Estimation of Rapidly Exchangeable Cellular Thyroxine from the Plasma Disappearance Curves of Simultaneously Administered Thyroxine-131I and Albumin-125I*

Abstract

Summary. A mathematical analysis of the plasma disappearance curves of simultaneously injected thyroxine-131I and albumin-1251 allows the development of simple formulas for estimating the pool size and transfer kinetics of rapidly exchangeable intracellular thyroxine in man. Evidence is presented that the early distribution kinetics of albumin-125I can be used to represent the expansion of the thyroxine-13I-plasma protein complex into the extracellular compartment. Calculations indicate that approximately 37% of total body extrathyroidal thyroxine is within such exchangeable tissue stores. The average cellular clearance of thyroxine is 42.7 ml per minute, a value far in excess of the metabolic clearance of this hormone. Results of external measurements over the hepatic area and studies involving hepatic biopsies indicate that the liver is an important but probably not the exclusive component of the intracellular compartment. The partition of thyroxine between cellular and extracellular compartments is determined by the balance of tissue and plasma protein binding factors. The fractional transfer constants are inversely related to the strength of binding of each compartment and directly proportional to the permeability characteristic of the hypothetical membrane separating compartments. Appropriate numerical values for these factors are assigned. An increased fractional entrance of thyroxine-""1I into the cellular compartment was noted in a patient with congenital decrease in the maximal binding capacity of thyroxine-binding globulin and in three patients after the infusion of 5,5-diphenylhydantoin. Decreased intracellular space and impaired permeability characteristics were observed in five patients with hepatic disease. Studies of the rate of entrance of thyroxine-'81I and albumin-125I into the pleural effusion of a patient with congestive heart failure suggested that transcapillary passage of thyroxine independent of its binding protein is not a predominant factor in the total distribution kinetics of thyroxine-'31I. The thesis is advanced that the distribution of thyroxine,

A new method for the measurement of acute alterations in thyroxine deiodination rate in man

“…A pulse tracer dose of [20][21][22][23][24][25][26][27][28][29][30] votied it ap150xmlgsurinesecime virtually excluded from the urine in the absence of ntained 3 cc of IRA 400 anion exchange proteinuria as a result of its avid binding to the serum ycle, 20-50 mesh (Mallinckrodt Chemical T4 binding proteins. In contrast to T4, I which is proMo.).…”

Thyroxine transport and distribution in Nagase analbuminemic rats.

“…Their plasma disappearance curves were analyzed by the method of Oppenheimer et al (15), as described previously (16). Movement of T4 into the extraalbumin space was assumed to represent movement of T4 from the extracellular compartment into the rapidly equilibrating intracellular compartment (14,15).…”

Factors Influencing the Early Plasma Disappearance Rate and Liver Uptake of Thyroxine

“…Conversely estrogens, which increase the TBG concentration in plasma, decrease the early disappearance of T, from plasma and also the liver uptake (8,12) while the conditions are reversed in TBGdeficiency (3,10). These findings strongly suggest that in the early distribution phase of T,, the free binding sites extracellularly and the available intracellular binding locations compete for T, until a state of equilibrium is reached.…”

“…injection has been studied in healthy volunteers, in patients with functional thyroid disorders or liver disease and in subjects with abnormal concentration of thyroxine-binding globulin (TBG) (3,7,8,10,12). The aim of the present study was to find a simple biochemical parameter which could be correlated to the early disappearance rate of T, in health and disease and to study the intracellular uptake of T, during its early distribution phase as reflected by the time for the peak count rate over the liver.…”