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Hans Perrild and Bendt Brock Jacobsen

Thyrotoxicosis during the first two decades of life is rare compared to that in adults, with an incidence of 0.8 per 100000 children per year (1). This limits the experience in the paediatric clinics, and adult treatment strategies are often applied to the thyrotoxic child.

About 95% of thyrotoxic children have Graves' disease (1, 2), in contrast to findings in adults where a significant number of toxic adenomas and multinodular toxic goitres are seen, especially in areas with a relatively low iodine intake (3). It is suggested that Graves' disease in childhood is a self-limiting disorder with a remission rate of 25% every 2 years (4). These observations have to be considered in the choice of therapy.

There are three principal treatments today: antithyroid drugs (ATD), surgery or radioiodine. It is well known that the primary management of thyrotoxicosis in adults is different in Europe, Japan and the USA (5).

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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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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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Peter S Oturai, Lars Friberg, Ian Sam and Hans Perrild

To assess the regional changes in cerebral blood flow, 10 healthy volunteers were given 400 μg thyrotropin-releasing hormone iv in a double-blind, randomized, cross-over study. Regional cerebral blood flow was determined simultaneously in two slices of the brain, using a single photon emission computerized tomograph and inhalation of 133Xe. Thyrotropin-releasing hormone caused a significant mean increase of 3.7% (range −8.8–22.7) in blood flow in a region consistent with the left thalamus compared to placebo (3.2% decrease). In 25 other regions no significant change was detected. The thalamic region has previously been shown to be a region especially affected by thyrotropin-releasing hormone in animal studies. The thyrotropin-releasing hormone injection was followed by a minor rise in systemic blood pressure, but not a rise that could affect the cerebral blood flow. The effect of thyrotropin-releasing hormone on the regional cerebral blood flow in the thalamic region was much lower compared to changes found in sedated animals given a hundredfold higher dose of thyrotropin-releasing hormone.

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Caroline Raun Hansen, Hans Perrild, Birgitte Gade Koefoed and Mette Zander

Objective

To examine whether video consultations preceded by measurements of blood glucose, weight and blood pressure as add-on to standard care could contribute to achieving and maintaining good diabetes control among patients with poorly regulated type 2 diabetes (T2D).

Design

Randomized controlled trial.

Methods

165 patients with T2D were randomized 1:1 to telemedicine intervention as add-on to clinic-based care or control (clinic-based care). The intervention consisted of monthly video conferences with a nurse via a tablet computer and lasted for 32 weeks. Regularly self-monitored measurements of blood sugar, blood pressure and weight were uploaded and visible to patient and nurse. Both groups were followed up six months after the end of the intervention period.

Primary endpoint

HbA1c after eight months.

Results

Video conferences preceded by uploads of measurements as add-on to clinic-based care led to a significant reduction of HbA1c compared to that in standard care (0.69% vs 0.18%, P = 0.022). However, at six-month follow-up, the inter-group difference in HbA1c-reduction was no longer significant. Non-completers had higher HbA1c levels at baseline and a lower degree of education.

Conclusion

Video consultations preceded by uploading relevant measurements can lead to clinically and statistically significant improvements in glycemic control among patients who have not responded to standard regimens. However, continuing effort and attention are essential as the effect does not persist when intervention ends. Furthermore, future studies should focus on differentiation as the most vulnerable patients are at greater risk of non-adherence.

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Hans Perrild, Ulla Feldt-Rasmussen, Karine Bech, Preben Ahlgren and Jens Mølholm Hansen

Abstract. Nine consecutive patients with unilateral ophthalmopathy with suspected endocrine pathogenesis were investigated with a TRH test, a T3 suppression-test, thyroid autoantibodies and a subsequent computerized tomography (CT)-scan. All patients were clinically and biochemically euthyroid. Seven of 9 patients had a normal TRH test and 6 of 7 had a normal T3 suppression test. Slightly to moderately elevated microsomal and thyroglobulin (determined with radioimmunoassay) autoantibodies were found in 5 of 8 patients and in 1 patient thyroid stimulating immunoglobulins (TSI) were found. Three of the patients had normal thyroid function tests and no detectable thyroid autoantibodies. The subsequent CT-scan revealed that one of these had a maxillary tumour protruding into the orbita. The remaining 8 patients had enlargement of one (3 patients) or more (5 patients) eyemuscles. Two of the 8 patients had bilaterally enlarged eyemuscles, one of which was the patient with positive TSI. The remaining 6 patients had unilateral extraocular muscle enlargement. Thus, 2 of 9 patients had ophthalmopathy without thyroid dysfunction so-called isolated autoimmune ophthalmopathy or Graves' ophthalmopathy.

Thyroid function tests seem to be of limited value in the diagnosis between endocrine and non-endocrine eye disease, and we recommend the use of diagnostic imaging (e.g. CT-scan) in patients with unilateral exophthalmus in order to diagnose malignant processes.

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Hans Perrild, Anette Grüters-Kieslich, Ulla Feldt-Rasmussen, David Grant, Enio Martino, Lars Kayser and Francois Delange

Perrild H, Grüters-Kieslich A, Feldt-Rasmussen U, Grant D, Martino E, Kayser L, Delange F. Diagnosis and treatment of thyrotoxicosis in childhood. A European questionnaire study. Eur J Endocrinol 1994;131:467–73. ISSN 0804–4643

A covering letter and a questionnaire covering the diagnosis and treatment of thyrotoxicosis in childhood was circulated between October 1992 and February 1993 amongst 672 European members of the European Thyroid Association (ETA) and members of the European Society for Pediatric Endocrinology (ESPE). Almost 50% replied to the letter and 99 individuals or groups from 22 countries completed the questionnaire. A consensus was reached on the use of total thyroxine (T4) and/or free T4 and thyrotropin as routine diagnostic tools. Two-thirds included total triiodothyronine (T3) and/or free T3 and 32% used a thyrotropin-releasing hormone test. Surprisingly, thyroglobulin autoantibodies were used as a routine test by 78%; 63% included thyrotropin receptor antibodies and 60% microsomal antibodies, whereas only 50% measured thyroperoxidase antibodies. For thyroid imaging, 40% performed a thyroid scintigram and 56% measured the size of the thyroid gland by ultrasound. Antithyroid drugs (ATD) were the basic initial treatment of choice given by 99% of the respondents for children with uncomplicated Graves' disease. Carbimazole, methimazole and thiamazole were the most frequently used drugs, with a median initial dose of 0.8 mg · kg1 · day1. Two-thirds added betablockers and a few used sedatives. The ATD dose was adjusted for each patient by 39%, whereas 56% combined ATD with T4 for long-term treatment; 84% gave treatment for a fixed period (44% for 1–2 years). Surgery was considered the treatment of choice in children with an adenoma (83%), with a nodular (53%) or large goiter (16%) and recurrence after ATD (14%). Radioiodine was the treatment of choice by 18% of the respondents for patients with recurrence after surgery and recurrence after ATD (7%).

Hans Perrild, Department of Medicine B, Bispebjerg University Hospital, 2400 Copenhagen, Denmark

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Inge Bülow Pedersen, Peter Laurberg, Nils Knudsen, Torben Jørgensen, Hans Perrild, Lars Ovesen and Lone Banke Rasmussen

Background: Thyroid autoimmunity is more common in females than in males. One possible explanation for this female preponderance may be the effect of oestrogens on the immune system. It has also been suggested that foetal microchimerism involving transfer of foetal cells into maternal tissue during pregnancy may play an important role.

Objective: We investigated the association between the presence of circulating thyroid autoantibodies and previous pregnancy, parity and the use of oral contraceptives (OCs) and hormone replacement therapy (HRT) in a population cohort.

Methods: We examined 3712 women randomly selected from the general population. Serum was analysed for thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) using assays based on an RIA technique (DYNO test). Data were analysed in logistic regression models to adjust for possible confounders. Women previously treated for thyroid disease or with pregnancy within 1 year prior to the study were excluded from the analyses.

Results: In both univariate and multivariate models and whether the presence of TPO-Ab and Tg-Ab was investigated alone or in combination, findings were negative with respect to an association between circulating thyroid antibodies and previous pregnancy, number of pregnancies, parity and previous abortion. There was no association between thyroid autoantibodies and use of OCs. Women aged 60–65 years receiving HRT now or previously had a lower prevalence of Tg-Ab (univariate, P = 0.01; multivariate, P = 0.02). No such association was observed between HRT and TPO-Ab.

Conclusion: In this population study there was no association between previous pregnancy, parity and thyroid antibodies, which argues against the role of microchimerism as a trigger of thyroid autoimmunity. Exogenous oestrogens may reduce aspects of autoimmunity.

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Inge Bülow Pedersen, Peter Laurberg, Nils Knudsen, Torben Jørgensen, Hans Perrild, Lars Ovesen and Lone Banke Rasmussen

Background

Autoimmune thyroid diseases are common and the prevalence of circulating thyroid antibodies (thyroid peroxidase antibody, TPO-Ab and thyroglobulin antibody, Tg-Ab) is high in the population. The knowledge of a possible association between lifestyle factors and circulating thyroid antibodies is limited.

Aim

To evaluate the correlation between smoking habits and the presence of circulating TPO-Ab and Tg-Ab.

Material and methods

In a cross-sectional comparative population study performed in two areas of Denmark with moderate and mild iodine deficiency, 4649 randomly selected subjects from the population in some predefined age groups between 18 and 65 years were examined. Blood tests were analysed for TPO-Ab and Tg-Ab using assays based on the RIA technique. The participants answered questionnaires, were clinically examined and blood and urine samples collected.

Results

Data were analysed in multivariate logistic regression models. There was a negative association between smoking and the presence of thyroid autoantibodies in serum. This association was observed for the presence of TPO-Ab and/or Tg-Ab, TPO-Ab (without respect to Tg-Ab status), Tg-Ab (without respect to TPO-Ab status) and both antibodies together. The association between smoking and thyroid autoantibodies was stronger for Tg-Ab than for TPO-Ab. There was no association between smoking and TPO-Ab measured alone or between smoking and TPO-Ab when Tg-Ab was included in the model as an explanatory variable.

Conclusion

Smoking was negatively associated with the presence of thyroid autoantibodies with the strongest association between smoking and Tg-Ab. The study design precludes any conclusions as to the cause of the negative association between smoking thyroid autoantibodies.

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Charlotte Cerqueira, Nils Knudsen, Lars Ovesen, Peter Laurberg, Hans Perrild, Lone B Rasmussen and Torben Jørgensen

Objective

Iodization of salt was introduced in Denmark in 1998 because of mild-to-moderate iodine deficiency (ID). The aim of this study was to analyze the utilization rate of surgery and radioiodine therapy for benign thyroid disorders before and after the introduction of iodization, and to study a possible association between the changes and the raised iodine intake.

Design

A nationwide register study.

Methods

Information on operations and radioiodine treatments for benign thyroid disorders was extracted from nationwide registers in the years 1990 to 2007. Treatment rates are presented for surgery and for radioiodine separately, and as a combined rate, both nationwide and split by the regions of prior mild and moderate ID.

Results

A total of 65 605 treatments were identified: 26 456 operations and 39 149 radioiodine treatments. In the first years of iodization (1998–2000; rate ratio 2000/1997), the combined treatment rate increased with 2.5% (95% confidence interval (CI): −1.8–7.1). Split by prior ID level, the increase was seen in the region of moderate ID, but a decrease was seen in the region of mild ID. After 2000, the combined rate decreased, and ended up being 11.1% (95% CI: 7.1–15.0) lower in 2007 than before iodization (rate ratio 2007/1997). The changes were primarily due to changes in the use of radioiodine therapy as the surgery rates remained almost constant.

Conclusions

Iodization seemed to be associated with a temporary increase in the utilization rate of surgery and radioiodine therapy in the region of prior moderate ID, probably as a result of treatment of iodine-induced hyperthyroidism, but the rates ended up being lower than before iodization.