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Elevated 3,5-Diiodothyronine Concentrations in the Sera of Patients with Nonthyroidal Illnesses and Brain Tumors

Department of Radiological Diagnostics and Nuclear Medicine, Neurosurgery (T.H.), Neuropathology (G.S.-D.), and Endocrinology (R.F.), Universitätsklinikum Benjamin Franklin, Free University of Berlin; the Department of Medicine (K.-J.G.), Universitätsklinikum Rudolf Virchow, Humboldt University of Berlin; and Formula GmbH (R.T.), Berlin, Germany

Address all correspondence and requests for reprints to: Dr. A. Baumgartner, Department of Radiological Diagnostics and Nuclear Medicine and Radiochemistry, Hindenburgdamm 30, 12200 Berlin, Germany.

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.

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