Hyperthyroid Graves' disease without detectable thyrotropin receptor antibodies.

TSH receptor antibodies are generally held responsible for the stimulation of the thyroid that characterizes patients with Graves' disease. Here, we describe nine patients with hyperthyroidism (triiodothyronine 4.9, 3.2-6.7 nmol/L; median, range) who were referred for radioiodine treatment and who had increased thyroid radioiodine uptake values but lacked TSH receptor antibodies determined by a radioreceptor assay. Furthermore, when serum immunoglobulins were studied in a bioassay based on a rat thyroid cell line (FRTL-5), no evidence of stimulant activity was observed. Subsequent to radioiodine therapy, TSH receptor antibodies appeared in all nine patients. The antibodies competed for TSH in the radioreceptor assay and, of the eight patient samples studied with the bioassay, six stimulated cAMP production whereas another two blocked the latter. The results show that a small proportion of patients with active hyperthyroid Graves' disease, in this study 9 out of 130 cases, do not have detectable TSH receptor stimulatory antibodies. A local production of antibodies within the thyroid can be suggested, although a more likely explanation might be that the thyroid in Graves' disease is activated also by other mechanisms than antibody-dependent ones.