Changes in Thyroid Function in Euthyroid Subjects with a Family History of Graves' Disease: A Foliow-Up Study of 69 Patients*

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Abstract
TRH [thyrotropin-releasing hormone, thyroliberin] tests were performed in 206 clinically and biochemically euthyroid relatives of patients with Graves'' disease. In 117 of the 206, T3 [triiodothyronine] suppression tests were performed. Results revealed that 56 of the 206 (27.1%) showed abnormal responses to TRH. Of these, 29 (14.1%) revealed absent or decreased responses, and 27 (13.1%) revealed augmented responses to TRH. Of the 117, 8 (6.8%) were T3 nonsuppressible. These 8 subjects consisted of 4 subjects out of 17 hyporesponders and 4 subjects out of 90 normal responders. The majority of suppressible subjects (86 among 109) demonstrated normal responses to TRH. Of the 206 subjects, 69 were followed for 6 mo. to 5 yr to observe changes in their thyroid functions. Among all 69 subjects, 3 became clinically thyrotoxic 12, 12 and 18 mo. after their initial visit, respectively, and 2 became clinically hypothyroid 2 yr after their initial visit. Since 69 subjects were clinically and biochemically euthyroid and had no goiter or exophthalmos at their initial visit, the incidence of thyrotoxicosis or hypothyroidism in these subjects could be considered to be remarkably high. The 3 thyrotoxic patients were TRH hyporesponders at their 1st visit. One patient was T3 suppressible; T3 suppression tests were not performed in the other 2 patients at their initial visit. There was no abnormality in the 1st TRH test in 2 relatives who became hypothyroid. Among euthyroid relatives with a family history of Graves'' disease, there may be many with abnormalities in TRH responsiveness and T3 suppressibility. Nonsuppressible subjects are more likely to be TRH hyporesponders and vice versa. Hyperthyroidism or hypothyroidism apparently occurs frequently in euthyroid relatives with a family history of Graves'' disease. Thyrotoxicosis evidently occurs frequently in TRH-hyporesponders and hypothyroidism occurs in the others.