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Birte Nygaard, Jens Faber, Laszlo Hegedüs and Jens Mølholm Hansen

The traditional treatment of a growing nodular non-toxic goitre has for many years been surgical resection or levothyroxine suppressive treatment. During recent years, several studies have reported promising results of 131I treatment in terms of thyroid size reduction (1–6).

This review outlines the different treatment modalities of non-toxic nodular goitre with special emphasis on 131I treatment. By the term nodular goitre we include glands with solitary or multiple thyroid nodules with uptake on a scintiscan (hot nodules).

Assessment of goitre size

Goitre is usually defined clinically, as a visible or palpable thyroid gland, and usually WHO grade 0 (absent) to grade III (large goitre) (7) is applied. This is an inaccurate definition, however, mainly due to both large inter- and intraobserver variations. Jarløv et al. (8) found an average error of 39% (range 0–170%) in the clinical assessment of thyroid size compared to ultrasonically determined volume. Therefore, the

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Jeppe Lerche la Cour, Lars Thorbjoern Jensen, Anders Vej-Hansen and Birte Nygaard

Background and objective

Hyperthyroid patients treated with radioiodine have increased morbidity and mortality from cerebrovascular events. This risk has until now has been attributed to the hyperthyroidism. However, radioiodine therapy of benign thyroid diseases exposes the carotid arteries to radiation and is capable of inducing atherosclerosis. The objective of the study was to elucidate whether ionizing radiation from radioiodine might contribute to cerebrovascular morbidity.

Methods

In a retrospective register cohort study, 4000 hyperthyroid and 1022 euthyroid goitre patients treated with radioiodine between 1975 and 2008 were matched 1:4 on age and sex with random controls. The cohort was followed from the date of treatment until hospitalization due to cerebrovascular event, death, 20 years of follow-up or March 2013. Data were analyzed in competing risk models adjusting for age, sex, Charlson's comorbidity score, atrial fibrillation and previous cerebrovascular events.

Results

Mean follow-up time was 11.5 years, mean age 61 years, with a total number of 3228 events. Comparing all radioiodine-treated patients with controls, the fully adjusted model showed increased risk of cerebrovascular events among all treated patients, hazard ratio (HR) 1.18 (95% CI 1.09–1.29). The risk was increased among hyperthyroid (HR 1.17; 95% CI 1.07–1.28) as well as euthyroid patients (HR 1.21; 95% CI 1.02–1.44).

Conclusions

We report an increased risk of cerebrovascular events in hyperthyroid as well as euthyroid patients treated with radioiodine for benign thyroid disorders. That these patient groups have similar risks suggests the possibility that radiation from radioiodine contributes to cerebrovascular morbidity via acceleration or initiation of atherosclerosis.

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Birte Nygaard, Peter Gideon, Harriet Dige-Petersen, Niels Jespersen, Karsten Sølling and Annegrete Veje

In order to throw light upon the eventual need for iodine supplementation in Denmark, four age groups of women (15, 30, 45 and 60 years) from the Holbaek municipality were invited for a clinical and ultrasound study of thyroid volume, structure and function. Of the 570 women invited, 391 accepted and were divided into the following groups: group I: 15 years, N= 113; group II: 30 years, N= 100; group III: 45 years, N=98; group IV: 60 years, N=80. The results were as follows: the thyroid gland was palpable in 39% and visible in 16% of the entire group; 19% had a family history of thyroid disorders and 7.6% had a previous thyroid disorder. Thyroid volumes (median (range)) as measured by ultrasound were 12 ml (4–29 ml), 18 ml (5–47 ml), 18 ml (7–64 ml) and 18 ml (9-51 ml) in groups I– IV, respectively. The calculated 24-h iodine excretion was 65 μg (19–365 μg), 88 μg (15-274 μg), 97 μg (40–737 μg) and 83 μg (50–999 μg) in groups I–IV, respectively. An abnormal echo structure was present in 3, 10, 21 and 30%, respectively. Defining a goitre as a thyroid volume above 28 ml indicated a goitre prevalence of 17% in females aged 30–60 years in the Holbaek area of Denmark. Among the 60-year-old women, 3% had a clinically significant goitre (WHO grade III). Thyroid volume did not correlate with iodine excretion. The benefit of iodine supplementation is discussed.

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Birte Nygaard, Ebbe Winther Jensen, Jan Kvetny, Anne Jarløv and Jens Faber

Background

Treatment of hypothyroidism with 3,5,3′-triiodothyronine (T3) is controversial. A recent meta-analysis concludes that no evidence is present in favour of using T3. However, the analysis included a mixture of different patient groups and dose-regimens.

Objective

To compare the effect of combination therapy with thyroxine (T4) and T3 versus T4 monotherapy in patients with hypothyroidism on stable T4 substitution.

Study design

Double-blind, randomised cross-over. Fifty micrograms of the usual T4 dose was replaced with either 20 μg T3 or 50 μg T4 for 12 weeks, followed by cross-over for another 12 weeks. The T4 dose was regulated if needed, intending unaltered serum TSH levels.

Evaluation

Tests for quality of life (QOL) and depression (SF-36, Beck Depression Inventory, and SCL-90-R) at baseline and after both treatment periods.

Inclusion criteria

Serum TSH between 0.1 and 5.0 mU/l on unaltered T4 substitution for 6 months.

Results

A total of 59 patients (55 women); median age 46 years. When comparing scores of QOL and depression on T4 monotherapy versus T4/T3 combination therapy, significant differences were seen in 7 out of 11 scores, indicating a positive effect related to the combination therapy. Forty-nine percent preferred the combination and 15% monotherapy (P=0.002). Serum TSH remained unaltered between the groups as intended.

Conclusion

In a study design, where morning TSH levels were unaltered between groups combination therapy, (treated with T3 20 μg once daily) was superior to monotherapy by evaluating several QOL, depression and anxiety rating scales as well as patients own preference.