[Automated recording of precision profiles for the radioimmunological determination of T4 using a pocket calculator of the HP-41 CV type]. / Obtention automatisée des profils de précision des dosages radioimmunologiques de T4 à l'aide d'une calculatrice de poche de type HP-41 CV.

Precision profiles as useful tool for assurance of assay quality in 10 independent T4RIAs have been automatically obtained using a small programmable pocket calculator HP-41 CV. For each T4 assay batch, the within-assay coefficient of variation varied from 7 to 11% in the hormone concentration range of 2 to 20 micrograms/dl. The difference in coefficient of variation for all the 10 successive assay batches of T4, never exceeded 1% in the same hormone concentrations regions. All the above findings demonstrate that the precision profile can be used as a powerful tool for assessing the assay quality and consistency of overall random error between successive assay batches.

Meaning of serum free-thyroxin values in nonthyroidal illnesses: seven methods compared.

Serum free thyroxin (FT4) was determined in 40 patients with various nonthyroidal illnesses. We studied seven methods: (1) a free thyroxin index calculated from total T4 and triiodothyronine resin uptake; (2) a free T4 index determined by enzyme inhibitor assays (Abbott's "Tetrazyme" and "Thyrozyme"); (3) a free T4 index calculated from total T4 and thyroxin-binding globulin; (4) free T4 by equilibrium dialysis; (5) Amersham's free T4 RIA; (6) Clinical Assays' one-step free T4 RIA; and (7) Clinical Assays' two-step free T4 RIA. Approximately half of the free T4 results were in the euthyroid range and the other half in the hypothyroid range by methods 1, 2, 5, and 6. Results for free T4 by methods 3 and 7 were similar to those by equilibrium dialysis (method 4), the percentages of patients with results in the euthyroid range being 68%, 65%, and 76%, respectively.

Clinical evaluation of two direct procedures for free thyroxin, and of free thyroxin index determined nonisotopically and by measuring thyroxin-binding globulin.

We have investigated the clinical utility of two direct radioimmunoassays for free thyroxin, an enzyme-inhibition immunoassay, and a direct measurement of thyroxin-binding globulin (TBG) by radioassay. All assay methods correctly identified greater than or equal to 90% of euthyroid, hyperthyroid, and hypothyroid patients who had normal TBG concentrations. In patients with altered TBG concentrations, none of the assays correctly classified all categories of patients. However, the direct assays of free thyroxin concentrations were able to classify correctly more patients with altered TBG concentrations than did the free thyroxin index methods. The free thyroxin index methods evaluated may be acceptable for routine use, if the concentration of thyroxin and the measurement of TBG capacity are reported along with the index value. Patients with altered TBG concentrations included a group of euthyroid pregnant patients. Significant decreases in free thyroxin in the third trimester were detected by all the assays studied. For patients in the first and second trimester, the mean free thyroxin concentration measured varied with the assay method.

Clinical assessment of a radioimmunoassay for free thyroxine using a modified tracer.

A radioimmunoassay for measuring free thyroxine in plasma was introduced by Amersham using a I-125-labeled T4 derivative that does not bind significantly to the thyroxine-binding proteins. We evaluated this RIA for its clinical utility in assessing 278 patients with thyroid and nonthyroidal diseases. The precision of the Amerlex free T4 assay, expressed as coefficient of variation, was 20% at 0.16 ng/dl, 6.9% at 0.55 ng/dl, 4.2% at 1.08 ng/dl, 5.3% at 2.29 ng/dl, and 6.3% at 3.18 ng/dl. A reference range for free T4 was established as 0.68-1.8 ng/dl, n = 171. The correlation coefficients (r) of a dialysis method and a free thyroxine index were 0.871 and 0.911, respectively. Free T4 correctly classified 98% euthyroid, 92% hypothyroid, 100% hyperthyroid, 100% euthyroid with elevated TBG, and 87% of phenytoin patients. In addition, 80 patients with acute nonthyroidal illness were studied. Most of these patients have normal to low free T4, very low T3, and elevated rT3. We found this free T4 assay to be precise, easy to perform, and reliable in classifying thyroid status in most patients.

Chemical hyperthyroidism: serum triiodothyronine levels in clinically euthyroid individuals treated with levothyroxine.

We have observed many patients treated with levothyroxine sodium who have elevated serum thyroxine (T4) levels but appear clinically euthyroid. Such patients generally have normal serum triiodothyronine (T3) values. A retrospective review at The Johns Hopkins Hospital, Baltimore, comparing the correlation of T3 and T4 values in levothyroxine-treated patients with that in patients not so treated was carried out from 1977 to 1979. Mean free thyroxine index (FTI) value in 104 levothyroxine-treated patients was 4.70 +/- 0.2 and mean T3 value was 177 +/- 9 ng/dL. In a group of 50 hyperthyroid patients, mean FTI value was 7.26. +/- 0.5, with a mean T3 value of 389 +/- 26 ng/dL. In 71 euthyroid patients, mean FTI value was 2.36 +/- 0.1, with a T3 value of 137 +/- 3 ng/dL. Computed ratios of T3 to FTI and T3 to T4 were significantly lower in the group treated with levothyroxine than in either the hyperthyroid or euthyroid nontreated groups. Levothyroxine-treated patients with high T4 levels but normal T3 levels were clinically euthyroid. Patients not treated with levothyroxine with similarly elevated T4 levels had elevated T3 levels and were clinically hyperthyroid. It is concluded that lower relative T3 levels in levothyroxine-treated patients may explain why these patients appear clinically euthyroid despite elevated T4 values. Serum T3 determination is the procedure of choice for evaluation of levothyroxine-treated individuals. Furthermore, an elevated FTI value in such an individual does not, in itself, dictate need to reduce dosage.

Liver aldolase anomeric specificity.

Stopped-flow kinetic studies of liver aldolase and of mixed liver-muscle aldolase catalyzed reactions of fructose 1,6-bisphosphate (FBP) have been carried out and interpreted by computer simulation. These experiments indicate no utilization or binding of the alpha anomer by the liver enzyme unlike the findings for either the muscle aldolase which binds the alpha anomer nonproductively or the yeast aldolase which catalyzes its cleavage. Both beta-fructose 1,6-bisphosphate and its acyclic keto form may serve as substrates, necessitating the spontaneous anomerization of the alpha anomer before its utilization. Thus, liver aldolase cleaves 100% of the substrate present in the millisecond time scale because of the inability to bind alpha-FBP, allowing rapid spontaneous anomerization. This result fulfills earlier predictions of the differing specificities and substrate binding properties for aldolases from yeast, muscle, and liver.