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A patient presenting with hyperthyroidism was treated initially with antithyroid drugs and subsequently radioiodine. Thereafter he was noted to have inappropriately elevated thyrotropin. A bitemporal visual field defect was noted and CT scan confirmed the presence of a pituitary tumour. TSH was elevated and unresponsive to TRH stimulation. alpha subunit was not elevated. Long-term bromocriptine therapy (doses up to 50 mg/day) resulted in partial, but incomplete suppression of thyrotropin secretion. Following radiotherapy there was resolution of the visual field defect; the TSH, however, remains elevated at greater than 20 mU/l. Radiotherapy and bromocriptine may provide a clinically useful alternative to pituitary surgery in patients with TSH-secreting macroadenoma with suprasellar extension.

Thyroidal binding of iodide was studied by kinetic analysis of [123I]iodide uptake and its discharge by perchlorate in 80 hyperthyroid subjects receiving antithyroid drug therapy. Five dosage regimens ranging from 5 mg carbimazole twice daily to 15 mg methimazole twice daily were studied. Binding inhibition was estimated at 5-7 h after drug as an index of the mean effect of the 12 hourly regimen. In all cases, except one in the lowest dose group, binding was found to be markedly reduced with mean binding rates ranging from 0.002 to 0.020 min-1 (normal greater than 0.15 min-1). The net clearance of iodide in the lowest dose group was reduced to a mean value near the upper limit of the euthyroid range, whereas in the highest dose group it lay at the lower limit of the euthyroid range. These results were reflected in the serum thyroid hormone response. There was a reducing incidence of inadequate control of hyperthyroidism and an increasing incidence of hypothyroidism with increasing thiourylene dose. The exit rate constant of free iodide for the various doses showed values from 0.048 to 0.055 min-1. Corresponding mean values for the discharge rate constant after perchlorate were 0.087 to 0.105 min-1. This suggests that perchlorate increases the rate of iodide release from the thyroid gland. Studies at a later interval after drug (12-14 h) showed no change in discharge rate constant. This leads to the conclusion that perchlorate may further inhibit iodide binding in subjects receiving antithyroid drug therapy.

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.

The kinetics of [123I]iodide uptake were studied when organification of iodine by the thyroid gland was normal and when this binding function was diminished by drugs or disease. Each study was terminated by a sodium perchlorate discharge test (300--600 mg iv) at 60 min or, in some cases, 10--30 min. The results confirmed that binding takes place rapidly in the uninhibited gland with the binding rate constant being at least 0.150 min-1. Discharge from the uninhibited gland is less than 3.5% of the gland uptake when perchlorate is given 60 min after the radioiodide. Subjects with an intrinsic binding defect manifested discharges of 11% of greater of the 60 min uptake and the estimated binding rate constants ranged from 0.003--0.057 min-1. Thyrotoxic subjects receiving 5 mg carbimazole twice daily manifested discharges ranging from 5.4--64.2%, and in those receiving 20 mg twice daily the observed discharges were 67.6--94.6% of the 60 min uptake. The study shows that a correctly performed perchlorate discharge test will detect minimal inhibition of iodine binding. An important factor is the duration of the follow-up period after perchlorate is given. In some of the cases studied discharge was not complete until 60 min after the perchlorate.

Thirty-six patients with non-toxic goitre were reviewed after a mean period of 13 years. Initially 19 patients were iodine deficient (Group I) and 17 had normal plasma inorganic iodine (Group II). In general the iodine deficient patients had larger goitres, developed more complications (26% became hyperthyroid, hypothyroid or required partial thyroidectomy), and required more treatment. There were marked changes in thyroid function tests. In both groups thyroid uptake fell and PII rose though the final PII remained significantly lower in Group I patients. Thyroid and renal iodide clearance fell significantly in Group I patients only. In both groups the final mean total serum T3 levels were abnormally elevated whereas the mean PBI levels did not change significantly during the period of study and the final mean total T4 concentrations were noraml. All goitres became smaller and there were no complications in patients whose goitre became impalpable. No cases of malignancy and no postoperative recurrences of goitre were observed. It is suggested that the incidence of complications in those patients who persist with palpable goitres is sufficent to merit follow-up of this group.

In spite of the long-established use of antithyroid drugs, there are many unsettled questions connected with this treatment of Graves' disease. There is a lack of controlled prospective trials studying the results of antithyroid drug therapy while considering the many variables such as disease heterogeneity, regional differences, drug dosage and duration of treatment. Therefore, a multicenter study has been set up in order to compare the effects of two fixed doses of methimazole (10 vs 40 mg) with thyroid hormone supplementation on the clinical, biochemical and immunological course of Graves' disease and on remission rates. Experience accumulated so far suggests that treatment is safe using either 10 or 40 mg of methimazole. While there is a tendency for an advantage of the higher dose within the first weeks (higher effectiveness in controlling hyperthyroidism), this difference is not significant. The impact of dosage on remission rates remains to be shown.