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S. Deboel, M. Bonnyns, M. Jonckheer, P. Buydens, J. Smitz, E. Finne, and L. Vanhaelst

Abstract. Basal (B) and peak (P) serum levels of thyroxine (T4), free thyroxine (FT4), triiodothyronine (T3), free triiodothyronine (FT3), and TSH were measured before and after oral TRH (40 mg) administration in 79 subjects affected with asymptomatic autoimmune thyroiditis (AAT) and in 69 normal subjects. The area under the curve (AUC) and peak values of T4, FT4, T3 and FT3 were considered as parameters of thyroid hormone reserve. Intrathyroidal iodine (ITI) was measured by the X-ray fluorescence method. The AAT subjects were divided into three groups on the basis of their basal and peak TSH values. In group I, these parameters were similar to those in the normal controls; in group II, basal TSH remained normal but peak TSH was significantly increased, and in group III both values were significantly increased. Group I differed from the controls by a decrease in P FT4 and AUC FT4, whereas in groups II and III B FT4 was also significantly lowered. T3 levels were similar in all groups except in group III, in whom they dropped. ITI was already lower in group I than in the controls. Its decline went further in groups II and III. An inverse correlation with significant r values was evidenced between log B and P TSH on one hand and log B FT4, P FT4 and AUC FT4 on the other. When group III was excluded, log P TSH was positively correlated with log B T3, P T3, AUC T3, and AUC F T3. The present study shows that the thyroid T4 reserve gradually decreases with the severity of AAT, and suggests that except in the most severe stage, a preferential T3 secretion occurs probably as a consequence of the decrease in intrathyroidal iodine.

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Jiri Horacek, Jaroslav Maly, Ioannis Svilias, Lukas Smolej, Jitka Cepkova, Jaroslav Vizda, Petr Sadilek, Ilona Fatorova, and Pavel Zak

Objective

With increasing free thyroxine levels, a gradually rising risk of venous thromboembolism has been described in case–control studies. However, reports on the influence of thyroid hormones on haemostasis, while suggesting a hypercoagulable state in thyrotoxicosis, have often been inconclusive. This study evaluates multiple markers of haemostasis and fibrinolysis in a paired design, making it more sensitive to changes in thyroid hormone levels.

Design

We analysed multiple variables in patients who shifted from severe hypothyroidism to mild hyperthyroidism during thyroid cancer treatment. Those with possible residual disease were excluded.

Methods

Ninety patients following total thyroidectomy were tested on two occasions: i) before radioiodine remnant ablation and ii) 6 weeks later, on levothyroxine (lT4) suppression treatment, and the results were compared using the Wilcoxon's test for paired data.

Results

During lT4 treatment, significant increases (all P<0.001) in fibrinogen (from median 3.4 to 3.8 g/l), von Willebrand factor (from 85 to 127%), factor VIII (from 111 to 148%) and plasminogen activator inhibitor 1 (from 6.5 to 13.9 μg/l) were observed. In addition, the activation times of platelet adhesion and aggregation stimulated with collagen and epinephrine (EPI)/ADP, i.e. closure times in platelet function analyser (PFA-100), were significantly shortened (P<0.001): for EPI from median 148 to 117 s and for ADP from 95 to 80 s. Changes in other tests were less prominent or insignificant.

Conclusions

An increase in thyroid hormone levels shifts the haemostatic balance towards a hypercoagulable, hypofibrinolytic state. This may contribute to the increased cardiovascular morbidity and mortality observed even in mild thyrotoxicosis.

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Hans Thorsøe

ABSTRACT

The effect of 1-thyroxine and d-thyroxine on the content of mucopolysaccharides in rabbit ovaries was studied histologically and biochemically. The doses of 1-thyroxine and d-thyroxine completely blocked the pituitary release of thyroid-stimulating hormone (TSH) as shown by the inhibition of 131I release from the thyroid gland. The treatment with 1-thyroxine as well as with d-thyroxine was continued for 15 and 30 days respectively. 1-Thyroxine brought about a loss of weight in the rabbits and caused a decrease in ovarian weight.

d-Thyroxine produced no loss of weight and did not affect the ovarian weight.

Neither 1-thyroxine nor d-thyroxine altered the gross appearance of the ovaries. Histological examination showed the quantity, distribution, and intensity of metachromatic substance to be identical in all experimental groups. Autoradiography showed no changes in the distribution of the 35S-containing mucopolysaccharides. Neither 1-thyroxine nor d-thyroxine altered the ovarian concentration of water or hexosamine, or the uptake of 35S-sulphate.

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F Bogazzi, L Bartalena, S Brogioni, A Burelli, L Manetti, ML Tanda, M Gasperi, and E Martino

OBJECTIVE: Thyroid blood flow is greatly enhanced in untreated Graves' disease, but it is not known whether it is due to thyroid hormone excess or to thyroid hyperstimulation by TSH-receptor antibody. To address this issue in vivo patients with different thyroid disorders were submitted to color flow doppler sonography (CFDS). SUBJECTS AND METHODS: We investigated 24 normal subjects, and 78 patients with untreated hyperthyroidism (49 with Graves' hyperthyroidism, 24 with toxic adenoma, and 5 patients with TSH-secreting pituitary adenoma (TSHoma)), 19 patients with thyrotoxicosis (7 with thyrotoxicosis factitia, and 12 with subacute thyroiditis), 37 euthyroid patients with goitrous Hashimoto's thyroiditis, and 21 untreated hypothyroid patients with Hashimoto's thyroiditis. RESULTS: Normal subjects had CFDS pattern 0 (absent or minimal intraparenchimal spots) and mean intraparenchimal peak systolic velocity (PSV) of 4.8+/-1.2cm/s. Patients with spontaneous hyperthyroidism due to Graves' disease, TSHoma, and toxic adenoma had significantly increased PSV (P<0.0001, P=0.0004, P<0.0001 respectively vs controls) and CFDS pattern. Patients with Graves' disease had CFDS pattern II (mild increase of color flow doppler signal) in 10 (20%) and pattern III (marked increase) in 39 cases (80%). Mean PSV was 15+/-3cm/s. Patients with toxic adenoma had CFDS pattern I (presence of parenchymal blood flow with patchy uneven distribution) in 2 (8%), pattern II in 16 (70%) and pattern III in 5 (22%). Mean PSV was 11+/-2.4cm/s. Patients with TSHoma showed CFDS pattern I in one case (20%) and pattern II in 4 (80%). Mean PSV was 14.8+/-4.2cm/s. Patients with thyrotoxicosis had normal PSV (4.2+/-1. 1cm/s in subacute thyroiditis, 4+/-0.8cm/s in thyrotoxicosis factitia, P=not significant vs controls) and CFDS pattern 0. Untreated euthyroid patients with goitrous Hashimoto's thyroiditis had CFDS pattern 0, and mean PSV (4.3+/-0.9cm/s; P=not significant vs controls). Untreated hypothyroid patients with goitrous Hashimoto's thyroiditis had CFDS pattern I in 14 cases (67%), pattern II in 4 (19%) and pattern 0 in 3 (14%) and mean PSV (5.6+/-1. 4cm/s) was higher than that of controls (P=0.026). CONCLUSIONS: An increase in both intrathyroidal vascularity and blood velocity was observed in patients with spontaneous hyperthyroidism but not in thyrotoxicosis due to either ingestion of thyroid hormones or to a thyroidal destructive process. The slightly increased vascularity and blood velocity observed in patients with hypothyroid Hashimoto's thyroiditis suggests that thyroid stimulation by either TSH-receptor antibody or TSH is responsible for the increased thyroid blood flow.

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Shioko Kimura

Introduction

Thyroid-specific enhancer-binding protein (T/EBP), also called thyroid-specific transcription factor-1 (TTF-1) is a trans-activating transcription factor which was originally shown to be involved in thyroid-specific gene expression. The same factor was later found to be involved in regulating the expression of lung-specific genes. Recent production of a mutant mouse line which lacks T/ebp expression, established an additional role of T/EBP in organogenesis of the thyroid, lung, ventral forebrain and pituitary. This review summarizes the current state of knowledge regarding T/EBP.

Involvement of T/EBP in thyroid hormone synthesis

Thyroid hormone synthesis consists of multiple steps including iodide uptake by the thyroid, iodination of tyrosine residues in thyroglobulin (TG), and coupling of the iodinated tyrosine residues to produce the thyroid hormones tri-iodothyronine (T3) and thyroxine (T4) (1). Thyroid peroxidase (TPO) catalyzes both the iodination and the coupling reactions. Thyroid hormone synthesis is under the precise feedback control mechanism of

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FA Karlsson, P Burman, O Kömpe, J-E Westlin, and L Wide

A unique thyrotrophin (TSH)-secreting pituitary tumour is described in a patient with a history of recurrent thyrotoxicosis. Unlike other previously reported TSHomas, the tumour is insensitive to octreotide, a somatostatin analogue. It does not accumulate [111In]octreotide but expresses functional dopamine receptors and responds to the d-isomer of thyroxine, two characteristics beneficial in the management of the patient.

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Helen E. A. Farran, Christine Haiste, and R. Hoffenberg

ABSTRACT

Serum PBI and thyroxine iodine (T4I) levels have been compared in a large series of patients. A mean difference of 0.35 μg/100 ml was found in euthyroid subjects, but a much greater difference obtained when both values were high, whether the elevation resulted from hyperthyroidism, pregnancy or the administration of thyroxine or oestrogen. This discrepancy was greater in a group of patients with diffuse goitre than in those with nodular glands. A circulating non-thyroxine iodinated compound is thought to account for this discrepancy, the origins of which could lie in the thyroid gland, although peripheral deiodination of thyroxine seems more likely.

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A. K. Medda and B. N. Premachandra

ABSTRACT

Metamorphosis of Rana catesbeiana tadpoles immersed in a medium containing thyroxine (T4) occurred in 58 days, whereas 79 days were required for tadpoles treated with albumin + T4 complex in media, and at 121 days 50 % metamorphosis occurred in the group whose medium contained normal rabbit serum + T4. No metamorphosis occurred in tadpoles which had rabbit antiporcine thyroglobulin + T4 complex in media. Similarly the retardation of hind limb growth in comparison to the control at 58 days was most severe in animals treated with antithyroglobulin + T4 complex in media (74.3 % depression) followed by normal serum + T4 (60.1 % less) and bovine albumin + T4 complex (30 % inhibition) treated animals. In further investigations, in comparison to controls (only 125I-T4 in media), 62.4%, 77.0%, and 82.4% less 125I-T4 concentration was seen in viscera, tail, and carcass respectively of tadpoles treated with immune globulin + 125I-T4 in the media, whereas no change was seen in the group treated with normal gammaglobulin + 125I-T4 complex; similarly no changes in visceral 125I-T4 concentration were noted in groups whose media contained thyroglobulin in complex with 125I-T4. Present investigations therefore show that normal rabbit serum (apparently any good T4 binding protein) is a potent inhibitor of metamorphosis of tadpoles, the effectiveness mediated at least in part, on the inability of the larva to split thyroxine-protein complexes in their body. Antiporcine thyroglobulin rabbit serum was shown to be superior to normal rabbit serum in inhibiting tadpole metamorphosis, evidently due to additional T4 binding sites provided by the immune globulin. Available evidence indicates that antithyroglobulin binding of T4 is distinct and is evidently not due to thyroglobulin that may be in complex with the thyroid antibody.

Free access

Jiri Horacek, Sylvie Spitalnikova, Blanka Dlabalova, Eva Malirova, Jaroslav Vizda, Ioannis Svilias, Jitka Cepkova, Catherine Mc Grath, and Jaroslav Maly

Objective

Screening of thyroid disorders in pregnancy has been controversial. Recent recommendations favour targeted high-risk case finding, though this approach may miss a significant number of those affected. We aimed to assess the prevalence of accepted high-risk criteria in women with autoimmune thyroiditis and/or hypothyroidism detected from universal screening in an iodine-sufficient population.

Design

In 400 non-selected women in the 9–11th gestational week, thyroid-related tests were performed, and those with abnormalities were offered consultation.

Methods

TSH was determined by IRMA, and the upper cut-off value for screening was set at 3.5 mIU/l. For free thyroxine (FT4) and thyroperoxidase antibodies (TPO-Ab), RIAs were used, with cut-offs of <10 pmol/l and >50 IU/ml respectively. Endocrinological consultation included Doppler ultrasonography and was aimed to confirm autoimmune thyroiditis and/or hypothyroidism. The prevalence of consensus high-risk criteria was assessed.

Results

Among the 400 women, 65 (16.3%) had ≥1 abnormality: higher TSH was found in 10.3%, lower FT4 in 2% and positive TPO-Ab in 8.3%. Fifty-one women were examined and followed up. Levo-T4 treatment was initiated in 49 women for autoimmune thyroiditis (in 42), hypothyroidism (in 34) or both (in 27). Only 22 (45%) of 49 treated women fulfilled ≥1 high-risk criterion: most commonly family history (31%), history of miscarriage or preterm delivery (14%) and personal history (8%).

Conclusions

Over half (55%) of pregnant women with abnormalities suggestive of autoimmune thyroiditis and/or hypothyroidism would be missed if only those with high-risk criteria were examined. A more extensive screening of thyroid autoimmunity and dysfunction seems warranted.

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Peter Laurberg

Abstract.

Previous studies on the secretion of thyroxine (T4), 3,5,3'-triiodothyronine (T3), and 3,3',5'-triiodothyronine (rT3) from perfused dog thyroids have indicated that a differential rate of secretion of various iodothyronines may take place.

The aim of the present study was to evaluate whether the proteolysis of thyroglobulin taking place during secretion could be involved in this phenomenon. Homogenate from the same dog thyroid was incubated either at pH 3.6 for 18 h without added protease or with pronase at pH 8.4 for 18 h. Iodothyronines were measured radioimmunologically in ethanol extracts of the hydrolysates. No significant deiodination of T4 to T3 and rT3 took place during incubation. During acid autolysis 17.5 ± 3.5% (mean ± SE, n = 5) of the T4 found after pronase hydrolysis was liberated, while 31.6 ± 4.8% of the T3 and 21.2 ± 4.2% of the rT3 were liberated (both values were significantly higher than that found for T4). Since iodothyronines in thyroglobulin are released nearly quantitatively during pronase hydrolysis, the results indicate that thyroid proteases acting at acid pH, liberates T3 and rT3 more easily than T4 from thyroglobulin.

This could be the mechanism behind the relatively high secretion of T3 and rT3 observed during acceleration of secretion from perfused thyroid lobes, and the relatively high secretion of T4 observed during deceleration of secretion.