thyronines and Kidney-Failure--Chronic

A simple and accurate method for estimation of the free fractions (FFT) of T4, T3, rT3, 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) in serum is presented. The method is based on ultrafiltration of serum pre-incubated with tracers of high specific activity, followed by purification of the ultrafiltrate on small Sephadex columns. The addition of tracer only dilutes serum negligible (about 5%) and the ultrafiltration procedure only removes about 7% of the volume of serum, thus probably not disturbing the equilibrium between the free and protein bound fraction of iodothyronine. Progressive reduction of tracer to less than 10% of the amount usually used did not reduce the FFT of any of the iodothyronines. In contrast, addition of T4 to serum led to an increase of all FFTs except that of 3',5'-T2. These data suggest that FFT of T4, T3, rT3 and 3,3'-T2 primarily is determined by the amount of T4 present in serum and that significant amounts of these iodothyronines are bound to TBG, whereas 3',5'-T2 possibly primarily is bound to albumin. The median FFT of T4, T3, rT3, 3,3'-T2 and 3',5'-T2 in serum from euthyroid subjects (n = 38) was: 0.030, 0.29, 0.14, 1.10 and 1.07%, respectively. The corresponding median free concentrations in pmol/l were: 30, 4.79, 0.59, 0.44 and 0.77, respectively. Pregnant women in 3rd trimester had normal levels of free T4, free T3 and free rT3, whereas the median free 3,3'-T2 was reduced in contrast to elevated median free 3',5'-T2.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Diiodothyronines; Female; Humans; Hyperthyroidism; Kidney Failure, Chronic; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Pregnancy; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Ultrafiltration

The present study evaluates the sequential extra-thyroidal monodeiodination of thyroid hormones through tri-, di-, and monoiodothyronines in chronic renal failure (CRF) in man. Simultaneous turnover studies of T4, T3, rT3, 3,5-diiodothyronine (3,5-T2), 3,3'-T2, 3',5'-T2, 3'5'-T2, and 3'-monoiodothyronine (3--T1) were conducted in six patients with CRF (creatinine clearance, 9-18 ml/min) using the single-injection, noncompartmental approach. Serum levels of T4, T3, and 3,5-T2 were reduced to two thirds of control levels (P less than 0.05), whereas serum rT3 and 3,3'-T2 levels were reduced to a minor degree. Serum 3'-5'-T1 was doubled (p less than 0.05). The MCRs of T4, rT3, and 3',5'-T2 were enhanced to 168%, 127%, and 187% of normal (P less than 0.05), respectively, whereas those of T3, 3,5-T2, 3,3'-T2, and 3'-T1 were unaffected. The mean production rates (PRs) of the iodothyronines in CRF were as follows (CRF vs. control values, expressed as nanomoles per day/70 kg): T4, 119 vs. 125; T3, 26 vs. 44 (P less than 0.01); rT3, 49 vs, 48; 3,5-T2, 3.5 vs. 7.2 (P less than 0.001); 3,3'-T2, 25 vs. 35 (P less than 0.01); 3',5'-T2, 25 vs. 14 (P less than 0.01); and 3'-T1, 39 vs. 30. Previous studies have demonstrated reduced phenolic ring (5'-) deiodination of T4 in CRF, which is supported by the present finding of unaltered PR of T4 and reduced PR of T3. In contrast the 5'-deiodination of T3 leading to the formation of 3,5-T2 was found unaffected by CRF, since the conversion rate (CR) of T3 to 3,5-T2 (PR 3,5-T2/PR T3) was unaltered (16% vs. 15% in controls). The tyrosylic ring (5-) deiodination of T4 to rT3 was unaffected in patients with CRF, the CR being 42% vs. 40% in controls, in contrast to an enhanced CR of rT3 to 3',5'-T2 (53% vs. 29%, P less than 0.01), which also is a 5-deiodination step. In conclusion, our data show that CRF profoundly changes the kinetics of all iodothyronines studied. Furthermore, our data are compatible with the existence of more than one 5'-deiodinase as well as more than one 5-deiodinase in man.

Topics: Adult; Aged; Diiodothyronines; Female; Humans; Iodine Radioisotopes; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Serum Albumin; Thyroid Hormones; Thyronines; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Binding, Competitive; Diiodothyronines; Fatty Acids, Nonesterified; Humans; Kidney Failure, Chronic; Radioimmunoassay; Renal Dialysis; Thyroid Function Tests; Thyronines; Thyroxine

Serum 3'monoiodothyronine (3'-T1) levels were estimated by means of a specific radioimmunoassay (RIA) preceded by an ethanol extraction. The recovery of 3'T1 was in mean (+/-SEM) 110 +/- 9%, and the lower detection limit was 23 pmol/l. Serum levels of 3'T1 in 34 euthyroid healthy subjects were (median (range)) 55 pmol/l (less than 23 - 168 pmol/l), in 13 hyperthyroid patients 133 pmol/l (70 - 265 pmol/l) (P less than 0.01) and in 13 hypothyroid patients less than 23 pmol/l (less than 23 - 68 pmol/l) (P less than 0.01). In 11 patients with chronic renal failure serum 3'-T1 levels were highly increased 285 pmol/l (115 - 1538 pmol/l) (P less than 0.01) and correlated inversely to creatinine clearance (R = -0.68, P less than 0.05). In patients with liver cirrhosis serum 3'-T1 levels were unaffected, whereas in 19 patients with endogenous depression studied before and after recovery from the depression serum levels decreased from 70 pmol/l (less than 23 - 248 pmol/l) to 30 pmol/l (less than 23 - 95 pmol/l) (P less than 0.01). Administration of propranolol 40 mg b.i.d. for 2 weeks did not affect serum 3'-T1 levels. The study shows that 3'-T1 is present in serum from euthyroid man and varies with thyroid function. Further, it is suggested that 3'-T1 in contrast to other iodothyronines primarily is eliminated by the kidneys.

Topics: Adult; Depression; Female; Humans; Hyperthyroidism; Hypothyroidism; Kidney Failure, Chronic; Male; Middle Aged; Propranolol; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adult; Blood Protein Disorders; Female; Goiter; Humans; Hyperthyroidism; Kidney Failure, Chronic; Proteinuria; Radionuclide Imaging; Thyroglobulin; Thyronines; Thyroxine

Topics: Adolescent; Adult; Blood Urea Nitrogen; Edema; Exophthalmos; Eye Manifestations; Female; Humans; Hyperthyroidism; Kidney Failure, Chronic; Long-Acting Thyroid Stimulator; Male; Middle Aged; Nephrectomy; Ophthalmoscopy; Pituitary Gland; Pituitary Hormone-Releasing Hormones; Renal Dialysis; Thyroid Function Tests; Thyroid Gland; Thyronines; Thyrotropin; Thyroxine-Binding Proteins; Uremia