Measurements of Serum 3′,5′-Diiodothyronine and 3,3′-Diiodothyronine Concentrations in Normal Subjects and in Patients with Thyroid and Nonthyroid Disease:Studies of 3′,5′-Diiodothyronine Metabolism*

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Abstract
A RIA of 3′,5′-diiodothyronine (3′,5′-T2) in serum has been established using small Sephadex G-25 (fine) columns. The lower detection limit was 0.3 ng/dl, which was sufficiently low to measure the concentration of 3′,5′-T2 in all sera except three from hypothyroid patients (n = 13). The mean (±SD) serum 3′,5′-T2 concentration in 34 euthyroid healthy subjects was 3.9 ± 1.5 ng/dl. No difference was found between males and females, and the concentration was not influenced by age. The concentration in 27 hyperthyroid patients was 14.4 ± 5.6 ng/dl, and in 13 hypothyroid patients was 1.3 ± 1.0 ng/dl. Both values differed significantly from that found in controls (P < 0.01). Normal values were found in patients suffering from liver cirrhosis (n = 12), uremia (n = 11), disseminated malignancies (n = 13), and acute myocardial infarction (n = 13). Administration of propylthiouracil (n = 15), but not carbimazole (n = 8), to L-T4-substituted hypothyroid patients resulted in an increase of serum 3′,5′-T2 from 2.7 ± 1.1 to 3.8 ± 1.6 ng/dl (P < 0.01). Using a similar method serum 3,3′-T2 also was measured. The lower detection limit was 0.2 ng/dl, sufficiently low to measure the concentration in all sera except five from hypothyroid patients (n = 13). The mean (±SD) serum 3,3′-T2 concentration in the control group was 1.9 ± 0.8 ng/dl. No difference was found between males and females, while serum 3,3′-T2 decreased slightly with age (P < 0.05). The hyperthyroid group had elevated levels (7.8 ± 4.2 ng/dl), while the hypothyroid group showed decreased values (0.5 ± 0.4 ng/dl). Both values differed significantly from that found in controls (P < 0.01). Normal levels were found in the patients with liver cirrhosis, while significantly decreased values were found in the patients with uremia (0.5 ± 0.3 ng/dl), disseminated malignancies (1.1 ± 0.5 ng/dl), and acute myocardial infarction (1.2 ± 0.6 ng/dl). The administration of propylthiouracil, but not of carbimazole, led to a decrease in serum 3,3′-T2 from 2.2 ± 0.6 to 1.8 ± 0.6 ng/dl (P < 0.05). The extrathyroidal metabolism of 3′,5′-T2 was studied in five L-T4-substituted hypothyroid patients using a noncompartmental method. Radioactive 3′,5′-T2 was separated from radioactive iodine, iodoproteins, and 3′-T1 by means of gel and antibody separation. The mean metabolic clearance rate was 299 liters/ day-70 kg (range, 190-459 liters/day · 70 kg). The mean 3′,5′-T2 production rate was 12.6 μg/day-70 kg; the mean half-life time in serum was 10.6 h. (J Clin Endocrinol Metab48: 611, 1979)