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The efficacy of treatment with TSH-suppressive doses of L-thyroxine (T4, 2.5 micrograms/kg body weight daily) either alone or combined with carbimazole (CBZ, 40 mg daily) was studied in 78 patients with sporadic non-toxic goitre in a prospective placebo-controlled double-blind randomised clinical trial. Treatment was given for 9 months, with 9 months of follow-up. A response to treatment as measured by ultrasonography was found in 58% of the T4 group, in 35% of the T4/CBZ group, and in 5% of the placebo group. The mean (SEM) decrease of thyroid volume at 9 months in the responders was 25% (2). After discontinuation of treatment, thyroid volume increased in the responders and had returned to base-line values after 9 months of follow-up. In the placebo group mean thyroid volume had increased by 6% (4) at 4 months, 20% (7) at 9 months, and 27% (8) at 18 months. The findings show that untreated sporadic non-toxic goitre continues to increase in size; T4 is effective in the treatment of the disorder; and the addition of CBZ has no therapeutic advantage.

Thyroid hormones were serially measured over a 2-week period in thirty-four consecutive patients with acute myocardial infarction (AMI). A transient increase in plasma rT3 and a decrease in plasma T3 was found, with the maximum changes occurring on the third day after the onset of AMI. The changes in plasma rT3 and T3 were greater in the seventeen patients with a complicated AMI (mean peak SGOT 145 mu/l) than in the seventeen patients with an uncomplicated AMI (mean peak SGOT 79 mu/l). A correlation was found between infarct size (as estimated by the peak SGOT value) and the following indices: delta r T3, delta T3, highest rT3/t3 and highest rT3/T4 ratios. A transient increase in plasma TSH (peak on days 4 and 5) and in plasma T4 and FT4 index (peak on days 6 and 7) was also observed, whereas T3 resin uptake (T3U) decreased. These findings suggest that the following sequence of events occurs in thyroid hormone metabolism during AMI: (1) inhibition of the 5'-deiodination of T4, resulting in increased plasma rT3 and decreased plasma T3 values, and in a lower metabolic clearance of T4. (2) Increased secretion of TSH (provoked by the lower T3 levels) resulting in increased thyroidal secretion of T4 and T3, which is then switched off by the negative feedback of thyroid hormones on the pituitary.

Studies were undertaken to elucidate whether orphenadrine influences thyroid function. Seven volunteers were given orphenadrine in weekly increasing dosage up to 300 mg per day; in 5 patients chronically treated with 300 mg orphenadrine daily the drug was gradually discontinued. No changes were found in PBI, RT3U, TT3 and TSH during or after orphenadrine medication; also TSH- and TT3-responses to 200 microgram TRH iv were not influenced by the drug. Orphenadrine medication increased serum thyroxine values (P less than 0.001) as measured with the competitive protein binding (CPB) technique, but did not influence serum thyroxine values measured by radioimmunoassay. Orphenadrine added to serum in vitro in the Murphy-Pattee assay did not increase thyroxine values; two out of eight tested metabolites however did. It is concluded that orphenadrine in a dosage up to 300 mg per day does not influence thyroid function. It increases serum thyroxine levels as measured by the competitive protein binding technique of Murphy and Pattee. This is due to an in vitro competition between ethanol-extractable orphenadrine metabolites and thyroxine for binding sites on the thyroxine binding globulin.

A model for the in vitro study of the conversion of thyroxine into triiodothyronine using isolated rat liver parenchymal cells is described. Isolated liver cells (mean protein content 18 mg/ml) convert approximately 0.8% of 1.3 microM exogenously added T4 into T3 during thirty minutes incubation. Carbimazole (50 microM) has no effect on the conversion process, whereas propylthiouracil (50 microM) inhibits the conversion. The beta-adrenoceptor blocking agent propranolol lowers the conversion ratio when added in concentrations of 580 and 1160 microM, but has no inhibitory effect when 290 microM is added.

The effect of the beta-adrenoceptor blocking agent propranolol on plasma levels of thyroxine and triiodothyronine was studied in eleven hyperthyroid patients and in six hypothyroid patients on L-thyroxine substitution therapy. In all patients a decrease in plasma-triiodothyronine was found. The per cent decrease of plasma-triiodothyronine was the same in both groups. Plasma levels of thyroxine and thyrotropin increased in the hypothyroid patients, but remained constant in the hyperthyroid subjects. The decrease in plasma-triiodothyronine during propranolol medication is most likely caused by an inhibition of the peripheral conversion of thyroxine into triiodothyronine.