Studies on the Treatment of Thyrotoxicosis With Radioactive Iodine (131I) and Antithyroid Drugs

Connell, John Muir Cochrane (1986) Studies on the Treatment of Thyrotoxicosis With Radioactive Iodine (131I) and Antithyroid Drugs. MD thesis, University of Glasgow.

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Radioactive iodine (131I) is widely used in the treatment of thyrotoxicosis: an estimated 500,000 patients have been given this form of therapy since its widespread availability in the late 1940s. Despite this experience there is still uncertainty about the response of patients to 131I, particularly in the first year after treatment; the lag between administration and biochemical response can cause problems in patient management. There are also surprisingly few data on the effects of 131I on thyroid physiological processes: much of what is known was published before the availability of accurate measurement of thyroid hormone levels and thyroid stimulating hormone. This thesis attempts to address these points. The effects of antithyroid drug treatment on response to 131I are also examined, and the possible reasons for interactions between antithyroid drugs and 131I treatment explored. In the first part of the experimental section of the thesis the early effects of radioiodine (131I) treatment in patients with thyrotoxicosis were examined. In 50% of patients serum concentrations of thyroxine (T4) and tri-iodothyronine (T3) rose 48 hours after 131I administration, although in none was this associated with clinical deterioration. A similar finding was noted in patients who had been given carbimazole treatment for a minimum of three months before 131I administration. There were no major changes in serum thyroglobulin or TRAb levels following 131I treatment, and no relationship between changes in these variables and thyroid hormone concentrations was observed. The effect of 131I therapy on early (20 minute) uptake of following intravenous injection of radioisotope was examined serially in 55 patients with thyrotoxicosis: 24 of these had been treated before 131I with carbimazole. In all subjects 20 minute uptake of 123I which was taken to represent iodide trapping by the thyroid, fell by four weeks after 131I administration. In those patients who subsequently developed permanent hypothyroidism within the next few months uptake values remained low. In contrast, a small rise in uptake measurements following the initial fall occurred in those patients who were biochemically euthyroid one year after 131I administration. Patients who were still thyrotoxic one year after 131I administration had a higher 20 minute uptake of 123I before 131I administration (p<0.05), and showed only a small fall in uptake after 131I treatment. Thus, by four weeks after treatment 20 minute uptake in those patients who were euthyroid one year after treatment was higher than in those who became hypothyroid, and lower than in those who remained thyrotoxic (both p<0.05). All patients whose uptake of was 4% or less four weeks after 131I administration subsequently became either euthyroid or hypothyroid, while all whose uptake was greater than 8% at this time failed to enter remission. The maximum change in uptake of 123I occurred within four weeks of 131I therapy, and it is suggested that early iodide uptake measurements may be used to predict outcome after 131I administration. Six patients had an episode of transient hypothyroidism following 131I therapy. In two of these patients, in whom measurements were made, this was shown to be associated with reversible defects of iodide organification (measured by perchlorate discharge). In three others 123I uptake measurements 20 and 60 minutes after intravenous administration of radioisotope were consistent with a defect of iodide organification. It appears, therefore, that permanent hypothyroidism is a consequence of major impairment of iodide trapping; in contrast, if trapping is not irreversibly damaged, and there is a defect of iodide organification present, the tendency for such defects to recover means that the associated hypothyroidism may be transient. If early iodide uptake after treatment is > 2% in a patient with hypothyroidism, an iodide organification defect may be partially responsible for the hypothyroidism. Iodide organification was formally studied in 24 patients given 131I treatment using an intravenous perchlorate discharge test. Nine had evidence of an organification defect within three months after treatment. In all patients there was a tendency for these defects to improve with time, and there was no evidence that iodide organification impairment had a major influence on thyroid biochemical function. A major theme of the thesis is the interaction between carbimazole and 131I treatment. Of 79 patients studied, 36 were made euthyroid with carbimazole before 131I administration. Carbimazole pretreatment (drug stopped at least 72 hours before 131I) caused a reduction in the incidence of hypothyroidism during the first twelve months after 131I treatment (19% v 42%, p <0.05). (Abstract shortened by ProQuest.).

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Medicine, Nuclear physics and radiation, Pharmacology
Date of Award: 1986
Depositing User: Enlighten Team
Unique ID: glathesis:1986-77495
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 09:07
Last Modified: 14 Jan 2020 09:07

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