Stable Iodide Research Articles

Radiation Hazards of Primary Concern to Public Health—Present Status and Outlook

The radiation hazards currently of primary concern to public health are fallout of radioiodine from testing nuclear weapons and excessive x-ray exposures performed by careless and sometimes poorly trained physicians. Because of the relatively short half life of I/sup 131/(8 days), it might be expected to be of little consequence as a public health hazard following nuclear weapons testing. However, the yield of I/sup 131/ from a nuclear weapon is sufficiently high that considerable contamination of the environment takes place, and the hazard to the general population becomes greatest when the weapon is detonated at low altitude. The ground contamination problem increases as the altitude of detonation decreases. After the USSR tests of 1961, levels of I/sup 131/ contamination rose rapidly-in a few communities to a level which, if continued over a period of several months, would cause a dose in excess of the Federal Radiation Council's (FRC) radiation protection guide of 0.5 rem. The meteorologic aspect is of interest to public health authorities because it clearly indicates the manner in which variation in the weather pattern may cause fallout to occur from time to time in quite unexpected places. As a result of later detonations, estimates indicate that inmore » some regions of the United States the radiation dose received by the thyroid glands of children may reach a level of 1.5 rem/yr, which represents the ingestion of 100,000 mu mu C of radioiodine. This amount is 3 times the quantity of radioiodine recommended by the FRC as a maximum limit. The FRC has announced that its radiation standards, applicable to the peacetime uses of radionuclides, do not apply to environmental contamination from fallout. The political implications of this decision, as well as the confusion it has introduced among public health authorities, are discussed. Reduction of the I/ sup 131/ hazard by the use of dried or stored fresh milk by infants and lactating mothers, and addition of stable iodide to the diet, are also discussed. Problems of medical overexposure to radiation are, in general, the result of the use of unsafe x-ray equipment or careless use of x-ray equipment. It is recommended that exposure dose values to such tissues as the reproductive organs be reduced to 15 mr/yr or about 15% of the exposure dose from natural background sources, as an The duties and experiences encountered during the 4-yr operation of a radiation control agency are recounted. The most important part of a comprehensive radiation control program, in terms of overall exposure of the population, is the effort to minimize the radiatlon exposure from the medical and dental use of x-rays. The fact that much of the equipment is installed in apartmert houses, other multiple dwelling structures, and office buildings means that a more critical evaluation of the structural shielding is necessary. An inspection of existing x-ray installations showed that much equipment had been installed in multiple dwellings without having the basic structural shielding considered standard practice for many years. Public health considerations relating to siting nuclear reactors in cities are discussed, particularly with respect to nuclear-powered vessels entening the harbors of large cities. The problem of safeguarding the public from hazards associated with the transportation of radioactive materials in a large city is also discussed. Dosimetry tests showed that many watches being sold with luminous dials exceeded permisnible dose rates, and many jewelry and department stores have been restrained from selling such watches. Other tests showed that, under normal use, television equipment does not emit a sufficiently hlgh dose rate of x-rays to constitute a health hazard. (BBB)« less

The Rate of Return of Radioiodine Uptake by the Normal Thyroid After Suppression by Pharmacological Doses of Stable Iodide

AbstractIt is well known that large doses of stable iodine in any form from Lugol's iodine to “Telepaque” will inhibit thyroid uptake of radioiodine for a variable period, which may be several months in the case of a cholecystogram.(1,2) It has also been shown that further uptake by the thyroid of r

GENERAL ASPECTS OF IODINE METABOLISM IN SPORADIC GOITRE

ABSTRACT Studies on iodine metabolism were performed in 17 patients with sporadic non-toxic goitre. A group of 11 normal subjects served as control. These investigations show that goitrous patients are at least iodine deficient: there is a low urinary excretion of stable and radioactive iodine with high thyroid uptake of radioiodine. Various rate constants of the iodide cycle in the body have been calculated. In particular, the concentration of stable iodide in the plasma as well as the pool of inorganic iodine are significantly reduced as compared with controls. The great avidity of the thyroid allowed an equal accumulation of stable iodine per unit of time in goitrous and non-goitrous subjects. Iodine deficiency undoubtly plays a role in the pathogenesis of sporadic non-toxic goitre in Belgium. The importance of lack of iodine is discussed in relation to other goitrogenic factors.

Stop flow analysis of renal tubular site of reabsorption of radioidide in dogs.

SummaryThe renal tubular site of reabsorption of iodide has been determined in the dog using the stop flow technic. The pattern for I131 was found to be qualitatively similar to that for chloride or sodium. However, I131 was reabsorbed to a lesser extent than chloride or sodium in both distal and proximal segments. Administration of large doses of stable iodide, perchlorate or thiosulfate did not greatly affect the stop flow ratios of I131. These experiments are interpreted as indicating passive reabsorption of iodide in both proximal and distal portions of the renal tubules of the dog.

Administration of stable odide as a means of reducing thyroid irradiation resulting from inhalation of radioactive iodine.

Despite the emphasis placed on safety considerations during the design and operation of nuclear power stations, it is prudent to consider the possibility of a reactor accident capable of causing radiological injury to the general public residing in the vicinity. This implies the emission of radioactive material from the reactor. The first danger which must be reduced in connection with certain types of reactor is that resulting from inhalation of radioactive materials by persons in the path of the cloud. All existing evidence suggests that for the type of reactor under consideration, the inhalation of radioactive iodine is the most immediate hazard. Iodine is selectively absorbed and concentrated in the thyroid gland where it is retained for relatively long periods. In this report an analysis is given of the factors governing the uptake of iodine by the thyroid glands, and, by using data available in the literature, it is shown to be probable that the ingestion of small amounts of inorganic iodide would significantly reduce the dose due to concurrently inhaled radioactive iodine. It is therefore advocated that the administration of stable iodide shouid be seriously considered as an alternative or supplement to evacuation of any persons at risk frommore » inhalation, following a reactor accident. The adoption of this suggestion would simplify emergency plans by reducing the need for evacuation or at least add valuable time during which evacuation could be better organized. (auth)« less

CONTAMINATION OF MILK BY RADIO-IODINE

To show the speed and completeness with which oral iodides in pharmacological dosage inhibit further radioiodine uptake, the length of time during which thyroid iodine uptake continues to be depressed following such a dose was studied. Thyroid uptakes were measured by profile countlng methods at 3 hr after an oral test dose of I/sup 132/, before a 200-mg oral dose of stable iodide, and at various intervals after it. Preliminary data on 3 subjects are consistent in showing that the uptake is small at 1 day after iodide, is still only about 20% of normal at 2 days, but has returned to about 50% of normal at 3 to 4 days after the dose. It would seem, therefore, that doses every few days, rather than a single dose, would be required to suppress thyroid uptake of radioiodine during any prolonged period of high milk contamination with I/sup 131/ . There is some evidence suggesting a faster iodine turnover in children than adults; this indicates a need for more frequent and perhap daily doses if I/sup 131/ uptake is to be kept at a low value. (P.C.H.)

Use of neutron activation analysis for studying stable iodide uptake by the thyroid.

A technique of neutron activation analysis was used to measure trace quantities of inorganic iodide in urine. Anion exchange resins and selective elution permitted removal of interfering sodium and chloride from urine prior to the activation procedure. The uptake of stable iodide by the thyroid was determined by measuring the radioiodine uptake and specific activity (I131/I127) of simultaneously excreted urine. ln 34 fasting euthyroid subjects the mean iodide uptake by the thyroid was 3 plus or minus 2 mu g per hour. Plasma concentration of inorganic iodide averaged 0.005 mu g per ml. Day to day variations in iodide intake resulted in corresponding variations in the amount of stable iodide accumulated by the thyroid, since iodide accumulation approximated a first-order reaction. Prolonged administration of exogenous iodide resulted in a gradual decrease in radioiodine accumulation. This resulted in a decreased accumulation of stable iodide only after several weeks of greatly increased iodide uptake by the thyroid. A mechanism postulated to explain the dynamics of iodide accumulation by the thyroid is presented.

The effect of iodides on Hashimoto's thyroiditis.

Eighteen patients with Hashimoto's thyroiditis and 4 with a solitary hyperfunctioning thyroidal nodule were given I131 before and after administration of 2000 μg. of stable iodide as potassium iodide. The difference between the 24-hour thyroidal uptakes of the pre-potassium iodide and post-potassium iodide tracers was reduced to a percentage in the manner described by Feinberg and associates. The percentage inhibition of thyroidal I131 uptake in all the cases studied was striking, and differed appreciably from the values for normal persons. It simulated the findings in Graves' disease and iodide goiter. The administration of TSH to normal subjects did not consistently alter the pattern of response to the “iodide inhibition test.” From these preliminary studies it is postulated that iodides enhance a pre-existing intrathyroidal defect that is conceivably related to the organification of iodide.

Effect of thiocyanate, stable iodide and perchlorate on the kinetics of radioiodide transport between thyroid gland and blood of rats

Equilibration of radioiodide between thyroid and blood was studied in rats fed propylthiouracil with or without subsequent acute administration of thiocjanate, stable iodide or perchlorate. The results were analyzed in terms of Wollman and Reed's open two-compartment model of the thyroidal iodide pump. All three anions examined were found to inhibit thyroidal radioiodide collection predominantly through lowering of the unidirectional clearance of plasma radioiodide by the thyroid, and to a lesser extent by enhancing the exit rate constant of thyroidal radioiodide. These observations are scrutinized for information regarding the anatomical site of the thyroidal iodide pump.

On the reactions of a few functional groups with hydriodic acid reagents

The reactions of a number of functional groups with hydriodic acid reagents for the Zeisel method have been investigated. Only normal primary alkoxy groups quantitatively form volatile iodides which are stable in the reagent solutions at 100° C. The isomers of propoxy and butoxy groups, propylene glycol compounds and glycerol give varying yields of less stable iodides. The reaction for the formation and that for the decomposition of these iodides compete with each other under the conditions of the analysis, with different rates for different compounds. It therefore appears difficult to design analytical methods of general applicability. Methods with or without the use of empirical factors can be used for the analytical control of known substances or types of substances.

Biphasic effect of TSH on thyroidal iodide collection in rats.

Assessing the activity of the thyroidal iodide pump by measuring the thyroid/serum radioiodide gradient (T/S), we found the stimulatory effect of TSH to have a latency of from about 8 hours to 12 hours or more. The longer latent periods were observed in rats whose initial T/S was relatively high. The rise in the T/S was preceded by a depression of this ratio, whether hypophysectomized, normal, or triiodothyronine (T3) treated rats were injected with TSH. This biphasic response was elicited with Armour TSH, lyophilized rat pituitary tissue and Bates' highly purified mouse tumor and bovine TSH preparations; it seems therefore reasonable to attribute it to TSH proper rather than some contaminant(s). The same kind of response was also observed in rats whose thyroids were purged of organic iodine with goitrogens and whose endogenous TSH output was subsequently inhibited by giving T3 along with the antithyroid drugs; this indicates that the initial depression of the T/S is not due to flooding of the thyroidal iodide pool with stable iodide derived from iodotyrosines through deiodination, nor to inhibition of iodide pump activity by iodothyronines liberated from thyroglobulin by TSH. When organic binding of iodine was not blocked, stimulation of thyroidal I131 uptake was observed in hypophysectomized rats 4 hours after the injection of TSH, although in blocked glands of similar animals the T/S was depressed. Unidirectional active iodide clearance by the thyroid (estimated on the basis of clearance during the first 3 minutes following injection of I131) was unchanged in hypophysectomized rats examined 4 hours after the injection of TSH, but the thyroids of such rats lost in vivo accumulated radioiodide at a faster rate in vitro than did those of untreated hypophysectomized animals. It therefore appears that a relatively early effect of TSH may be an enhancement of the exit rate constant for thyroidal iodide (increased permeability of thyroid cell membranes?). The stimulating influence of TSH on the active uptake of iodide by the rat thyroid, on the other hand, is remarkably slow. Differences between the periods of latency for the effects of TSH on various thyroid functions are discussed.

Serum concentration and thyroidal uptake rate of stable iodide in various states of thyroid function.

ABSTRACT The thyroidal uptake rate of stable iodide is equal to the product of the thyroidal clearance rate of iodide and the serum concentration of stable iodide. A new method is reported for the determination of serum iodide concentration from the specific activity of saliva iodine. The determined values of serum iodide concentration are smaller than those reported by others, but there was no significant difference in a series of 16 patients with various states of thyroid function. Daily hormone formation and release may be calculated from the thyroidal uptake rate of stable iodide. By comparison of the quantitative results of iodide metabolism with the clinical state, evaluation of effective thyroid function may be possible under various clinical or experimental conditions. The thyroidal radioiodide accumulation rate is a function of the thyroidal clearance rate of iodide, i.e., the capacity of the total gland to accumulate iodide. However, neither of these rates reflects the actual uptake rate of stab...

The effects of varying amounts of stable iodide on the function of the human thyroid.

ABSTRACT The effect of addition of varying amounts of stable iodine to doses of radioiodine was studied in 64 euthyroid persons and in 46 with disturbed thyroid function. The addition of 1 to 2 mg. of stable iodine, as potassium iodide, reduced the uptake of radioiodine to a significantly greater degree in patients with Graves' disease than in euthyroid patients. The difference in response to the added load of iodine suggests that a relatively brief and precise test of thyroid function, an “iodide inhibition test,” may be evolved from these studies. The concentration of serum inorganic iodide was found, by indirect means, to be considerably less than 0.5 μg. per 100 ml. in most instances, regardless of thyroid function. Calculation of the rate of accumulation of iodine by the thyroid revealed that, when the serum iodide level was raised to about 6 μg. per 100 ml., the normally functioning thyroid gland accepted the load and accumulated more than ten times the normal amount of stable iodide per unit time. ...

Renal excretion of radioiodide in rats.

Elimination of radioiodide by the kidney of adult male rats pretreated with a single dose of propylthiouracil was measured. Rats given water or isotonic saccharose served as controls. Renal clearance of radioiodide (CI131) was greatly enhanced (up to 100-fold) by the sodium salts of chloride, perchlorate, stable iodide, bromide and bicarbonate, and by choline iodide, but not by sodium thiosulfate. Under most conditions CI131 markedly exceeded the CCl and CNa of the same animals, which suggest that renal tubules are less permeable to iodide than to chloride or sodium. CI131/CNa varied greatly, its magnitude being dependent on the loading solution used. CI131 showed no correlation with urine flow or excretion of endogenous creatinine-like chromogen (UCrV) when groups receiving different treatments were compared. Both urine flow and UCrV showed only minor variations among these groups. Our findings are most easily explained by the hypothesis that tubular reabsorption of iodide filtered by the glomeruli involves, possibly in addition to a passive process, an active transport mechanism capable of saturation by iodide and (competitive?) inhibition by other anions.

Chromatographic techniques for separation of iodinated thyroid products from human urine

The low concentration of iodinated thyroid products in human urine necessitates either the concentration of these compounds or the application of large volumes of urine to papers for the production of paper partition chromatograms. Present day techniques of electrolytic desalting or separations on ion exchange resins are not practicable in this case. Too large a fraction of the low molecular weight iodinated compounds are lost through electrolytic desalting in addition to partial deiodination of some of the compounds. Thicker than ordinary membranes partially eliminates the former effect. The possibility of loss of small quantities of unknown compounds is always present when ion exchange resins are used. Water saturated butanol extraction of urine for concentration of the iodinated compounds is less dangerous when the residual urine or fresh urine is also chromatographed for comparison. Unfortunately, butanol extracts also concentrate many of the organic and inorganic compounds which interfere with the flow of the iodinated thyroid products so they have disadvantages similar to those in applying large volumes of urine to the papers. Two dimensional chromatohraphy diminishes the need for removal of interfering substances such as urea and inorganic salts. Through use of the proper solvents, the iodinated compounds can be chromatographed free of the interfering substances in the first dimension and subsequently separated from each other by the use of a different solvent in the second dimension. Volumes of urine as large as 1 ml have been applied to 18 × 22 in. papers and reasonably good separations obtained. Much oxidation and artifact formation takes place in butanol-dioxane ammonia solvents, but this is partly controlled with cyanide. Pure amino acids and thyroid hormones on paper chromatograms in the presence of iodide are more subject to oxidation and exchange of I 131 for stable iodide than the same compounds on chromatograms of urine.

Accumulation of radioactive iodine; observations on its early phase in hyperthyroid, euthyroid and hypothyroid subjects.

THE purpose of this paper is to record observations on the early phase of accumulation of radioactive iodine by the thyroid glands of patients with normal and disordered thyroid function, and on the effects both of small and of large amounts of stable iodide given shortly after the tracer. The data indicate that observations made during the first hour after the administration of radioactive iodine provide clear separation between overactivity of the thyroid gland on the one hand and normal or depressed activity on the other and that, despite a most rapid rate of accumulation of radioactive iodine in hyperthyroid . . .

Effect of anesthesia and thyroid surgery on the plasma level of PBI 131.

MANIPULATION of the thyroid gland during surgery, with the consequent release into the circulation of significant amounts of preformed thyroid hormone, has been suggested as a possible factor in the genesis of postoperative “storm” (1–4). In addition, it has been postulated that a definite correlation exists between the magnitude of this phenomenon and the severity of the postoperative reaction (1, 5). Reports of data obtained prior to the use of radioactive iodide in the assessment of thyroid function are conflicting in regard to changes in serum proteinbound iodine levels under these circumstances (1, 5–9). Measurements of the renal excretion of stable iodide have demonstrated a significant increase immediately following both thyroid (7, 10) and non-thyroid surgery (11, 12). That elevations of protein-bound iodine concentration can occur in response to therapeutic doses of radioiodide (13) and irradiation of the thyroid gland with radium or x-rays (5, 14) seems well documented.

Treatment of Multiple Myeloma with Radioactive Iodine and Radioactive Iodinated Serum Albumin

Since the lesions of multiple myeloma are widespread, satisfactory control of the disease process would appear possible only with an effective systemic therapeutic agent. Unfortunately, the results of treatment by chemotherapeutic agents such as urethane, steroid hormones, and diamidines remain, by and large, unsatisfactory (1–4). External irradiation has been successful in relieving isolated painful areas, or lesions of unusual size or destructiveness. Radioactive isotopes given internally can irradiate all the lesions but are limited by the tolerable total-body dose. Radioactive phosphorus (P32) has received a trial (5–7) because, in general, leukemic and neoplastic tissues concentrate this isotope preferentially. Radiophosphorus collects preferentially also in the bone marrow, and the dose must be held below that which will produce a severe reduction in granulocytes, platelets, and red blood cells. It seemed logical to try radioactive iodine (I131), which would be evenly distributed in vascularized tissues without selectively concentrating in the blood formers. It is the purpose of this paper to report experience with two forms of I131 therapy: (a) massive doses of the isotope in patients pretreated with stable iodide, and (b) radioactive iodinated serum albumin (RISA).2 The diagnosis of multiple myeloma in all cases was established by examinations of urine, peripheral blood and bone marrow, roentgenograms of the bones, and electrophoretic study of the plasma pro-teins. Series I: Treatment With I131 Series I comprises 24 treatments given to 7 men and 2 women, ranging in age from forty to seventy years. Pertinent clinical and laboratory data on these cases are summarized in Table I. All patients were hospitalized for the isotope therapy. Loss of circulating I131 to the thyroid gland was prevented by giving stable potassium iodide, 15 drops daily, for five days before and seven days after the isotope treatment. This, however, does not prevent rapid loss of I131 through the urine. For this reason, large doses are required to achieve suitable radiation to the blood. Doses of 100 to 200 mc of I131 are widely reported in the treatment of thyroid carcinoma (8, 9) and are known to be well borne. After preliminary stable iodide treatment, each patient drank about 150 mc of I131. All urine was collected in waxed cartons for several days. Venous blood samples were obtained about two hours after treatment and daily thereafter for a number of days. The urine and 1-c.c. samples of blood were measured with a scintillation counter. Unless the patient was too ill, the body was scanned daily with a collimated counter until the pattern of isotope distribution appeared established and most of the I131 had been recovered in the urine.

Analysis of the modifying effect of dietary iodine levels on the thyroidal response of hypophysectomized rats to thyrotrophin.

VANDERLAAN and Caplan (1954) and Halmi (1954b) have shown that the response of the thyroidal iodide concentrating mechanism of hypophysectomized rats to exogenous thyrotropin (TSH) is influenced by the iodine content of the diet. The same dose of TSH was found to be more effective in raising the thyroid: serum radioiodide gradient when iodine intake was low than when when it was high. A priori this phenomenon is amenable to three interpretation: a) the stable iodide of the diet, being the substrate of the concentrating mechanism, could diminish the gradient of the subsequently administered radioiodide by overloading the iodide concentrating mechanism, whose capacity is limited; b) prolonged elevation of serum iodide levels per se may actually depress the iodide concentrating mechanism and/or inhibit its responsiveness to TSH, or c) a rise in the level of serum iodide may exert such an influence indirectly by enhancing the concentration of organic iodinecontaining compounds in the thyroid.

Thyroidal iodide trapping as influenced by serum iodide levels and thyrotrophin.

IT IS well established that the thyroid possesses a mechanism whereby it concentrates (“traps”) inorganic iodide (VanderLaan and VanderLaan, 1947; Taurog et al., 1947). Studies using tracer doses of radioactive iodine have disclosed the thyroid: serum iodide gradient to be profoundly influenced by thyrotrophin (TSH) (VanderLaan and VanderLaan, 1947; Vander- Laan and Greer, 1950; Ingbar and Roberts, 1952; Halmi et al., 1953). Up to 100 jug of stable iodide carrier added to the tracer had no appreciable effect on the thyroid: serum radioiodide concentration ratio (T/S) of normal (VanderLaan and VanderLaan, 1947) or of goitrous rats (Vander- Laan and VanderLaan, 1947; Taurog xyiet al., 1947). However, further increase of the dose of stable iodide caused the T/S of propylthiouracil (PTU)-treated rats to drop (VanderLaan and VanderLaan, 1947; Wyngaarden et al., 1953). This suggested to Raben and Astwood (1949) that the capacity of the thyroid for iodide is limited, and indeed