scholarly journals Type 1 and type 2 iodothyronine deiodinases in the thyroid gland of patients with 3,5,3′-triiodothyronine-predominant Graves' disease

2011 ◽  
Vol 164 (1) ◽  
pp. 95-100 ◽  
Author(s):  
Mitsuru Ito ◽  
Nagaoki Toyoda ◽  
Emiko Nomura ◽  
Yuuki Takamura ◽  
Nobuyuki Amino ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Mrna Level ◽  
Antithyroid Drug ◽  
High Serum ◽  
Graves Disease ◽  
Iodothyronine Deiodinase ◽  
Iodothyronine Deiodinases ◽  
Antithyroid Drug Therapy

Objective3,5,3′-triiodothyronine-predominant Graves' disease (T3-P-GD) is characterized by a persistently high serum T3 level and normal or even lower serum thyroxine (T4) level during antithyroid drug therapy. The source of this high serum T3 level has not been clarified. Our objective was to evaluate the contribution of type 1 and type 2 iodothyronine deiodinase (D1 (or DIO1) and D2 (or DIO2) respectively) in the thyroid gland to the high serum T3 level in T3-P-GD.MethodsWe measured the activity and mRNA level of both D1 and D2 in the thyroid tissues of patients with T3-P-GD (n=13) and common-type GD (CT-GD) (n=18) who had been treated with methimazole up until thyroidectomy.ResultsThyroidal D1 activity in patients with T3-P-GD (492.7±201.3 pmol/mg prot per h) was significantly higher (P<0.05) than that in patients with CT-GD (320.7±151.9 pmol/mg prot per h). On the other hand, thyroidal D2 activity in patients with T3-P-GD (823.9±596.4 fmol/mg prot per h) was markedly higher (P<0.005) than that in patients with CT-GD (194.8±131.6 fmol/mg prot per h). There was a significant correlation between the thyroidal D1 activity in patients with T3-P-GD and CT-GD and the serum FT3-to-FT4 ratio (r=0.370, P<0.05). Moreover, there was a strong correlation between the thyroidal D2 activity in those patients and the serum FT3-to-FT4 ratio (r=0.676, P<0.001).ConclusionsOur results suggest that the increment of thyroidal deiodinase activity, namely D1 and especially D2 activities, may be responsible for the higher serum FT3-to-FT4 ratio in T3-P-GD.

scholarly journals Thyroglobulin Gene Mutations Producing Defective Intracellular Transport of Thyroglobulin Are Associated with Increased Thyroidal Type 2 Iodothyronine Deiodinase Activity

2007 ◽  
Vol 92 (4) ◽  
pp. 1451-1457 ◽  
Author(s):  
Yasuhiko Kanou ◽  
Akira Hishinuma ◽  
Katsuhiko Tsunekawa ◽  
Koji Seki ◽  
Yutaka Mizuno ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Intracellular Transport ◽  
Mrna Level ◽  
Thyroid Tissue ◽  
Compound Heterozygous ◽  
Free T4 ◽  
Iodothyronine Deiodinase ◽  
Normal Thyroid ◽  
Thyroid Glands

Abstract Context: Most patients with defective synthesis and/or secretion of thyroglobulin (Tg) present relatively high serum free T3 (FT3) concentrations with disproportionately low free T4 (FT4) resulting in a high FT3/FT4 ratio. The mechanism of this change in FT3/FT4 ratio remains unknown. Objective: We hypothesize that increased type 2 iodothyronine deiodinase (D2) activity in the thyroid gland may explain the higher FT3/FT4 ratio that is frequently observed in patients with abnormal Tg synthesis. Design: We recently identified a compound heterozygous patient (patient A) with a Tg G2356R mutation and one previously described (C1245R) that is known to cause a defect in intracellular transport of Tg. In the current study, after determining the abnormality caused by G2356R, we measured D2 activity as well as its mRNA level in the thyroid gland. We also measured the thyroidal D2 activity in three patients with Tg transport defect and in normal thyroid tissue. Results: Morphological and biochemical analysis of the thyroid gland from patient A, complemented by a pulse-chase experiment, revealed that G2356R produces a defect in intracellular Tg transport. D2 activity but not type 1 deiodinase in thyroid glands of patients with abnormal Tg transport was significantly higher than in normal thyroid glands, whereas D2 mRNA level in patient A was comparable with that in normal thyroid glands. Furthermore, there was a positive correlation between D2 activity and FT3/FT4 ratios. Conclusion: Increased thyroidal D2 activity in the thyroid gland is responsible for the higher FT3/FT4 ratios in patients with defective intracellular Tg transport.

Type 1 and type 2 iodothyronine deiodinases in the thyroid gland of patients with huge goitrous Hashimoto’s thyroiditis

Endocrine ◽  
2019 ◽  
Vol 64 (3) ◽  
pp. 584-590 ◽  
Author(s):  
Azusa Harada ◽  
Emiko Nomura ◽  
Kumiko Nishimura ◽  
Mitsuru Ito ◽  
Hiroshi Yoshida ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Hashimoto’S Thyroiditis ◽  
Hashimoto's Thyroiditis ◽  
Iodothyronine Deiodinases

scholarly journals Comparative kinetic characterization of rat thyroid iodotyrosine dehalogenase and iodothyronine deiodinase type 1

2004 ◽  
Vol 181 (3) ◽  
pp. 385-392 ◽  
Author(s):  
JC Solis-S ◽  
P Villalobos ◽  
A Orozco ◽  
C Valverde-R
Keyword(s):  
Thyroid Gland ◽  
Distinct Group ◽  
Kinetic Properties ◽  
Iodothyronine Deiodinase ◽  
Iodothyronine Deiodinases ◽  
Iodine Metabolism ◽  
Rat Thyroid ◽  
Rat Thyroid Gland

The initial characterization of a thyroid iodotyrosine dehalogenase (tDh), which deiodinates mono-iodotyrosine and di-iodotyrosine, was made almost 50 years ago, but little is known about its catalytic and kinetic properties. A distinct group of dehalogenases, the so-called iodothyronine deiodinases (IDs), that specifically remove iodine atoms from iodothyronines were subsequently discovered and have been extensively characterized. Iodothyronine deiodinase type 1 (ID1) is highly expressed in the rat thyroid gland, but the co-expression in this tissue of the two different dehalogenating enzymes has not yet been clearly defined. This work compares and contrasts the kinetic properties of tDh and ID1 in the rat thyroid gland. Differential affinities for substrates, cofactors and inhibitors distinguish the two activities, and a reaction mechanism for tDh is proposed. The results reported here support the view that the rat thyroid gland has a distinctive set of dehalogenases specialized in iodine metabolism.

A second course of antithyroid drug therapy is effective in patients with relapsed Graves' disease

2018 ◽  
Author(s):  
Khyatisha Seejore ◽  
Fozia Nawaz ◽  
Katherine Kelleher ◽  
Julie Kyaw-Tun ◽  
Julie Lynch ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Antithyroid Drug ◽  
Graves Disease ◽  
Antithyroid Drug Therapy

Successful Treatment of Graves Disease in Pregnancy with Lugol's Iodine

2000 ◽  
Vol 45 (1) ◽  
pp. 20-21 ◽  
Author(s):  
A. Jamieson ◽  
C.G. Semple
Keyword(s):  
Drug Therapy ◽  
Successful Treatment ◽  
Surgical Intervention ◽  
Antithyroid Drug ◽  
Primary Treatment ◽  
Graves Disease ◽  
Lugol’S Iodine ◽  
Organic Iodine ◽  
Antithyroid Drug Therapy ◽  
In Pregnancy

We report a case of Grave's disease in pregnancy complicated by intolerance of standard antithyroid drug therapy. We describe the success of prolonged use of organic iodine as a primary treatment prior to surgical intervention.

scholarly journals Standardized grey scale ultrasonography in Graves' disease: correlation to autoimmune activity

1999 ◽  
pp. 332-336 ◽  
Author(s):  
U Schiemann ◽  
R Gellner ◽  
B Riemann ◽  
G Schierbaum ◽  
J Menzel ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Antithyroid Drug ◽  
Thyroid Volume ◽  
Control Group ◽  
Graves Disease ◽  
Laboratory Findings ◽  
Grey Scale ◽  
Antithyroid Drug Treatment ◽  
Student’S T ◽  
A Prospective Study

OBJECTIVE: Graves' disease leads to thyroid enlargement and to reduction of tissue echogenicity. Our purpose was to correlate grey scale ultrasonography of the thyroid gland with clinical and laboratory findings in patients with Graves' disease. DESIGN: Fifty-three patients with Graves'disease were included in our study, 100 euthyroid volunteers served as control group. Free thyroxine (FT(4)), TSH and TRAb (TSH receptor antibodies) values were measured and correlated with sonographic echogenicity of the thyroid gland. METHODS: All patients and control persons underwent ultrasonographical histogram analyses under standardized conditions. Mean densities of the thyroid tissues were determined in grey scales (GWE). RESULTS: Compared with controls with homogeneous thyroid lobes of normal size (25.6 +/- 2.0GWE, mean +/- S.D.) echogenicity in patients with Graves' disease was significantly lower (21.3 +/- 3. 3GWE, mean +/- S.D., P < 0.0001). Among the patients with Graves' disease significant differences of thyroid echo levels were revealed for patients with suppressed (20.4 +/- 3.1 GWE, mean +/- S.D., n=34) and normalized TSH values (22.5 +/- 3.6GWE, mean +/- S.D., n=19, P < 0.02). Significantly lower echogenicities were also measured in cases of persistent elevated TRAb levels (19.9 +/- 2.9GWE, mean +/- S.D., n=31) in comparison with normal TRAb levels (22.9 +/- 3.5 GWE, mean +/- S.D., n=22, P < 0.0015). No correlation could be verified between echogenicity and either still elevated or already normalized FT(4) values or the thyroid volume. In coincidence of hyperthyroidism and Graves' ophthalmopathy (19.7 +/- 3.5GWE, mean +/- S.D., n=23) significantly lower echogenicity was measured than in the absence of ophthalmological symptoms (22.3 +/- 3.3GWE, mean +/- S.D., n=30, P < 0.016). Patients needing active antithyroid drug treatment revealed significantly lower thyroid echogenicity (20.3 +/- 3.1 GWE, mean +/- S.D., n=40) than patients in remission (23.7 +/- 3.4 GWE, mean +/- S.D., n=13, P < 0.001). Statistical evaluation was carried out using Student's t-test. CONCLUSIONS: Standardized grey scale histogram analysis allows for supplementary judgements of thyroid function and degree of autoimmune activity in Graves' disease. Whether these values help to estimate the risk of recurrence of hyperthyroidism after withdrawal of antithyroid medication should be evaluated in a prospective study.

Erratum

1989 ◽  
Vol 121 (2) ◽  
pp. 304
Author(s):  
H. Schleusener ◽  
J. Schwander ◽  
C. Fischer ◽  
R. Holle ◽  
G. Holl ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Relapse Rate ◽  
Clinical Course ◽  
Antithyroid Drug ◽  
Graves Disease ◽  
Trh Test ◽  
Prospective Multicentre Study ◽  
Antithyroid Drug Therapy ◽  
Significant Difference ◽  
The Individual

Abstract. Graves' disease is an autoimmune disease characterized by a course of remission and relapse. Since the introduction of antithyroid drug treatment, various parameters have been tested for their ability to predict the clinical course of a patient with Graves' disease after drug withdrawal. Nearly all these studies were retrospective and often yielded conflicting results. In a prospective multicentre study with a total of 451 patients, we investigated the significance of a variety of routine laboratory and clinical parameters for predicting a patient's clinical course. Patients who had positive TSH receptor antibodies activity at the end of therapy showed a significantly higher relapse rate than those without (P < 0.001). However, the individual clinical course cannot be predicted exactly (sensitivity 0.49, specificity 0.73, N = 391). The measurement of microsomal (P = 0.99, sensitivity 0.37, specificity 0.63, N = 275) or thyroglobulin antibodies (P = 0.76, sensitivity 0.18, specificity 0.84, N = 304) at the end of antithyroid drug therapy did not show a statistically significant difference in the antibody titre between the patients of the relapse and those of the remission group. Additionally, HLA-DR typing (HLA-DR3: P = 0.37, sensitivity 0.36, specificity 0.58, N = 253) was proven to be unsuitable for predicting a patient's clinical course. Patients with abnormal suppression or an abnormal TRH test at the end of antithyroid drug therapy relapse significantly more often (P< 0.001) than patients with normal suppression or normal TRH test. Patients with a large goitre also have a significantly (P< 0.001) higher relapse rate than those with only a small enlargement. The sensitivity and specificity values of all these parameters, however, were too low to be useful for daily clinical decisions in the treatment of an individual patient. This is also true for the combinations of different parameters. Though the highest sensitivity value (0.94) was found for a combination of the suppression and the TRH test at the end of therapy, the very low specificity value (0.13) for this combination reduced its clinical usefulness.

scholarly journals Synthesis and Metabolism of Thyroid Hormones Is Preferentially Maintained in Selenium-Deficient Transgenic Mice

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1306-1313 ◽  
Author(s):  
Lutz Schomburg ◽  
Cornelia Riese ◽  
Marten Michaelis ◽  
Emine Griebert ◽  
Marc O. Klein ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Thyroid Hormones ◽  
Knockout Mice ◽  
Serum Levels ◽  
Mrna Levels ◽  
Normal Range ◽  
Growth Defects ◽  
Low Levels

The thyroid gland is rich in selenium (Se) and expresses a variety of selenoproteins that are involved in antioxidative defense and metabolism of thyroid hormones (TH). Se deficiency impairs regular synthesis of selenoproteins and adequate TH metabolism. We recently generated mice that lack the plasma Se carrier, selenoprotein P (SePP). SePP-knockout mice display decreased serum Se levels and manifest growth defects and neurological abnormalities partly reminiscent of thyroid gland dysfunction or profound hypothyroidism. Thus, we probed the TH axis in developing and adult SePP-knockout mice. Surprisingly, expression of Se-dependent 5′-deiodinase type 1 was only slightly altered in liver, kidney, or thyroid at postnatal d 60, and 5′-deiodinase type 2 activity in brain was normal in SePP-knockout mice. Thyroid gland morphology, thyroid glutathione peroxidase activity, thyroid Se concentration, and serum levels of TSH, T4, or T3 were within normal range. Pituitary TSHβ transcripts and hepatic 5′-deiodinase type 1 mRNA levels were unchanged, indicating regular T3 bioactivity in thyrotropes and hepatocytes. Cerebellar granule cell migration as a sensitive indicator of local T3 action during development was undisturbed. Collectively, these findings demonstrate that low levels of serum Se or SePP in the absence of other challenges do not necessarily interfere with regular functioning of the TH axis. 5′-deiodinase isozymes are preferentially supplied, and Se-dependent enzymes in the thyroid are even less-dependent on serum levels of Se or SePP than in brain. This indicates a top priority of the thyroid gland and its selenoenzymes with respect to the hierarchical Se supply within the organism.

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