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Evaluation of serum triiodothyronine and adjusted triiodothyronine (free triiodothyronine index) in pregnancy.

We measured serum thyroxine (free and total), triiodothyronine (free and total), thyroxine-binding globulin, and triiodothyronine uptake by talc in 97 normal men and 50 pregnant women. Mean serum thyroxine and triiodothyronine concentrations were higher in the pregnant subjects (104 vs. 78 mug/liter and 1.69 vs. 1.30 mug/liter) because of a higher mean thyroxine-binding globulin concentration (70 vs. 38 mg/liter). Mean triiodothyronine uptake by talc was lower in the pregnant subjects (0.82 vs. 1.03). Mean free thyroxine concentrations were similar in the two groups, but mean free triiodothyronine concentrations were 10% lower in the pregnant subjects. Triiodothyronine uptake by talc and the diayzable thyroxine and triiodothyronine fractions were highly correlated (r = 0.85 and r = 0.82, P less than 0.001). Calculated free thyroxine index and free triiodothyronine index values (hyroxine and triiodothyronine indirectly adjusted, using triiodothyronine talc uptake to compensate for differences in thyroxine-binding globulin concentration), were statistically similar (84 vs. 82 and 1.38 vs. 1.34) in pregnant and male subjects. The results indicate that the total triiodothyronine concentration can be normalized on the basis of the triiodothyronine uptake by talc to correct for variations in thyroxine-binding globulin concentration.

Adolescent↗

Contributions of plasma triiodothyronine and local thyroxine monodeiodination to triiodothyronine to nuclear triiodothyronine receptor saturation in pituitary, liver, and kidney of hypothyroid rats. Further evidence relating saturation of pituitary nuclear triiodothyronine receptors and the acute inhibition of thyroid-stimulating hormone release.

Injections of triiodothyronine (T(3)) and thyroxine (T(4)) into chronically hypothyroid rats were used to evaluate the contribution of intracellular T(4) to T(3) conversion to nuclear T(3) in pituitary, liver, and kidney, and to correlate the occupancy of pituitary nuclear T(3) receptors with inhibition of thyroid-stimulating hormone (TSH) release. Injection of a combination of 70 ng T(3) and 400 ng T(4)/100 g body wt resulted in plasma T(3) concentrations of 45+/-7 ng/dl (mean+/-SD) and 3.0+/-0.4 mug/dl T(4) 3 h later. At that plasma T(3) level, the contribution of plasma T(3) to the nuclear receptor sites resulted in saturation of 34+/-7% for pituitary, 27+/-5% for liver, and 33+/-2% for kidney. In addition to the T(3) derived from plasma T(3), there was additional T(3) derived from intracellular monodeiodination of T(4) in all three tissues that resulted in total nuclear occupancy (as percent saturation) of 58+/-11% (pituitary), 36+/-8% (liver), and 41+/-11% (kidney), respectively. The percent contribution of T(3) derived from cellular T(4) added 41% of the total nuclear T(3) in the pituitary which was significantly higher than the contribution of this source in the liver (24%) or the kidney (19%). 3 h after intravenous injection of increasing doses of T(3), the plasma T(3) concentration correlated well with both the change in TSH and the nuclear occupancy, suggesting a linear relationship between the integrated nuclear occupancy by T(3) and TSH release rate. The contribution of intrapituitary T(4) to T(3) conversion to nuclear T(3) was accompanied by an appropriate decrease in TSH, supporting the biological relevance of nuclear T(3). Pretreatment of the animals with 6-n-propylthiouracil before T(4) injection decreased neither the nuclear T(3) derived from intrapituitary T(4) nor the subsequent decrease in TSH. These results indicate that intracellular monodeiodination of T(4) contributes substantially to the nuclear T(3) in the pituitary of the hypothyroid rat, and suggest a linear inverse relationship between nuclear receptor occupancy by T(3) in the pituitary and TSH release rate. The data further indicate that T(4) to T(3) monodeiodination is considerably more important as a source of nuclear T(3) in the pituitary than in the liver and kidney. This provides a mechanism whereby the TSH secretion could respond promptly to a decrease in thyroid secretion (predominantly T(4)) before a decrease in plasma T(3) would be expected to lead to significant metabolic hypothyroidism.

Animals↗

No inhibition by Li+ of thyroxine monodeiodination to 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine (reverse triiodothyronine).

The possibility that lithium affects the conversion of thyroxine to 3,5,3"-triiodothyronine and 3,3',5'-triiodothyronine (reverse triiodothyronine) was studied by measurement of the serum concentractions of these parameters in five patients during the first week of lithium therapy. In three patients there was a decrease in serum thyroxine concentration and a slightly less pronounced decrease in that of serum 3,5,3'-triiodothyronine. In two patients, who also received L-tryptophan or flupentixol, no change was noted in the concentrations of these compounds. There was no increase in serum 3,3',5'-triiodothyronine concentration in any of the patients. No systematic change was found in the serum concentrations of thyrotropin or unsaturated thyroid-hormone binding proteins. The results obtained do not support the contention that lithium should inhibit the monodeiodenation of thyroxine to its active and inactive metabolites.

Adult↗

Relation of triiodothyronine and reverse triiodothyronine administration in rats to hepatic L-triiodothyronine aminotransferase activity.

The effects of administration of 3,5,3'-triiodothyronine (T3) to normal and to hypothyroid male rats upon the hepatic activity of L-triiodothyronine aminotransferase were determined using 3,5-dinitro-L-tyrosine as substrate in the assay. Initial studies in normal rats demonstrated that basal enzyme activity was highest in liver and kidney of the organs tested, and that virtually no activity was detectable in skeletal muscle, serum, thyroid or pituitary gland. Hepatic enzyme activity increased from birth to a peak at 80-120 days and declined thereafter. Daily administration of T3 to normal rats in doses of 5 mug/100g BW for 8 days significantly elevated hepatic enzyme activity above normal. In daily doses of 2.5mug/100g BW, T3 restored the depressed enzyme activities in hypothyroid rats to normal. Daily administration of 3,3',5'-triiodothyronine (reverse T3) to normal rats in doses of 17.5 mug/100g BW and greater for 3 days increased L-T3 aminotransferase activity more than 30% above normal levels. Reverse T3 appeared to be approximately as active as T3 in increasing the hepatic activity of L-T3 aminotransferase.

Aging↗

Simultaneous measurement of free thyroxine and free 3,5,3'-triiodothyronine in undiluted serum by direct equilibrium dialysis/radioimmunoassay: evidence that free triiodothyronine and free thyroxine are normal in many patients with the low triiodothyronine syndrome.

UNLABELLED: We have devised a practical, sensitive and specific method for simultaneous measurement of free thyroxine (FT4) and free triiodothyronine (FT3) in undiluted serum by direct equilibrium dialysis radioimmunoassay (RIA). Two hundred microliters serum sample was dialyzed against buffer (pH 7.4) for 20 hours at 37 degrees C and approximately 800 microL of the dialysate was used for measuring FT4 and FT3 simultaneously. The assay was set up in polystyrene tubes coated with anti-T4 antibody and available commercially for FT4 measurement (Quest-Nichols Institute, San Juan Capistrano, CA). The mean +/- SE (range) FT4 concentration (ng/dL) was 1.2 +/- 0.04 (0.7.0 to 2.30) in 54 normal subjects. It was significantly increased (3.6 +/- 0.4 [1.8 to 9.6], n = 20) in hyperthyroidism and clearly decreased (0.40 +/- 0.04 [1.10 to 0.70], n = 26] in hypothyroidism. All nonthyroid illness (NTI) patients had normal FT4 except 3, 2 of whom were on amiodarone and 1 had received heparin. Serum FT4 concentration was minimally elevated in 18 newborn cord blood serum (1.40 +/- 0.08 [0.90 to 2.2], cf. normal p < .05). The mean serum FT3 concentration (pg/dL) was 285 +/- 10 (134 to 454) in 54 normal sera. It was clearly increased in hyperthyroidism (1033 +/- 98 [593 to 2134], n = 20, p < .001). However, serum FT3 varied widely in hypothyroidism (27 to 597, mean 235 +/- 24, NS) as did serum total T3 (19 to 175). Interestingly, however, the mean serum FT3 concentration was normal (273 +/- 28 [62 to 575, NS]) in 25 NTI patients. All of these patients had low serum total T3 (46 +/- 5.0 [10 to 84], ng/dL; normal 84 to 160, p < 0.001), while FT3 was clearly normal in 21 of 25 patients and low in the remaining 4 patients. Similarly, among 18 newborn cord blood sera serum FT3 concentration was normal in 15 and subnormal only in the remaining 3 while all had clearly subnormal total T3 (28 to 74 ng/dL). CONCLUSIONS: (1) A practical, sensitive, and specific assay for simultaneous measurement of FT4 and FT3 is described; (2) FT3 is consistently elevated in hyperthyroidism while FT4 is elevated in most (approximately 85%) cases; (3) FT4 is consistently decreased in hypothyroidism but FT3 varies widely; (4). Serum FT3 concentration is normal in approximately 83% of patients with the low T3 syndrome in NTI and newborn cord blood serum. These data suggest that normal FT3 may explain clinical euthyroidism in many patients with the low T3 syndrome.

Dialysis↗

[Triiodothyronine, reverse-triiodothyronine, thyroxine, resin-triiodothyronine-uptake and protein bound jodide in the fluid of thyroid cysts (author's transl)].

T3, rT3, T4, PBI and the saturation of T3-T4-binding proteins in yellow and brown cyst fluids of nontoxic goiters differ from the values in sera. In the brown cyst fluids, resulting from a hemorrhage, T3, rT3, T4, PBI and T3 U are significantly higher than in sera and no correlation could be found with the values in sera. In the yellow cyst fluids T3 and T3 U are significantly higher then in sera, T4 is lower, PBI and rT3 do not differ from the values in sera. Only T3 and rT3 are not correlated. Various reasons for higher concentrations of hormones in the cyst fluid such as destruction of thyroid follicles and lymphvessels, a high protein concentration and direct secretion of hormones and iodoproteins from thyroid tissue in the cyst wall into the cyst fluid are taken into consideration. As these hormones in the cyst fluid may be absorbed, the results are also of clinical value.

Blood Proteins↗

[Behavior of the levels of free triiodothyronine, triiodothyronine, free thyroxine, thyroxine, thyrotropin and thyroxine-binding globulin in the serum of children with nephrotic syndrome].

Concentrations of free triiodothyronine, triiodothyronine, free thyroxine, thyroxine, thyrotropin, thyroxine-binding globulin, urea, creatinine, cholesterol and total protein were determined in serum of four children (ages from 8 to 16 years) with nephrotic syndrome undergoing therapy. The results showed that at serum protein concentration of less than 4.5 g/dl the concentration of free thyroxine was 3.35 +/- 2.32 pg/ml and that of free triiodothyronine 2.65 +/- 0.96 pg/ml. Elevation of the protein concentration to 4.5-5.7 g/dl lead to an increase in the concentration of free thyroxine to 6.53 +/- 3.69 pg/ml and of free triiodothyronine to 3.32 +/- 1.08 pg/ml. The age-matched reference values for free thyroxine are 15.72 +/- 1.9 pg/ml and for free triiodothyronine 5.10 +/- 1.29 pg/ml. The concentration of thyroxine, triiodothyronine and thyroxine-binding globulin were decreased whereas that of thyrotropin was elevated. Although free triiodothyronine and triiodothyronine were decreased they remained close to the normal range thus preventing apparent hypothyroidism. Improvement in the concentration of serum protein and cholesterol lead to an improvement of serum levels of thyroid hormones and thyroxine-binding globulin; concentrations of thyrotropin remained elevated.

Adolescent↗

Thyroxine, triiodothyronine, reverse-triiodothyronine, and other physiological characteristics of periparturient cows fed restricted energy.

Eighty-six cows were assigned to two equal groups with group A fed according to National Research Council recommendations for total digestible nutrients for the 8 wk before parturition and group B was fed 21% higher energy in the first 6 wk and 15% higher in the last 2 preparturient wk. Thyroxine in blood serum decreased in both groups 14 days before and on the day of delivery. It was significantly lower in group A. Findings were similar with triiodothyronine. Blood serum concentrations of reverse-triiodothyronine of group A was significantly higher in group A on day 28 and 14 than group B before delivery. Energy intake had little influence on the serum concentrations of other constituents (albumin, total protein, immunoglobulin G, total and free cholesterol, nonesterified fatty acids). Restricted energy intake that does not alter thyrotropin-thyrotropin-releasing hormone secretion results in higher rate of production of reverse-triiodothyronine and in decreased serum concentration of triiodothyronine. Slight changes of energy balance might be indicated readily by reverse-triiodothyronine concentration in blood serum.

Animal Nutritional Physiological Phenomena↗

Changes of circulating thyroxine, triiodothyronine and reverse triiodothyronine after radiographic contrast agents.

Thyroid function was studied for 42 days in 58 patients, 28 of whome had euthyroid goiter, after urography (diatrizoic acid), cholangiography (ioglycamic acid), and cholecystography (Naiopanoate). After urography and cholangiography short-lived increases of the serum thyroxine occurred in a few patients, but the mean thyroxine and triiodothyronine concentration did not change. By contrast, 7 days after oral cholecystography serum thyroxine had risen consistently by 22% with a concomittant rise of the free thyroxine, while triiodothyronine declined by 15%. The thyroxine metabolite 3,3',5'-triiodo-1-thyronine (reverse T3) rose by 50% and serum thyrotropin concentration doubled. After 42 days thryoxine and triiodothyronine had returned to baseline, and none of the 58 patients developed clinical hyperthyroidism. In patients with severe myxoedema kept on a constant replacement dose with 1-thyroxine NA-iopanoate produced similar changes with the exception of the rise of the serum thyroxine. The primary event after Na-iopanoate seems to be a fall of the serum triiodothyronine, which in turn augments thyrotropin and indirectly thyroxine secretion. the marked and sometimes sustained rose of serum thyroxine after cholecystography may lead to the erroneous diagnosis of hyperthyroidism.

Adult↗

Transient elevation of triiodothyronine caused by triiodothyronine autoantibody associated with acute Epstein-Barr-virus infection.

A unique 16-year old female patient presented after acute Epstein-Barr virus (EBV) infection with severe primary hypothyroidism. Her thyroid test results were thyrotropin level (TSH) of 198 mU/L (normal, 0.4-4 mU/L), free thyroxine [FT(4)], 2.5 pmol/L (normal, 10-25 pmol/L), total triiodothyronine (TT(3)) > 19.5 nmol/L (normal, 1.3-2.7 nmol/L), and free triiodothyronine (FT(3)), 0.77 pmol/L (normal, 3.3-6.3 pmol/L). She had high titers of thyroglobulin and thyroid peroxidase autoantibodies. In vitro triiodothyronine (T(3))-binding measured by radioimmunoprecipitation was 86% (normal, up to 8.5%) and thyroxine (T(4))-binding 8.2% (normal, 6.4%). Serum immunoglobulin G (IgG) absorption, achieved by protein-G Sepharose beads, decreased TT(3) toward normal. Levothyroxine treatment normalized the low baseline FT(4) and FT(3) values, and suppressed TSH to normal. However, TT(3) remained highly elevated and returned to normal after 20 months, while T(3 )binding gradually decreased. Thus, her severe hypothyroidism was masked by this unusual phenomenon. Thirty-four patients with EBV infection (15 with acute disease and 19 with previous infection) were tested for thyroid hormone levels. EBV antibodies (early antigen immunoglobulin M [IgM] and IgG and anti-Epstein-Barr virus nuclear antigen [EBNA] IgG) were measured by enzyme-linked immunosorbent assay (ELISA). In 15 patients with acute EBV the mean TT(3) level was 2.47 +/- 0.39 nmol/L (5 had TT(3) values above normal) compared to a mean TT(3) of 1.70 +/- 0.53 nmol/L in 19 subjects with previous infection (p < 0.0005; only 1 had a TT(3) result above normal), with no differences in FT(4) and TSH concentrations between the two groups. Acute EBV infection may be associated with transient mild to severe TT(3) elevation as a result of assay interference by anti-T(3) autoantibodies.

Acute Disease↗

Extrathyroidal conversion of thyroxine to 3,3',5'-triiodothyronine (reverse-T3) and to 3,5,3'-triiodothyronine (T3) in humans.

In order to estimate the relative magnitude of the two alternative pathways of monodeiodination of thyroxine (T4) in adult humans, the metabolic clearance rates (MCR) and production rates (PR) of 3,3',5'-triiodothyronine (reverse-T3,rT3) and of 3,5,3'-triiodothyronine (T3) were determined in six euthyroid control subjects (C) and in five hypothyroid patients (H) receiving L-T4 as replacement therapy (0.15-0.3 mg/day). MCR was computed by a non-compartmental method of analysis from the plasma disappearance of 125I rT3 and 131I T3 during 72 h following simultaneous injection of tracers. PR was calculated from MCR and the serum concentration of rT3 and T3, respectively, determined by radioimmunoassay. In the H subjects, rT3 MCR averaged 97.1 +/- 12.8 (SD) 1/day and rT3 PR, 34.3 +/- 12.8 microng/day; T3 MCR was 28.7 +/- 6.1 1/day and T3 PR, 20.3 +/- 6.6 microng/day (all corrected to 70 kg body weight). These results were not significantly different from those in the control group; rT3 MCR 104 +/- 24 1/day, rT3 PR 33.0 +/- 9.2 microng/day; T3 MCR 24.0 +/- 5.9, T3 PR 24.2 +/- 4.1. The proportionof total triiodothyronine (rT3 averaged 62% in H patients and was similar (57%) in the C group. The results obtained in the H subjects indicate that the production of rT3 is a major route of T4 metabolism, equal to or exceeding that of T3. From the close agreement between the mean values for rT3 PR in the C and H groups it is concluded that most, if not all of the rT3 produced in normal humans is derived by extrathyroidal conversion from T4.

Aged↗

The relative distribution of thyroxine, triiodothyronine and 3,3',5'-(reverse)-triiodothyronine in various fractions of thyroglobulin.

Thyroglobulin fractions rich and poor in new thyroglobulin were separated by means of DEAE-cellulose chromatography of dog thyroid extracts and by zonal ultracentrifugation in a sucrose gradient of guinea pig thyroid extract incubated at low temperature. The distrubtion of thyroxine, triiodothyronine and 3,3',5'-(reverse)-triidothyronine in hydrolysates of the different fractions was estimated by radioimmunoassays. Following DEAE-cellulose chromatography there was a small but statistically significant increase in T4/T3 ratio in thyroglobulin fractions eluted at high ionic strength--that is fractions relatively rich in stable iodine but poor in fresh thyroglobulin. There was no differences in the T4/rT3 ratios between the different fractions. The ratios between iodothyronines were almost identical in the various thyroglobulin fractions following zonal ultracentrifugation in a sucrose gradient of cold treated guinea pig thyroid extract. These findings lend no support to the possibility that a relatively high content of triiodothyronines in freshly synthesized thyroglobulin modulates the thyroid secretion towards a preferential secretion of triiodothyronine and 3,3',5'-(reverse)-triidothyronine at the expense of the secretion of thyroxine.

Animals↗

[Measurement of free triiodothyronine (FT3) using an electrochemiluminescence immunoassay in patients with autoantibodies to triiodothyronine].

Thyroid hormone autoantibodies may lead to abnormal values of free triiodothyronine (FT3) and free thyroxine (FT4) by interference with the radio immunoassay (RIA). We examined thyroid function in six patients with known triiodothyronine-binding autoantibodies using a RIA and an electro-chemiluminescence immunoassay (ECLIA). FT3 values measured by RIA were spuriously high, ECLIA measurement of FT3 led to correct values according to the patients' thyroid status. We conclude from these results that in patients with triiodothyronine-binding autoantibodies FT3 measurement by ECLIA is more useful than measurement by RIA.

Adult↗