Peak T3 Research Articles

Thyroid hormone levels after acute L-thyroxine loading in hypothyroidism.

While extrathyroidal conversion of T4 to T3 sustains circulating T3 blood levels in patients receiving maintenance doses of L-T4, the serum T3 rise after the acute administration of large doses of L-T4 may involve an additional mechanism, T3 contamination in L-T4 preparations. L-T4 (1000 micrograms; Synthroid) was given orally to four noncompliant hypothyroid individuals (mean T4, 1.0 micrograms/dl; mean T3, 28 ng/dl). Continuously withdrawn blood sampling revealed a mean rise in serum T4 to 7.7 micrograms/dl at 4 h and a parallel rapid mean rise in serum T3 to 66 ng/dl (136% over baseline) at 4 h. RIA analysis of the experimental batches of Synthroid revealed 0.7-0.9% T3 contamination. Oral administration of 5 or 10 micrograms Cytomel (T3; corresponding to 0.5% and 1% T3 contamination in 1000 micrograms Synthroid) to two of the hypothyroid subjects at a later date resulted in T3 serum elevations 12% and 68% as great as post 1000 micrograms L-T4. To eliminate basal hormone changes between these experiments, a third subject received 7.5 micrograms Cytomel on day 1 (corresponding to the measured T3 contamination in 1000 micrograms Synthroid), followed by 1000 micrograms Synthroid on day 2. Resulting peak T3 levels were identical. In summary, hypothyroid individuals rapidly absorb acute L-T4 loads, with parallel increases in T4 and T3 blood levels. The major source of this T3 elevation is the contaminant in L-T4 preparations. This degree of T3 contamination becomes clinically significant in acute large dose T4 regimens and results in euthyroid levels of T3.

Twenty-four hour variations of triiodothyronine (T3) levels in patients who had thyroid ablation for thyroid cancer, receiving T3 as suppressive treatment.

Measurements of serum triiodothyronine (T3) concentrations were made in 46 patients who had thyroid ablation for thyroid cancer and who were receiving T3 three times a day as suppressive treatment. In all patients thyrotropin (TSH) suppression was confirmed by the inhibition of TSH response to thyrotropin releasing hormone (TRH). The suppressive dose of T3 varied from 40 to 100 micrograms/day (mean +/- SD 72.39 +/- 13.07 micrograms/day). Related to body weight the dose varied from 0.95 to 1.35 micrograms/kg/day (mean +/- SD 1.13 +/- 0.13 micrograms/kg/day). In ten hospitalized patients serum T3 levels were measured at hourly intervals from 08:00 to 23:00. Before the first dose of T3, serum T3 levels were 153 +/- 43 mg/100 ml; after T3 the levels increased promptly reaching after 4 h a peak of 264 +/- 90 ng/100 ml. Afterwards T3 levels showed a similar peak after each dose: 262 +/- 77 and 266 +/- 78 ng/100 ml, slightly decreasing in the intervals between the doses: 227 +/- 63 and 255 +/- 69 ng/100 ml. After the last peak T3 levels showed a slow decline during the night. TSH response to TRH was completely inhibited both at 08:00 and at 16:00. In 36 outpatients T3 levels were measured twice a day and T3 levels were found similar to the ones of the first group. In these patients also TSH response to TRH evaluated at 08:00 was completely inhibited. No important side effect was noted in both groups of patients.

Evidence That Triiodothyronine and Reverse Triiodothyronine Are Sequentially Deiodinated in Man*

We have demonstrated that in patients given a single iv injection of T3, rT3, or, to a lesser extent, T4, all labeled with 125I in the outer or phenolic ring, chromatography of serum on columns of Sephadex G-25 superfine revealed the presence of a labeled material, separate from the administered hormone and from both iodide and iodoprotein. This peak has been termed pre-T3 because it elutes just before the T3 peak. Identification of the various compounds in pre-T3 was carried out by cation exchange chromatography. Pre-T3 generated from [125I]T3 consistently contained labeled compounds with the chromatographic behavior of 3,3'-diiodothyronine and 3'-monoiodothyronine, while pre-T3 generated from [125I]rT3 contained labeled products with the chromatographic mobility of 3',5'-diiodothyronine, 3,3'-diiodothyronine, and 3'-monoiodothyronine. In addition, pre-T3 also contained the glucuro- and sulfoconjugates of these several labeled products. These studies demonstrate that T3 and rT3 undergo progressive and probably sequential deiodination in the peripheral tissues, resulting in the formation of a variety of diiodothyronines and monoiodothyronine, as well as their glucuro- and sulfoconjugates.

Plasma Thyroxine and Triiodothyronine Levels in Spontaneously Metamorphosing Rana catesbeiana Tadpoles and in Adult Anuran Amphibia*

We have developed sensitive and reliable radioimmunoassays for T4 and T3 in amphibian plasma and have used these procedures to measure plasma T4 and T3 levels in spontaneously developing Rana catesbeiana tadpoles at various stages of metamorphosis. During premetamorphosis circulating levels of both T4 and T3 were below the limits of detection of the RIA procedures (T4 less than 50 ng/100 ml, T3 less than 5 ng/100 ml). A gradual rise in plasma T3 and T4 became apparent during prometamorphosis, and at the onset of metamorphic climax the levels of both T4 and T3 increased sharply. Peak levels for both hormones were observed in the middle of metamorphic climax (stage XXIII). The circulating T3 level reached a mean peak of 78 ng/100 mg, at least 15 times greater than the level during premetamorphosis. The peak T4 level was 0.5 microgram/100 ml, about a 10-fold increase over the premetamorphosis level. The surge in thyroid hormone secretion lasted only for several days, and during the latter half of metamorphic climax there was a fairly rapid decrease in plasma T4 and T3. By 2 days post-climax the levels had declined to about 20% of their peak values. Free T4 and T3 levels in plasma followed the same general pattern as the total hormone levels during the various stages of tadpole development. In adult R. catesbeiana, plasma T4 and T3 levels were surprisingly low. Similarly low values were observed in Bufo marinus and in Rana pipiens. The very low levels of circulating T4 and T3 both in premetamorphosis tadpoles and in adults suggest that thyroid hormones in anuran Amphibia may be of importance only during the period of metamorphosis.

Ontogenesis of thyroid function in the neonatal rat. Thyroxine (T4) and triiodothyronine (T3) production rates.

The ontogenesis of thyroxine (T4) and triiodothyronine (T3) production in the neonatal rat (from 5 days to adulthood) was examined by measuring [125I]T4 and [125I]T3 kinetic parameters by single-compartmental analysis. T4 and T3 serum concentrations were measured by specific radioimmunoassay. The volume of distribution (VD) and the metabolic clearance rate (MCR) of T4, high at 5 days, increase to a peak at 22–26 days and decline to adult values. The T4 production rate (PR) low at 5 days, increases to peak values at 14 to 32 days and then declines toward adult values. The T4 fractional removal rate (K) is similar from birth to adulthood. No difference is observed for K, VD and MCR of T3 during the life of the rat. The T3 PR rises from minimal values at 5 days to attain peak values at 26 days. There is therefore a delay of about 12 days between the peak of T4 PR and the attainment of the peak T3 PR. The T4/T3 PR ratio decreases from a maximal value at 5 days to values approaching those seen in the adult at ...

Serum Triiodothyronine Measurements by the Sterling Method : A Critical Evaluation

The Sterling method for measurement of triiodothyronine (T3) in serum has been modified to improve separation of thyroxine (T4) and T3 by prolonging the time of chromatography. By altering the elution procedure, less unwanted competitive binding material was eluted from the paper strips, resulting in a lower “blank effect” in the zero tube of the binding assay. A more sensitive binding assay was found by using a granular resin (Rexyn 202, Cl-SO4, Fisher) and lowering the serum concentration in the binding solution. Possible sources of error were evaluated and their magnitude was calculated. Deiodination of T4 to T3 occurs during the assay procedure, but it is small in the range of normally occurring T4 levels (about 0.5% of T4). Contamination of the T3 peak with T4 (or other deiodination products) can be avoided if proper care is taken during chromatography. When the immunoassay procedures are not readily available, this assay can give valuable information to the physician confronted with a difficult diagnostic problem in a patient suspected to have disease of the thyroid gland.