title: Elevated 3,5-diiodothyronine concentrations in the sera of patients with nonthyroidal illnesses and brain tumors.
abstract: 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.
authors.affiliation: Department of Radiological Diagnostics and Nuclear Medicine, Universitätsklinikum Benjamin Franklin, Free University of Berlin, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Pinna
authors.forename: H
authors.initials: H
authors.lastname: Meinhold
authors.forename: L
authors.initials: L
authors.lastname: Hiedra
authors.forename: R
authors.initials: R
authors.lastname: Thoma
authors.forename: T
authors.initials: T
authors.lastname: Hoell
authors.forename: K J
authors.initials: KJ
authors.lastname: Gräf
authors.forename: G
authors.initials: G
authors.lastname: Stoltenburg-Didinger
authors.forename: M
authors.initials: M
authors.lastname: Eravci
authors.forename: H
authors.initials: H
authors.lastname: Prengel
authors.forename: O
authors.initials: O
authors.lastname: Brödel
authors.forename: R
authors.initials: R
authors.lastname: Finke
authors.forename: A
authors.initials: A
authors.lastname: Baumgartner
mesh_terms: 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
chemical_list: D004104:Diiodothyronines; D014284:Triiodothyronine; C030103:3,5-diiodothyronine; D013974:Thyroxine