B.-A. Lamberg

Spontaneous hypothyroidism after antithyroid treatment of hyperthyroid Graves’ disease

Out of 54 patients with hyperthyroid Graves’ disease 35 remained euthyroid after treatment with antithyroid agents and have been continuously followed from 1 to 9 yr (4.85 ± 2.55 yr, mean ± SD). In 4 patients an exaggerated TSH response to TRH developed from 30 to 111 months after interrupting the treatment and one of them became hypothyroid 60 months (5.0 yr) thereafter. The annual incidence of subclinical hypothyroidism (exaggerated response to TRH) as calculated from the total number of observation yr was 2.5% and that of overt hypothyroidism was 0.6%. These figures are similar to those reported recently in 2 retrospective studies.

Response to TRH, serum thyroid hormone concentration, and serum markers of autoimmunity after antithyroid therapy in Graves' disease.

In order to study the clinical significance of the TRH stimulation test the response to 200μg TRH given iv was studied in 33 patients with Graves’ disease from 3 to 70 months after discontinuation of antithyroid therapy. The relationship between the maximal increment in serum TSH and the level of thyroid hormones, the presence of circulating thyroid antibodies and the leucocyte migration inhibition, which is a measure of cellular hypersensitivity, was studied. In one group comprising 21 patients who had a normal response to TRH when tested 3 months after withdrawal of treatment or later in a few cases there was only one relapse which occurred within the first year after therapy; two patients who remained euthyroid had a temporary decrease of the response to subnormal levels (Δ TSH <3.0 mU/I) during the first year. In another group comprising 12 patients who initially had subnormal responses there were 5 relapses and these occurred during the first 2 years after therapy. The difference between the groups with regard to the relapse rate was statistically significant. In two patients the response became ultimately normal but in 4 the response is still subnormal 2 to 6 years after therapy. Two patients, one from each group, developed an exaggerated response (Δ TSH >30.0 mU/I) 2 1/2 and 3 years after therapy and this has remained abnormal although the patients are still euthyroid. The mean T4 and T3 and free hormone indices were significantly higher in the group of patients who had a subnormal response in comparison to the other group, although mostly the individual values were within the normal range. There was no correlation between the response and the circulating antibodies or migration inhibition. The results indicate that the TRH stimulation test has some although a limited value for the prediction of outcome after long-term antithyroid therapy. Absence of response may persist for several years without relapse and seems in some way to be related to the level of thyroid hormones in the blood, although mostly the individual values are within the normal range. No relationship exist, however, to common autoimmune parameters.

Low TSH-response to TRH in a former endemic goiter area

During 30 yr of iodine prophylaxis endemic goiter in school children had disappeared in the Savonlinna area which has been the location of continuous surveillance in the East of Finland. In adults goiter is still found to some extent especially in older people. The iodine intake has increased from about 50 to 300 μg per day during these yr and the thyroidal uptake of radioactive iodine has decreased from over 60% to between 20 and 30%. However, there is a significant difference in this regard between nongoitrous individuals and goiter patients. In the present study comprising only goiter patients it was found that the thyroidal uptake was significantly higher in the group of patients with a subnormal response to TRH. These patients also had larger goiters and more palpable thyroid nodules than those with a normal response to TRH. The mean age was significantly higher (60.3 yr) as compared to that in the group which had a TSH-response to TRH of > 20 mU/l, smaller glands and less thyroid nodules (45.1 yr). The data fit well with the reports on increasing autonomy with increasing age in nontoxic goiter.