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The effect of acetylsalicylic acid analogue (aloxiprinum; Superpyrin® Spofa) administered perorally in a daily dose of 1 g per 10 kg body weight on serum levels of free thyroxine (FT4), total thyroxine (T4), triiodothyronine (T3), cortisol (F) and thyrotrophin (TSH) was studied in healthy human volunteers. In a first experiment the drug was administered for 3 days to 7 subjects, the total daily dose being divided into 4–5 aliquots, while the same total dose was administered within 4 h to another 8 subjects in a second experiment. In both experiments a highly significant increase of FT4was found during the period of treatment, while the levels of other hormones i. e. (T3, T4, F and TSH) were decreased, in most cases significantly. After the withdrawal of the drug there was not only a return of all levels to the initial value, but in most cases an "overshoot" above this value was detected.

Increased activity of adenylate cyclase in whole anterior pituitary was repeatedly found in groups of 3–6 adult male rats 5 min after iv injection of 10, 100 and 200 nmol of TRH kg−1. After the administration of 100 nmol TRH kg−1the activity of adenylate cyclase was significantly increased at 2, 5, 10 and 30 min with a peak level at 5 min, while at 60 min the values did not differ from controls. The level of TSH in serum was significantly increased in all TRH injected groups with a peak value at 10 min, while no dose-response relationship was found at 5 min. Finally, the activity of adenylate cyclase was significantly decreased in animals injected with 20 nmol of l-triiodothyronine kg−1180 min before sacrifice, the decrease being not overcome by 100 nmol TRH kg−1injected 5 min before sacrifice.

Rats were injected with [125I]L-thyroxine (T4) ip 16 h before the experiment and samples of blood were frequently taken from polyethylene tubing inserted into the femoral artery in anaesthetized and heparin injected animals, isovolaemia being maintained. In each sample of plasma T4counts per ml were estimated with the aid of paper chromatography. Rapid decrease of circulating T4level was found at 20 min after iv injection of various compounds (thiocyanate, iodide, fluoroborate, theophylline and salicylate) and a dose-response relationship was established between such a decrease and the administered dose of salicylate (5–160 mg/400 g b. w.). A similar decrease was observed at 60 min after ip injection of some general anaesthetics (thio-, pento- and allo-barbiturate, urethane) or tranquilizers (Innovar-Vet®). Finally, an increase of T4fractional disposal rate was found between 120 and 480 min after the administration of some of the above mentioned anaesthetics and this effect was abolished by the administration of thiocyanate.It was concluded that there are two different effects of drugs on the circulating T4level: 1. the immediate effect resulting apparently from a decreased plasma protein binding; 2. the prolonged effect which presumably results from the increased turnover of T4by peripheral tissues, the metabolic basis of which remains unexplained.

Abstract. An increase of thyroxine (T4; 36% in average) and 3,5,3'-triiodothyronine (T3; 9% in average) levels in plasma was found in rats after 2 min of immobilization stress (IMO), while later (from 5 to 240 min of IMO) the level of both hormones decreased sharply. This increase was prevented by ip injection of phenoxybenzamine (4 or 16 mg kg−1), prazosin (2.5 mg kg−1), yohimbin (4 or 16 mg kg−1) and fluoxetine (10 mg kg−1) at 60 min before IMO, but similar injections of phentolamine (4 or 16 mg kg−1), tolazoline (4 or 16 mg kg−1), methysergide (10 mg kg−1), cyproheptadine (10 mg kg−1) as well as of lower doses of prazosin (0.6 or 1.2 mg kg−1) did not show such an effect. The level of TSH was increased after 2 min IMO too, but this was considered to be a separate phenomenon from the increase of T4and T3, since in several groups injected with some of the above drugs the level of TSH was decreased together with increased levels of T4and T3. It is suggested that the acute release of thyroid hormone might be due to the effect of biogenic amines which may be blocked by some alpha-adrenergic blocking agents. Since neither adrenalectomy nor adrenal-medullectomy prevented such a release, it may be concluded that circulating catecholamines of adrenal origin did not play any role in this process. The possibility of participation of intrathyroidal sympathetic nerve endings was also repeatedly tested after pharmacological sympathectomy achieved by a long-term administration of guanethidine, but data obtained to date have been inconsistent.

The disapperarance of loading doses of thyroxine (T4) (100–20 000 μg T4iv per rat weighing about 400 g) was measured with the aid of new technique allowing frequent blood sampling with maintenance of isovolaemia in anaesthetized animals. It was found that as early as 2 min after the injection more than half of the administered dose disappeared from the blood, while after 300 min only about 2 % of that remained in the plasma. The direct relationship between the administered dose of T4and both the relative and absolute level of free dialyzable T4as well as of per cent of T4displaced from the plasma by sodium salicylate in vivowas demonstrated. Moreover, it was found that about 60 % of administered T4is excreted by the bile within 300 min irrespective of the dose given, about 15 and 50% of that being found in the small intestine after 15 and 180 min, respectively. When two loading doses of T4were subsequently administered and labelled with different isotopes, the amount of T4from the first dose excreted by the bile was proportional to the amount of T4from a second dose administered 18 h later. From all these observations it was concluded that, in vivo, an effective system for removal of the loading doses of thyroxine from the blood exists, and is presumably located in rapidly equilibrating tissues, mainly in the liver. From this point of view it appears that plasma protein carriers play an important role in the whole body economy of thyroxine, namely by maintaining a certain level in the blood to cover the actual functional needs of peripheral tissues.