Serum Protein-bound Iodine Levels Research Articles

The History and Future of Treatment of Hypothyroidism.

Thyroid hormone replacement has been used for more than a century to treat hypothyroidism. Natural thyroid preparations (thyroid extract, desiccated thyroid, or thyroglobulin), which contain both thyroxine (T4) and triiodothyronine (T3), were the first pharmacologic treatments available and dominated the market for the better part of the 20th century. Dosages were adjusted to resolve symptoms and to normalize the basal metabolic rate and/or serum protein-bound iodine level, but thyrotoxic adverse effects were not uncommon. Two major developments in the 1970s led to a transition in clinical practice: 1) The development of the serum thyroid-stimulating hormone (TSH) radioimmunoassay led to the discovery that many patients were overtreated, resulting in a dramatic reduction in thyroid hormone replacement dosage, and 2) the identification of peripheral deiodinase-mediated T4-to-T3 conversion provided a physiologic means to justify l-thyroxine monotherapy, obviating concerns about inconsistencies with desiccated thyroid. Thereafter, l-thyroxine monotherapy at doses to normalize the serum TSH became the standard of care. Since then, a subgroup of thyroid hormone-treated patients with residual symptoms of hypothyroidism despite normalization of the serum TSH has been identified. This has brought into question the inability of l-thyroxine monotherapy to universally normalize serum T3 levels. New research suggests mechanisms for the inadequacies of l-thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms. Understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euthyroidism.

Iodine and Magnesium Levels in Maternal and Umbilical Cord Blood of Preeclamptic and Normal Pregnant Women

The objective of this study was to investigate the relationship between preeclampsia and iodine levels and magnesium concentration in the blood of subjects in the northeast Anatolia region where iodine deficiency is common. Blood specimens were obtained from 24 preeclamptic and 16 healthy pregnant women. Iodine levels in blood were determined by the Foss method based on the Sandell-Kolthoff reaction. Serum protein-bound iodine (PBI) levels and magnesium concentration in maternal blood were lower in patients with severe preeclampsia compared to normal pregnant women (8.46 +/- 1.22 vs. 11.46 +/- 1.71 microg/dL, p < 0.001, 1.63 +/- 0.05 vs. 1.86 +/- 0.05 mg/dL, p < 0.001, respectively). Serum PBI levels and magnesium concentration in umbilical cord blood were higher in patients with severe preeclampsia than in normal pregnant women (8.84 +/- 1.9 vs. 7.33 +/- 1.07 microg/dL, p < 0.05, 2.48 +/- 0.03 vs. 2.02 +/- 0.01 mg/dL, p < 0.001, respectively). There was a positive correlation between the serum PBI levels in maternal blood and magnesium concentration in maternal blood in patients with severe preeclampsia (r = 0.41, p < 0.05). Thus, iodine may be one factor contributing to the pathophysiology of preeclampsia. Iodine supplementation may be effective therapy in preeclamptic in pregnant women.

Human Serum Protein-Bound iodine and Protein Fractions at Different Physiological and Narcotic States

Iodine profile of Nigerians at different ages in both sexes and in pregnant women, and under narcotic influence, such as alcoholism, cigarette smoking and marijuana addiction were studied. Their serum total protein, albumin and globulin concentrations were also determined. Results of the study showed that serum protein bound iodine levels increased significantly with age in both sexes and in pregnant women, while it decreased significantly in alcoholics, cigarette smokers and marijuana addicts. Serum total protein, albumin and globulin levels increased with age in both sexes and in pregnant women, but were decreased significantly in alcoholics, cigarette smokers and marijuana addicts. Data of the study indicate that serum protein bound iodine levels were potentiated by age, sex and pregnancy, but were impaired by alcoholism, cigarette smoking and marijuana addiction. In addition, serum total protein, albumin and globulin levels were affected by age, sex, pregnancy, cigarette smoking and marijuana addiction. Alcoholism, cigarette smoking and marijuana addiction may have deleterious effects on thyroid function and protein synthesis. NQJHM Vol. 14 (3&4) 2004: pp. 257-261

Blood and Urine Iodine Levels in Patients with Gastric Cancer

In this study, we aimed to investigate whether there is any relationship between gastric cancer and iodine concentrations in blood and urine in the northeast Anatolia region, where iodine deficiency is common. A total of 56 patients, diagnosed as gastric cancer and 25 healthy volunteers were included in the study. The methods used were based on the Sandell-Kolthoff reaction. The urine iodine concentration (UIC) and serum protein-bound iodine (PBI) levels were higher in patients with gastric cancer compared with healthy control subjects. The UIC in stage IV was higher than all other stages and the control group. The UIC was higher in stages III and IV compared with stages I and II. However, serum PBI levels in stage III were higher compared with stages I and II and also control group. The serum PBI level in stage IV was higher than stage II and the control group. In the patient and control groups, there were no significant differences in serum PBI and UIC with regard to age or sex. Our results suggested that urinary and blood iodine concentration might be a useful marker for following the disease.

THE NON-HORMONAL ICDINE STATUS OF MOTHERS OF HYPOTHYROID INFANTS

Excessive intake of iodine by mothers can result in congenital hypothyroidism (CH) in their offspring. To assess such a possibility in a group of 17 newborns with CH, we evaluated the iodine status of their mothers by assessing iodine intake during pregnancy (by dietary recall) and by measuring maternal serum protein bound iodine (PBI) levels 3 weeks after delivery. In 7 out of 17, 24 hr urinary excretion of iodine (UEI) was also measured. Thyroid disfunctions in newborns (low serum T4 levels with elevated TSH) were detected at 3 days of age by the N.Y. State Screening Program for CH and confirmed, usually at 2 weeks of age. Eight infants had goitrous hypothyroidism, 5 ectopic thyroid gland and 4 thyroid agenesis. The dietary recall revealed that none of the mothers was consuming an excessive amount of iodine during pregnancy. The mean ±SD serum PBI levels in all mothers were normal (6.24±1.0ug/dl). The mean±SD PBI levels of mothers of infants with goitrous hypothyroidism were the same as those with other types of CH (5.96±0.8ug/dl). The mean±SD 24 hr UEI was 10.7±6.7 ug/dl. None of the mothers was found to have any abnormalities of the thyroid function, and did not have anti-thyroid antibodies. An excessive intake of iodine during pregnancy appears to be a rather infrequent event and thus an unlikely cause of CH in newborns. Nor a lack of iodine in the mothers' diet appears to be a cause of CH.

Serum protein bound iodine level in the goitrous school children.

612 children between the age of 6–16 years were examined for the presence of goitre. Prevalence of goitre was found to be higher in males (73.4%) than females (67.1%) but females tended to suffer from larger goitres than males. Serum PBI level in goitrous children was found to be low. A significant difference in PBI level was found in 2 and 3+stages of goitre in both the sexes. The low serum PBI level had revealed the inadequate adaptation of the population to low iodine in the region.

Response of Adrenal Catecholamine to a Newly Synthesized Chemical Radioprotector

This study was undertaken to try a newly synthesized compound (1-acetyl hydrazinyl thiophenyl formamidine dihydrochlorie) as a chemical radioprotector and to observe its effects on adrenal catecholamine and protein bound iodine (PBI). After whole-body irradiation, the catecholamine and serum PBI levels decreased significantly but treatment with the drug before irradiation increased the same. The whole-body irradiation resulted in a 50% mortality within a fortnight whereas the use of the drug prevented it.

NUTRITIVE VALUE OF RAPESEED FLOUR FOR MINK: EFFECTS ON LIVE PERFORMANCE, NUTRIENT UTILIZATION, THYROID FUNCTION AND PELT QUALITY

A trial for testing the replacement value of rapeseed flour (RF) (blend of Brassica napus and campestris) for raw meat was conducted with growing-furring mink. The RF contained 67% crude protein and approximately 1/10 of the quantity of glucosinolates normally found in commercial meal. Forty male pastel mink were fed diets containing 0, 6.5, 13.4 and 20% RF (dry-matter basis) from the end of July to pelting. On a dry-matter basis, the diets contained approximately 41% protein and the percentages of protein as RF protein were 0, 4.3, 9 and 12.4. Initially, the animals ate significantly (P &lt; 0.05) more feed and grew significantly (P &lt; 0.05) faster on the 0 and 6.5% RF diets, but later, weight gain and feed consumption were the same for all groups (P &gt; 0.05). After 70 days on trial, weight gain was less (P &lt; 0.05) on the 20% RF diet compared with the 0 and 6.5% diets. There was a significant (P &lt; 0.05) reduction in the apparent digestibilities of dry matter, gross energy and nitrogen, and in nitrogen retention for the mink receiving the diets containing 13.4 and 20% RF. Mink fed the 20% RF diet showed significant (P &lt; 0.05) thyroid hypertrophy, but at slaughter serum protein-bound iodine level was the same (P &gt; 0.05) for all groups. There was little difference among groups with respect to pelt size and pelt quality.

Serum enzyme activities in accidental hypothermia and hypothermic myxoedema

The high serum activities of the enzymes creatine kinase, “α-hydroxybutyrate dehydrogenase” and aspartate aminotransf erase found in 75 patients with accidental hypothermia and 18 with hypothermic myxoedema have been shown to be unrelated to either the severity or the duration of the hypothermia, but to be directly related to disturbances of acid—base equilibrium, hypoxia and hypotension. An inverse relationship also exists between the “α-hydroxybutyrate dehy drogenase’d and the serum protein bound iodine levels, suggesting that a thyroid hormone-lack cardiomyopathy may be contributing to the exceptionally poor prognosis of those with hypothermic myxoedema. These findings have important implications for the rational management of patients with accidental hypothermia or hypothermic myxoedema.

Thyrotropin and PBI in radioiodine treated hyperthyroid patients.

In 58 patients treated with radioiodine for hyperthyroidism 5–22 yr previously levels of serum endogenous thyrotropin (TSH) were elevated in about 50% of patients with normal serum protein-bound iodine (PBI) and in about 20% of patients with normal serum PBI treated with thyroid. The levels of serum PBI were normal in about 25% of patients with elevated serum TSH and in about 50% of patients with elevated serum TSH on thyroid. Of 33 patients with elevated serum TSH, 31 did not respond to exogenous TSH. Of 11 euthyroid patients with normal serum PBI and high serum TSH, 4 had developed low serum PBI 3 yr later, whereas others continued normal 19–41 months later. Of 21 patients with low serum PBI and high serum TSH given thyroid, none of those who were euthyroid and all of those who were hypothyroid responded clinically; those who could not be classified clinically as either euthyroid or hypothyroid varied in response. There is good correlation between high levels of endogenous serum TSH and lack of response to exogenous TSH; but often patients have high endogenous serum TSH with a) normal serum PBI, b) euthyroidism remaining for years, or c) no clinical response to thyroid extract.

Lithium Carbonate-Induced Myxedema

To the Editor.— E.D. Luby and his collaborators ( 218 :1298, 1971) present an interesting observation. The mild antithyroid effect of lithium is well-known, although the mechanism of its action is incompletely understood. A goiter developed or increased in twelve of 330 patients in one series, but all remained clinically euthyroid. 1 In another Danish study, serum protein-bound iodine level was significantly decreased after one week of lithium treatment, 2 but there was a tendency toward control levels after some weeks. Dr. Luby's patient appears to be the first to become clinically hypothyroid during lithium treatment. Interestingly, this patient received an iodine-containing drug in addition to large doses of lithium carbonate during the month preceding the appearance of clinical signs of hypothyroidism. This drug, isopropamide iodide, has an iodine content of 26%; as the daily dose was 4 mg, it will have added 1 mg/day of iodine to the dietary iodine

Sebum excretion in acromegaly.

The sebum excretion rate (S.E.R.) was measured in 20 patients with acromegaly. Eleven were untreated at the time of the measurement and nine had previously undergone surgical hypophysectomy or had received pituitary irradiation by yttrium-90 or radiotherapy. In five patients the S.E.R. was measured before and after such treatment. The mean S.E.R. in the untreated acromegalics was much greater than in a normal population and decreased significantly after successful pituitary ablation. No significant decrease in mean S.E.R. occurred in the group of patients with a poor clinical response to ablation. The correlations between S.E.R. and log serum growth hormone, plasma 11-hydroxycorticosteroid levels, and heel-pad thickness were significant, but there was no significant correlation between S.E.R. and serum protein-bound iodine levels. This suggests that the changes in S.E.R. were due to pituitary ablation but could not necessarily be attributed solely to changes in growth hormone, thyroid-stimulating hormone, or adrenocorticotrophic hormone. The association between the clinical state of the acromegaly and the S.E.R. was better than the association between acromegaly and serum growth hormone. We conclude that the S.E.R. is a useful addition to the clinical and endocrinological data used in assessing acromegaly.

The role of the phagocyte in host-parasite interactions: XXXI. Serum and cellular iodine levels and their relationship to the hyperbactericidal activity of pregnancy

The generally increased bactericidal activity noted in leukocytes collected from pregnant women was postulated to be due to the increased protein-bound iodine (PBI) levels noted during pregnancy. Therefore, the relationship of iodine levels to the bactericidal activity of polymorphonuclear neutrophils (PMN) has been studied. Injection of triiodothyronine (T3) resulted in low PBI and free thyroxine serum levels while causing an increase in bactericidal and phagocytic activity of PMN. PMN collected from T3-treated animals also had increased oxygen consumption, hexose monophosphate shunt, and myeloperoxidase activities in the resting state. In contrast to that of whole cells, cell homogenates from T3-treated animals did not show increased bactericidal activity, suggesting that engulfment and its associated metabolic activities may be involved in the hyperbactericidal activity. Serum and cellular PBI and total iodine levels were increased by the addition of Lugol's iodine to the animals' drinking water. Cells obtained from these animals did not show hyperbactericidal activity. The addition of serum from either treated or control animals to cells from untreated animals did not increase bactericidal activity. An increase in serum or cellular PBI or total iodine does not appear to directly affect cellular bactericidal activity.

The distribution of euthyroid serum protein-bound iodine levels

The distribution of euthyroid serum protein-bound iodine levels

The Distribution of Euthyroid Serum Protein-Bound Iodine Levels

The dispersion of serum protein-bound iodine levels in euthyroid subjects does not allow a normal curve of distribution. Therefore, the mean ± 2 standard deviations does not define the central 95% of a "normal" population for this test. The logarithmic transformation provides a reasonably good fit to the normal distribution curve and allows the calculation of the central 95% of the values. In this study the limits of the central 95% of values were 3.4 to 8.2μg/100 ml.

Tests for hypothyroidism in school children.

Venous blood samples were obtained from 1,759 children, 6 to 14 years of age, in 12 schools in Los Angeles with a total enrollment of 2,502. Serum protein-bound iodine (PBI) and cholesterol were measured and 131I T3 resin uptake and T4 iodine were determined by column tests. For 139 children, column values for T4 iodine were compared with manual PBI results in the same sera; the means were, respectively, 4.7 and 5.6 μ g. per 100 ml. Semiautomated Robot Chemist PBI values (range 4.0 to 8.1) were compared with manual PBI values (range 3.2 to 13.2). The percentages of 131I T3 resin uptake had a negative correlation with the PBI values, coefficient –0.31096. No diagnostic value of this test was evident. In serum PBI determinations done by the manual technic for 570 Caucasian school children, 4.5% of the values were below 4 μ g. per 100 ml. These children were studied for evidence of need for thyroxine medication; 2.6% are being treated. Examples of high serum PBI levels maintained for three years on thyroxine medication are shown. It is suggested that biochemical values affected by hypothyroxinemia should be used to establish the diagnosis of hypothyroidism, of thyroid hormone in the serum.

Studies with lithium in euthyrotic, hyperthyrotic and hypothyrotic rats

The thyroid function of euthyrotic, hypothyrotic and hyperthyrotic rats was studied before and after a 2 weeks' LiCl treatment. 1. 1. The weights of the adenohypophyses, neurohypophyses, adrenals and especially thyroid glands were greater in Li-treated hypo- or hyperthyrotic animals. 2. 2. Serum protein-bound iodine levels were unaffected by Li. 3. 3. The neck 131I uptake values showed that Li decreased the uptake in euthyrotic animals but increased it in all the other groups. When the mass of the thyroid lobe was taken into consideration, Li increased the uptake in the control and hyperthyrotic animals. 4. 4. In electrophoretic analysis Li caused an increase of thyroidal inorganic iodine in all groups. Chromatographically it was noticed that Li decreased the formation of iodothyronines. The results suggest that Li increases thyroidal iodide, which decreases the formation of T 4 and T 3. The goitrogenic effect of Li seems to be augmented by a previously pathologic thyroidal state.

Controlled Clinical Trial of Combined Triiodothyronine and Thyroxine in the Treatment of Hypothyroidism

A -double-blind crossover trial of a combined preparation of triiodothyronine and thyroxine (1:4 ratio) compared with thyroxine alone was conducted with 99 patients previously stabilized on. thyroxine as treatment for hypothyroidism. Four patients were excluded during the trial and eight afterwards owing to gross deficiencies in taking the tablets. Of the remaining 87 patients 42 (48%) had no -preference for either medication, 29 (33%) preferred thyroxine alone, and 16 (18%) the combination. A high incidence of unpleasant symptoms was experienced during the two months' treatment with the combined preparation. The serum protein-bound iodine levels were lowered (mean reduction 1.8 mug./100 ml.) on the combination, but the labelled T(3)-resin sponge uptake values were not altered and remained in the normal range. on both treatments.

Familial thyroxine-binding globulin deficiency.

Genetically determined thyroxine-binding globulin deficiency is described in two families in the United Kingdom. All subjects in both pedigrees were euthyroid. Transmission was by sex-linkage; males showed low serum protein bound iodine and high thyroxine (T4) resin uptake due to complete absence of serum thryroxine-binding globulin; females were less severely affected. The distinctive biochemical results disclosed the diagnosis and emphasize that serum protein bound iodine levels should be interpreted carefully and tests, such as triiodothyroinine (T3) or T4 resin uptake, used to prevent erroneous diagnoses of hypothyroidism.

Serum thyroxine specific activity (T 4SA) in the diagnosis of thyroid dysfunction

The determination of thyroxine specific activity (T 4SA) in blood three days after the injection of 10 μc. of I 131-labeled thyroxine (T 4I 131) is a reliable index of thyroid function not only in patients with hyper- or hypothyroidism but also in euthyroid patients with abnormal serum protein-bound iodine or thyroxine iodine (T 4I) levels resulting from abnormal T 4 binding by plasma protein. T 4SA is determined by three factors: (1) the rate of T 4 secretion. (2) the amount of T 4 present in the body pool and (3) the rate of T 4 degradation. All three factors are increased in hyperthyroidism causing low T 4SA's and decreased in hypothyroidism resulting in high T 4SA's. Values are expressed as per cent of the administered radioactivity per 100 μg. T 4, and the following results were obtained: Normal 13.4 ± 3.1 (mean ± standard deviation), hyperthyroid 2.9 ± 1.7, hypothyroid 78.7 ± 49.8. No overlap was found between these groups. In euthyroid patients with abnormal T 4 binding by plasma proteins, the following T 4SA values were found: estrogen-treated female subjects 11.4 ± 2.2, patients receiving chronic Dilantin ® therapy 10.9 ± 2.2, patients receiving salicylate therapy 14.8 ± 3.5, patients with hypoalbuminemia 12.6 ± 5.0. Serum T 4SA is a simple and reliable test of thyroid function which is especially useful in patients with abnormal circulating thyroid hormone levels caused by extrathyroidal factors.