Iodine Release Research Articles

Thyrotrophin receptor binding, intracellular cyclic AMP levels and iodine release in isolated thyroid cells

There is now considerable evidence that hormonereceptor interactions activate adenylate cyclase and the resulting increases in cyclic AMP levels mediate the effects of the hormone [ 1 ] . However, a study of corticotrophin (ACTH) stimulation of cyclic AMP production and steroidogenesis in isolated adrenal cells has suggested that cyclic AMP is not involved in the stimulation of steroidogenesis by small amounts of ACTH [2]. Similarly, human chorionic gonadotrophin (hCG)-stimulated testosterone production in dispersed interstitial cells appears to be independent of changes in cyclic AMP levels [3]. Scranton and Tong [4] have reported that thyrotrophin (TSH) causes a rapid stimulation of iodine release from isolated thyroid cells in the absence of stimulation of iodine uptake and in this paper. We describe a study of the relationship between TSH stimulation of iodine release, intracellular cyclic AMP levels and TSH receptor binding using isolated porcine thyroid cells. Since sera from patients with Graves’ disease contain antibody molecules which mimic the effects of TSH by interacting with the TSH receptor [S] , the effects of these Graves’ immunoglobulins on the isolated thyroid cells have also been studied.

The Release of Iodine from Iodide Salts by Gamma Radiolysis

Gamma irradiation was found to release iodine in small amounts from powdered samples of cesium iodide and barium iodide, but not from zirconium iodides. The amount of iodine released was measured using silver foil detectors in sealed capsules that contained the salt. The amount of release was markedly affected by impurities, especially water, that were difficult to control; therefore, G values calculated were inaccurate but of the order of 10/sup -3/ atoms of iodine released for 100 eV of energy absorbed for CsI and BaI/sub 2/ near room temperature. The G values for the zirconium iodides were much smaller. The phenomenon of release of iodine from the ionic iodides by gamma radiation is discussed on the basis of published theories of the formation of defects in solids.

The Effect of Elevated Doses of Thyrotropin on Mouse Thyroid

In the course of validating the McKenzie assay it was found that large doses of bovine or rat TSH have a retarding effect on hormonal secretion from the thyroid. TSH in doses less than 10 mU had a maximal effect on thyroidal secretion at about 2-3 h after administration. Doses of TSH in excess of 10 mU caused the peak of secretion to appear at about 9-10 h and caused, as well, a decreased thyroidal iodine release at earlier times. This effect was not due to changes in the pattern of iodocompounds secreted by the thyroid or to a change in the clearance of the blood [125I] thyroxine. An estimate of the integrated secretion with time was linear with log dose up to 100 mU TSH. This pattern of response to TSH is also seen when colloid droplet formation is the parameter studied. cAMP accumulation shows a different pattern of response to TSH. Control levels of cAMP were 1-2 pmoles/mg thyroid. Doses of TSH smaller than 5 mU caused no significant increase in cAMP. With a further increase in TSH up to 200 mU per mouse, cAMP levels increased linearly with the log of TSH and reached 400 pmoles/mg thyroid. Theophylline administered together with large doses of TSH increased the level of the thyroidal cAMP and further decreased the release of iodocompounds at 2 h. These results indicate that there may be an intrathyroidal mechanism which prevents a surge of secretion of thyroid hormones with acute changes in blood TSH levels. The mechanism sensitive to excess TSH is probably associated with steps in thyroidal activation between the accumulation of cAMP and colloid droplet formation.

Fission iodine and xenon release from the UO 2-U 3O 8 system with emphasis on radiation damage

Post-irradiation techniques were used to measure releases of fission iodine and xenon from uranium oxides with different O U ratios ranging from 2.00 to 2.62. Heating curves for the releases revealed several peaks changing with the O U ratios. The peaks coincided with each other between iodine and xenon and corresponded to the annealing processes of fission-fragment induced defects. The total release of iodine up to 1000°C was higher than that of xenon for the entire range of compositions studied. The total releases increased with O U ratios, reached the maximum at UO 2.20 and dropped to the minimum at UO 2.25. These observations lead to the following conclusions: 1. (1) fission iodine and xenon are trapped at fission-fragment induced defects and released when they are annealed 2. (2) the more susceptible to radiation damage, the more fission gas is released 3. (3) the susceptibility to radiation damage seems to be related to isotropy (symmetry) of the crystal structure 4. (4) xenon tends to enter rather larger defects such as dislocation loops, pores, etc. due to the difference in trapping ability of the defects between iodine and xenon.

Failure of propranolol to alter thyroid iodine release, thyroxine turnover, or the TSH and PRL responses to thyrotropin-releasing hormone in patients with thyrotoxicosis.

A dual isotope method allowing simultaneous analysis of both endogenous thyroidal release and peripheral thyroxine disposal was employed in four patients with thyrotoxicosis before and during propranolol therapy (160 mg/day) to determine whether beta adrenergic blockade with this agent affected the secretion or metabolism of thyroid hormone. Since catecholamines may be involved in the regulation of both thyrotropin (TSH) and prolactin (PRL) release from the pituitary, the effect of propranolol on the TSH and PRL responses to thyrotropin-releasing hormone (TRH) was also examined. In the dosage employed in these patients, propranolol had no demonstrable effect on either thyroid hormone secretion, the peripheral disposal of T4, or the TSH and prl responses to TRH.

Comparison of Various Treatment Schedules for Accelerating the Elimination of Radioiodine from the Thyroid and the Human Body

In 68 euthyroid patients undergoing 131I thyroid function tests the thyroidal, urinary and plasma protein-bound radioactivity has been serially measured for 14 days. The patients were subdivided in controls and 9 groups treated with potassium iodide, carbimazole, potassium perchlorate and TSH, singly or in combination. The aim was to devise a treatment scheme for accelerating the release of iodine from the thyroid and the elimination from the body in cases of accidental radioiodine poisoning if the patient is seen after the radioiodine has already been taken up by the gland. All treatment schedules were effective, but TSH injections gave the best results, especially if combined with carbimazole and potassium perchlorate. This combination is the treatment of choice under these circumstances.

Effects of Colchicine on the Formation of Thyroid Hormone

Colchicine, a substance which disaggregates microtubules, was used to assess the role of microtubular integrity on hormone synthesis and other oxidative processes in the thyroid. Under experimental conditions shown to block in vitro endocytosis and glandular release of iodine, colchicine 10–5M, consistently inhibited organic binding of iodine in the mouse thyroid both under basal conditions and in the presence of TSH; cAMP did not reverse the inhibitory action of colchicine. The inhibition of organic binding was associated with a significant lowering of iodothyronine formation and of the DIT⁄MIT ratio. The action of colchicine was not attributable to decreased iodide uptake, enhanced release of iodoprotein, nor impaired utilization of H0O2. Stimulation by TSH and dbcAMP of thyroid oxidation of glucose- 1-C and of formate was significantly diminished in the presence of colchicine, basal values were unaffected. The results suggest that thyroid generation of H2O2, formation of hormone and oxidation of glucos...

The effects of lithium on thyroid iodine release in patients with primary affective disorder.

Thyroid iodine release measured by the double isotope method of Nicoloff was studied in patients with manic-depressive illness before, during and after treatment with lithium carbonate. The urinary 125I/131I isotope ratio was measured following administration of Na125I and 131I-thyroxine. In three of four subjects, lithium caused a transient decrease in diurnal variation and a temporary reduction in the normal increase of the 125I/131I ratio during the first week of therapy or after a lithium dose increase. In addition, in two of three subjects, a rebound increase in the isotope ratio occurred following cessation of lithium administration. These changes most likely represent a direct inhibitory effect of lithium on the thyroid iodine release process.

Assessment of thyrotropin-releasing hormone and thyrotropin reserve in man.

Endogenous thyrotropin-releasing hormone (TRH) reserve and pituitary thyrotropin (TSH) reserve were assessed in four normal subjects, three patients post-cryohypophysectomy, one patient with a hypothalamic lesion secondary to trauma, and four patients with Sheehan's syndrome. TSH reserve was determined by the immunoassayable TSH response to 500 mug TRH given i.v. (TRH stimulation test). TRH reserve was assessed by the rebound response in thyroidal iodine release (TIR) following withdrawal of pharmacologic doses of prednisolone (glucocorticoid withdrawal test). When compared with normals, the post-cryohypophysectomy patients demonstrated parallel impairment of TRH stimulation and glucocorticoid withdrawal testing. The patient with the hypothalamic lesion and the four patients with Sheehan's syndrome all had normal TRH stimulation tests, indicating adequate TSH reserve capacity, yet had abnormal glucocorticoid withdrawal tests, indicative of impairment in endogenous TRH reserve or neurohumoral transport. Three of the patients (hypothalamic injury and two Sheehan's) with impaired TRH reserve were euthyroid. THE FOLLOWING CONCLUSIONS WERE REACHED: (a) A combination of the TRH stimulation test and glucocorticoid withdrawal test may allow for differentiation between pituitary and suprahypophyseal disorders. (b) Certain cases of Sheehan's syndrome appear to have impaired endogenous TRH reserve or transport. (c) Euthyroidism can be maintained in spite of diminished TRH reserve.

Effect of insulin induced hypoglycaemia on thyroid function and thyroxine turnover.

Abstract. The effect of long‐term hypoglycemia induced by insulin on thyroid metabolism has been investigated in 13 normal subjects. No modification of the uptake or release of radioactive iodine by the thyroid has been observed. A significant increase of circulating thyroxine was found for as long as 8 h after insulin injection. Turnover studies with radioactive thyroxine indicate that during the period of insulin administration, there is a slower disappearance rate of labelled thyroxine from the plasma which occurs simultaneously with a significant drop of the hepatic radioactivity. It seems likely that the enhanced concentration of serum thyroxine is related to the release of thyroxine molecules stored in the liver.

Verflüchtigung von Spaltproduktjod aus Festem UCl4

It is possible to volatilize about 95% (at temperatures between 200°C and 600°C) of the iodine, which has been produced by irradiating solid UCl4 with thermal neutrons. The delay times for iodine are decreasing from 2 hrs (at 200°C) to 7 sec (at 600°C). The release of the iodine is improved by using an inert carrier gas. When adding AgCl to the UCl4 before irradiation is carried out, the release of iodine is suppressed at temperatures lower than 400°C. The adding of KI leads to a more rapid release of iodine at low temperatures.

Cyclic AMP formation and thyroid secretion by incubated mouse thyroid lobes.

The effects of TSH on the concentration of cyclic AMP, the number of intracellular colloid droplets and the release of hormonal radioiodine was studied in incubated mouse thyroid lobes. TSH increased all 3 parameters with a similar time course but cyclic AMP accumulation preceded colloid droplet formation and iodine release. The increase in thyroidal cyclic AMP was induced by TSH in a concentration range of 0.3-30 mU/ ml in contrast to the other measures of secretion which were elicited by a ten—fold lower concentration of TSH. Theophylline increased the response to TSH only for concentrations of TSH which by themselves increased cyclic AMP. The TSH stimulated increase in cyclic AMP was blocked by chlorpromazine but was unaffected by colchicine, vinblastine or cytochalasin B. Ouabain, removal of Na+ from the medium, or elevation of the medium concentration of Ca++ partially reduced the TSH stimulated rise in cyclic AMP whereas removal of Ca++ from the medium or addition of Li+ was without effect. (Endocri...

Selective breeding for variations in thyroidal iodine release rate in mice.

SUMMARY Mice were selectively bred for high and low thyroidal 131I release rates. Two lines with sharp contrast in the selection criterion were produced, and an estimate of heritability was made. There were correlated differences in thyroid histology, protein-bound 131I, cholesterol level, haematocrit, adrenal and testicular weights, and some behavioural characteristics. It was concluded that multiple genetic factors affect the rate of thyroidal iodine release, and that the high release strain had greater thyroid activity than the low release strain. Some genetic aspects of thyroid function are discussed.

Non-thyroxine iodine release from the thyroid during acute malaria.

ABSTRACT Non-thyroxine (T4) iodine release from the thyroid gland has been estimated in six euthyroid volunteer subjects undergoing experimental falciparum malaria infection. Values for non-T4 iodine secretion during a control period were >300% of estimates for T4-iodine release. During the period of acute clinical illness, non-T4 iodine release decreased to levels equivalent to those for T4-iodine secretion. During convalescence, an increased secretion of both T4 and non-T4 iodine was observed. T4-iodine secretion during recovery exceeded control values, whereas non-T4 iodine release did not attain control levels. These data suggest a greater efficiency of thyroidal iodine metabolism following recovery from the suppressive effects of malarial infection on the thyroid gland.

The use of lithium in the treatment of thyrotoxicosis.

Since lithium has been shown to inhibit release of iodine from the thyroid, we have investigated its therapeutic potential in thyrotoxicosis. Eight detailed (131)I kinetic studies were performed on seven thyrotoxic women and data was analyzed using a computer program. Lithium at serum levels of about 1 mEq liter decreased the loss of (131)I from the thyroid, led to a fall in serum (131)I levels and diminished urinary (131)I excretion. Computer simulation of the lithium effect required, in every case, that lithium inhibit hormonal and nonhormonal thyroid iodine release. In five cases a second lithium effect was required for a satisfactory fit of the model soluton with observed data: namely, an inhibition of hormone disappearance from serum. NEITHER INHIBITION OF RELEASE NOR OF HORMONE DISAPPEARANCE SEEMED TO BE AFFECTED BY METHIMAZOLE (RELEASE: 52% decrease without methimazole, 60% with methimazole; hormone disappearance: approximately 60% decrease in both). When Li(+) was discontinued, recovery of the iodine release rate and hormone disappearance rate over the observed time span was variable, ranging from no recovery to rates that exceeded pre-Li(+) values. When Li(+) is used alone its effect on serum hormone levels is diminished due to continued accumulation of iodide by the thyroid. Thus, serum thyroxine-iodine levels fell 21-30% in 6-8 days in patients who did not receive methimazole and 15-67% in the methimazole-treated subjects. For prolonged therapy, therefore, a thiocarbamide drug must be used in conjunction with Li(+). The similarity of inhibition of iodine release from the thyroid produced by Li(+) and iodides is discussed.

Alterations in thyroid iodine release and the peripheral metabolism of thyroxine during acute falciparum malaria in man.

Previous studies of thyroid function during various infections have yielded conflicting results, but most have suggested an acceleration of peripheral thyroxine (T(4)) turnover during the acute infectious illness. In the present studies, thyroid function was examined by a method allowing simultaneous analysis of both endogenous thyroidal release and peripheral T(4) disposal in normal volunteers after induction of acute falciparum malaria. Subjects received iodide-(125)I, followed in 5-7 days by (131)I-T(4) intravenously. 4 days later, infection was induced by the injection of parasitized red blood cells. Bidaily measurements of serum protein-bound (125)I and protein-bound (131)I, and urinary (125)I and (131)I, together with frequent estimates of serum (127)I-T(4) (Murphy-Pattee) and free T(4) (FT(4)), were made during a control period, during acute illness, and during convalescence. Alterations in the peripheral metabolism of (131)I-T(4) during infection included significant decreases in the fractional disappearance rate for T(4) [(k)], and in the clearance and daily disposal of T(4), all of which returned to control values during convalescence. Total serum (127)I-T(4) increased late in the infected period to become greater during convalescence than either before or during infection, while FT(4) did not increase significantly until convalescence. An analysis of serum (131)I-T(4)/(127)I-T(4) and (131)I-T(4)/PB(125)I ratios confirmed these observations. The slope with time of ratios for urinary (125)I/(131)I, a reflection of thyroidal iodine release, was decreased during infection, but rebounded to control values during the convalescent period. The observed increments in serum (127)I-T(4) concentration in the convalescent phase may reflect in part the slowing of (k), but together with the rising ratios of urine (125)I/(131)I suggests enhanced thyroidal T(4) secretion immediately after the acute illness. Thus, with malarial infection, there appears to be an initial depression followed by a rebound in rates of thyroidal iodine release. In contradistinction to other infections, fractional turnover and daily disposal of hormone is decreased in malaria, perhaps due to hepatic dysfunction and the consequent impairment in cellular deiodinative processes.

Comparison of the effects of various agents on thyroidal adenyl cyclase activity with their effects on thyroid hormone release.

SUMMARY Intact mouse thyroid glands were used to measure the formation of cyclic [3H]AMP from [3H]adenine, and the release of thyroidal iodine. These two parameters of thyroid activity responded to similar concentrations of human thyroid-stimulating hormone (TSH). Both were stimulated by prostaglandin E1, although the response was always very much less than to TSH. Both were inhibited by NaF, which appeared to have a toxic effect on the gland. The response to TSH was in each case reduced by lithium, suggesting that the antithyroid effect of Li+ is associated with a direct action on adenyl cyclase; however, Li+ also reduced thyroidal hormone secretion induced by dibutyryl cyclic AMP and may therefore have a second site of action. In general, the effects of these agents on cyclic [3H]AMP formation correlated well with their effects on thyroidal iodine release. The results support the hypothesis that the activation of adenyl cyclase is closely associated with, and precedes, thyroid hormone secretion.

Estimation of the triodothyronine secretion rate in euthyroid man.

ABSTRACT Daily T3 secretion rates were estimated in 6 euthyroid subjects by administering increasing doses of triiodothyronine (T3) and utilizing suppressibility of thyroidal iodine release (TIR) as an endpoint. Daily T4 and T3 production rates were calculated so that T4 to T3 interconversion could be estimated. The estimated mean daily T3 secretion rate for the 6 subjects was 16 μg, while the T3 derived from peripheral interconversion was determined to be 12 μ/day. Therefore, approximately 58% of circulating T3 is derived from thyroid gland secretion and 42% from peripheral T4 to T3 interconversion. Since the mean daily T4 production was 92 μg, the amount of T4 metabolized via interconversion to circulating T3 would approximate 15%. The effects of pharmacological doses of T3 on TIR were also studied. It was noted that oral administration of 50 μg of T3 every 8 hr did not achieve full suppression of TIR. The addition of pharmacological doses of prednisolone, 20 mg every 8 hr to the high doses of T3, marke...

Thyrotropin Secretion in Genetically Obese Rats

The hypothalamic-pituitary-thyroid axis has been studied in genetically obese rats, in lean littermates and littermates which became obese following hypothalamic injury (lesioned). After exposure to cold (3°C), the half-life for thyroid radioactivity in the genetically obese rats decreased from 4.73 d to 2.44 d; the plasma FFA showed no elevation and body temperature fell significantly. Lean littermates had a decrease in thyroidal half-life from 1.73 d to 0.92 d, showed the expected rise in FFA but had no fall in body temperature. Lesioned rats had no change in release of thyroid iodine but increased their FFA, and showed no significant change in body temperature. In rats maintained at 18°C the weight of the pituitary was significantly reduced in the genetic obese rats, but the concentration of thyrotropin (TSH) was similar in lean and genetically obese rats. Plasma TSH in fatties rose slightly after feeding a diet supplemented with propylthiouracil. Plasma TSH did not rise when genetic obese rats were fe...

Estimation of the rate of release of non-thyroxine iodine from the thyroid glands of normal subjects and patients with thyrotoxicosis.

A method is described which makes possible estimation of the rate of thyroidal secretion of iodine in forms other than thyroxine (T4), relative to the rate of secretion of T4. Patients are given a tracer dose of inorganic 125I. When serum protein-bound 125I (PB125I) reaches an approximate plateau, a single tracer dose of 131I-labeled T4 is administered. Sequential analyses of serum for PB125I and PB131I, and of urine for total 125I and 131I, are made. Calculated values of the ratio of urinary 131I excretion and PB131I provide an estimate of the rate of appearance of iodine in urine as a result of T4 deiodination. Values for urinary 125I/PB125I ratios in excess of those for 131I indicate thyroidal secretion of iodine in forms which yield urinary iodine more rapidly than does T4. This phenomenon, termed iodide leak by other workers, has been designated as non-T4iodine secretion. On the assumption that plateau values of serum PB125I indicate achievement of specific activity equilibrium between thyroidal and extrathyroidal iodine pools, the absolute rate of non-T4 iodine secretion can be estimated from values for the rate of T4 secretion, as judged by peripheral T4 disposal rates in the steady state. This technique gave evidence of non-T4 iodine secretion in all of seven euthyroid and seven hyperthyroid patients studied. In euthyroid patients, the ratio non-T4 iodine secretion/T4 iodine secretion averaged 3.42±1.69 (mean ±sd); in hyperthyroid patients, 1.63±0.27. Absolute rates on non-T4 iodine secretion in the two groups were 123±81 and 118±51 μg/day, respectively. In euthyroid patients, a close linear correlation was was observed between the rate of non-T4 iodine secretion and daily iodine intake, as judged from urinary iodine excretion. It is uncertain whether the greater relative and absolute rate of non-T4 iodine secretion in euthyroid than in hyperthyroid patients is the result of inherent differences in the two functional states or of differences in dietary iodine intake.