Effects of Norethandrolone on the Transport and Peripheral Metabolism of Thyroxine in Patients Lacking Thyroxine-Binding Globulin

Abstract

A B S T R A C T Studies of the effect of norethandrolone on the transport and peripheral metabolism of thyroxine were carried out in four patients lacking thyroxine-binding globulin. Before norethandrolone administration, values for serum protein-bound iodine (PBI) were decreased (1.8 ±0.5 Ag/100 ml) and the proportion of free thyroxine increased (0.036 ±0.008%). As a result, values for the absolute concentration of free thyroxine iodine were at the lower end of the normal range (0.63 +0.12 mjug/100 ml). During the control thyroxineturnover study, the thyroxine distribution space was strikingly increased (18.2 ±7.9 liters) and the fractional rate of thyroxine turnover moderately increased (17.1 ±11.3%/day), as compared to the expected mean values for normal subjects. Therefore, calculated values for the daily rate of thyroxine clearance were increased even more, ranging between 255 and 500% of normal values. However, owing to the low PBI in these patients, the daily disposal of thyroxine iodine was similar to that expected in normals on the basis of age and weight. During the administration of norethandrolone, the thyroxine-binding capacity of the thyroxine-binding prealbumin increased strikingly in all patients, values averaging 162% of those found during the control period. This increase was associated with a highly significant increase in PBI (133% of control values) and a small but significant decrease in the proportion of free thyroxine, resulting in no significant change in the abReceived for publication 21 January 1971 and in revised form 3 March 1971. solute concentration of free thyroxine iodine. In all four patients, administration of norethandrolone was associated with a pronounced decrease in the thyroxine distribution space to values which averaged 69% of those found during the control period. Values for the fractional rate of thyroxine turnover increased slightly. As a result, thyroxine-clearance rate decreased in all patients. Owing to the reciprocal changes in clearance rate and PBJ, no significant change in total daily thyroxine disposal was observed. The present studies reveal that when the thyroxine-binding prealbumin is increased in patients lacking thyroxine-binding globulin, several indices of peripheral thyroxine transport and metabolism are altered. However, these changes were small, even in the absence of thyroxine-binding globulin. It is suggested, therefore, that the effect of changes in thyroxine-binding prealbumin would be even smaller in individuals in whom thyroxine-binding globulin is present.

Effect of Estrogen on Serum Total and Free Thyroxine and Triiodothyronine in a Thyroxine-binding Globulin Deficient Family

“…but unchanged in Case H.T., while T4 binding capacity of TBPA was decreased in both cases. On the other hand, Braverman et al (1971) reported that T4 binding capacity of TBPA was found to be increased by androgen administration.…”

Metabolism of thyroxine-binding globulin in man. Abnormal rate of synthesis in inherited thyroxine-binding globulin deficiency and excess.

“…The Journal of Clinical Investigation Volume 57 February 1976-485-495 tration of estrogens or androgens, are euthyroid and have a normal total daily degradation (D) of thyroxine (T4) despite gross alterations in the concentration of total serum T4 (1)(2)(3)(4). The observed changes in T4 kinetics seem to be related to changes in the fractional turnover rate and/or the extrathyroidal T4 pool associated with the increased or decreased total T4-binding capacity of TBG in serum (5).…”