The secretion rates of T4, T3, and rT3 were studied in experiments of short duration by a new method based on determinations of the hormone difference across the thyroid combined with simultaneous electromagnetic thyroid blood flowmetry during surgery in 70 euthyroid patients. The secretion rate of T3 was similar in normal thyroid tissue and nodular goitre, but those of T4 and rT3 were lower in nodular goitre and solitary adenoma (P < 0.05). In 61 patients with normal thyroid tissue or nodular goitre the secretion rates during surgery (mean \ m=+-\ sem) were for T4 222 \ m=+-\ 28 nmol/day, for T3 27.4 \m=+-\ 3.1nmol/ day, and for rT3 3.5 \ m=+-\ 0.5 nmol/day. In relation to the individual T4 secretion rate, the secretion rate of T3 was 12.5 \m=+-\3.0% and that of rT3 1.2 \ m=+-\0.9%.In these short-term experiments we found a secretion rate for T4 during operation about 50% greater than in earlier long-term kinetic studies, but which tallied with a recent report using a 4-compartment model. For T3 and rT3 it was 2\p=n-\3times greater than earlier estimates. The secretion was estimated to be 50% of the total production rate for T3 and 6% for rT3. If proportional adjustment were performed to yield a T4 secretion of about 130 nmol/day, T3 and rT3 secretion rates would still be greater than earlier reported.No method as yet exists for measuring directly the rate of thyroid hormone secretion in man (Chopra 1978). Indirect measurement of production rates of thyroid hormones has been achieved with radionucleides using different compartment models (Sterling et al. 1954;DiStefano & Fisher 1979). However, the methods for separation of iodothyronines other than T4 have been criticized (Aickin et al. 1977;Rudolph et al. 1978); and it is difficult by kinetic methods to distinguish secretion from extraglandular conversion of the hormones.In animals the secretion rates of thyroid hor¬ mones have been estimated as the product of the arteriovenous hormone difference and the thyroid blood flow (Mowbray & Peart 1960;Falconer 1967). Application of this method to man should avoid some of the problems in compartment models. Hormone differences across the thyroid may be measured during surgery (Tegler et al. 1976) and a method for thyroid flowmetry has recently been reported (Tegler et al. 1981). Our aim was therefore to study the secretion rates of T4, T3, and rT3 in man by a direct method using hormone differences across the thyroid gland and simultaneous electromagnetic blood flowmetry.Material and Methods PatientsTen men and 21 women, aged 57 (33-78) years (mean and range), with normal thyroid tissue in the lobe studied were admitted for surgery for hyperparathyroidism (n = 25), unilateral adenoma, nodular goitre or follicular carcinoma (n = 6). All lobes studied were macroscopically normal; and 15 randomly chosen were histologically normal. All patients were euthyroid on the basis of clinical findings and serum concentrations of T4, T3, and thyrotrophin (Odell et al. 1965).Thirty euthyroid subjects, 5 men and 25 women aged 56 (26 -...

The secretion rates of thyroglobulin were measured under basal conditions and after exogenous and endogenous thyrotropin stimulation in 23 patients during surgery. In 11 patients with normal thyroid glands the median secretion rate of thyroglobulin was 0.7 pmol/24 h. Higher secretion rates were observed in 8 patients with nontoxic nodular goiter (median 22 pmol/24 h; p < 0.001) and in 4 patients with thyroid malignancy (median 2.2 pmol/24h; p < 0.05). Within 10 min after administration of highly purified human thyrotropin into the thyroid artery an increase of the secretion rates was observed in the 9 patients studied with normal thyroid glands and 5 patients with nontoxic nodular goiter. TRH administration to 5 patients induced a slight but nonsignificant increase of the secretion rate of thyroglobulin after 20 min. These results show that thyroglobulin is secreted directly into the thyroid venous blood. They also confirm that thyrotropin is an important regulator of the thyroglobulin secretion.

The thyroid hormone secretory response to TSH was studied in twenty-eight patients undergoing thyroid and parathyroid surgery. Eighteen patients received bovine or human exogenous TSH by injection into a thyroid artery, and 10 received TRH to stimulate endogenous TSH secretion. Thyroid secretion rates of T4, T3, and rT3 were determined directly from measurement of blood flow and the hormone gradient across the gland. A significant secretory response was seen for all three hormones following TSH increase. T3 secretion accelerated more rapidly than that of T4 and rT3, thus reducing the T4/T3 and rT3/T3 ratios. The T4/rT3 ratio fell during the first 30 min but then increased. The responses correlated with the area under the curve of the TSH serum concentration, and were similar after administration of bovine and human exogenous TSH, and TRH. Conclusions regarding preferential secretion ought to be made by comparing ratios of thyroid hormone secretion with those of the hormone content of the gland, but our results indicate that TSH induces preferential secretion of triiodothyronines in man.

Special-purpose languages have several advantages for rapid prototyping purposes: they allow very fast development of applications; facilitate the dialogue with end users in the specification work; and simplify the work of updating the prototype iteratively. We have been working with a modelling language based on the concept of information flow in organizations, and a number of software tools which support this language. Previous papers from the project have described the first generation of tools; the present paper describes the experience from using the system in a large scale development effort, as well as the second generation of support tools.

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