Sources of circulating 3,5,3'-triiodothyronine in hyperthyroidism estimated after blocking of type 1 and type 2 iodothyronine deiodinases

Peter Laurberg, Henrik Vestergaard, Soren Nielsen, Stig E Christensen, Torben Seefeldt, Kjeld Helleberg, Klaus M Pedersen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2007-Jun
OriginalsprogEngelsk
TidsskriftJournal of Clinical Endocrinology and Metabolism
Vol/bind92
Udgave nummer6
Sider (fra-til)2149-56
Antal sider7
ISSN0021-972X
DOI
StatusUdgivet - 1. jun. 2007

Fingeraftryk

Propylthiouracil
Iodide Peroxidase
Ipodate
Poisons
Serum

Citer dette

Laurberg, Peter ; Vestergaard, Henrik ; Nielsen, Soren ; Christensen, Stig E ; Seefeldt, Torben ; Helleberg, Kjeld ; Pedersen, Klaus M. / Sources of circulating 3,5,3'-triiodothyronine in hyperthyroidism estimated after blocking of type 1 and type 2 iodothyronine deiodinases. I: Journal of Clinical Endocrinology and Metabolism. 2007 ; Bind 92, Nr. 6. s. 2149-56.
@article{8100dd004e5f11ddb1a1000ea68e967b,
title = "Sources of circulating 3,5,3'-triiodothyronine in hyperthyroidism estimated after blocking of type 1 and type 2 iodothyronine deiodinases",
abstract = "CONTEXT: Graves' hyperthyroidism and multinodular toxic goiter lead to high serum T(3) compared with serum T(4). The source of this high T(3) has not been clarified. OBJECTIVE: Our objective was to assess the role of iodothyronine deiodinase type 1 (D1) and type 2 (D2) for T(3) production and to estimate the sources of T(3) in hyperthyroidism. DESIGN AND SETTING: The study was a prospective, randomized, open-labeled study in a secondary care setting. PATIENTS AND METHODS: Consecutive patients with hyperthyroidism caused by Graves' disease or by multinodular toxic goiter were randomized to be treated with high-dose propylthiouracil (PTU) to block D1, PTU plus KI, or PTU plus sodium ipodate to additionally block D2. T(3) and T(4) were measured in serum, and we estimated the sources of T(3). RESULTS: PTU reduced the T(3)/T(4) in serum to 47.7 +/- 2.5{\%} (mean +/- sem) of the initial value on d 4 of therapy in patients with Graves' disease. The addition of KI to PTU led to a greater fall in T(3) and T(4), but the balance was unaltered. After PTU plus ipodate, T(3)/T(4) on d 4 was lower, 34.1 +/- 1.2{\%} of the initial value. Similar variations were observed in patients with multinodular toxic goiter. Thus, the major source of the excess T(3) was D1-catalyzed T(4) deiodination, with a minor role for D2. It was estimated that the majority of this D1-catalyzed T(3) production takes place in the hyperactive thyroid gland. CONCLUSION: Although thyroidal T(3) contributes only around 20{\%} of total T(3) production in normal individuals, this is much higher in patients with a hyperactive thyroid, ranging up to two thirds. The major part is produced from T(4) deiodinated in the thyroid.",
keywords = "Adolescent, Adult, Antithyroid Agents, Child, Drug Therapy, Combination, Female, Goiter, Nodular, Graves Disease, Humans, Hyperthyroidism, Iodide Peroxidase, Ipodate, Male, Middle Aged, Propylthiouracil, Prospective Studies, Thyroxine, Treatment Outcome, Triiodothyronine",
author = "Peter Laurberg and Henrik Vestergaard and Soren Nielsen and Christensen, {Stig E} and Torben Seefeldt and Kjeld Helleberg and Pedersen, {Klaus M}",
year = "2007",
month = "6",
day = "1",
doi = "10.1210/jc.2007-0178",
language = "English",
volume = "92",
pages = "2149--56",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Heinemann",
number = "6",

}

Sources of circulating 3,5,3'-triiodothyronine in hyperthyroidism estimated after blocking of type 1 and type 2 iodothyronine deiodinases. / Laurberg, Peter; Vestergaard, Henrik; Nielsen, Soren; Christensen, Stig E; Seefeldt, Torben; Helleberg, Kjeld; Pedersen, Klaus M.

I: Journal of Clinical Endocrinology and Metabolism, Bind 92, Nr. 6, 01.06.2007, s. 2149-56.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Sources of circulating 3,5,3'-triiodothyronine in hyperthyroidism estimated after blocking of type 1 and type 2 iodothyronine deiodinases

AU - Laurberg, Peter

AU - Vestergaard, Henrik

AU - Nielsen, Soren

AU - Christensen, Stig E

AU - Seefeldt, Torben

AU - Helleberg, Kjeld

AU - Pedersen, Klaus M

PY - 2007/6/1

Y1 - 2007/6/1

N2 - CONTEXT: Graves' hyperthyroidism and multinodular toxic goiter lead to high serum T(3) compared with serum T(4). The source of this high T(3) has not been clarified. OBJECTIVE: Our objective was to assess the role of iodothyronine deiodinase type 1 (D1) and type 2 (D2) for T(3) production and to estimate the sources of T(3) in hyperthyroidism. DESIGN AND SETTING: The study was a prospective, randomized, open-labeled study in a secondary care setting. PATIENTS AND METHODS: Consecutive patients with hyperthyroidism caused by Graves' disease or by multinodular toxic goiter were randomized to be treated with high-dose propylthiouracil (PTU) to block D1, PTU plus KI, or PTU plus sodium ipodate to additionally block D2. T(3) and T(4) were measured in serum, and we estimated the sources of T(3). RESULTS: PTU reduced the T(3)/T(4) in serum to 47.7 +/- 2.5% (mean +/- sem) of the initial value on d 4 of therapy in patients with Graves' disease. The addition of KI to PTU led to a greater fall in T(3) and T(4), but the balance was unaltered. After PTU plus ipodate, T(3)/T(4) on d 4 was lower, 34.1 +/- 1.2% of the initial value. Similar variations were observed in patients with multinodular toxic goiter. Thus, the major source of the excess T(3) was D1-catalyzed T(4) deiodination, with a minor role for D2. It was estimated that the majority of this D1-catalyzed T(3) production takes place in the hyperactive thyroid gland. CONCLUSION: Although thyroidal T(3) contributes only around 20% of total T(3) production in normal individuals, this is much higher in patients with a hyperactive thyroid, ranging up to two thirds. The major part is produced from T(4) deiodinated in the thyroid.

AB - CONTEXT: Graves' hyperthyroidism and multinodular toxic goiter lead to high serum T(3) compared with serum T(4). The source of this high T(3) has not been clarified. OBJECTIVE: Our objective was to assess the role of iodothyronine deiodinase type 1 (D1) and type 2 (D2) for T(3) production and to estimate the sources of T(3) in hyperthyroidism. DESIGN AND SETTING: The study was a prospective, randomized, open-labeled study in a secondary care setting. PATIENTS AND METHODS: Consecutive patients with hyperthyroidism caused by Graves' disease or by multinodular toxic goiter were randomized to be treated with high-dose propylthiouracil (PTU) to block D1, PTU plus KI, or PTU plus sodium ipodate to additionally block D2. T(3) and T(4) were measured in serum, and we estimated the sources of T(3). RESULTS: PTU reduced the T(3)/T(4) in serum to 47.7 +/- 2.5% (mean +/- sem) of the initial value on d 4 of therapy in patients with Graves' disease. The addition of KI to PTU led to a greater fall in T(3) and T(4), but the balance was unaltered. After PTU plus ipodate, T(3)/T(4) on d 4 was lower, 34.1 +/- 1.2% of the initial value. Similar variations were observed in patients with multinodular toxic goiter. Thus, the major source of the excess T(3) was D1-catalyzed T(4) deiodination, with a minor role for D2. It was estimated that the majority of this D1-catalyzed T(3) production takes place in the hyperactive thyroid gland. CONCLUSION: Although thyroidal T(3) contributes only around 20% of total T(3) production in normal individuals, this is much higher in patients with a hyperactive thyroid, ranging up to two thirds. The major part is produced from T(4) deiodinated in the thyroid.

KW - Adolescent

KW - Adult

KW - Antithyroid Agents

KW - Child

KW - Drug Therapy, Combination

KW - Female

KW - Goiter, Nodular

KW - Graves Disease

KW - Humans

KW - Hyperthyroidism

KW - Iodide Peroxidase

KW - Ipodate

KW - Male

KW - Middle Aged

KW - Propylthiouracil

KW - Prospective Studies

KW - Thyroxine

KW - Treatment Outcome

KW - Triiodothyronine

U2 - 10.1210/jc.2007-0178

DO - 10.1210/jc.2007-0178

M3 - Journal article

C2 - 17389703

VL - 92

SP - 2149

EP - 2156

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 6

ER -