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H. Perrild, L. Skovsted and L. Korsgaard Christensen

Abstract.

Alkaline Sephadex G-25 columns were used to separate labelled 3,5,3',5'-thyroxine, 3,5,3'-triiodothyronine, 3,3',5'-triiodothyronine and 3,3'-diiodothyronine from the serum binding proteins followed by a quantitative elution of each hormone by coupling to its respective antibody. It is shown that although these antibodies (diluted 1:1500–1:100 000) in our radioimmunoassays are highly specific they show a high degree of non-specific binding when they are used in the concentrations necessary to get a maximal recovery of the hormones in column separating experiments.

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H. Perrild, F. Pedersen, S. L. Rasmussen, H. J. Jürgensen and L. Skovsted

Abstract. After treatment with alprenolol for 1 year, serum 3,3',5'-triiodothyronine (rT3) was significantly increased (P < 0.01) in a group (n = 20) of euthyroid subjects compared to a control group (n = 20) given placebo. All subjects had definite or suspected myocardial infarction one year previously. Serum thyroxine (T4), free T3 index (FT4I), serum 3,5,3'-triiodothyronine, (T3) and free T3 index (FT3I) were not significantly different in the two groups. Alprenolol and placebo were gradually withdrawn over 14 days. On the first day after withdrawal a significant decrease in serum rT3 in the alprenolol treated group was the only change observed. Fourteen days after withdrawal a significant fall in serum T4, FT4I, rT3 and a rise in serum T3 and FT3I was found in the alprenolol treated group. Six months after withdrawal the only further change observed in the alprenolol treated group was an increase in T3 and FT3I. No changes occurred in the placebo treated group in any of the hormones studied. The results are consistent with a direct effect of long-term alprenolol treatment on the peripheral levels of serum T4, T3 and rT3 in euthyroid subjects. The changes in the thyroid hormones after withdrawal further indicate withdrawal of a permanent inhibition of 5'deiodinase during long-term treatment with alprenolol in euthyroid subjects.

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N Knudsen, H Perrild, E Christiansen, S Rasmussen, H Dige-Petersen and T Jorgensen

OBJECTIVE: Multinodular goitre has been found with a high prevalence in iodine-deficient areas, but less frequently in iodine-replete areas; the iodine intake sufficient to prevent goitre has not been established, however. METHODS: We report data from an ultrasonic investigation of the thyroid glands of 2656 randomly selected subjects aged 41 to 71 years in an area with borderline iodine deficiency. RESULTS: Median iodine concentration in spot urine samples was 70microg/l. Multinodular thyroid structure was found in 23% of the population, increasing in women from 20 to 46% with increasing age, and in men from 7 to 23%. Solitary, scintigraphically cold, thyroid nodules >10mm were found in 2.4% of the population with the same prevalence in the different age and sex groups. Two years of follow-up of these cold nodules revealed no signs of malignancies. Median thyroid volume was 11.0ml. Thyroid enlargement (>18ml for women and >25ml for men) was found among 13. 1% of the women and 6.2% of the men, and the prevalence increased with age. The presence of thyroid nodules was related to positive anti-thyroperoxidase antibody (TPO Ab) titres, whereas thyroid enlargement was associated with iodine excretion <50microg/day. CONCLUSIONS: Thyroid enlargement was associated with low iodine excretion and median thyroid volume was slightly increased compared with iodine-replete areas. Multinodular thyroid structure was found with a high prevalence and was associated with TPO Ab >200kU/l. Cold thyroid nodules were moderately prevalent, with no cases of detected malignancies during 2 years of follow-up.

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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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Å. Krogh Rasmussen, L. Kayser, K. Bech, U. Feldt-Rasmussen, H. Perrild and K. Bendtzen

Abstract.

Interleukin 6 has been suggested as second mediator of the effects of interleukin 1 in some cell systems. Interleukin 1 has previously been shown to inhibit the function of human thyrocytes in secondary cultures. We have therefore studied the influence of interleukin 6 (10−1−5·107 U/l) on the function of thyroid cells. Recombinant interleukin 6 slightly inhibited the production of cAMP, but failed to influence the production of thyroglobulin or the DNA content. Endotoxins (lipopolysaccharides from Salmonella abortus equi or Yersinia enterocolitica) had only a slightly inhibitory effect on thyroid cell functions, and the effect of interleukin 6 could not by itself be explained by endotoxin contamination. The effect of interleukin 6 did not mimick effects on thyroid cells afforded by recombinant interleukin 1α and 1β. Furthermore, antibodies to interleukin 6 were not able to inhibit the interleukin 1β-induced inhibition of thyroid cell functions. In conclusion, it is unlikely that interleukin 6 by itself mediates the biological effects of interleukin 1 on human thyroid cells.

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Å. Krogh Rasmussen, L. Kayser, K. Bech, U. Feldt-Rasmussen, H. Perrild and K. Bendtzen

Abstract

The effects of human recombinant interleukin 1α (20 pg/1-2 μg/l) and 1β (200 pg/1-20 μg/l) on two systems of thyroid cells have been compared. The thyroglobulin and cAMP secretion and the DNA content of human thyroid cells cultured in monolayer and of continuously grown rat thyroid cells, Fischer rat thyroid cell line have been studied. The growth of the rat thyroid cell line was inhibited by interleukin 1β (20 ng/1-20 μg/l), but not by interleukin 1α. None of the cytokines changed the cAMP production of the rat thyroid cells. In contrast, both cAMP production and thyroglobulin secretion were inhibited dose-dependently by the cytokines in human thyroid cells in secondary cultures. These results caution the interpretation and extrapolation of changes induced by interleukin 1 from one cell system to the other.

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N Knudsen, I Bulow, T Jorgensen, P Laurberg, L Ovesen and H Perrild

OBJECTIVE: The pattern of thyroid dysfunction seems to depend on the iodine status of the population. Prevalence of thyroid dysfunction could be a parameter to consider when evaluating iodine deficiency disorders in a population. DESIGN: Comparative cross-sectional investigation in two regions in Denmark with marginally different iodine excretion. METHODS: A random selection of 4649 participants from the Civil Registration System in Denmark in age groups between 18 and 65 years were examined. Thyroid dysfunction was evaluated from blood samples and questionnaires, and compared with results from ultrasonography. RESULTS: Median iodine excretion was 53 microg/l in Aalborg and 68 microg/l in Copenhagen. Previously diagnosed thyroid dysfunction was found with the same prevalence in the regions. Serum TSH was lower in Aalborg than in Copenhagen (P=0. 003) and declined with age in Aalborg, but not in Copenhagen. Not previously diagnosed hyperthyroidism was found with the same overall prevalence in the regions, but in age >40 years hyperthyroidism was more prevalent in Aalborg (1.3 vs 0.5%, P=0.017). Not previously diagnosed hypothyroidism was found more frequently in Aalborg (0.6 vs 0.2%, P=0.03). Hyperthyroidism was more often associated with macronodular thyroid structure at ultrasound in Aalborg and hypothyroidism was more often associated with patchy thyroid structure in Copenhagen. CONCLUSIONS: Significant differences in thyroid dysfunction were found between the regions with a minor difference in iodine excretion. The findings are in agreement with a higher prevalence of thyroid autonomy among the elderly in the most iodine-deficient region.

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N Knudsen, I Bulow, P Laurberg, L Ovesen, H Perrild and T Jorgensen

OBJECTIVE: Pregnancy has been suggested as part of the explanation of the gender difference in the prevalence of goitre, but opposing results have been reported on the association between pregnancy and goitre. We investigated the association between parity and thyroid volume and a possible impact of iodine deficiency and tobacco smoking on this association. DESIGN: A comparative, cross-sectional study of 3712 women randomly sampled from the general population in two geographical areas with moderate and mild iodine deficiency. METHODS: The participants answered questionnaires with an obstetric anamnesis, and ultrasonography of the thyroid was performed. Data were analysed in linear models and logistic regression analysis to adjust for age, iodine status, use of oral contraceptives and smoking habits. Women with present or recent pregnancies were excluded from the analyses. RESULTS: A higher thyroid volume was found among parous than among nulliparous women (P=0.007). The association between parity and thyroid volume was strongest in the youngest age groups, in the region with the most severe iodine deficiency, and among smokers. No association was found between parity and the prevalence of solitary or multiple thyroid nodules. Number of births, age at menarche or menopause, the number of fertile years, and age at first childbirth were not associated with thyroid volume. CONCLUSION: Pregnancy increases thyroid volume, particularly when combined with tobacco smoking and iodine deficiency. The effect is probably reversible seen over a spectrum of several years.

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TV Elberling, AK Rasmussen, U Feldt-Rasmussen, M Hording, H Perrild and G Waldemar

OBJECTIVE: In the acute, thyrotoxic phase, patients with Graves' disease often have both thyrotoxic and neuropsychiatric symptoms. The purpose of this prospective study was to examine health-related quality of life (HRQOL) in newly diagnosed and untreated Graves' patients and the effect of antithyroid medical treatment on HRQOL. In addition, we examined the potential influence of thyroid hormones and psychiatric symptoms on the impairment of HRQOL in the thyrotoxic phase. METHODS: A total of 30 consecutively referred patients with newly diagnosed and untreated Graves' disease and 34 age-, sex- and education-matched healthy volunteers were included in the study. HRQOL was assessed with the Medical Outcome Study 36-item Short-Form Health Status Survey (SF-36) before treatment, after reaching euthyroidism and 1 year after initiation of treatment. RESULTS: In the thyrotoxic phase of Graves' disease, HRQOL was significantly impaired, in physical, mental and social dimensions. After reaching euthyroidism, the patients reported much fewer limitations on the subscales of SF-36. One year after initiation of treatment, all SF-36 scores had normalized. However, in some patients, HRQOL continues to be impaired even 1 year after initiation of treatment, as reviewed by the individual analysis. The reduced HRQOL in the acute phase of Graves' disease was correlated to depressive and anxiety symptoms, but thyroid-associated orbitopathy also influenced HLQOL. CONCLUSIONS: Impaired HRQOL is common in the acute phase of Graves' disease. A significant proportion of the patients demonstrated persistent HRQOL impairment 1 year after initiation of treatment. Improvement of HRQOL in these patients remains a challenge for the clinician.