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Biomedical subjects

W D Alexander

Publications and source records attributed to W D Alexander.

At least 91 records · Page 5Linked to original sources
PubMed1975

Iodine organification defect following treatment of thyrotoxicosis with antithyroid drugs.

Two patients remained clinically euthyroid following treatment for thyrotoxicosis with antithyroid drugs in spite of persistently elevated thyroid radioiodine uptakes not suppressable by exogenous triiodothyronine. Perchlorate discharge tests showed a defect in the intrathyroidal organification of iodine. Circulating levels of thyroxine were normal. From our study of 105 patients treated for thyrotoxicosis with antithyroid drugs, apparent remission of thyrotoxicosis by this mechanism might occur in up to 2 percent of patients.

Carbimazole↗
PubMed1975

35-S-antithyroid drug concentration and organic binding of iodine in the human thyroid.

35S-methimazole (MMI), 35S-carbimazole or 35S-propylthiouracil (PTU) were given orally to fifty-five patients at various times up to 12 h before surgical thyroidectomy. The amount of 35S radioactivity and labelled drug in thyroid and plasma samples was measured. Intrathyroidal inhibition or organic binding of iodine by MMI, carbimazole and PTU was measured after intravenous administration of 131I, 132I or 125I-iodide. After administration of 35S-carbimazole or 35S-MMI the thyroid to serum (T/S) ratio of 35S radioactivity was greater in thyrotoxic glands than in non-toxic adenoma tissue. 35S-MMI was found in thyroid and plasma samples after administration of 35S-carbimazole. The T/S 35S-MMI was greater than 1 in most but not all patients. 35S radioactivity was also concentrated in the thyroid after administration of 35S-PTU. In thyrotoxic glands there was an 80% inhibition of iodine organification in patients receiving MMI and 60% for those receiving PTU. It is suggested that carbimazole and MMI can be given once or twice daily in some patients but PTU would be less suitable for this dose schedule.

Antithyroid Agents↗
PubMed1975

Effect of frequency of administration on the accumulation and metabolism of (35S) propylthiouracil by the rat thyroid.

Repeated administration (every 8 h) of (35S) Propylthiouracil (PTU) resulted in gradual accumulation of unmetabolised PTU by the thyroid gland until the 9th dose was given. Subsequently a plateau-level was attained which was proportional to dose with the two dose levels used. During repeated administration once daily the intrathyroid concentration of free PTU varied markedly in the course of each 24-h period. Chromatographic analysis showed four compounds: PTU, sulphate and two unidentified compounds as well as origin material. The proportions of these compounds were different in the different dose studies. Thus, the ratio of compound Y/compound X was found to be inversely related to dose. The plasma 35S-radioactivity increased throughout the studies and was proportional to dose.

Animals↗
PubMed1975

Relation between thyroid iodine content and the accumulation and oxidation of [35-S] Methimazole in the rat.

The thyroid accumulation and oxidation of a single intraperitoneal dose of [35-S] methimazole has been studied in iodine-deficient, normal and iodine-treated rats. A highly significant positive linear correlation was found between the thyroid oxidation of methimazole to sulfate and intrathyroidal iodine content. A single dose of potassium iodide given intraperitoneally (ip) to rats 1 h before administration of [35-S] methimazole (1 mg/kg ip) increased the thyroid accumulation and oxidation of methimazole. Conversely, the thyroids of rats maintained on a low iodine diet for 21 days showed a markedly reduced capacity to accumulate and oxidize methimazole. The level of oxidation found in the iodine-deficient, normal and iodide-treated groups was 0.21, 4.15 and 12.6 nmol sulfate/g thyroid respectively. The animals maintained on the low iodine diet for 21 days showed significant increases in thyroid weight and thus the decrease in methimazole oxidation occurred in spite of increased stimulation by endogenous TSH. These results show that the intrathyroidal iodine content is a critical factor in the metabolism of methimazole in the thyroid.

Animals↗
PubMed1975

Thyroid function in patients in clinical remission after medical treatment of thyrotoxicosis.

This paper described the changes in the levels of serum triiodothyronine, serum thyroxine,serum thyrotrophin and other indices of thyroid function between 2-5 y after completion of antithyroid drug therapy in 35 patients who were euthyroid on clinical criteria. There was a small but significant elevation of the mean triiodothyronine and thyroxine levels with a relative hypersecretion of Triiodothyronine. No correlation was found between the levels of either thyroid hormone measured or their ratio and the radioiodine uptakes and clearance rate, the plasma inorganic iodine level, the absolute iodine uptake or the serum TSH level. There was no case of clinical hypothyroidism but in one patient the TSH level was at the upper limit of the nrmal range and an exaggerated TSH response to TRH was found.

Adult↗
PubMed1975

Binding of the 35-s of 35-s-propylthiouracil by follicular thyroglobulin in vivo and in vitro.

Radioactivity was found bound to follicular thyroglobulin after administration of 35-S-propylthiouracil (PTU) to rats. Denaturation of the thyroglobulin using various procedures could not separate the 35-S from the protein; it was concluded that the 35-S is bound to thyroglobulin covalently. Fractionation of saline-soluble thyroid proteins was performed by ultracentrifugation on sucrose gradients. The PTU-sulphur/thyroglobulin (S/Tg) molar ratio was calculated in all fractions. One hour after the injection of PTU the S/Tg molar ratio was the same for 19S thyroglobulin from rats on stock diet and 18S thyroglobulin from rats on low iodine diet. Injection of KI to the animals before administration of 35-S-PTU significantly reduced the ratio. The highest S/Tg ratio 1.10 was noted at 19S thyroglobulin, 17 h after a single injection of PTU. Daily injection of PTU for six days increased the S/Tg ratio to 3.3. Inverse relationship between dose of PTU and S/Tg ratio was noted at one hour. In animals injected with large dose of 35-S-PTU and sacrificed several hours later the S/Tg was higher at the 12S subunits than at the 19S protein. The amount of PTU bound to 3-8S subunits was minimal. Sulphite liberated 64 percent of the 35-S bound to thyroglobulin which appeared as four compounds on thin layer chromatography plates. The main 35-S compound liberated by sulphite was sulphate.

Animals↗
PubMed1973

Remission of thyrotoxicosis during treatment with propranolol.

Twenty-eight thyrotoxic patients were treated with propranolol. In seven patients the drug had to be discontinued after one or two months, but in the remaining 21 clinical improvement was observed. Serial clinical studies and tests of thyroid function performed at monthly intervals showed that in four patients thyrotoxicosis remitted and all indices of thyroid function returned to normal. A fifth patient shows distinct evidence of remission with the 20-minute (132)I uptake falling to normal, although the free-thyroxine index remains slightly raised. It is likely that these remissions reflect the natural tendency of the disease to remit since propranolol is not considered to have any direct in-vivo effect on thyroid function.However, because of failure to gain adequate control of symptoms in all patients treated, and the fact that circulating thyroid hormone levels were often not restored to normal, propranolol is considered an unsatisfactory alternative to conventional antithyroid drugs for routine treatment.

Female↗