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


METHODS
The study was a prospective, randomized, open-labeled study in a secondary care setting.


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.


CONCLUSIONS
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.
Laurberg
Peter
P
Department of Endocrinology and Medicine, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. peter.laurberg@rn.dk
Vestergaard
Henrik
H
Nielsen
Soren
S
Christensen
Stig E
SE
Seefeldt
Torben
T
Helleberg
Kjeld
K
Pedersen
Klaus M
KM
D000293:Adolescent; D000328:Adult; D013956:Antithyroid Agents / Q000008:administration & dosage*; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D006044:Goiter, Nodular / Q000188:drug therapy / Q000378:metabolism; D006111:Graves Disease / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy* / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007487:Ipodate / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011441:Propylthiouracil / Q000008:administration & dosage*; D011446:Prospective Studies; D013974:Thyroxine / Q000097:blood; D016896:Treatment Outcome; D014284:Triiodothyronine / Q000096:biosynthesis / Q000097:blood*; D000097564:Iodothyronine Deiodinase Type II
D013956:Antithyroid Agents; D007453:Iodide Peroxidase; D007487:Ipodate; D011441:Propylthiouracil; D013974:Thyroxine; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II; C109812:iodothyronine deiodinase type I