3,3'-Diiodothyronine Concentrations in the Sera of Patients with Nonthyroidal Illnesses and Brain Tumors and of Healthy Subjects during Acute Stress

Abstract

In this article we describe the development of a highly sensitive, accurate, and reproducible RIA for the measurement of 3,3'-diiodothyronine (3,3'-T2) in human serum and brain tissue. The detection limits were 1.8 fmol/g and 1.5 pmol/L in human brain tissue and serum, respectively. Serum concentrations of 3,3'-T2 were measured in 4 groups of patients with nonthyroidal illnesses (NTI), i.e. brain injuries (n = 15), sepsis (n = 24), liver disease (n = 22), and brain tumors (n = 23). The mean serum concentration of 3,3'-T2 in 62 healthy controls was 46.6 +/- 20.0 pmol/L. 3,3'-T2 levels declined significantly with increasing age. They were significantly lower in patients with brain injury (34.2 +/- 19.4 pmol/L; P = 0.006), were at the upper limit of normal in patients with sepsis (57.0 +/- 36.9 pmol/L; P = 0.06), and were elevated in patients with liver disease (72.6 +/- 56.7 pmol/L; P = 0.04) and brain tumors (89.0 +/- 40.9 pmol/L; P = 0.01). The serum levels of T3 were significantly lower than those in controls in all 4 patient groups. Serum concentrations of 3,3'-T2 were significantly enhanced in 9 patients with hyperthyroidism (85.4 +/- 43.0 pmol/L; P = 0.01) and were reduced in 12 patients with hypothyroidism (14.9 +/- 9.2 pmol/L; P = 0.001). In both normal brain tissue, obtained either intraoperatively or excised postmortem, and brain tumors, the concentrations of 3,3'-T2 ranged between 50-300 fmol/g. In healthy controls, 2 different forms of acute stress (sleep deprivation and delivering a lecture) significantly increased serum levels of T4 and T3, but did not affect those of 3,3'-T2 or 3,5-T2. In conclusion, our results show that, contrary to expectation, a low T3 syndrome in NTI is not always associated with low serum concentrations of 3,3'-T2. The production of 3,3'-T2 in NTI seems to be regulated in a disease-specific manner, resulting in unchanged, reduced, or elevated hormone concentrations.

Thyroid Hormone Supplementation in Sepsis: An Experimental Study

“…The levels of the thyroid hormones were found to increase in the serum of patients with sepsis as compared to other diseases. 45 Other reports has also shown a striking correlation between the low levels of the T3, T4, and a high ratio of mortality. When the T4 levels were below 3 µg/dl, the mortality rate increased from 64% to 84%, whereas the mortality was only 22% at normal levels of serum T4.…”

Circulating 3-T1AM and 3,5-T2 in Critically Ill Patients: A Cross-Sectional Observational Study

“…In critically ill animals that received a substitution dose of T4, circulating T4 was even further reduced, without a concomitant change in T3, rT3, or 3,3'-T2 (13). Patients suffering from NTI also display low to normal 3,3'-T2 concentrations (14)(15)(16). Together the available data suggest that increased TH breakdown during critical illness may be due to conversion or conjugation of T4 to other metabolites.…”

Concentrations of Seven Iodothyronine Metabolites in Brain Regions and the Liver of the Adult Rat

“…5Ј-125 I-T 4 , 3Ј-125 I-T 3 , and [ 125 I]-3,3Ј-T 2 were prepared for iodothyronine deiodinase assays and RIAs by radioiodination of T 3 , 3,5-T 2 , and 3-T 1 , respectively, as previously described (23)(24)(25). The tracers with specific radioactivities of 50 -75 megabecquerels (MBq)/nmol were repurified immediately before use with disposable Sep-Pak C18 cartridges (Waters Associates, Milford, MA) yielding a purity Ͼ99% with 125 I-as the only contaminant.…”

“…T 4 , T 3 , 3,3Ј-T 2 , and 3,5-T 2 RIAs were performed as reported previously (23)(24)(25). The RIAs for T 3 S and 3,3Ј-T 2 S were performed as follows.…”