Clinical characteristics of subacute thyroiditis classified according to human leukocyte antigen typing.

We investigated human leukocyte antigen (HLA) class I and class II antigens in 56 Japanese patients with subacute thyroiditis (SAT) who visited our out-patient clinic between 1988 and 1990. We found SAT to be associated with not only HLA-B35 (40 patients; P < 0.000001; relative risk, 18.02), but also with HLA-B67 antigens (9 patients; P < 0.00001; relative risk, 11.20). No heterozygotes of HLA-B35 or HLA-B67 were found in any of the 56 patients with SAT. Either HLA-B35 or HLA-B67 antigen is found in 87% of patients with SAT. When season of onset and clinical course of SAT were compared in the 49 patients with HLA-B35-positive SAT (B35-SAT) and HLA-B67-positive SAT (B67-SAT), we were able to identify certain characteristics: 1) B67-SAT often followed the course from transient thyrotoxicosis to a hypothyroid phase to a euthyroid phase [6 of 9 B67-SAT (67%) vs. 10 of 40 B35-SAT (25%); P < 0.05]; and 2) B67-SAT occurred mostly during the summer or autumn and at a higher rate than did B35-SAR [8 of 9 B67-SAT (89%) vs. 17 of 40 B35-SAT (43%)], whereas B35-SAT occurred throughout the year. We conclude that there are at least two types of SAT that can be classified by association with either HLA-B35 or HLA-B67 antigens.

A study of thyroid function after subtotal thyroidectomy for Graves' disease: particularly on TRH tests, T3 suppression tests and antithyroid antibodies in euthyroid patients.

Of 305 patients who underwent subtotal thyroidectomy for Graves' disease between 1969 and 1975, recurrent hyperthyroidism was found in 31 (10.2%) and hypothyroidism in 18 (5.9%). The remaining 256 patients were clinically euthyroid, but an elevated serum TSH level was found in 104 (34.1%) and an elevated serum T3 level in 19 (6.28%). In 57 of 133 clinically and biochemically euthyroid patients, a TRH test, T3 suppression test and measurement of antithyroid antibodies were performed. Twenty-nine of the 57 patients (50.9%) showed an abnormal response to TRH. Eight of these (14.0%) showed an impaired or absent response. The T3 suppression test showed that 15 of the 57 patients (26.3%) were non-suppressible. Positive antithyroid antibodies, especially antimicrosomal antibodies, were more frequent in non-suppressible and TRH-non-responsive patients than in suppressible and TRH-responsive patients. It is suggested that after operation for Graves' disease: 1) only half of the clinically euthyroid patients were biochemically euthyroid, 2) of the clinically and biochemically euthyroid patients, there were many with abnormalities in TRH responsiveness and T3 suppressibility, and 3) thyroid functional status is unstable and long careful follow-up is important after operation for Graves' disease.

Responses to TRH, T3 suppression tests and histological findings by needle biopsy in patients with simple goitre in Japan.

Studies were performed in 120 patients with simple goitre, defined as relatively soft diffuse goitre. All were clinically and biochemically euthyroid and their antithyroid antibodies were negative. The TRH test was performed in 99 after the TRH test, while satisfactory biopsies of the thyroid were obtained in 37. The results showed that 28 of the 115 cases (24%) had an abnormal response to TRH; 8 (7%) were hyporesponders and 20 (17%) were hyperresponders. The T3 suppression test showed that 3 of 99 cases (3%) were non-suppressible. As determined by histological examination of the needle biopsy specimen, 17 of the 37 cases (46%) had normal follicles without lymphocytic infiltration, 10 (27%) had diffuse chronic thyroiditis, 5 (14%) had focal thyroiditis and 4 (11%) had diffuse epithelial hyperplastic change, and 1 (3%) had an adenomatous goitre. It is suggested that simple goitre defined as above includes various thyroid diseases and that the results of TRH tests, antithyroid antibody estimations and histological findings do not correlate in many patients.

Changes in thyroid function in euthyroid subjects with a family history of Graves' disease: a follow-up study of 69 patients.

TRH tests were performed in 206 clinically and biochemically euthyroid relatives of patients with Graves' disease. In 117 of the 206, T3 suppression tests were performed. Results revealed that 56 of the 206 (27.1%) showed abnormal responses to TRH. Twenty-nine of these (14.1%) revealed absent or decreased responses, and 27 (13.1%) revealed augmented responses to TRH. Eight of the 117 (6.8%) were T3 nonsuppressible. These eight subjects consisted of 4 subjects out of 17 hyperesponders and 4 subjects out of 90 normal responders. The majority of suppressible subjects (86 among 109) demonstrated normal responses to TRH. Sixty-nine of the 206 subjects were followed for 6 months to 5 yr to observe changes in their thyroid functions. Among all 69 subjects 3 became clinically thyrotoxic 12, 12, and 18 months 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. It is of interest that the 3 thyrotoxic patients were TRH hyporesponders at their first 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 first TRH test in 2 relatives who became hypothyroid. It is suggested that 1) among euthyroid relatives with a family history of Graves' disease, there are many with abnormalities in TRH responsiveness and T3 suppressibility, 2) nonsuppressible subjects are more likely to be TRH hyporesponders and vice versa, 3) hyperthyroidism or hypothyroidism occurs frequently in euthyroid relatives with a family history of Graves' disease, and 4) thyrotoxicosis occurs frequently in TRH-hyporesponders, and hypothyroidism occurs in the others.

Thionamide therapy in Graves' disease: relation of relapse rate to duration of therapy.

The present study was undertaken to investigate whether there is a rational basis for the usual long periods of thionamide therapy in patients with hyperthyroid Graves' disease. Eighty untreated patients were given the minimum dose of thionamide drug needed to maintain serum thyroxine, triiodothyronine, and thyrotropin (TSH) concentrations within their normal ranges. Thyrotropin-releasing hormone (TRH) tests were done at 6 monthly intervals for 2 years. Among patients who had positive responses of TSH to TRH, approximately 10 patients every 6 months were asked to stop thionamide therapy and were followed up for at least 1 year after discontinuation of drugs. In the groups treated for 6, 12, 18, and 24 months, relapses occurred in nine of 13, five of nine, three of 12, and two of 11 patients, respectively. Values for thyroid function tests before and at the end of treatment were not different among these four groups of patients. The overall remission rates were not ascertained. However, a minimum of 1 year's treatment is recommended, at least in Japan.