Iodine-induced hypothyroidism (author's transl)

Excessive administration of iodine over a long period may cause hypothyroidism in suitably disposed individuals and provoke the formation of a goiter. The underlying reason for this is the pathological lack of adaptation of the thyroid gland to high doses of iodine with persisting inhibition of hormone production through excess of intracellular iodine (Wolff-Chaikoff effect). Asthmatic patients--as in the case described - are usually affected, when they have taken iodine-containing expectorants over a long time. Provocation of an iodine-induced hypothyroidism by the recently required iodine prophylaxis of endemic goiter is not to be expected because the quantities of iodine lie within the physiological range.     

Study of serum 3,5,3''-triiodothyronine sulfate concentration in patients with systemic non-thyroidal illness

The thyroid doses received by the juvenile population of Belarus following the Chernobyl accident ranged up to about 10 Gy. The thyroid cancer risk estimate recommended in NCRP Report No. 80 was used to predict the number of thyroid cancer cases among children during 1990-1992 in selected Belarussian regions and cities. The results obtained using this risk estimate show an excess of thyroid cancer cases being registered vs. the predicted cases. Thyroid cancer incidence rate among boys under investigation is higher than among girls in the postaccident period. The excess of the observed over the expected incidence in the general juvenile population is caused by the high thyroid cancer incidence rate among boys. These results, which can be considered part of the first stage of a thorough thyroid cancer risk estimation after the Chernobyl accident, demonstrate the critical need to complete these studies in depth.     

Thyroid radiation doses during radioimmunotherapy of CEA-expressing tumours with 131I-labelled monoclonal antibodies

A number of radioimmunotherapy (RAIT) trials with iodinated antibodies have shown a high variability in the radiation doses to the thyroid. Therefore, the aim of this study was to evaluate which factors influence these thyroid doses during RAIT with 131iodinated monoclonal anti-carcinoembryonic antigen (CEA) antibodies. Data from 36 patients with CEA-expressing tumours were analysed. The patients underwent RAIT with the 131I-labelled IgG1 anti-CEA antibody, MN-14 (Ka = 10(9) l mol-1) or its F(ab')2 fragment (activity range 45.8-220.0 mCi). The thyroid was blocked with 120 mg iodine (lugol's orSSKI solution) and 400 mg perchlorate per day, starting 1 day prior to the first study. Blood clearance and molecular composition of labelled plasma compounds were determined by blood sampling and size-exclusion high-performance liquid chromatography analysis. The cumulated activities of tissues were determined from daily imaging and blood clearance data. Doses were derived from the MIRD scheme. Thyroid radiation doses showed a high variability, between 1.2 and 37.7 cGy mCi-1 (mean +/- S.D.: 11.1 +/- 8.3 cGy mCi-1), corresponding to absolute doses between 2.5 and 43.6 Gy. However, the maximal iodine uptake in the thyroid was 2.4 +/- 1.9 microCi mCi-1 (range 0.2-10.0 microCi mCi-1), which was less than 1% of the injected activity, indicating that more than 99% of the thyroid was blocked in all cases. No correlation was found between these thyroid doses and conditions leading to an enhanced exposure to free radioiodine, such as unbound I- in the mAb preparation, rapid metabolic breakdown of the labelled antibody due to human anti-mouse antibodies (HAMA), or immune complex formation with circulating antigen. However, a relationship between the thyroid doses and the patients' compliance in taking their Lugol's and perchlorate blocking medications, as well as to a relatively high variability in the biological half-life of the iodine in the thyroid (range from 31.1 h to virtual infinity), is indicated. No rising TSH titres or other signs of (latent) hypothyroidism were seen in these patients during a 2 year follow-up period. Longer follow-up was not possible because of the terminal condition of most of the patients. These data show that thyroid doses in an appropriately blocked individual given a standard, non-myeloablative dose of RAIT, are generally lower than those assumed to be required to cause late hypothyroidism. Even if higher activities are used, potential hypothyroidism may be overcome easily by hormone replacement. Thyroid doses are independent of parameters leading to an enhanced exposure of the thyroid to free radioiodine, suggesting that patient compliance in taking their blocking medication may be the most crucial factor for reducing thyroid doses in RAIT with 131I-labelled antibodies.     

Urinary bladder organ culture with a continuous nutrient system]

From the differences in radiation profiles between 131I and 125I isotopes of iodine it would be expected that they would show different effects on thyroid function. The differences should lead to lower rates of thyroid gland destruction with 125I and hence less post-irradiation hypothyroidism. This difference in biological effect has been demonstrated in rats by indirect assessment of thyroid function. In this report the long-term effects of a range of similar doses of 131I and 125I were compared, in male and female rats, by direct assessment of thyroid function. Seventeen months after receiving 25 and 125 muCi of 131I, male and female rats showed significant elevation of serum TSH concentration and a reduction in 3 h radioiodine uptake. Rats receiving 1 and 5 muCi of 131I and all doses of 125I showed no significant changes in thyroid function. These findings confirm the previously reported differences in effect between the 131I and 125I isotopes of iodine in the rat.     

Preventive iodine administration and iodine excretion in the Vienna area and in the forest quarter

In order to reduce the still substantial iodine deficiency in the Austrian population, compulsory iodisation of salt was increased in 1990 from 10 mg potassium iodide/kg salt to 20 mg potassium iodide/kg. In this investigation we evaluated the adequacy of iodine supply in Vienna and the Waldviertel, a rural region northwest of Vienna. Daily iodine excretion (which reflects daily iodine intake) was investigated in 92 persons from the Waldviertel (all without thyroid gland pathology) and 110 persons from Vienna (54 with unremarkable thyroid glands, 56 with endemic goiter). Daily iodine excretion was higher in persons from the Waldviertel (161 +/- 90.7 micrograms/24 h, p < 0.05) than in those from Vienna (with healthy thyroid glands 126.4 +/- 42.9 micrograms/24 h and with goiter 117.2 +/- 60.5 micrograms/24 h, resp.). In both populations iodine supply as defined by the WHO (excretion of > 150 ug iodine/day) was inadequate. The recommended level was not achieved in 50% of the persons from the Waldviertel region and in 75% of persons from Vienna (healthy thyroid glands 76%, goiter: 75%). Iodine deficiency (intake < 100 micrograms/24 h) was present in 42% persons from the Waldviertel and in 31% and 24% persons, respectively, from Vienna with unremarkable thyroid glands and goiter. We conclude that although the iodine content of salt was increased, an iodine deficiency was present in a considerable portion of the population of an industrialized country (approximately 40% of persons from a rural region and 30% from the city of Vienna).     

Hypothyroid patients showing shortened responsiveness to oral iodized oil have paradoxically low serum thyroglobulin and low thyroid reserve. Thyroglobulin/thyrotropin ratio as a measure of thyroid damage

In Central Africa, all of northern Zaire is very severely deficient in iodine. A peculiar feature of this endemia is that iodine deficiency and the ensuing thyroid gland stimulation not only leads to goitre formation but also to progressive thyroid involution and to myxoedematous cretinism. An iodine supplementation trial based on oral administration of small doses of iodine was made in 81 schoolchildren. All of them received a small dose of iodine (0.1 ml containing 48 mg) per os and the thyroid status was followed during 4 months. Blood and urine samples were collected at the start of the study, then 2 weeks, 2 months and 4 months after iodine administration. Before iodine supplementation the mean urinary iodine level was 0.18 +/- 0.02 micromol/l, and 10% of the subjects had a urinary iodine level below 0.08 micromol/l. Fifty-two percent of the subjects had a serum thyrotropin (TSH) level above 10 mU/l. All the subjects responded to the administration of iodine. and all of them recovered a euthyroid status. Most of them were still euthyroid at the end of the study. However. within 4 or even 2 months, some subjects (15 % of the total) reverted to hypothyroidism. At the entry of the study these subjects were all hypothyroid and had elevated TSH and paradoxically low serum thyroglobulin (TG) values. In myxoedematous cretins living in the same area, even lower serum TG levels were found. Together with the absence of goitre, a paradoxically low serum TG Suggests a low thyroid reserve, and in the present case a reduced amount of functional thyroid tissue. We show that the serum TG/TSH ratio may be used as a predictive index of thyroid reserve and of positive response to iodine administration. These data further suggest that thyroid damage is not confined to myxoedematous cretins. but is widely distributed in the phenotypically normal population. Widely distributed thyroid damage may render iodine prophylaxis based on oral administration unpredictable.     

Potency comparison of peptidomimetic inhibitors against HIV-1 and HIV-2 proteinases: design of equipotent lead compounds

The results of investigation of haptoglobin (Hp) types in 596 donor blood samples in some towns of Ukraine (Dnepropetrovsk, Kharkov, Odessa, Kiev, Uzhgorod, Zhitomir) are presented. Three normal Hp types (Hp1-1, Hp2-1 and Hp2-2) have been found. The reliable interpopulation differences in the Hp types frequency were not found. On the whole the Hp types frequency in the type Hp1-1 comprised 12.7%. In the type Hp2-1-48.1% and in the type Hp2-2-36.5%. The frequency of the gene Hp1 is 0.38. The frequency of the Hp types and of the gene Hpl in Ukraine is similar to that in population of Eastern Europe and European Part of Russia.     

The isothermal diagram of transformation of the residual austenite by tempering

Bertold Vinokur, formerly Professor, Institute of Casting Problems, Academy of Science of the Ukraine, Kiev, the Ukraine, recently relocated to the United States.     

The efficiency of goiter prevention due to iodine deficiency in pregnant women

The iodine is indispensable element for life that is also fundamental substract for thyroid hormone synthesis which make very important influence on protein's lipid's, carbohydrate's and highly caloric substances metabolism and are a requisite of proper man development. The pregnant women are one of population group which is the most sensitive on iodine's deficiency. The results of researches indicate on insufficient iodine intake in pregnant women diet, whose take food even according to diet's recommendation given by physician. The wide iodine's prophylaxis which was provided as yet is insufficient in case of pregnant and nursing women. It is confirmed the necessity of additional iodine supplementation. A set of control tests should be done in requires cases that inform physician about changes in function and size of thyroid gland and make possible the individualization of treatment. The supplementation doses of iodine about 150 micrograms are safe and there was not observed any side effects during their taking.     

The dynamics of thyroid diseases in the inhabitants of Kiev and Kiev Province after the accident at the Chernobyl Atomic Electric Power Station

Autoimmune affections of the thyroid gland were found to be on the increase as were Hashimoto's disease and follicular adenoma, as evidenced by a pathomorphic study in surgically removed thyroid glands of 12684 patients over 1984-1993. Rise in the frequency of malignant tumors was moderate. Increase in the incidence of papillary microcarcinoma against the background of another surgical pathology of the thyroid gland may be an unfavourable prognostic sign of further growth of morbidity of clinically manifest forms of carcinoma in Kiev and the Kiev Province.     

Retarded incorporation of [14C]mannose into thyroglobulin of human thyrotoxic thyroid glands

In vitro studies using thyroid slices from human non-toxic goitres and from thyrotoxic glands show retarded incorporation of [14C]mannose into the 19S protein of thyrotoxic glands. This was not found using [14C]galactose with thyrotoxic glands or using either labelled sugar with slices from non-toxic goitres. Experiments with thyroid tissue from rats on a variety of treatment regimes such as iodine supplements, carbimazole alone or with iodine supplements did not show this differential delay of [14C]mannose incorporation. This suggests that there may be some abnormality of carbohydrate incorporation into thyroglobulin in thyrotoxicosis.     

Epidemiology of iodine deficiency in the middle Ob regions

AIM: Epidemiological rvaluation of goiter endemia and iodine deficiency in population of the Middle Ob region. MATERIALS AND METHODS: Thyroid palpation and ultrasonic investigations, iodine measurements in the urine were made in 6256 children and adolescents aged 8-17 years. RESULTS: Euthyroid condition was clinically stated in all the examinees. Palpation discovered thyroid enlargement in 36.78% of the examinees. Age prevalence was: 27.3, 33.28, 42.8, 46.18% in children and adolescents aged 8-10, 11-12, 13-14 and 15-17 years, respectively. Ultrasound detected goiter in 30.6% of the examinees. The occurrence was 34.78, 31.68, 28.2, 19.8% in the above age groups, respectively. No significant differences by thyroid size existed in girls versus boys. Urinary iodine was low in all the age groups. CONCLUSION: The Middle Ob regions belong to zone of goiter endemia with mild to moderate iodine deficiency. This dictates the necessity of introduction of special programs of iodine deficiency control and prevention.     

Immunohistochemical assessment of prostaglandin H-synthase in bovine endometrial biopsy samples collected throughout the oestrous cycle

In the Zhytomyr region, about 52,000 measurements of the 131I activity in thyroids were performed. On the basis of these measurements, individual doses have been assessed for the people monitored and age-dependent average doses have been estimated for those settlements with more than 11 direct measurements. In order to estimate the pattern of thyroid exposure in the Zhytomyr region, these doses have been interpolated or extrapolated to population groups who were not monitored during May-June 1986. For this purpose, a model has been developed based on a correlation between thyroid dose estimates with the 137Cs deposition and the co-ordinates of the settlements relative to Chernobyl. Collective doses of people who were born in the years 1968 to 1986 were calculated. The radiation-induced thyroid cancer incidence in the period 1991 to 1995 was assessed by subtracting the spontaneous incidence from the observed incidence. The result is considerably lower than that observed in longer periods after external exposures. Possible reasons for this difference are discussed.     

Methionine metabolism. 2. Biochemical and histological studies in rats]

Male rats weighing 100 g were used in a 19-day trial. The rats received diets containing varying proportions of methionine. Their absolute liver weight was lower, due to the high methionine levels, than that of the animals fed optimum rations, whereas the relative liver weight was found to be lower only in the pair-fed group. No essential differences were observed between the levels of dry matter, protein, and fat. Glycogen levels were found to be lowered only in cases when high methionine doses were administered. Pathologically low levels of glycogen were found in animals of the pair-fed group. High methionine consumption reduced the percentages of 12 glucogenetic amino acids in the liver. This, in turn, suggests an increased rate of glucose formation from amino acids, a process which was not observed in animals of the pair-fed group. High methionine doses produced a condition of hyperglycaemia, while in the pair-fed group hypoglycaemia was observed. The highest rate of secretion of thyroid hormones was found in animals receiving the optimum ration; a lower rate of secretion was observed in the animals consuming less or more methionine. In animals receiving high methionine levels the rate of hormone secretion decreased in a stepwise manner with increasing methionine supplementation. Only the highest methionine doses (5,3%) were found to have a negative effect on the maximum rate of iodine incorporation into the thyroid gland. These findings were also substantiated by histological investigations because a true pathological picture was only found in histological sections of thyroid tissue from animals fed the highest methionine doses (5,3%) The thyroid tissue of these animals consisted predominantly of small glandular alveoli whose colloid was slightly coloured. The epithelial cells of these alveoli were degenerated; some cases of liver cell disintegration and, more rarely, cellular necrosis were noted.     

Isopycnic centrifugation of thyroid iodoproteins: selectivity of endocytosis

Isopycnic centrifugation in RbCl was shown to be an effective method both for evaluating the iodine content of thyroglobulin labelled in vivo and for the fractionation of thyroglobulin molecules as a function of their iodine content. Iodination and degradation of thyroid iodoproteins were studied by this method and by zonal centrifugation in sucrose density gradients. Based on these methods it was shown that iodination in vivo is a selective process, 19-S and poorly iodinated thyroglobulin having a higher reactivity toward iodine than 27-S and iodine-rich thyroglobulin. The disappearance of iodoproteins from the thyroid was evaluated by equilibrium, labelling the iodoproteins, blocking iodine incorporation with thiourea derivatives and observing (by sucrose gradient and by RbCl isopycnic centrifugation) at different times the properties of the remaining molecules. Among molecules of different size (19-S and 27-S) and among molecules of the same size (19 S) but different iodine content it was shown that reabsorption from the thyroid gland occurred at the same rate. It was concluded, therefore, that the degradative pathway is essentially a random, non-selective process. Newly iodinated (pulse-labelled) iodoproteins were degraded faster than preexisting molecules. Among the pool of those newly iodinated thyroid proteins, 27-S molecules were reabsorbed faster than 19-S molecules and iodine-rich thyroglobulin molecules were reabsorbed faster than the iodine-poor ones. Since iodination in vivo occurs as repeated pulses of iodine incorporation, it is suggested that this latter phenomenon is a regulatory mechanism which minimizes degradation of molecules which are iodine-poor and have a lower hormonal content.     

Studies on the mechanism of action of potassium iodide on thyroid protein biosynthesis

Potassium iodide (KI) has been shown to have an antigoitrogenic action and to inhibit in vivo thyroid protein biosynthesis. Beef thyroid slices were used to clarify further the mechanism of action of KI. Incubations were performed in Krebs-Ringer-bicarbonate (KRB) buffer under 95%O2 and 5% CO2. KI caused a slight decrease in the uptake of [3H]eucine by the tissue. When labelled leucine incorporation into protein was measured it was found that 10(-6) M KI caused a marked inhibition. Increasing concentrations of KI up to 10(-3) M did not further increase this inhibition. This effect of KI was reduced by simultaneous addition of 0.5 mM KClO4 or 1 mM methylmercaptoimidazole (MMI). In several experiments it was found that equimolar amounts of thyroxine (T4) or triiodothyronine (T3) were more potent than KI in inhibiting thyroid protein biosynthesis. In double plabelled studies KI decreased [3H]leucine incorporation into thyroid soluble proteins and into immunoprecipitable thyroglobulin (T4) while it did not modify that of [14C]galactosamine. When tissue specificity was examined, KI failed to alter [3H]leucine incorporation into proteins either in the liver or in the submaxillary gland. The present results indicate that intracellular KI is necessary to exert its effect on protein synthesis, and that this effect is mediated through a organic form of iodine, probably iodothyronines. This action of KI is specific for the thyroid gland.     

Toxicological investigations of the combination sulfamoxole/trimethoprim, a new broad-spectrum chemotherapeutic (author's transl)

The chemotherapeutically effective 5:1 combination N1-(4,5-dimethyl-2-oxazolyl)-sulfanilamide (sulfamoxole) and 2,4-diamino-5-(3,4,5-trimethoxy-benzyl)-pyrimidine (trimethoprim) (CN 3123, Nevin, Supristol) was investigated to determine any evidence of toxicological potentiation or new toxic signs. It was found that CN 3123 had a very low acute toxicity when administered orally to mice, rats and dogs (oral LD50: mouse greater than 12 000 mg/kg; rat greater than 14 000 mg/kg; dog greater than 1000 mg/kg body weight). The combination was also tolerated by rats and dogs in repeated doses administered over a period of 4 or 26 weeks, that greatly exceeded the therapeutic dose. The only change observed occurred in the thyroid, which in all doses administered exhibited a dose-related increase in weight accompanied by histological changes indicating an activation of thyroid function and a hypersecretion of basophilic thyrotropic cells in the anterior lobe of the pituitary. Six weeks after discontinuation of treatment this condition showed a tendency to reversibility or had already returned to normal. In dogs there was a dose-related increase in iodine uptake by the thyroid and a decrease in serum thyroxine over a period of 6 months under the highest dosage of CN 3123 administered. Whereas the thyroid changes observed under the combination could be reproduced with sulfamoxole, no effect on thyroid weight was observed in rats and dogs in the subacute toxicity phase of a comparative investigation with trimethoprim. Moreover, trimethoprim did not increase the effect of sulfamoxole on the thyroid gland. The effect of sulfamoxole on the thyroid is discussed in detail with a review of the literature. It can be characterized as species-specific for sulfonamides in mice, rats, rabbits and dogs but not in monkeys or in man and appears to be caused by the inhibition of the organic binding of iodine in the thyroid, whereby the predisposing factors must vary considerably from species to species. The thyroid hypertrophy observed is due to the activation of the regulatory cycle via the anterior lobe of the pituitary. The following systemic changes occurred after 600 mg CN 3123/kg, a lethal-toxic dosage and the highest administered in the study: reduced body weight, decreased food consumption leading to cachexia, slightly increased SGPT and alkaline phosphatase, slight thrombocyte depression, enlargement and increased fatty degeneration of the liver, occurrence of necrotic areas in the liver, hemosiderin accumulation in Kupffer's cells, and an increase of reticular cells in the spleen. The acute toxicity of CN 3123 and all major functional and histological changes under repeated administration were due exclusively to sulfamoxole. The combination sulfamoxole/trimethoprim gives no indication of toxicological potentiation or new toxic signs.     

Contribution of the electromyogram in the diagnosis of infantile spinal muscular atrophy in the neonatal period

Iodide inhibits several thyroid parameters through an organic intermediate, and this process has been related to thyroid autoregulation. The aim of this study was to determine the effect of iodine on thyroglobulin (Tg) synthesis in the rat thyroid cell line FRTL-5. TSH stimulated amino acid incorporation into the cells by 400% and iodine had no effect on this parameter. No effect of TSH or iodide on [35S] methionine incorporation into protein was found under our experimental conditions (approximately 80% of total [35S]methionine incorporated was found in TCA-precipitable material). TSH caused an increase in Tg synthesis, after 1 h, while iodide partially blocked the effect of TSH (control 6.4% of TCA precipitable radioactivity; TSH 10.7%; iodide 8.4%). After 24 h, the protein released into the medium was measured. TSH stimulated total protein liberation and iodide inhibited this parameter. TSH stimulated total RNA content, and iodide caused an inhibition. Northern analysis did not show inhibition by iodide of TSH-stimulated Tg mRNA levels. The present results show an inhibitory effect of excess iodide on TSH-stimulated thyroglobulin biosynthesis in FRTL-5 cells.     

Colposcopy and the management of cervical intraepithelial neoplasia

The stable, bound iodine in the thyroid colloid of Triturus helveticus has been studied with the electron microprobe. Some animals show a normal development. Others are accidentally neotenic due to certain ecological conditions. The values of punctate iodine concentrations (CPI) have been computed and expressed in relative units (counts/s). The mean CPI per lumen is very variable from one follicle to another in the same thyroid section. During normal development, the mean CPI per animal is generally higher in metamorphosing individuals than in larvae. During development with neoteny, the mean CPI per animal attains high values if the larval state is maintained in its totality; the CPI decreases in partially metamorphosed animals, but increases again after metamorphosis. The amount of halogen contained in the thyroid colloid has been computed in relative units (colloid iodine pool). Throughout normal development, the pool remains small if the animals have not attained the adult state. In increases considerably in entirely larval neotenic newts, decreases during metamorphosis but increases afterwards. In totally neotenic newts, the thyroid gland receives only a low hypophyseal stimulation and reacts as the thyroid gland of various hypophysectomized Urodeles. Our results pose the problem as to whether TSH regulates the transepithelial iodine flows, which permit the expansion of the colloid iodine pool, when this hormone is secreted at a very low levels.     

Dependence of the properties of conductive pastes on the dispersity of nickel boride

Institute of Materials Science Problems, Academy of Sciences of the Ukraine, Kiev. Translated from Poroshkovaya Metallurgiya, No. 8(368), pp. 91–93, August, 1993.