Doses Of Iodide Research Articles

Successful Management of Graves' Disease in a Patient Undergoing Regular Dialysis Therapy

Classic Graves' disease associated with thyroid-stimulating hormone receptor antibodies developed in a woman undergoing regular hemodialysis for uremia from chronic pyelonephritis. Her condition responded well to treatment initially with carbimazole and then an ablative dose of sodium iodide I 131 therapy. To our knowledge this is only the second documented case of hyperthyroidism in a patient with chronic renal failure, and it demonstrates that conventional forms of therapy are efficacious and safe.

Thiocyanate Feeding with Low Iodine Diet Causes Chronic Iodine Retention in Thyroids of Mice*

Effects of KSCN on thyroidal iodine metabolism were studied in weanling mice fed a low iodide diet (LID) labeled continuously with 125I as iodide. The addition of KSCN (0.3 and 0.6 mg/g diet) resulted in the accumulation of an unusual iodinated protein within the follicles of the mouse thyroids. After 60 days, total thyroidal iodine was 4 times greater than in controls without thiocyanate. The iodinated protein was essentially insoluble at pH 8.0 and was very slowly released from the thyroids; it contained more MIT than DIT and little thyroid hormone. By use of three isotopes (125I, 127I, and 131I) and auto-radiographs, there were shown different iodinated proteins synthesized during high and low iodine intakes and coexistent but segregated in the colloid. Low doses of perchlorate or iodide inhibited or prevented accumulation of the essentially insoluble iodinated protein. It is suggested that when mouse thyroids are iodine depleted, thiocyanate increases the formation of an essentially insoluble iodinated thyroglobulin within the thyroid. Only a small fraction of the iodination may have occurred by this route, but the rate of formation exceeded the rate of release, so the product continuously accumulated.

Some factors affecting the cerebral and extracerebral accumulation of N-isopropyl- p-iodo-Amphetamine (IAMP)

The whole body distribution of IAMP was studied in mice, rats, rabbits, dogs and marmosets by tissue counting. scintigraphy and quantitative macroautoradiography. Identical distribution patterns of IAMP were observed in these species showing high concentration in the brain, lungs, eyes, liver and kidneys. Following the initial distribution, IAMP was released from the lungs and accumulated in the blood and liver. In the cerebrum the activity decreased with time whereas it progressively increased in the eyes and juxtamedullary region of kidneys. The effect of ACTH, propranolol and metopyrone (metyrapone, USP) on the distribution of IAMP was studied in normal mice. The distribution of IAMP in Dahl salt-sensitive hypertensive rats was compared to Dahl salt-sensitive normotensive rats. Blocking doses of potassium iodide (KI) in marmosets and rats did not affect the distribution pattern of IAMP. Carrier amphetamine in doses of up to 1.5 mg/kg also did not significantly alter the biodistribution of IAMP. When higher doses (up to 8.0 mg/kg) were given, the activity in the gut, lungs, and liver decreased but there was no effect on the uptake in the brain, kidneys. eyes, adrenals, muscle and spleen. This suggests a higher ratio of saturable to nonsaturable binding sites in the latter organs

Peripheral tissue mechanism for maintenance of serum triiodothyronine values in a thyroxine-deficient state in man.

The present study was undertaken to define the source of endogenous triiodothyronine (T3) production responsible for maintaining serum T3 levels in euthyroid subjects with depressed serum thyroxine (T4) values. After withdrawal from 4 wk of exogenous T3 administration, a 22% decline in serum T3 values (from 129 +/- 6 to 99 +/- 4 ng/dl) was observed in six euthyroid subjects, despite a twofold reduction in serum T4 concentrations (from 7.5 +/- 0.5 to 3.2 +/- 0.5 micrograms/dl). This was accompanied by a nearly twofold increase in serum T3/T4 ratio values (17 +/- 1 to 29 +/- 6) but no significant alteration in reverse T3/T4 ratio values. This phenomenon did not appear to be thyroid stimulating hormone (TSH) dependent, since base-line serum TSH values were subnormal. Nor was it dependent on changes in thyroid gland function, since a blunted T3 response to exogenous bovine TSH occurred and pharmacologic doses of iodide did not influence the phenomenon. The finding in three athyreotic subjects that serum T3/T4 ratio values increased from 14 +/- 1 on T4 therapy (mean serum T4, 9.6 +/- 0.8 micrograms/dl and T3, 132 +/- 8 ng/dl) to 40 +/- 2 after withdrawal from 2 wk of T3 administration (serum T4 1.2 +/- 0.1 micrograms/dl and T3 46 +/- 3 ng/dl) provided direct evidence that an alteration in peripheral thyroid hormone metabolism was probably responsible for these findings previously observed in euthyroid subjects. The results of this study support the possible existence in euthyroid man of a peripheral tissue autoregulatory mechanism for maintaining serum T3 values in states of T4 deficiency. Whether this process involves an alteration in the efficiency of T4 to T3 conversion or the rate of T3 clearance is presently unknown.

The Influence of Elevated Iodide Supply on the Autonomously Functioning Thyroid Gland

A pharmacokinetic two-compartment model of iodine metabolism has been established on the basis of data from the literature and our own experimental investigations. By this model it is possible to estimate the effects either of prolonged elevation of iodide supply or of a single administration of a high dose of inorganic iodide in the presence of autonomously functioning thyroid tissue. Prolonged elevation of iodide supply in regions of iodine deficiency will cause manifest hyperthyroidism in many cases of thyroidal autonomy (cases with facultative hyperthyroidism). The administration of a single high dose of iodide, as it is proposed for the situation of an accident in a nuclear power station (100 mg NaI) in order to reduce the radiation burden to the surrounding population, carries almost no risk in cases of thyroid autonomy.

The adaptation of the human thyroid gland to a physiological regimen of iodide intake: evidence for a transitory inhibition of thyroid hormone secretion modulated by the intrathyroidal iodine stores.

The effects of iodide on thyroid function were so far only studied after administration of pharmacological or small continuous doses. We were interested to know how the human thyroid gland would react to a more physiological situation: small doses taken in intermittently. Ten normal male volunteers were given weekly doses of iodide: 1 mg for the first 6 weeks and 2 mg afterwards for another 6 weeks period. Intrathyroidal iodine stores were evaluated by the X-Ray-Fluorescence method. The following thyroid parameters were estimated during the 3 months period: total thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine, reverse triiodothyronine, plasma inorganic iodide, thyroid stimulating hormone and thyrotropin-releasing hormone tests. The following observations were made: i) a steady increase of intrathyroidal iodine (p less than 0.01); ii) no changes in free thyroxine, free triiodothyronine, thyroid stimulating hormone, thyrotropin-releasing hormone test or plasma inorganic iodide. iii) a decrease of total thyroxine (and total triiodothyronine) with a nadir at about 3 weeks and a spontaneous rise afterwards; repetition of this phenomenon by doubling the dose of iodide. It is concluded that 1 mg or 2 mg iodide a week does not inhibit incorporation into the normal human thyroid gland and suggested that these physiological doses of iodide cause a transitory inhibition of thyroxine secretion, representing a form of autoregulation of the thyroid cell, since it was modulated by the intrathyroidal iodine stores and no evidence of pituitary mediation could be evidenced in the experimental protocol.

The mechanism of biliary excretion of methyl mercury: studies with methylthiols.

The S-methylated derivatives of N-acetylpenicillamine, thiola and cysteine as well as methyl iodide decreased biliary excretion of methyl mercury markedly. Excretion of sulfhydryl in bile was not influenced by S-methyl-cysteine, S-methylthiola, S-methyl-N-acetylpenicillamine or a low dose of methyliodide (0.5 mmol/kg body weight). This seems to indicate that coupling of methyl mercury to glutathione in the liver before biliary excretion is a glutathione S-transferase dependent reaction. It also indicates that the methylthiols tested, or metabolites of these compounds are likely to be inhibitors of S-transferase. The effect of S-methylcysteine and low doses of methyl iodide probably reflects glutathione S-transferase inhibition as both compounds are metabolized to the S-transferase inhibitor S-methylglutathione in the liver. A higher dose of methyl iodide (1 mmol/kg body weight) seems to deplete the liver of reduced glutathione through S-methylation as illustrated by decreased biliary excretion of sulfhydryl. S-methylthiola and S-methyl-N-acetylpenicillamine are metabolized in the liver to unknown components which are excreted in bile. Whether S-methylthiola and S-methyl-N-acetylpenicillamine are inhibitors of S-transferase themselves or cause inhibition through metabolites cannot be stated from the present investigation.

Effect of variations in acute and chronic iodine intake on the accumulation and metabolism of [ 35S]propylthiouracil by the rat thyroid gland

Studies were performed to ascertain the effect of varying levels of chronic iodine intake and varying doses of iodide [0.002–100 μmoles KI/100 g body weight (BW)] given acutely on the rat thyroid metabolism of [ 35S]PTU (8.76 μmoles/kg BW). With variations in both acute and chronic iodine intake, as much as four-fold changes in the thyroid content of total 35S and unchanged [ 35S]PTU were observed. In the low, normal and high chronic iodine intake groups increasing doses of iodide given acutely produced a biphasic response in the thyroid accumulation of total 35S and unchanged [ 35S]PTU. In each of the three chronic iodine intake groups, increasing iodide doses up to 0.1 μmoles/100 g BW were associated with an increase in total 35S and unchanged [ 35S]PTU. At this level of acute iodide dosage, the increase averaged 45% (P < 0.01). Following acute iodide doses greater than 0.1 and up to 5.0 μmoles/100 g BW, the mean total 35S and unchanged [ 35S]PTU decreased to levels significantly (P < 0.001) lower than those at the peaks. Greater doses of iodide (up to 100 μmoles/100 g BW) produced no consistent further change in the thyroid content of total 35S or unchanged [ 35S]PTU. Irrespective of the acute iodide dose, the higher the level of chronic iodide intake, the higher the thyroid accumulation of total 35S and the lower the overall mean percentage of total 35S present as unchanged [ 35S]PTU. As would have been expected, increasing acute doses of iodide were associated with progressive decreases in thyroid: serum iodide concentration gradients, and the dose of acute iodide required to induce an acute Wolff-Chaikoff effect was greater the higher the level of chronic iodine intake. No correlation was evident, however, between the effects of acute doses of iodide on aspects of intrathyroid iodine metabolism and their effect on the thyroid metabolism of [ 35S]PTU.

Effects of Excessive Iodide Administered in the Dry Period on Thyroid Function and Health of Dairy Cows and Their Calves in the Periparturient Period

Experiments were conducted in three successive years in which iodide (I) doses of 1.25, 2.5, 5.0 and 7.5 mg/kg body weight were given to 47 dairy cows during the dry period, compared with 16 control cows on basal diets of 1 ppm I. Effects on cows dosed at 1.25 and 2.5 mg I/kg (50 and 100 ppm dry feed) were not different from controls in terms of vitality of calves, changes in plasma thyroxine (T4), plasma triiodothyronine (T3), thyroxine secretion rate and 10-mo milk yields of the lactation after treatment. Cows dosed with 5 and 7.5 mg I/kg (200 and 300 ppm dry feed) averaged 272.8 d gestation, which was significantly shorter than 279.5 d for all cows on lesser I intakes. Abnormal calves at birth were 25% from the two highest I dosages vs 8% from controls plus the two lowest I dosages. Average plasma T4 and T3 decreased on the day of calving by about 30%, while plasma total I increased about 20%. Changes were greatest in cows fed high I dosages for the longest period prepartum. Plasma I and T3 of calves at birth were about three times the concentrations in their dam's plasma and plasma T4 of neonatal calves was four to five times greater than their dams. Highest dosages of I for dams tended to depress plasma T4 and T3 in neonatal calves.

Effect of variations in acute and chronic iodine intake on the accumulation and metabolism of [ 35S]methimazole by the rat thyroid gland : Differences from [ 35S]propylthiouracil

Studies were performed to ascertain the effect of various levels of chronic iodine intake and varying doses of iodide [0.002–100 μmoles KI/100 g body weight (BW)] given acutely on the rat thyroid metabolism of [ 35S]methimazole ([ 35S]MMI, 8.76 μmoles/kg BW). Variations in both acute and chronic iodine intake were associated with as much as four-fold changes in thyroid levels of total 35S and unchanged [ 35S]MMI. Chronic low iodine intake resulted in a considerable reduction in the thyroid uptake of [ 35S]MMI (40% decrease) from high or normal chronic iodine intake. Unlike [ 35S]PTU studies, the effect of increasing acute iodide dosage produced a biphasic response in the thyroid uptake of [ 35S]MMI only in low chronic iodine intake. In these animals 0.1 μmoles KI/100 g BW produced the maximum uptake of [ 35S]MMI (300% increase) but had no effect on high or normal chronic iodine intake. In these latter groups of rats, thyroidal total 35S increased to plateau levels with increasing acute iodide dosage in the range of 0.1–1 μmoles/100 g BW which were unaffected by increased iodide up to 100 μmoles/100 g BW. In low chronic iodine intake rats also, the thyroid 35S level seen at 1 μmole/100 g was unaffected by increased iodide dosage up to 100 μmoles/100 g. The steady thyroid 35S levels seen in this acute iodide dose range in low, normal and high chronic iodine rats were 100, 70 and 110% respectively greater than their control values. Unlike [ 35S]PTU studies, in general, an increase in thyroid total 35S achieved by varying acute or chronic iodine intake was found to be associated with a large increase in the percentage thyroid 35S occurring as free inorganic sulphate with a consequent effect on thyroid unchanged [ 35S]MMI. In chronic low iodine intake animals treated with acute radioidide, in agreement with [ 35S]PTU studies, no direct correlation was found between thyroid uptake or oxidation of [ 35S]MMI and thyroidal total iodine, the accumulation or organification of acute [ 125I]iodide, the occurrence of the Wolff-Chaikoff effect or saturation of thyroid iodide transport.

The effect of varying iodine content on the proteolytic activity of rat thyroid lysosomes.

The possibility that the iodine supply modulates thyroid lysosomal activity was investigated in rats receiving chronic or acute increasing doses of iodide. The lysosomal activity or the various experimental groups was determined by measuring the activity of beta-glycerophosphatase and cathepsin D both in thyroid homogenates and in semipurified thyroid lysosomal preparations, and the degradation of labelled thyroglobulin by the various lysosomal fractions. In the chronic experiments beta-glycerophosphatase and cathepsin D activities increased with the iodide supply of the animals up to 100 micrograms I/rat and decreased slightly thereafter. In the acute experiments the activity of these enzymes increased up to 1000 micrograms I/rat and decreased above 5000 micrograms I/rat. The proteolytic activity of lysosomal fractions from the various experimental groups towards thyroglobulin decreased slightly with increased iodide supply both in chronic and acute experiments. The results suggest that thyroid lysosomal activity may participate in the autoregulation of thyroid secretion by inducing synthesis of new enzymes and modulating thyroglobulin degradation.

Adverse effect of iodide containing contrast agents on newborn thyroid function

Administration of iodine containing antiseptic agents during perinatal life is known as the most frequent reason for transient hypothyroidism in newborns. Since we have detected one newborn infant who developed transient hypothyroidism after angiocardiography(ACG), we investigated thyroid function in 30 babies with congenital heart disease before and after ACG. Informed consent was given by the parents. RESULTS: After ACG with 20 ml diatrizoate 76%(iodide content 200-400 ug) 6 newborns developed transient hypothyroidism within 5 days. In 3 of them renal function was reduced for a few days. Thyroid function returned to normal within 2 weeks in 4 newborns and after 2 weeks in 2 infants. All infants with transient hypothyroidism were less than 4 weeks of age.Infants older than 4 weeks did not develop hypothyroidism, but showed a slight increase of their T4- and T3-serum concentrations 2 to 4 weeks after ACG. CONCLUSION: Newborn infants develop transient hypothyroidism after ACG in more than 80%.Even the administration of relatively small doses of iodide may be followed by an acute Wolff-Chaikoff-Effect. This may be due to immaturity of thyroid autoregulative function.

Serum Cholinesterase, Serum Lipase, and Serum Amylase Levels During Long-Term Echothiophate Iodide Therapy

Previous studies have found increased pancreatic intraductal pressures in dogs and the development of acute pancreatitis in humans after cholinergic stimulation. However, we did not find abnormally high levels of serum lipase or serum amylase in 44 patients with glaucoma using therapeutic doses of echothiophate iodide for intraocular pressure control on a long-term basis.

Suppression of thyroid radioiodine uptake by various doses of stable iodide.

We studied the effect of various doses of sodium iodide on thyroid radioiodine uptake in euthyroid volunteers by giving single doses of 10, 30, 50, and 100 mg and then daily doses of 10, 15, 30, 50, or 100 mg for 12 days thereafter. All single doses above 10 mg suppressed 24-hour thyroid uptake of 123I to 0.7 to 1.5 per cent. Continued daily administration of 15 mg of iodide or more resulted in values consistently below 2 per cent. A small but statistically significant fall in serum thyroxine (T4) and triiodothyronine (T3) and a rise in serum thyrotropin (TSH) concentrations were observed after eight and 12 days of iodide treatment. These data suggest that the thyroid uptake of radioactive iodine can be markedly suppressed by single-dose administration of 30 mg of stable iodide and that suppression can be maintained with daily doses of at least 15 mg. This study provides guidelines for stable iodide prophylaxis in the event of exposure to radioactive iodine.

Pseudocholinesterase levels and rates of chloroprocaine hydrolysis in patients receiving adequate doses of phospholine iodide.

Pseudocholinesterase levels and rates of chloroprocaine hydrolysis in patients receiving adequate doses of phospholine iodide.

Effets de l'iode sur la croissance des frondes d'Asparagopsis armata (Rhodophycées, Bonnemaisoniales) obtenues en culture à partir de rameaux à harpons

Abstract Effects of iodine on the growth of the « fronds » of Asparagopsis armata (Rhodophyceae, Bonnemaisoniales) in culture from spear bearing branches. – By adding doses of 5 μ moles per litre of iodide or iodate to a medium changed every six days, maximum growth for the « fronds » of Asparagopsis armata is obtained. Initial doses of iodide and iodate higher than 15 μ mole per litre inhibit the growth of this alga.

Relationship of iodide-induced increase in TSH response to TRH to changes in serum thyroid hormones.

Large doses of iodide (500 mg three times a day) administered to normal men for 10--12 days caused a rise in basal serum TSH and a concomitant rise in the peak TSH response to TRH. The basal and peak levels of TSH were highly correlated (p less than 0.001). However, the iodide-induced rise in the peak TSH after TRH was poorly correlated with concomitant changes in serum thyroid hormones. Serum T3 wa not lower after iodide and, while serum T4 was somewhat lower, the fall in serum T4 was unexpectedly inversely rather than directly correlated with the rise in the peak TSH response to TRH. Thus, increased TSH secretion after iodide need not always be directly correlated with decreased concentrations of circulating thyroid hormones even when large doses of iodide are used. Clinically, a patient taking iodide may have an increased TSH response in a TRH stimulation test even though there is little or no change in the serum level of T3 or T4.

Comparison of inhibitory effects of 3,5,3'-triiodothyronine (T3), thyroxine (T4), 3,3,',5'-triiodothyronine (rT3), and 3,3'-diiodothyronine (T2) on thyrotropin-releasing hormone-induced release of thyrotropin in the rat in vitro.

In order to compare, in vitro, the TSH suppressive effects of iodothyronines, rat pituitary quarters were first preincubated with T4, T3, rT3, or 3,3'-diiodothyronine (T2) in Gey and Gey buffer containing 1% bovine serum albumin for 2 h at 37 C and then incubated at 37 C for 1 h with the iodothyronine under study and TRH. TSH released into the medium during incubation was compared to that released by control pituitary fragments, which were not exposed to iodothyronines. All four iodothyronines (T3, T4, rT3, and T2) were able to significantly inhibit the TRH-induced release of TSH from pituitary fragments in a dose range of 0.015-2.2 microgram/ml. However, much larger doses of sodium iodide (1.25 mg/ml) and diiodotyrosine (10 and 30 microgram/ml) had no significant effect on the release of TSH. Among T3, rT3, and T4, T3 was the most potent and rT3 was the least potent. The relative potency of T3:T4:rT3 appeared to be approximately 100:12:1 when estimated from the lowest doses that caused significant inhibition of TRH-induced release of TSH, and approximately 100:6:0.5 when estimated from the doses that caused 50% inhibition of TSH release; the TSH inhibiting potency of T2 was similar to that of rT3. The activity of T4 could not be explained entirely on the basis of contamination of T4 with T3 or by in vitro conversion of T4 to T3. Similarly, the available data suggested that rT3 and T2 possess some, albeit modest, intrinsic TSH-Suppressive activity. TSH-inhibiting activities of T3, T4, and rT3 were also studied using pituitary fragments from starved and iodine-deficient rats. There was no evidence of a change in the sensitivity of the thyrotroph to either T3 or T4 in starvation. Similarly, comparison of the responses to several doses of rT3 did not indicate any significant abnormality in the sensitivity of the thyrotroph to rT3 in starvation or iodine deficiency. However, comparison of the TSH-suppressive effects of T4 in the iodine-deficient and normal rat indicated a significant increase in the sensitivity of the thyrotroph to T4 in iodine deficiency. A similar trend was also evident in the effect of T3 in iodine deficiency, but it fell short of statistical significance.

Monodeiodination of 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine to 3,3'-diiodothyronine in vitro.

To study conversion of 3,5,3'-triiodothyroinine (T3) and 3,3',5'-triiodothyronine (rT3) to 3,3'-diiodothyronine (T2) in vitro, T3 or rT3 was incubated at pH 7.35 with homogenates of several rat tissues (liver, kidney, muscle, heart, ling, spleen, intestines, and brain) for 15 min at 37 C. The T2 generated during incubation was measured in an ethanol extract of the incubation mixture by a specific RIA of T2; T4, T3, and rT3 cross-reacted in the T2 RIA only to an extent of 0.006, 0.2, and 0.04%, respectively. T2 was produced regularly when T3 or rT3 was incubated with liver or kidney homogenates; other tissues generated little or no T2 under similar conditions. Studies with liver homogenates revealed that production of T2 from both T3 and rT3 was influenced significantly by tissue and substrate concentractions, temperature, pH and duration of incubation. T3- as well as rT3-monodeiodinating activities were unaffected by large doses (greater than or equal to 3 micrometer) of sodium iodide, diiodotyrosine, and methimazole, but were inhibited in a dose-dependent manner by propylthiouracil, iodiacetic acid, and dinitrophenol. The apparent Km for conversion of T3 to T2 approximated 6.0 micrometer and that for conversion of rT3 to T2' 65 nM. Propylthiouracil and iodoacetic acid inhibited conversion of both T3 and rT3 to T2 in an uncompetititve and a non-competitive manner, respectively. The various data suggest that 1) monodeiodination of T3 and rT3 to T2 is enzymic in nature; 2) liver and kidney may be the major sites of metabolic transformations of T3 and rT3 to T2.

A computer simulation study of optimal thyroid radiation protection during investigations involving the administration of radioiodine-labelled pharmaceuticals.

The administration of iodide for thyroid blocking is now known to carry its own risks, at least in certain categories of patients. We have therefore made a theoretical study by computer simulation of the efficacy of various thyroid blocking regimes. In the case of injected 125I- or 131I-iodide, substantial thyroid protection may theoretically be achieved by a single oral dose of inorganic iodide, for example a 90% reduction in radiation dose is produced by only 20 mg iodide. Repeating the initial blocking dose is of little value. A single blocking dose, however, affords poor protection against radioiodine released from labelled plasma proteins. Both for short-lived proteins such as fibrinogen, and for the longer-lived proteins such as albumin, the optimum dosage schedule appears to be stable iodide given daily for two to three weeks. For instance, 10 mg daily for a fortnight will reduce thyroid irradiation by a factor of ten following injection of 125I-fibrinogen.