A Radioimmunoassay for Measurement of 3′-Monoiodothyronine*

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Abstract
A simple, sensitive, and highly specific RIA has been developed to measure 3′-monoiodothyronine (3′-T1) in unextracted serum. The detection threshold of RIA was 0.5 ng/dl. Recovery of nonradioactive 3′-T1 added to serum averaged 100% (n = 24). 3,3′-Diiodothyronine (3,3′-T2) cross-reacted maximally (0.71%) in the RIA, followed by 3′,5′-T2 (0.32%), 3-T1 (0.04%), and L-thyronine (0.014%); T4, T3, and rT3 cross-reacted less than 0.0001%, 0.004%, and 0.005%, respectively. The coefficient of variation averaged 6.3% within an assay and 16% between assays. The serum concentration of 3′-T1 averaged (mean ± SD) 1.4 ± 0.4 ng/dl in 25 normal subjects, 9.8 ± 0.6 ng/dl in 14 hyperthyroid patients, 0.7 ± 0.2 ng/dl in 9 hypothyroid patients, 1.9 ± 0.6 ng/dl in 12 euthyroid women with high T4-binding globulin, 12 ± 4.9 ng/dl in 34 newborns (cord blood), and 3.4 ± 3.3 ng/dl in 12 adult patients with nonthyroid illnesses. The values in each of the latter 5 groups were significantly different than normal (P < 0.02). The mean serum 3′-T1 concentration of 1.5 ± 0.5 ng/dl in 5 hypothyroid patients on replacement therapy with synthetic T4 did not differ significantly from normal. Oral administration of 50 ng 3′-T1 to 3 normal subjects led to a mean maximal serum 3′-T1 concentration of 23 ng/dl at 1 h. Oral administration of 300 fig rT3 to 2 euthyroid subjects was associated with an increase in serum 3′-T1 concentration from a mean baseline value of 2.2 ng/dl to a mean maximal value of 4.7 ng/dl at 2 and 4 h after rT3 administration. In 2 euthyroid obese subjects undergoing complete fasting for 4 days, there were 100% and 183% increases in the serum 3′-T1 concentration, respectively (baseline value, 0.6 ng/dl in both cases), at a time when serum rT3 increased 35% and 58% and serum T3 decreased 47% and 48%, respectively. As previously reported for serum rT3, the serum 3′-T1 levels of 2 hyperthyroid patients increased 59% and 82% above the baseline values of 9.0 and 8.8 ng/dl, respectively, 31 h after starting ingestion of dexamethasone (2 mg every 6 h). Serum 3′-T1 (and rT3) concentrations also increased transiently after each dose of sodium ipodate in 2 hyperthyroid patients given repeated oral doses of the drug (3 g every third day). 3′-T1 concentrations were examined in amniotic fluid (AF) at two stages of gestation. AF 3′-T1 concentration averaged (mean ± SD) 18 ± 6.7 ng/dl (n = 20) at 15–25 weeks gestation and 12 ± 3.6 ng/dl (n = 12) at 33–40 weeks gestation; the former value was significantly higher than the latter (P < 0.001), and both values were clearly higher than those in normal adult sera (P < 0.001). Pronase hydrolysates of 7 autopsy specimens of normal thyroid glands contained (mean ± SE) 502 ± 97.2 nmol T4 and 0.14 ± 0.03 nmol 3′-T1 per g wet wt tissue. The various data suggest that: 1) 3′-T1 is a normal component of human serum, AF, and the thyroid gland; 2) the serum 3′-T1 concentration usually changes in the same direction as serum rT3; and 3) extrathyroidal metabolism of T4 and rT3 is an important source of 3′-T1.