Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.459111
Title: A three-compartment model of thyroid uptake in man
Author: Hilditch, Thomas Erskine
ISNI:       0000 0001 3556 391X
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1978
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Abstract:
There is sufficient evidence to show that the kinetics of thyroidal uptake of iodide in man can normally be described in terms of an open three-compartment binding model. The parameters of this model consist of a unidirectional clearance of iodide from the plasma compartment into the iodide compartment of the gland, an exit rate constant describing return of iodide to plasma, and a binding rate constant describing incorporation of iodide into the bound iodine compartment. In the event of there being complete absence of binding, the bound compartment and binding rate are ignored. Published work with radioactive tracers has produced fairly consistent results as far as unidirectional clearance and exit rate are concerned, but there is considerable variance in the binding rate estimates for iodide. Values for the latter in the uninhibited gland have varied by almost two orders of magnitude; namely, from being similar in magnitude to the exit rate, to being much greater. A probable explanation for this discrepancy, however, is to be found in recent work where tracer levels in arterial plasma (which are greater at early times) were applied in the analysis rather than levels in venous blood. In these circumstances the net clearance of tracer into the gland was found to be constant with time, suggesting that the binding rate is normally much greater in magnitude than the exit rate. A new "least sum of squares" analysis of kinetic uptake data, which incorporates a correction for arterio/venous differences in tracer levels, is described in this thesis. The method is based on the open three-compartment binding model of the gland and assumes intravenous administration of the tracer; radioactivity levels in thyroid and plasma being monitored for a period of 60 minutes following administration of the tracer. No constraints are imposed on the parameters of the model but a further parameter, initial free uptake, is introduced to allow for uncertainty in plasma tracer levels imrnediately after injection. The use of the latter parameter also compensates for rapid early reduction in clearance due to protein binding of the tracer in plasma. A computer programme was written to provide estimates of the various parameters and the associated random errors. An analysis of the uptake changes after a blocking dose of perchlorate is also described which provides a means of verifying results from the uptake phase. (Empirical studies revealed also that an estimate of binding rate could be obtained from the fraction of uptake discharged by perchlorate). When the new method of analysis was applied to radioiodide uptake data from normal and untreated thyrotoxic subjects, neither exit nor binding rate could be satisfactorily determined. The results were consistent with theoretical predictions as to the problems that might arise if the binding rate were much greater than the exit rate. Thus it was concluded that,when the binding function of the gland is not inhibited by drugs or disease, the binding rate of iodide is normally greater than the exit rate. Further support for a relatively high binding rate was found in the results of perchlorate discharge studies in a number of untreated thyrotoxic subjects. Even at early times after administration of the radioiodide, there was only one subject in whom a significant discharge of radioiodide was observed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.459111  DOI: Not available
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