Total and free serum concentrations of thyroxine and triiodothyronine were measured in 122 subjects with hypothyroidism who were clinically well while receiving conventional replacement treatment with thyroxine. In a third of patients concentrations of total and free thyroxine were raised, often considerably; nevertheless concentrations of total and free triiodothyronine were usually normal. Though significant correlations were obtained between total triiodothyronine concentrations and total thyroxine concentrations (p <0 001) and between the triiodothyronine concentrations and free thyroxine concentrations (p<0001) the slope of the line of the regression equation describing these correlations was small, hence large increases in both total and free thyroxine concentrations were accompanied by only modest increases in total and free triiodothyronine concentrations.The presence of total or free thyroxine concentrations above normal in patients taking thyroxine therefore are not necessarily ofclinical consequence. In the assessment of adequacy of replacement treatment with thyroxine the most logical combination of in vitro thyroid function test results may be a normal thyrotrophin concentration and normal free triiodothyronine concentration.
SUMMARY1. The rise of plasma glucose consequent upon the release of adrenaline following the systemic administration of 3-O-methylglucose is prevented by previous infiltration with lignocaine of the lateral hypothalamic area on both sides.2. The similarity between this effect and that of the same procedure in preventing the hypersecretion of gastric acid in response to the same stimulus, together with the known fact that hypoglyeaemia or the systemic administration of some glucose analogues produce both gastric and adrenal medullary hypersecretion, provides strong presumptive evidence that there exists in the lateral hypothalamic area a chemoreceptor which controls the release of adrenaline. The cells of this receptor like those of the chemoreceptor controlling gastric acid secretion, are activated by an insufficiency of metabolizable glucose.
Two euthyroid subjects with high total concentrations of T4 in their sera have been studied (J.D.: T4, 170; T3, 1.90; rT3, 0.54 nmol/l. E.T.: T4, 185; T3, 1.63; rT3, 0.37 nmol/l). Concentrations of all three T4-binding proteins were within normal limits in both cases. However, on reverse-flow electrophoresis an abnormally large amount of thyroxine was found to travel with albumin. The three T4-binding proteins in the sera of both patients were separated from each other by a novel affinity chromatographic method using dye-Sepharose conjugates. Affinity constants for T4 binding to TBG and to prealbumin from both patients were normal. The albumin preparations were further purified and shown by physical and immunochemical techniques to be uncontaminated by other proteins. Scatchard plots of the binding of T4 to each of these pure albumins revealed two components, one having a normal affinity constant (J.D., 1.8 x 10(5) lmol-1 and E.T., 2.3 x 10(5) lmol-1), the other having a raised affinity constant (J.D., 5.4 x 10(6) lmol-1 and E.T., 5.8 x 10(6) lmol-1). Extrapolation of the plots showed that the high affinity components comprised 66% (J.D.) and 54% (E.T.) of the total purified albumin. The raised affinity and high concentrations of the variants thus account for the raised total T4 concentrations in the patients. The presumed amino acid substitution in the albumins may be different in the two patients since the affinities for rT3 differ. Some methods for the estimation of free T4 levels give misleading results in the presence of these albumin variants. In the course of two episodes of illness, patient J.D. manifested large falls in serum T4 levels which could only be accounted for by reduced carriage of T4 by the abnormal and conventional binding proteins. Many cases reported in the literature as partial peripheral resistance to thyroid hormone may be examples of similar albumin variants.
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