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L Hegedus and S Karstrup

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SJ Bonnema, VE Nielsen and L Hegedus

OBJECTIVE: The long-term effects of (131)I-therapy in patients with symptomatic non-toxic diffuse goitre were evaluated. DESIGN AND METHODS: In a prospective open study, 34 patients (median age: 40 yrs, range: 27-68 yrs) were enrolled who suffered from a non-toxic goitre absent of nodules on clinical examination and on ultrasonography. Treatment indication was the presence of goitre giving rise to cervical compression and/or cosmetic discomfort. The median (131)I activity was 600 MBq (200-600 MBq) administered orally on an outpatient basis. The patients were investigated by clinical examination, thyroid ultrasonography and thyroid function tests at regular intervals and for at least 12 months after the (131)I-therapy. Yearly follow-up continued until the end of the study period or if permanent hypothyroidism ensued. The severity of symptoms was evaluated by a Visual Analogue Scale (VAS) (range: 0-10). RESULTS: The median follow-up time was 36 months (12-84). Goitre volume was reduced from 67.9+/-28.5 ml to 43.4+/-18.7 ml (mean+/-S.D.) (P<0.001) 3 months after the (131)I-therapy. After 3 years of follow-up, only 28.1+/-2.0% (mean+/-S.E.) remained of the initial goitre mass (P<0.001). Goitre was no longer present in 76% of the patients at the end of follow-up. An inverse correlation was found 1 year after therapy, but not after 3 years, between the initial goitre size and the percent reduction (r=-0.44, P=0.01). Thirty-six percent had become hypothyroid after three years. Median VAS scores were reduced from an initial 7.0 (cervical compression) and 5.5 (cosmetic discomfort) to 0.0 at the end of follow-up (P<0.001). CONCLUSION: Our data justify treatment of non-toxic diffuse goitre with (131)I because goitre reduction is pronounced, along with a very high degree of patient satisfaction and few side effects. We suggest that (131)I-therapy can be used as an alternative to L-T(4) suppressive therapy and thyroidectomy in this group of patients.

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SJ Bonnema, L Bartalena, AD Toft and L Hegedus

In routine use for more than 50 years, radioiodine ((131)I) is generally considered safe and devoid of major side effects. Therefore, it is surprising that relatively many aspects of radioiodine therapy are controversial, as illustrated by recent international questionnaire studies. Our review aims at highlighting three of these areas - namely, the influence of (131)I on the course of Graves' ophthalmopathy, the possible radioprotective effects of antithyroid drugs, and the use of (131)I in large goitres. (131)I therapy carries a small (but definite) risk of causing progression of Graves' ophthalmopathy. Identification of risk factors (thyroid dysfunction, high level of thyroid-stimulating hormone (TSH) receptor antibodies, cigarette smoking) allows the identification of patients at risk and the institution of concomitant glucocorticoid treatment, thereby hindering progression of eye disease. On the basis, largely, of retrospective data, it appears that carbimazole (or methimazole), if stopped 3-5 days before treatment, does not influence the outcome of (131)I therapy. Simultaneous thyrostatic medication most probably reduces the efficacy of (131)I, as does restarting it within 7 days. Propylthiouracil seems to have a more prolonged radioprotective effect than carbimazole. Surgery is the treatment of first choice in patients with a large goitre. However, in the case of patient ineligibility or preference, (131)I therapy may be an option. The treatment has a favourable effect on tracheal compression and inspiratory capacity, but the reduction in thyroid volume is only 30-40%. Inpatient treatment, necessitated by the large doses, makes the treatment cumbersome. Controversy related to radioiodine therapy is mainly based on the lack of adequate prospective randomised studies comparing efficacy, side effects, cost and patient satisfaction.

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H. Perrild, J. M. Hansen, L. Hegedüs, L. Rytter, B. Holm, E. Gundtofte and K. Johansen

Abstract.

Ultrasonic scanning has been used to estimate changes in goitre size during and after treatment with a daily dose of either 100 μg thyroxine (T4) (n = 30), 150 μg T4 (n = 33), 200 μg T4 (n = 17) or 60 μg triiodothyronine (T3) (n = 30) for one year in patients with diffuse non-toxic goitre. The thyroid volume was measured before and every 3 months during and 3 months after withdrawal of therapy. All 4 treatments resulted in a decrease in goitre size after 3 months' therapy (P < 0.05) but only in the patients given 200 μg T4 and 60 μg T3 was the decrease long lasting during additional 9 months' therapy. The mean reduction in thyroid volume after 12 months therapy was 30 ± 26 sd and 22 ± 30 (sd)%, respectively. The free-T4-index was found significantly raised throughout the treatment with all three T4 doses, whereas the free-T3-index did not change. During treatment with 60 μg T3 no persistent rise in free-T3-index was seen while free-T4-index was decreased all 12 months.

No increase in goitre size was observed 3 months after withdrawal of the T3 therapy (n = 15), whereas all goitres in the T4 treated groups had returned to the pre-treatment values at that time. No rebound phenomenon was observed. The serum T3 and T4 levels were normalized 3 months after withdrawal in all four groups. Seven out of 8 patients on 200 μg T4 daily and 20 out of 25 patients on 60 μg T3 daily had no TSH response to TRH (200 μg iv) after 3 months' therapy. Forty-three out of 61 patients in the 4 groups showed no TSH response to TRH after 3 months' therapy. Only the group of patients showing no TSH response to TRH after 3 months' treatment had a significant decrease in goitre size in contrast to the group with a positive response to TRH.

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SJ Bonnema, FN Bennedbaek, J Gram, A Veje, J Marving and L Hegedus

OBJECTIVE: Retrospective studies have indicated that anti-thyroid drugs (ATD) might possess a radioprotective effect, leading to a higher rate of recurrence of hyperthyroidism after iodine-131 ((131)I) therapy. DESIGN: A randomized clinical trial was performed to clarify whether resumption of methimazole after (131)I influences the final outcome of this treatment. METHODS: We assigned 149 patients with Graves' disease or a toxic nodular goitre to groups either to resume (+ATD) or not to resume (-ATD) methimazole 7 days after (131)I. Before (131)I therapy, all patients were rendered euthyroid by methimazole, which was discontinued 4 days before the (131)I therapy. RESULTS: During the follow-up period of 12 Months, 13 patients developed hypothyroidism, 42 were euthyroid, and 18 had recurrence of hyperthyroidism in the +ATD group; the respective numbers in the -ATD group were 16, 42 and 18 (P=0.88). At 3 weeks after (131)I therapy, the serum free-thyroxine index was slightly decreased (by 5.7%; 95% confidence interval (CI) -15.5 to 5.4%) in the +ATD group, in contrast to an increase of 35.9% (95% CI 18.8 to 55.5%) in the -ATD group (P<0.001 between groups). In the subgroup that remained euthyroid during follow-up, thyroid Volume reduction, assessed by ultrasonography, was smaller in the +ATD group [38.7% (95% CI 33.3 to 44.1%)] than in the -ATD group [48.6% (95% CI: 41.5-55.6%)] (P<0.05). CONCLUSION: No radioprotective effect could be demonstrated, with regard to final thyroid function, for the resumpton of methimazole 7 days after (131)I therapy. Although resumption of methimazole slightly reduced the magnitude of shrinkage of the goitre obtained by (131)I, the prevention of a temporary thyrotoxicosis in the early period after radiation favours this regimen.

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D Hansen, FN Bennedbaek, M Hoier-Madsen, L Hegedus and BB Jacobsen

OBJECTIVE: Thyroid autoantibodies (TA) and thyroid ultrasonography are widely used in the diagnosis of autoimmune thyroid disease (AITD). However, we know little of the significance of having ultrasonographic abnormalities (USabn) without having any other signs of AITD. In a previous population-based study of 105 young patients with type 1 diabetes (T1DM) we found a high prevalence (42%) of USabn. In the present study we evaluate the development of both USabn and TA in a 3-Year follow-up of this cohort. DESIGN: Of the 105 previously investigated children and adolescents with T1DM (aged 5-21 Years), 101 were re-examined. Serum concentrations of tri-iodothyronine (T(3)), thyroxine (T(4)), TSH, thyroid peroxidase antibodies (TPOab) and thyroglobulin antibodies (Tgab), as well as thyroid size and morphology were determined in all patients. RESULTS: During the 3 Years follow-up period, the prevalence of thyroid dysfunction increased from 5 to 8%, the prevalence of TPOab was unchanged at 13%, while the prevalence of Tgab decreased from 14 to 7%. The prevalence of USabn increased from 42 to 49%. Most patients presented USabn at both examinations. Patients with USabn had a higher prevalence of TA than those without USabn (P=0.038) and higher serum levels of TSH (P=0.027). All patients with thyroid dysfunction presented with USabn. However, many patients with USabn had no other signs of AITD. CONCLUSIONS: A high prevalence of thyroid dysfunction, TA and thyroid USabn were found in young patients with T1DM. Thyroid USabn was a sensitive but non-specific marker of AITD and is therefore unsuitable for screening purposes. Instead, we recommend regular screening using serum TSH in the follow-up of young diabetic patients.

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D Hansen, FN Bennedbaek, LK Hansen, M Hoier-Madsen, BB Jacobsen and L Hegedus

OBJECTIVE: An association between insulin-dependent diabetes mellitus (IDDM) and autoimmune thyroid disease is well recognized. We have studied the prevalence of thyroid dysfunction, autoimmunity and morphological abnormalities by ultrasonography in young diabetics. SUBJECTS AND METHODS: Among young IDDM patients less than 18 years old and living in the county of Funen, Denmark, 105 of 116 eligible patients participated. They were compared with 105 healthy children matched for sex and age. Routine thyroid function parameters (thyroxine (T4), tri-iodothyronine (T3), T3 resin uptake and TSH) and thyroid autoantibodies (anti-thyroid peroxidase, TPOab, and thyroglobulin antibodies, Tgab) were measured. Thyroid size and morphology were determined by ultrasonography. RESULTS: Two of the diabetics had previously diagnosed hypothyroidism and three new cases of subclinical hypothyroidism were found. There were no significant differences in thyroid function variables or thyroid volume between diabetics and controls. Thyroid volume correlated significantly with age and weight in both groups. Among diabetics, 17 had thyroid autoantibodies (13 with TPOab, 14 with Tgab and 10 with both) compared with 2 children in the control group (P<0.001). Forty-four with IDDM as opposed to 11 of the controls (P<0.001) had morphological abnormalities at ultrasonography. Most of them had various degrees of hypoechogenicity thought to be a marker of thyroid autoimmunity. Among the 17 diabetics with autoantibodies, 10 had morphological abnormalities at ultrasonography. CONCLUSIONS: A high proportion of young IDDM patients without any clinical signs of thyroid disease have markers of thyroid autoimmunity. Many have thyroid autoantibodies, but even more have abnormalities by thyroid ultrasonography.