The occurrence of serum immunoglobulins with capacity to stimulate thyroid adenylate cyclase (TSAb) was studied in seventy-two healthy volunteers and 120 unselected patients with various thyroid diseases. A high frequency of TSAb (82.5%, P less than 0.00006) was found in Graves' disease, while TSAb was present only in 13--20% of serum from patients with nontoxic nodular goitre, nontoxic diffuse goitre, toxic adenoma, toxic nodular goitre and myxoedema. These patients had low level of TSAb compared to patients with Graves' disease. In patients with Graves' disease there was no correlation between the level of TSAb and hormonal status except serum triiodothyronine (rs = 0.29, P less than 0.05), and no relation with eye involvement or presence of microsomal thyroid antibodies was found. The results indicate that the human thyroid adenylate cyclase assay system with 1 hour incubation periods is a sensitive method for detection of immunoglobulins with TSH-like capacity to stimulate the thyroid gland.
The effect of a daily dose of 150 micrograms l-thyroxine for one year was studied in forty-five patients with diffuse non-toxic goitre. Thyroid volume was evaluated by ultrasonic scanning. A decrease in the median value of the thyroid volume of about 20% was found after 3 months of therapy and no further change in the median value was observed in the following 9 months of treatment. About 50% of the patients showed a response to therapy and about 30% obtained normal size of the thyroid gland. Median value of the thyroid volume returned to pretreatment value 3 months after thyroxine therapy was stopped. A considerable increase in serum T4 and free T4 index was noted after 3 months of therapy and these elevated values persisted unaltered during the following 9 months of treatment. Serum T3 was studied before and after 3 months of thyroxine therapy in eleven of the patients. A small and insignificant increase in serum T3 and free T3 index was observed.
The effects of neurogenic block on plasma concentrations of adrenaline, noradrenaline and cyclic AMP were studied. Eighteen patients were subjected to surgery of moderate or minor extent under enflurance anesthesia with or without epidural analgesia. The results show that adrenaline secretion during surgical stress is a response to neurogenic stimuli, since the increase found in patients subjected to hysterectomy under general anesthesia is blocked by the addition of epidural analgesia. Furthermore, plasma adrenaline after neurogenic block is comparable with adrenaline levels during minor surgical stress. The plasma noradrenaline concentration does not correlate with the extent of trauma. In contrast to adrenaline levels, noradrenaline concentrations varied insignificantly during and after surgery. However, the addition of epidural block induced a postoperative increase in noradrenaline apparently unrelated to changes in heart rate or blood pressure. Simultaneous measurements of the catecholamines and cyclic AMP indicate that adrenaline is of minor importance for plasma cyclic AMP in resting patients, whereas the increase in cyclic AMP elicited by surgery reflects adrenaline-stimulated beta-adrenergic activity.
SUMMARY Homogenates prepared from human thyroid tissue obtained at operation for non‐toxic goitre were separated by differential centrifugation into 1000 g, 5000 g, 10,000 g and 37,000 g fractions. The fractions showed varying amounts of TSH (12.5 mu/ml) and fluoride (10 mmol/1) sensitive adenylate cyclase activity. The 5000 g pellet contained the highest amount of TSH‐sensitive adenylate cyclase activity calculated per mg protein. Of other potential activators tested only fluoride, immunoglobulins from patients with Graves' disease and adrenaline (10−6 mol/l) caused significant stimulation in this fraction, which was selected for further studies. Maximal activation of adenylate cyclase was obtained with 75 mu TSH/ml incubate, half maximal stimulation with 2.9 mu TSH/ml and detectable stimulation was found with 0.0125 mu TSH/ml. Supramaximal concentrations (1.25 u/ml) gave a decreased response. Stimulation with TSH resulted in a linear production of cyclic AMP for 40–60 min dependent on the TSH concentration. 30 min pre‐incubation of homogenate with TSH at 4°C did not influence the response after addition of ATP‐buffer and subsequent incubation at 37°C, suggesting a very rapid equilibrium for binding of TSH to its receptor after addition of ATP‐buffer to the system. In the 5000 g fraction stimulation of adenylate cyclase with TSH 12.5–75 mu/ml incubate exceeded that obtained with fluoride, and when combined in maximal concentrations an additive effect was observed after incubation for 40 and 60 min, but not after 10 and 20 min, and fluoride caused a linearization of the cAMP response to maximally stimulatory concentrations of TSH. Thus, fluoride appears to maintain the TSH stimulated adenylate cyclases in a maximally activated state. The 5000 g fraction was sensitive to stimulation with immunoglobulins (TSI) from ten of eleven randomly selected patients with untreated Graves' disease. TSI stimulated adenylate cyclase activity could exhibit a lag‐phase of at least 20 min, and stimulation was most readily detected after 60 min incubation at 37°C. The TSI preparations from patients with Graves' disease exhibit varying degrees of lag‐phase indicating that TSI is a heterologous class of immunoglobulins with activation kinetics distinctly different from those of TSH.
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