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Carole A Spencer

The insensitivity of the early TSH radioimmunoassays limited investigations of thyroid hormone action on pituitary TSH secretion to studies of hypothyroid rats and humans (1, 2). Now that more sensitive TSH immunometric assays are able to measure serum TSH concentrations in the subnormal range (3), it is possible to study thyroid hormone inhibition of pituitary TSH secretion in euthyroid human subjects. In the welldesigned study of Sydow et al. (4), groups of euthyroid male volunteers were given different oral doses of thyroxine (25–150 μg q.i.d.) for 10 days, during which time the relationships between the thyroxine dose and the resultant suppression of serum TSH and thyroglobulin (TG) concentrations were studied. The data showed that both serum TSH and Tg concentrations fell over time with single monoexpontential suppression patterns. Further, the rates of decline for both serum TSH and serum Tg were proportional to the thyroxine dose administered. It should be emphasized

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Jan-Gustaf Ljunggren, Bertil Persson, and Monica Tryselius


A rapid simultaneous radioimmunoassay for the measurement of triiodothyronine and thyroxine in unextracted human serum is described. The method requires 25 μl serum. Approximately 150 human sera can be tested for triiodothyronine and thyroxine levels in one day by one technical assistant. The triiodothyronine levels in peripheral venous blood in euthyroid subjects and in patients with various thyroid diseases are as follows: euthyroid (50) 115 ± 22 (mean ± sd) ng/100 ml, hypothyroid (20) 33 ± 35 (mean ± sd) ng/100 ml and hyperthyroid (20) 411 ± 142 (mean ± sd) ng/100 ml. The corresponding levels for thyroxine are: 6.9 ± 1.3, 2.0 ± 1.4 and 21.4 ± 5.2 μg/100 ml. The levels of triiodothyronine in the thyroid venous blood are higher (P < 0.05) than in the peripheral venous blood. The levels of thyroxine in the thyroid venous blood was not significantly higher than in peripheral venous blood.

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Borghild Tveit and Torbjørn Almlid


The effect of starvation on thyroid hormones was studied during a starvation period of 48 h in 10 young bulls. Mean thyroxine degradation rate decreased from K/day 0.32 during feeding to 0.23 during fasting. Mean plasma concentration of T4 decreased to 75% of normal, and it was calculated that the mean thyroxine secretion rate during the starvation period was 24% of normal.

Plasma concentration of free thyroxine decreased to 54% of normal, indicating that the concentration of binding protein was not decreased.

T3 and reverse T3 decreased to about 60% of normal. This indicated a parallel decrease in the secretion of all 3 hormones. We did not find evidence of an inactivating pathway for T4 as has been shown in humans during starvation.

TSH decreased to 85% of normal.

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Angel A. Zaninovich, Osvaldo Degrossi, and Hector Gotta


The effects of oestrogens on serum thyroxine-binding globulin (TBG) capacity and on the peripheral metabolism of thyroxine were studied in patients with hepatic cirrhosis as well as in a group of normal subjects. Oestrogens increased TBG capacity in cirrhosis from 24.7 to 38.4 μg/100 ml whereas in normal subjects TBG capacity was raised from 22.8 to 48.6 μg. While the fractional turnover of thyroxine in cirrhosis did not change with the administration of oestrogens, the space of distribution was reduced. As a result of these changes, the extra-thyroidal thyroxine pool was similar to the pre-treatment values and hence the daily degradation rate of thyroxine remained unchanged.

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Minoru Fukuchi, Tohru Matsuoka, Tadashi Inoue, Kiyoshi Miyai, and Yuichi Kumahara


Serial changes in TSH, LATS, and thyroxine levels in the sera were studied following administration of an antithyroid drug or a thyroid hormone to thyrotoxic patients who became euthyroid after treatment. These changes were simultaneously determined by means of human TSH radioimmunoassay, McKenzie's bioassay. and the method of Murphy, respectively.

Administration of 1-methyl-2-mercaptoimidazole (MMI) led to a decrease in thyroxine concentration and to a 6–10 times increase of the initial values in serum TSH concentration. Following administration of thyroxine at the end of the MMI treatment, the elevated serum TSH was rapidly decreased with an increase in thyroxine concentration. LATS activity, however, showed no significant changes throughout these experiments in which the reciprocal changes between TSH and thyroxine concentrations were observed.

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Osamu Isozaki, Toshio Tsushima, Kanji Sato, Motoyasu Saji, Yoshito Ohba, Naoya Emoto, Yuji Sato, and Kauzo Shizume

Abstract. A 54 year old man with markedly elevated serum T3, but without an apparent thyroid disease, was found to have a specific antibody to T3. His serum thyroxine, TBG and TSH were in normal range, but T3-RSU was markedly low. Antibodies to thyroglobulin and microsome were negative. He was judged euthyroid because of a normal basal metabolic rate and a normal thyroidal 123I uptake which was suppressed by T3 adminnistration. When serum was extracted with ethanol prior to assay, serum T3 was found to be in the upper border of normal range. Several experiments revealed the presence of an antibody to T3 in his serum with an affinity constant of 3.3 × 109 m −1. The binding capacity of the antibody was 7.6 ng/mg of IgG. The binding of [125I]T3 was almost specific to T3, and potencies of T4 and fT3 in displacing [125I]T3 binding were only 1.0 and 0.3%, respectively, of that of T3. The antibody contained both kappa and lambda chains and was therefore polyclonal.

The T3 metabolic clearance rate, which was determined by disappearance of injected [125I]T3 from serum, was lower in this patient (7.44 I/day) than in normal. The T3-production rate was decreased to 14.9 μg/day, and serum free T3 concentration as well as urinary T3 excretion rate were also reduced. Since both serum total and free T4 concentrations were normal, the supply of T4 to peripheral tissues would be sufficient to keep this patient in a euthyroid state in spite of the anti-T3 antibody.

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Prakash Abraham, Alison Avenell, Christine M Park, Wendy A Watson, and John S Bevan

We assessed the effects of dose, regimen and duration of anti-thyroid drug therapy for Graves’ thyrotoxicosis on recurrence of hyperthyroidism, course of ophthalmopathy, adverse effects, health-related quality of life and economic outcomes. We undertook a systematic review and meta-analyses of randomised controlled trials (RCTs). We identified RCTs regardless of language or publication status by searching six databases, and trial registries. Dual, blinded data abstraction and quality assessment were undertaken. Trials included provided therapy for at least 6 months with follow-up at least 1 year after drug cessation. Fixed or random effects meta-analyses were used to combine study data. Twelve trials compared a Block-Replace regimen (requiring a higher dose of anti-thyroid drug treatment) with a Titration regimen. Overall, there was no significant difference between the regimens for relapse of hyperthyroidism (relative risk (RR) = 0.93, 95% confidence interval (CI) 0.84 to 1.03). Participants were more likely to withdraw due to adverse events with a Block-Replace regimen (RR = 1.89, 95% CI 1.25 to 2.85). Prescribing replacement thyroxine, either with the anti-thyroid drug treatment, or after this was completed, had no significant effect on relapse. Limited evidence suggested 12–18 months of anti-thyroid drug treatment should be used. The titration regimen appeared as effective as the Block-Replace regimen, and was associated with fewer adverse effects. However, relapse rates over 50% and high participant drop-out rates in trials mean that the results should be interpreted with caution, and may suggest that other strategies for the management of Graves’ disease, such as radioiodine, should be considered more frequently as first-line therapy. There were no data on the course of ophthalmopathy, health-related quality of life and economic outcomes.

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K. Liewendahl, J. Tötterman, and B.-A. Lamberg


The free thyroxine fraction in serum was determined by means of a rapid method based on the uptake of radioactive thyroxine by Sephadex (T4U). The corresponding values for percentage free thyroxine (PFT4) were obtained by simultaneous determination of the dialysable fraction. A good linear correlation was established between the two methods. Serum total thyroxine (T4) was determined by the competitive protein-binding technique. The concentration of the absolute free thyroxine (AFT4) was calculated. Of the three laboratory parameters tested, AFT4 showed the highest discrimination in both hyper- and hypothyroidism. The »free thyroxine index«, FT4I, which is a product of T4 and T4U, proved equally useful. Good results were also obtained with T4, whereas PFT4 showed the largest overlap with the normal values. PFT4 is important, however, for the calculation of AFT4. The rapid method for determination of the free thyroxine fraction described in this paper is suitable for routine use in the clinical laboratory.

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SJ Bonnema, FN Bennedbaek, J Gram, A Veje, J Marving, and L Hegedus

OBJECTIVE: Retrospective studies have indicated that anti-thyroid drugs (ATD) might possess a radioprotective effect, leading to a higher rate of recurrence of hyperthyroidism after iodine-131 ((131)I) therapy. DESIGN: A randomized clinical trial was performed to clarify whether resumption of methimazole after (131)I influences the final outcome of this treatment. METHODS: We assigned 149 patients with Graves' disease or a toxic nodular goitre to groups either to resume (+ATD) or not to resume (-ATD) methimazole 7 days after (131)I. Before (131)I therapy, all patients were rendered euthyroid by methimazole, which was discontinued 4 days before the (131)I therapy. RESULTS: During the follow-up period of 12 Months, 13 patients developed hypothyroidism, 42 were euthyroid, and 18 had recurrence of hyperthyroidism in the +ATD group; the respective numbers in the -ATD group were 16, 42 and 18 (P=0.88). At 3 weeks after (131)I therapy, the serum free-thyroxine index was slightly decreased (by 5.7%; 95% confidence interval (CI) -15.5 to 5.4%) in the +ATD group, in contrast to an increase of 35.9% (95% CI 18.8 to 55.5%) in the -ATD group (P<0.001 between groups). In the subgroup that remained euthyroid during follow-up, thyroid Volume reduction, assessed by ultrasonography, was smaller in the +ATD group [38.7% (95% CI 33.3 to 44.1%)] than in the -ATD group [48.6% (95% CI: 41.5-55.6%)] (P<0.05). CONCLUSION: No radioprotective effect could be demonstrated, with regard to final thyroid function, for the resumpton of methimazole 7 days after (131)I therapy. Although resumption of methimazole slightly reduced the magnitude of shrinkage of the goitre obtained by (131)I, the prevention of a temporary thyrotoxicosis in the early period after radiation favours this regimen.

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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.