Administration Of Excess Iodide Research Articles

Thyrotropin-induced acceleration of calcium efflux from mouse thyroid: evidence for inhibition by excess iodide.

We investigated the effect of TSH on calcium transport in mouse thyroid, as well as the influence of iodide thereupon. Thyroid lobes were incubated in Krebs-Ringer bicarbonate buffer containing [45Ca2+] and the time-dependent uptake of [45Ca2+] by the lobes was observed. In the presence of 0.5 mU/ml TSH, the uptake of [45Ca2+] was significantly depressed at early phases of incubation (from 20 to 40 min). Similarly, (Bu)2cAMP (DBC) depressed the [45Ca2+] uptake. The efflux of calcium was also studied by using thyroid lobes preloaded with [45Ca2+]. In the presence of 0.5 mU/ml TSH, [45Ca2+] release from the lobes was doubled in comparison with the control lobes incubated without TSH. DBC similarly accelerated [45Ca2+] release from the lobes. The acute administration of excess iodide to mice fed a low iodine diet inhibits the TSH-induced adenylate cyclase activation in thyroids. The acceleration of calcium efflux induced by TSH was completely abolished by the acute administration of excess iodide in thyroids obtained from animals fed a low iodine diet. Similarly, DBC-induced acceleration of calcium efflux was inhibited by pretreatment with excess iodide. However, the inhibitory effect of iodide on TSH- or DBC-induced acceleration of calcium efflux was not observed in thyroids obtained from mice fed a regular diet. Inhibition of TSH-induced acceleration of calcium efflux by iodide was diminished by treatment of mice with methimazole before iodide. These results suggest that 1) TSH accelerates calcium efflux from the thyroid as a result of accumulation of cAMP in the thyroid, and that 2) iodide inhibits calcium efflux by inhibition of TSH-induced adenylate cyclase activation and by inhibition of the mechanism(s) which is (are) activated by cAMP.

Altered Responsiveness to Thyrotropin in Thyroid Slices of Graves' Disease Preoperatively Treated with Excess Iodide

In a previous paper, we demonstrated that the acute administration of excess iodide inhibits the adenylate cyclase-cAMP system in mouse thyroid lobes. In the present study, we examined whether presurgical therapy with stable iodide reduces the responsiveness to TSH in thyroid tissues from patients with Graves' disease. Eight patients with Graves' disease were presurgically treated with methimazole and stable iodide and six were given methimazole alone. Normal tissues from five patients with thyroid nodules were also tested. We have found that stimulation by TSH (5 and 50 mU/ml) of cAMP formation in thyroid slices from patients preoperatively treated with methimazole and iodide is significantly less than in slices from patients treated with methimazole alone. Similar observations were also made with other thyroid stimulators, such as prostaglandin E2 and 4-methylhistamine. Furthermore, thyroid slices from patients treated with methimazole alone responded to TSH to the same degree as slices of normal tissues. The data suggest that one of the reasons for the hyporesponsiveness to TSH in thyroids from patients with Graves' disease is preoperative treatment with stable iodide.

The Inhibitory Effect of Acute Administration of Excess Iodide on the Formation of Adenosine 3′,5′-Monophosphate Induced by Thyrotropin in Mouse Thyroid Lobes

In a previous paper, we demonstrated that an inhibitory action of excess iodide on thyrotropin-induced thyroid hormone secretion occurs at a site subsequent to the generation of cyclic AMP. In the present study, however, we have found that thyroidal cyclic AMP formation induced by thyrotropin in vitro was markedly inhibited by the acute administration of excess iodide to mice fed a low iodine diet. In contrast, excess iodide failed to produce inhibition in animals fed a regular diet. In vitro stimulation by long-acting thyroid stimulator (LATS), prostaglandin E2, and 4-methylhistamine of cyclic AMP formation in mouse thyroid lobes was also significantly inhibited by the acute in vivo administration of excess iodide. The inhibition was completely relieved by the administration of methimazole prior to excess iodide. Furthermore, it has been shown that thyroid adenylate cyclase activity induced by thyrotropin was markedly depressed by excess iodide under similar experimental conditions. Therefore, it is suggested that one of the inhibitory actions of excess iodide is on the adenylate cyclase-cyclic AMP system and further, that iodide can elicit its inhibitory action after its conversion to some form of organic iodine.

The effect of epinephrine on thyroid hormone synthesis in the rat.

ABSTRACT The effect of epinephrine (100 μg/100 g body weight) on the distribution of 131I among the iodo-amino acids in the rat thyroid was studied. Chromatography of thyroid homogenates was carried out, using as solvent n-butanol:ethanol:2 n ammonia (5:1:2). Epinephrine resulted in elevation of the ratio of monoiodotyrosine (MIT) to diiodotyrosine (DIT), and decreased the incorporation of 131I into iodothyronines. The ratio of triiodothyronine (T3) to thyroxine (T4) was unchanged. Epinephrine did not influence the rate or extent of protein-binding of iodine, determined both by precipitation with trichloroacetic acid and by chromatography. The nature of the iodoprotein formed was studied by its solubility characteristics in phosphate buffer. No change was observed with epinephrine. The changes caused in the MIT/DIT ratio by epinephrine could be completely prevented by the administration of excess iodide, while the incorporation of iodide into T4 improved, but remained slightly below normal. It is postulated that the changes caused by epinephrine in 131I distribution occurred as a result of decreased iodination of thyroglobulin, but an additional effect on iodothyronine synthesis cannot be excluded.

Studies on the mechanism of inhibitory action of excess iodide on thyroid hormone secretion.

SummaryIn order to study the mechanism of inhibitory action of excess iodide on thyroid hormone secretion, effects of excess iodide on colloid droplet formation, susceptibility of thyroglobulin to exogenous protease and thyroidal hydrolytic enzyme activity were studied under several experimental conditions. Excess iodide was first converted to some form of organic iodine and then inhibited colloid droplet formation, an initial step of thyroid hormone secretion. Since this effect of excess iodide was very similar to those produced by lysosomal membrane stabilizers, a possible role of excess iodide on lysosomal membrane was suggested. Administration of excess iodide did not stabilize the thyroglobulin against an exogenous protease, pronase. Excess iodide did not affect thyroidal hydrolytic enzyme activity as evidenced by a normal autoproteolytic activity. It is suggested that excess iodide depressed the thyroid hormone secretion primarily by interfering with the engulfment of thyroglobulin at the apical cel...

An increase of thyroid hormone secretion in response to excess iodide in rats treated with thyroxine.

When more than 5 μg thyroxine was administered to rats with prelabeled thyroids, excess iodide increased blood PB131I for about 24 hr. This increase of blood P B m I was apparently due to an increase in labeled thyroid hormone. The increase was not due to a decrease of the thyroxine distribution space or to a decrease of fecal loss of labeled hormone. No increase of blood PB131I was found in thyroidectomized, 131I-injected and thyroxine-treated animals after administration of excess iodide. Since the number of intrathyroidal colloid droplets increased progressively with time after administration of excess iodide in thyroxine-treated rat thyroids, and since an increase of colloid droplets was preceded by a transitory increase of intrathyroidal cyclic AMP, it is suggested that excess iodide augments thyroid hormone release through an increase of thyroidal cyclic AMP in rats treated with thyroid hormone. (Endocrinology 93: S80, 1973)

An autopsy case of congenital goiter.

An autopsy case of so‐called congenital goiter of a female newborn is presented. It was an adult‐fist sized, horse‐shoe like goiter surrounding her fore‐neck, and caused air passage obstruction which most probably was the immediate cause of her death. Histologically, the mass consisted of hyperplastic follicles occasionally containing eosinophilic, colloid‐like substance. Clinically, the mother had had two episodes with possible relation to this change; (1) administration of potassium iodide (0.5 g/day) for the past 4 years including this pregnancy, (2) suspicious existence of latent hypothyroidism lasting for many years. Thus a possibility can be pointed out that the goiter was caused by administration of excess iodide and/or hypothyroidism of the mother during the pregnancy. A short discussion is also made on the relationship between histological findings of goiters and goitrogenic factors.

Effect of repeated administration of excess iodide on thyroid hormone secretion in rats, with special reference to the escape from the iodide effect.

Two hundred μg to 2 mg KI were injected every 12 or 24 hr ip for up to 7 days in rats, and thyroidal radioiodine release and the increase of intracellular colloid droplet formation induced by TSH were measured to assess the effect of repeated injections of excess iodide. A single injection of excess iodide blocked thyroidal radioiodine release, but this effect continued for about 34 hr in spite of repeated injections of excess iodide. An increase of colloid droplet formation induced by TSH was blocked by excess iodide, but 2 to 3 injections of excess iodide were required to produce maximal inhibition. This iodide effect on colloid droplet formation disappeared almost completely by the Sth day of iodide administration. However, a huge dose of KI again depressed the increase of TSH-induced colloid droplet formation in the thyroid which had escaped from the inhibitory effect of excess iodide. It is suggested that excess iodide blocks the release of thyroid hormone in rats, but only for a short time. (Endocri...