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Laszlo Hegedüs and Jens Faber

Radioactive iodine (131I) has been used for half a century and proved effective in treating hyperthyroidism. It is safe, cheap and relatively free from side effects. Iodine-131 is used in most cases of nodular toxic goitre and regarded as the treatment of choice for patients with Graves' disease who do not remit following a course of antithyroid drugs (1, 2). Although large surveys among European (3) and American (4) thyroidologists have disclosed some differences in attitude, this treatment is increasingly used. In fact, many thyroidologists have come to the conclusion that antithyroid drugs aiming at inducing remission of the hyperthyroidism should be reserved for young patients and those with normal or only slightly increased thyroid size. In Denmark this would limit the use of antithyroid drugs—for the purpose of inducing remission—to not more than 25% of the patients with hyperthyroidism (5, 6).

Recently, renewed interest in the treatment of

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Hans Perrild, Laszlo Hegedüs and Klaus Arnung

Abstract. Eight healthy males and 8 healthy females without a family history of thyroid disease or detectable thyroid autoantibodies were given 300 mg of lithium carbonate twice a day for 28 days. Using a precise and accurate ultrasonic technique we demonstrated an increase in median thyroid volume from 18 ml on day 0 to 34 ml on day 28 (P < 0.005) in the female group, whereas the median thyroid volume was unchanged in the male group. A significant increase in basal serum TSH level and serum TSH levels 20, 60 and 90 min after 200 μg of TRH iv was found in both groups after 28 days of lithium treatment. The means of the individual TSH increments during the TRH test were not significantly different between the two sexes neither before nor after lithium treatment. After 14 and 28 days a significant fall in serum T4 levels was found in both sexes. 131I uptake (24 h) in the thyroid gland was increased in both sexes, but only in the male group was the mean PB131I (24 h) significantly reduced after 28 days of lithium treatment. In conclusion the present study suggests a difference in susceptibility of the thyroid gland to the growth stimulating effect of minute increments in serum TSH in young healthy males and females given lithium carbonate.

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Steen Karstrup, Laszlo Hegedüs and Hans H Holm

Ultrasonically guided percutaneous injection of 96% ethanol into solitary parathyroid tumours in patients with primary hyperparathyroidism may be used as an alternative to surgery in selected patients. Contrary to surgical parathyroidectomy, the acute changes in parathyroid function following ultrasound-guided chemical parathyroidectomy have never been described. Seven consecutive and highly selected patients with primary hyperparathyroidism were treated with ultrasonically guided injection of ethanol (96%) into solitary and biopsy-verified parathyroid tumours. Basic treatment included a maximum of three injections separated by intervals of 24 h. In six of the seven patients normal serum values of ionized calcium were achieved within 36–120 h (median 36 h) and normal serum values of intact parathyroid hormone within 6–78 h (median 24 h). Three patients received two injections and three patients three injections. One patient remained hypercalcaemic in spite of three injections. Subsequent surgery showed the patient to have two parathyroid adenomas, of which only one had been detected ultrasonically. The present study has demonstrated a fast normalization of parathyroid function following two to three ethanol injections into solitary parathyroid tumours in selected patients with primary hyperparathyroidism.

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Enrico Papini, Claudio M Pacella and Laszlo Hegedus

In patients with thyroid nodules, ultrasound (US) imaging represents an indispensable tool for assessment of the risk of malignancy. Over approximately four decades, innovative technology and successive improvements have facilitated its entry into the routine management and greatly improved its predictive value. When US features cannot reliably rule out thyroid cancer, US guidance allows a correct and safe sampling also of small or deeply located thyroid lesions. Obtained in this way, cytological or microhistological specimens may reliably define the nature of most thyroid nodules, and the information from histochemical or molecular markers shows promise in the classification of the remaining indeterminate cases. While a prompt surgical treatment can be offered in the minority of suspicious or definitely malignant cases, most individuals warrant only a follow-up. However, at initial evaluation, or over the years, a fraction of these benign lesions may grow and/or become symptomatic. Such cases may benefit from US-guided minimally invasive procedures as an alternative to surgery. Image-guided percutaneous treatments most often achieve relief of neck complaints, are inexpensive, and can be performed on an outpatient basis. The risk of major complications, after adequate training, is very low. Importantly, thyroid function is preserved. Currently, percutaneous ethanol injection for cystic lesions and thermal ablation, with laser or radiofrequency, for solid nodules are increasingly used and disseminated beyond the initial core facilities. In centres with expertise and high patient volume, their use should be considered as first-line treatment alternatives to surgery for selected patients with benign enlarging or symptomatic thyroid lesions.

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Finn Noe Bennedbæk, Steen Karstrup and Laszlo Hegedüs

Abstract

Relevant English language articles published from 1966 to 1995 regarding ethanol therapy in the treatment of thyroid and parathyroid diseases were identified through a MEDLINE search and manual searches of identified articles.

The sclerosing properties of ethanol have been recognized for many years and have offered interventional possibilities in the management of various benign as well as malignant lesions. The mechanism of action of ethanol appears to be related to a direct coagulative necrosis and local partial or complete small vessel thrombosis. Ultrasound-guided percutaneous ethanol injection therapy (PEIT) is rapid and performed on an out-patient basis and has now gained wide acceptance due to the accumulating evidence of the efficacy and safety of this therapeutic tool. Yet, there is a lack of prospective, randomized clinical trials comparing PEIT with 131I therapy or surgery with regard to its effects, especially long-term ones and it should therefore still be considered an experimental procedure.

In benign endocrine diseases, PEIT has shown promising results in the treatment of autonomous thyroid nodules, benign solitary cold solid as well as cystic thyroid nodules and parathyroid tumours. Its use in pretoxic and toxic thyroid nodules has been evaluated in several uncontrolled studies, all demonstrating a high success rate in spite of the large number of treatments needed. So far efficacy and cost-effectiveness seem inferior to 131I and surgery. Short-term results of PEIT in benign cystic thyroid nodules are convincing with a high cure rate, but no controlled studies with long-term results are available. Preliminary results suggest that PEIT could become an alternative to surgical excision or levothyroxine therapy in the symptomatic solid cold benign thyroid nodule.

Ultrasound-guided PEIT of parathyroid tumours has proven to be a useful method in highly selected patients in whom surgery has been found non-attractive and medical treatment ineffective. However, no prospective randomized trials have been published comparing the results of PEIT in parathyroid tumours with conventional surgical and medical treatments.

PEIT has never been tested against standard therapy, but seems inferior to 131I and surgery. Side-effects caused by ethanol injection are generally few and transient and are related to the injection into solid nodules rather than cysts. Ethanol injection into solid profund nodules may seriously jeopardize subsequent surgery because of perinodular fibrosis. As an experimental procedure, not yet evaluated sufficiently, it should be reserved for patients who cannot or will not undergo standard therapy. Caution in routine use is advisable.

European Journal of Endocrinology 136 240–250

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Helle Døssing, Finn Noe Bennedbæk and Laszlo Hegedüs

Aim

To evaluate the long-term efficacy of interstitial laser photocoagulation (ILP) in solitary benign thyroid nodules.

Design and methods

A total of 78 euthyroid outpatients (45 participating in randomized trials) with a benign solitary solid and scintigraphically cold thyroid nodule causing local discomfort were assigned to ILP. ILP (using one laser fiber) was performed under continuous ultrasound (US) guidance and with an output power of 1.5–3.5 W. Thyroid nodule volume was assessed by US and thyroid function determined by routine assays, before and during follow-up. Pressure symptoms and cosmetic complaints were evaluated on a visual analogue scale (0–10 cm). Of the total patients, six had thyroid surgery 6 months after ILP and three were lost to follow-up. The median follow-up for the remaining 69 patients was 67 months (range 12–114).

Results

The overall median nodule volume decreased from 8.2 ml (range 2.0–25.9) to 4.1 ml (range 0.6–33.0; P<0.001) at the final evaluation, corresponding to a median reduction of 51% (range: −194 to 95%). This correlated with a significant decrease in pressure as well as cosmetic complaints. After 12--96 months (median 38 months) of ILP, 21 patients (29%) had thyroid surgery because of an unsatisfactory result. All had benign histology. Thyroid function was unaltered throughout and side effects were restricted to mild local pain.

Conclusion

US-guided ILP results in a satisfactory long-term clinical response in the majority of patients with a benign solitary solid cold thyroid nodule. Further large-scale studies should aim at optimizing selection criteria for ILP, preferably in randomized studies.

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Helle Døssing, Finn Noe Bennedbæk and Laszlo Hegedüs

Aim: To evaluate the efficacy of ultrasound (US)-guided interstitial laser photocoagulation (ILP) on thyroid function, nodule size and patient satisfaction in benign solitary solid cold thyroid nodules by comparing one ILP session with no treatment in a prospective randomised study.

Materials and methods: Thirty euthyroid outpatients with a benign solitary solid and a scintigraphically cold thyroid nodule causing local discomfort were assigned to one session of ILP (n = 15) or observation (n = 15) and followed for 6 months. Thyroid nodule volume and total thyroid volume were assessed by US and thyroid function was determined by routine assays before and during follow-up. Pressure and cosmetic complaints before and at 6 months were evaluated on a visual analogue scale. ILP was performed under US guidance and with an output power of 2.5–3.5 W.

Results: In the ILP group, the nodule volume decreased from 8.2 ml (6.1; 11.9) (median; quartiles) to 4.8 ml (3.0; 6.6) after 6 months (P = 0.001). The overall median reduction was 44% (37; 52), which correlated with a significant decrease in pressure symptoms as well as cosmetic complaints. In the control group, a non-significant increase in median nodule volume of 7% (0; 34) after 6 months was seen. No major side-effects were seen in the ILP group. There was no correlation between thermal energy deposition and nodule volume reduction. Thyroid function was unaltered throughout.

Conclusion: US-guided ILP, given as a single treatment, resulted in a satisfactory clinical response in the majority of patients with a benign solitary solid cold thyroid nodule, and may become a clinically relevant alternative to surgery in selected patients.

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Frans Brandt, Marianne Thvilum, Laszlo Hegedüs and Thomas Heiberg Brix

Objective

To examine the risk of disability pension and changes in labour market income in patients with hyperthyroidism.

Methods

From a 5% random sample of the Danish population and twins from the Danish Twin Registry we identified 1942 hyperthyroid singletons and 7768 non-hyperthyroid (matched 1:4) controls as well as 584 same-sex twin pairs discordant for hyperthyroidism. Singletons and twins were followed for a mean of 9 years (range 1–20). Cox regression analysis was used to examine the risk of disability pension and a difference-in-differences model was used to evaluate changes in labour market income.

Results

Hyperthyroid individuals had an increased risk of receiving disability pension: hazard ratio (HR) was 1.88, (95% CI: 1.57–2.24). Subdividing as to the cause of hyperthyroidism did not change this finding: Graves’ disease (GD) HR was 1.51 (95% CI: 0.87–2.63) and toxic nodular goitre (TNG) HR was 2.10 (95% CI: 1.02–4.36). With respect to labour market income, the income of hyperthyroid individuals increased on average 1189 € less than their controls (P<0.001). This difference in income was more pronounced in GD (2539 €) than in TNG (132 €). Essentially similar results, with respect to disability pension and labour market income, were seen within monozygotic twin pairs discordant for hyperthyroidism.

Conclusion

Hyperthyroidism is associated with severe work disability as reflected by an 88% increased risk of receiving disability pension and a significant loss of labour market income. Similar results in monozygotic twins discordant for hyperthyroidism suggest that genetic confounding is unlikely.

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Ulla Feldt-Rasmussen, Laszlo Hegedüs, Jens M. Hansen and Hans Perrild

Abstract. Twenty-five patients with non-toxic diffuse goitre were studied during and after 12 months of treatment with 60 μg triiodothyronine daily in order to see whether a correlation could be found between the reductions of thyroid volume, using ultrasonic scanning, and serum thyroglobulin. Thyroid function tests and thyroid volume determination were performed before treatment and after 3, 6 and 12 months of therapy in 19 patients (group 1). In patients of group 2 (n = 19) the same tests were performed at the end of 12 months treatment and 6 and 12 months after withdrawal. Before treatment all patients had a significantly increased thyroid volume compared to controls matched according to sex, age and body weight (P < 0.001). Serum thyroglobulin was elevated compared to controls (P < 0.02), with a significantly positive correlation to the thyroid volume (Spearmann's Rho = 0.52, P < 0.02). Both serum thyroglobulin and thyroid volume decreased during treatment in the majority of the patients, concomitantly in approximately half of them. After withdrawal of treatment (group 2) serum thyroglobulin showed a median increase of 54% after 6 months and remained unchanged thereafter, whereas the thyroid volume was unchanged after 6 months. These findings might support the concept that the regulation of thyroid growth and of protein synthesis and degradation might be determined by different factors.

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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