Elevated 3,5-diiodothyronine concentrations in the sera of patients with nonthyroidal illnesses and brain tumors.
This study reports the development of a highly sensitive and reproducible RIA for the measurement of 3,5-diiodothyronine (3,5-T2) in human serum and tissue. The RIA employs 3-bromo-5-[125I]iodo-L-thyronine (3-Br-5-[125I]T1) as tracer, which was synthesized carrier free by an interhalogen exchange from 3,5-dibromo-L-thyronine (3,5-Br2T0). The detection limits were 1.0 fmol/g and 0.8 pmol/L in human brain tissue and serum, respectively. T3, diiodothyroacetic acid, and 3-monoiodothyronine cross-reacted with a 3,5-T2 antibody to the extent of 0.06%, 0.13%, and 0.65%, respectively. Serum concentrations of 3,5-T2 were measured in 62 healthy controls and 4 groups of patients with nonthyroidal illness, i.e. patients with sepsis (n = 24), liver diseases (n = 23), head and/or brain injury n = 15), and brain tumors (n = 21). The mean serum level of 3,5-T2 in the healthy subjects was 16.2 +/- 6.4 pmol/L. Concentrations of 3,5-T2 were significantly elevated in patients with sepsis (46.7 +/- 48.8 pmol/L; P < 0.01), liver diseases (24.8 +/- 14.9 pmol/L; P < 0.01), head and/or brain injury (24.1 +/- 11.3 pmol/L; P < 0.05), and brain tumors (21.6 +/- 4.8 pmol/L; P < 0.01). In all 4 patient groups, serum levels of T3 were significantly reduced, confirming the existence of a low T3 syndrome in these diseases. Serum concentrations of 3,5-T2 were significantly elevated in patients with hyperthyroidism (n = 9) and were reduced in patients with hypothyroidism (n = 8). The levels of T4, T3, and 3,5-T2 were measured in normal human tissue samples from the pituitary gland and various brain regions and in brain tumors. In normal brain tissue, the concentrations of 3,5-T2 ranged between 70-150 fmol/g, and the ratio of T3 to 3,5-T2 was approximately 20:1. In brain tumors, however, T3 levels were markedly lower, resulting in a ratio of T3 to 3,5-T2 of approximately 1:1. Recent findings suggest a physiological, thyromimetic role of 3,5-T2, possibly stimulating mitochondrial respiratory chain activity. Should this prove to be correct, then the increased availability of 3,5-T2 in nonthyroidal illness may be one factor involved in maintaining clinical euthyroidism in patients with reduced serum levels of T3 during nonthyroidal illness.
Pinna
G
G
Department of Radiological Diagnostics and Nuclear Medicine, Universitätsklinikum Benjamin Franklin, Free University of Berlin, Germany.
Meinhold
H
H
Hiedra
L
L
Thoma
R
R
Hoell
T
T
Gräf
K J
KJ
Stoltenburg-Didinger
G
G
Eravci
M
M
Prengel
H
H
Brödel
O
O
Finke
R
R
Baumgartner
A
A
D001254:Astrocytoma / Q000378:metabolism; D001930:Brain Injuries / Q000097:blood; D001932:Brain Neoplasms / Q000097:blood* / Q000378:metabolism; D006259:Craniocerebral Trauma / Q000097:blood; D004104:Diiodothyronines / Q000032:analysis / Q000097:blood*; D005909:Glioblastoma / Q000378:metabolism; D006801:Humans; D008107:Liver Diseases / Q000097:blood; D011863:Radioimmunoassay / Q000379:methods* / Q000706:statistics & numerical data; D012016:Reference Values; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000032:analysis / Q000097:blood
D004104:Diiodothyronines; D014284:Triiodothyronine; C030103:3,5-diiodothyronine; D013974:Thyroxine