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Henric Blomgren and Goran Lundell


Peripheral lymphoid cells from euthyroid and hyperthyroid subjects were tested for proliferative responses to human thyroglobulin in vitro using [3H] thymidine incorporation as assay. Non-fractionated lymphoid cells from both groups displayed weak stimulation. Using a rosette technique for separating sub-populations of lymphoid cells it was concluded that T-cells constituted the responding cells. The results indicate that both hyperthyroid and euthyroid subjects possess clones of T-cells which are reactive against human thyroglobulin.

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Leif Tallstedt, Göran Lundell and Adam Taube

We have studied the smoking habits in a group of patients with hyperthyroidism caused by Graves' disease. One hundred and seventy-one patients were randomized to different forms of treatment for hyperthyroidism and the outcome of this study concerning Graves' ophthalmopathy has been described previously. There were 89 smokers (52%) and 82 non-smokers (48%). Among the smokers there were 32 patients (19%) who developed ophthalmopathy or deteriorated in an already present ophthalmopathy and 57 patients who did not (33%), whereas among the non-smokers, 14 (8%) had ophthalmopathy during the study and 68 (40%) did not (p =0.006). We could not obtain statistical significance when trying to demonstrate that smoking is a risk factor for the development of ophthalmopathy after treatment for hyperthyroidism. It was noted that smokers had higher pretreatment levels of thyrotropin-receptor antibodies (p = 0.027). In conclusion, these results support the previously described association between smoking and Graves' ophthalmopathy.

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Per Hall, Göran Lundell and Lars-Erik Holm

Causes of death were studied in 10,552 Swedish hyperthyroid patients treated with 131I diagnosed between 1950 and 1975. The patients were followed for an average of 15 years (range 0-35 years) and were matched with the Swedish Cause of Death Register. A total of 5,400 deaths were observed and the overall standardized mortality ratio was 1.47 (95% confidence interval (CI) 1.43-1.51). The standardized mortality ratio for females was 1.50(95% CI 1.46-1.55) compared to 1.31(95% CI 123-1.39) in males. The most common cause of death (61%) was from cardiovascular diseases (standardized mortality ratio 1.65; 95% CI 1.59-1.71). Significantly elevated risks were also seen for tumours, diseases of the endocrine system, respiratory system, gastro-intestinal system, and congenital malformations. In all causes of death, except tumours and trauma, decreasing standardized mortality ratios over time were seen. Patients followed for more than 10 years had significantly elevated risks for tumours, diseases of the endocrine, respiratory, and cardiovascular systems. Patients given higher 131I activity and younger patients had higher standardized mortality ratios than those given lower activity and older patients. The hyperthyroidism per se. rather than the 131I treatment, appeared to be the major explanation for the elevated mortality.

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Mirna Abraham-Nordling, Göran Wallin, Göran Lundell and Ove Törring

Objective: In a 14–21 year follow-up of health-related quality of life (HRQL) outcome of 179 patients after randomized treatment of Graves’ disease (GD) with surgical, medical or radioiodine, we found no differences. The HRQL for Graves’ patients, however, was lower compared with a large age- and sex-matched Swedish reference population. We have now studied whether the reported HRQL-scores by Medical Outcome Study 36-item Short-Form Health Status Survey (SF36) and quality of life 2004 (QoL2004) answers were related to the thyroid hormone state of the patient.

Methods: This report comprises 91 of the original patients in which both the results of SF36 and QoL2004 questionnaire as well as serum thyroid hormones and current use of l-thyroxine treatment were available.

Results: A large number of the patients had low or undetectable serum TSH concentrations. SF36 scores and answers to QoL2004 questionnaires were not correlated to TSH levels or associated with suppressed TSH. A low free triiodothyronine was weakly associated with a low GH score (P < 0.02) and elevated thyrotropin receptor antibody with a low physical component summary (P < 0.02).

Conclusion: HRQL do not seem to be influenced by the thyroid hormone state of the patient including subclinical thyrotoxicosis. It is possible that the personality of GD patients as such may have resulted both in the development of GD and lower HQRL scores later on in life. Alternatively, the generic SF36 may not be a proper instrument to detect relevant differences in HRQL related to the thyroid state.

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Elisabet Bucht, Margareta Telenius-Berg, Göran Lundell and Hans-Erik Sjöberg

Abstract. The level of immunoreactive calcitonin in the first produced breast milk was in totally thyroidectomized (TX) women 713 ± 307 pg-eq/ml (mean ± sd, N = 7) and in control women 772 ± 329 pg-eq/ml (N = 33), i.e. about 45 times higher than in plasma (see below). On gel chromatography of immunoextracted milk from TX women, immunoreactive calcitonin appeared as high molecular weight forms in the same pattern as in milk from healthy women when the same antiserum (1) was used for immunoextraction and radioimmunoassay (RIA). In another series of experiments, a new antiserum (2) raised in rabbits was used for measurement of immunoreactive calcitonin after immunoextraction with 1. Plasma levels of immunoreactive calcitonin in the TX women during pregnancy were 16 ± 6 pg-eq/ml (N = 6) and during lactation 14 ± 7 pg-eq/ml (N = 5). Immunoreactive calcitonin was undetectable (< 8 pg/ml) in plasma from those TX women in whom lactation had stopped (N = 5). Immunoextraction and gel chromatography of plasma collected during pregnancy and lactation from the TX women showed that the immunoreactive calcitonin present eluted in the region of monomeric calcitonin with both antiserum 1 and 2. In conclusion, high concentrations of high molecular weight forms of immunoreactive calcitonin have been demonstrated in milk from TX patients, most probably devoid of any calcitonin-producing thyroid C-cells. This points to a local production site in the mammary gland. Relatively high levels of immunoreactive calcitonin in plasma during pregnancy and lactation in TX women also indicate extrathyroidal production.

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Leif Tallstedt, Göran Lundell, Henric Blomgren and Johan Bring

Tallstedt L, Lundell G, Blomgren H, Bring J. Does early administration of thyroxine reduce the development of Graves' ophthalmopathy after radioiodine treatment? Eur J Endocrinol 1994:130: 494–7. ISSN 0804–4643

The roles of thyroid hormones and thryotropin (TSH) in the development of Graves' ophthalmopathy are not clear. Some studies suggest a protective effect of thyroid hormones on experimental exophthalmos and an adverse effect of increased TSH levels. In September 1988 we introduced early thyroxine (T4) administration after 131I therapy for hyperthyroidism caused by Graves' disease. We carried out a retrospective study of records from all patients with this disease treated with 131I for 4 years. During the first 2 years 248 patients were treated (group A). They received T4 when the serum concentration of TSH and/or T4 indicated hypothyroidism. During the next 2 years 244 patients were treated (group B). They were all given 0.05 mg of T4 daily, starting 2 weeks after therapy, and 0.1 mg after a further 2 weeks. With a follow-up of 18 months, 45 patients (18%) in group A and 27 patients (11%) in group B developed or deteriorated in an already present ophthalmopathy (p = 0.03, relative risk = 1.64, 95% confidence interval = 1.05–2.55). Twenty-six patients in group A required specific therapy for the ophthalmopathy (e.g. antithyroid drugs, steroids, etc.) compared to 11 patients in group B (p = 0.02, relative risk = 2.33; 95% confidence interval = 1.18–4.60). Our results suggest that early administration of T4 after 131I therapy reduces the occurrence of Graves' ophthalmopathy.

L Tallstedt, Department of Ophthalmology, Huddinge University Hospital, S-146 81 Huddinge, Sweden

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Peter Laurberg, Göran Wallin, Leif Tallstedt, Mirna Abraham-Nordling, Göran Lundell and Ove Tørring


Autoimmunity against the TSH receptor is a key pathogenic element in Graves' disease. The autoimmune aberration may be modified by therapy of the hyperthyroidism.


To compare the effects of the common types of therapy for Graves' hyperthyroidism on TSH-receptor autoimmunity.


Patients with newly diagnosed Graves' hyperthyroidism aged 20–55 years were randomized to medical therapy, thyroid surgery, or radioiodine therapy (radioiodine was only given to patients ≥35 years of age). l-thyroxine (l-T4) was added to therapy as appropriate to keep patients euthyroid. Anti-thyroid drugs were withdrawn after 18 months of therapy. TSH-receptor antibodies (TRAb) in serum were measured before and for 5 years after the initiation of therapy.


Medical therapy (n=48) and surgery (n=47) were followed by a gradual decrease in TRAb in serum, with the disappearance of TRAb in 70–80% of the patients after 18 months. Radioiodine therapy (n=36) led to a 1-year long worsening of autoimmunity against the TSH receptor, and the number of patients entering remission of TSH-receptor autoimmunity with the disappearance of TRAb from serum during the following years was considerably lower than with the other types of therapy.


The majority of patients with Graves' disease gradually enter remission of TSH-receptor autoimmunity during medical or after surgical therapy, with no difference between the types of therapy. Remission of TSH-receptor autoimmunity after radioiodine therapy is less common.

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Mirna Abraham-Nordling, Ove Törring, Mikael Lantz, Bengt Hallengren, Hans Ohrling, Göran Lundell, Jan Calissendorff, Gun Jörneskog and Göran Wallin


To investigate the incidence of hyperthyroidism in Stockholm County, in those patients who were diagnosed with hyperthyroidism for the first time during the years 2003–2005.


All new cases of hyperthyroidism ≥18 years of age were prospectively registered to calculate the total incidence of hyperthyroidism, as well as the incidence of the subgroups: Graves' disease (GD), toxic multinodular goitre and solitary toxic adenoma (STA). Eight specialized units/hospitals in Stockholm County participated in the registration. The participating physicians were all specialists in medical endocrinology, oncology, nuclear medicine or surgery.


During a 3-year period, 1431 new patients of hyperthyroidism were diagnosed in a well-defined adult population (>18 years of age) of in average 1 457 036 inhabitants. This corresponds to a mean annual incidence of hyperthyroidism of 32.7/100 000. The incidence of GD was 24.5/100 000 per year, toxic nodular goitre was 3.3/100 000 per year and STA was 4.9/100 000 per year.


The total incidence of hyperthyroidism in Stockholm County was found to be 32.7/100 000 per year, of which 75% had GD. There were a higher percentage of smokers among the patients with hyperthyroidism compared with the overall population in Stockholm, but no difference in the frequency of smoking between patients with GD and toxic nodular goitre.

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Mirna Abraham-Nordling, Göran Wallin, Frank Träisk, Gertrud Berg, Jan Calissendorff, Bengt Hallengren, Pavo Hedner, Mikael Lantz, Ernst Nyström, Peter Åsman, Göran Lundell, Ove Törring and The Thyroid Study Group of TT 96


The objective of this study was to investigate quality of life (QoL) in patients with Graves' disease treated with radioiodine or antithyroid drugs.

Design and methods

The design of the study consists of an open, prospective, randomized multicenter trial between radioiodine and medical treatment. A total of 308 patients were included in the study group: 145 patients in the medical group and 163 patients in the radioiodine group. QoL was measured with a 36-item Short Form Health Status Survey questionnaire (SF-36) at six time points during the 48-month study period.


Patient who developed or got worse of thyroid-associated ophthalmopathy (TAO) at any time point during the 4-year study period (TAO group) had lower QoL when no respect was paid to the mode of treatment.

TAO occurred in 75 patients who had radioiodine treatment at some time point during the study period as compared with TAO in 40 medically treated patients (P<0.0009).

Comparisons between the group of patients who have had TAO versus the group without TAO, in relation to treatments and time, showed significantly decreased QoL scores for the TAO groups at several time points during the study.

In patients without TAO, there were no differences in QoL related to mode of treatment.


The QoL in patients with Graves' ophthalmopathy was similar in radioiodine and medically treated patients, but patients who developed or had worsening of TAO had decreased QoL independent of mode of treatment. Furthermore, patients with TAO recovered physically within 1 year but it took twice as long for them to recover mentally.