other than Graves' disease, for practical purposes, the presence of these antibodies in a patient with subclinical hyperthyroidism is diagnostic of Graves' disease. Although 15 percent of patients with Hashimoto's thyroiditis were found to be positive for thyrotropin-receptor antibodies,1 all of these patients had presented with hypothyroidism; indeed, that was a necessary criterion for the diagnosis. In my experience, hyperthyroidism is rare in patients with Hashimoto's thyroiditis. Such patients have usually had long-standing hypothyroidism associated with the blocking of thyrotropin-receptor antibodies. Hyperthyroidism in this condition is caused by the new or increased production of stimulating antibodies. The distinction between Hashimoto's thyroiditis and Graves' disease in patients with hyperthyroidism is rather artificial and would not influence decisions about therapy.

Anthony Toft, M.D.
Royal Infirmary of Edinburgh, Edinburgh EH3 9YW, United Kingdom
toft41@hotmail.com

1 References

1. 1

   Costagliola S, Morgenthaler NG, Hoermann R, et al. Second generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves' disease. J Clin Endocrinol Metab 1999;84:90-97
   CrossRef | Web of Science | Medline