Serum PBI Research Articles

Effect of long-term iodide refeeding on the synthesis and secretion of T3, T4 and TSH in severe iodine deficient rats.

Abstract. For 6 months, male Wistar rats received an iodine deficient diet (LID), with propylthiouracil (PTU) for the last 2 months. At the end of this treatment (day 0), a daily iodide intake of 20 μg (group 20) and 50 μg (group 50) was supplied. Synthesis and secretion of T3, T4 and TSH as well as thyroid and serum PBI were studied during 140 days of iodine repletion. For the first 4 days of iodide refeeding, thyroid PBI remained low (0.4 ± 0.2 μg 127I/gland) whilst T3 and T4 were undetectable during 2 days only. Thereafter, these parameters increased regularly, reaching control values on days 80, 16 and 90, respectively. During 2 weeks, the thyroid T3/T4 ratio was 6-fold higher and reached the control value on day 45. Plasma T3 and T4 levels were low, but measurable for the first 4 days (0.5 ± 0.1 and 9.9 ± 2.6 nm, respectively). T3 rapidly reached a normal level on day 8, inducing a high plasma T3/T4 ratio for 16 days. This ratio decreased abruptly when T4 secretion increased, attaining the control value on day 45. Therefore, the preferential T3 secretion occurring during the first 16 days is directly linked to the preferential T3 synthesis. Plasma TSH levels remained 10-fold higher than the control value for the first 8 days (490 ± 99 vs 39 ± 15 μU/ml), then decreased abruptly and reached normal level after 1 month. Pituitary TSH contents varied in an opposite manner to the plasma TSH concentrations. In conclusion, the effect of iodide on thyroid function occurs sequentially, i.e. thyroid hormone synthesis precedes neosecretion (latency phase). In both processes, T3 appears preferentially. This phenomenon is linked to the low thyroglobulin (Tg) iodination rate. In addition, the re-establishment of a normal thyroid hormone secretion prevailing over the iodinated Tg store constitution represents an adaptative mechanism; this leads rapidly to a maximum supply of active hormone (T3) with iodine economy. Moreover, it takes 2–3 months for the complete thyroid function restoration. At the pituitary level, the normal plasma T3 concentration found during the latency phase of iodide refeeding is not sufficient by itself to inhibit TSH secretion. This parameter starts to decrease only when T4 has reached a critical level to generate adequate T3 from T4 deiodination. Inhibition of TSH synthesis is a less sensitive process since it occurs for more elevated T4 concentrations. Finally, the similar pattern of thyroid function's recovery in the two groups indicates that the 20 μg dose is a sufficient supply and that thyroid autoregulation occurs, thus avoiding a thyroid hyperfunction.

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.

Protein-Linked Iodotyrosines in Serum after Topical Application of Povidone-Iodine (Betadine)

Markedly elevated serum PBI levels occur after therapy with povidone-iodine (Betadine), an iodine-polyvinylpyrrolidone iodophor. In this study, we investigated the serum iodine compounds from a severely burned patient with normal initial thyroid function tests who was swabbed with Betadine ointment and received daily therapeutic baths in Betadine. Three and 9 days after therapy, his serum contained 93 and 168 micrograms PGI/dl, respectively (normal range, 4-8), while the serum T4 and free T4 index were normal; the serum T3 level, however, was abnormally depressed. Most of the PBI was in albumin, and hydrolysis of the serum proteins with proteases released 35% of the PBI as monoiodotyrosine, 3.2% as diiodotyrosine, 0.01% as T3, and 2.5% as T4, as determined by competitive radioassays, anion exchange, and reversed phase high pressure liquid chromatography. The same concentrations of T4 and T3 were detected before and after hydrolysis. Failure of the proteases to completely hydrolyze iodoalbumin partially explains why all of the PBI was not recovered as iodotyrosines in the serum protein hydrolysates. Povidone-iodine rapidly iodinated tyrosine residues in human serum albumin at pH 7.4 and 37 C in vitro, and the ratio of diiodotyrosine to monoiodotyrosine increased as the molar ratio of povidone-iodine to albumin was increased. It is concluded that the abnormal increase in serum PBI resulted from absorption of the iodophor into the blood where it primarily iodinated albumin and, to a lesser extent, the globulins.

Increase in thyroxine-binding globulin (TBG) in lysinuric protein intolerance.

The common occurrence of increased serum PBI concentration in patients with lysinuric protein intolerance (LPI) was elucidated by further studies. The reason was found to be an increase in the concentration of thyroid binding globulin (TBG), concomitantly with an increase in the binding capacity of TBG. The concentrations of serum thyroxine and triiodothyronine were elevated, whereas the free thyroxine index remained normal. The free triiodothyronine index was slightly increased. The binding capacity of thyroid hormone binding pre-albumin (TBPA) was significantly decreased. The concentrations of reverse triiodothyronine (3,3',5'-T3) and of 3,3'-diiodothyronine were normal. In all patients serum lactic acid dehydrogenase activities and ferritin concentrations were elevated. The reason for the almost constant increase in TBG remains obscure. It may be related to the primary disorder of LPI, a defect in diaminoacid transport.

Acquired Refractoriness to Thyroid Hormone Action in Treated Toxic Nodular Goiter

A case of apparent target organ refractoriness to thyroid hormones has been observed during the recovery phase of toxic nodular goiter after 131I therapy. The serum PBI was normal before the onset, but elevated serum PBI and T4 concentrations were observed during the toxic phase, and after recovery, with elevated T3 as well. The case differed in important respects from the congenital, hereditary disorder known as the Refetoff syndrome.

Cyanide, protein and iodine interactions in the performance, metabolism and pathology of pigs

Performance and metabolic and pathological changes were evaluated in 48 growing pigs fed different levels of dietary protein, cyanide and iodine. Protein deficiency reduced urinary iodine excretion and the concentrations in serum of protein, protein bound iodine and thiocyanate. It also reduced liver rhodanese activity and caused a decrease in urinary thiocyanate excretion which was not significant. Dietary cyanide increased urinary thiocyanate and iodine excretion and serum thiocyanate concentration while the basal diet reduced urinary iodine excretion and serum PBI. Pathological studies showed that cyanide treatment had no marked effect on the microanatomy of the tissues examined. Dietary protein deficiency caused histological changes in the thyroid gland and bone which suggested a decline in metabolic activity. Iodine deficiency caused hyperplastic goitre in the experimental animals.

Effects of organochlorine insecticides on serum proteins in occupationaly exposed people

This paper reports on the level of serum PBI in a group of 42 workers handling OCI as compared to a control group of 51 workers not occupationally exposed to these insecticides. Practically all the serum PBI values were within the range considered as normal. However, the serum PBI was significantly lower in workers occupationally exposed to OCI when compared to the non-occupationally exposed workers (p<0.01). It is suggested that the presence of OCI in the human body affects the metabolism of thyroxine. Homeostasis is maintained by a sustained effort of the hypophyso-thyroid system.

Thyroid function in patients undergoing maintenance hemodialysis: Unexplained low serum thyroxine concentration

Thyroid function was studied in 55 patients undergoing maintenance hemodialysis who were all judged to be clinically euthyroid. The dialysis patients, in comparison to normal control subjects, had significantly lower mean values for serum T 4(4.0 ± 1.4 [SD] μg/dl versus 7.9 ± 1.5 μg/dl, p < 0.001), T 3 (118 ± 31 ng/dl versus 147 ± 28 ng/dl, p < 0.001), free T 4 measured by equilibrium dialysis (1.22 ± 0.38 ng/dl versus 2.15 ± 0.67 ng/dl, p < 0.001), free T 3, free T 4 index, and free T 3 index. Serum TBG, measured by radioimmunoassay, was similar to that of the controls and serum TSH, 2.2 ± 1.3 μU/ml, was also similar to that of control values, 2.0 ± 1.1 μU/ml. The serum PBI did not change during the dialysis procedure, but serum inorganic iodine fell slightly from 2.1 ± 1.1 μg/dl before dialysis to 1.2 ± 0.6 μg/dl after dialysis ( p < 0.05). The marked reduction in serum total T 4 and free T 4 concentrations and the moderate reduction in serum total T 3 and free T 3 levels in apparently euthyroid patients undergoing hemodialysis has not been explained. The normal serum TSH levels in the face of these low concentrations of thyroid hormone suggests an abnormality in the control of TSH secretion in these patients.

A study on endemic goiter in East Java of the Republic of Indonesia (author's transl)

We conducted a medical survey on subjects living in the mountain districts, located at about 400 to 500 m above sea level, near Malang City in the eastern part of Java, the Republic of Indonesia. Serum levels of thyrotropin (TSH) and thyroid hormones were measured in 163 subjects from 9 to 70 years of age, of which 45 were male and 118 were female. A synthesized thyrotropin releasing hormone (TRH) 500pg infusion test was performed on 41 of the subjects from 14 to 70 years of age (7 males, 34 females) and on 15 normal Japanese subjects from 19 to 35 years of age (7 males, 8 females) as controls.Serum TSH and triiodothyronine (T3) were measured by means of radioimmunoassay, serum thyroxine (T4) by competitive protein binding analysis, and serum PBI by the auto-analyser method. The incidence of antithyroglobulin antibody (thyroid test) and antimicrosomal antibody (microsome test) was also studied to assess the role of auto-immunity in goitrogenesis. Goiter size was classified into five grades : from Grade 0 (without goiter) to Grade IV (with huge goiter) by our criteria.Mean serum PBI values were low in all groups with goiters, especially in subjects with huge goiters, but there was no significant difference between non-goitrous and goitrous groups. In one of the 28 non-goitrous subjects, the serum T4 level was low while that of the remaining 27 was within the normal range. Serum T4 values of subjects with big and huge goiters were significantly lower than those of the non-goitrous group. There was no significant difference between the control and non-goitrous groups.On the other hand, serum T3 levels were normal in only two of the 28 non-goitrous subjects and were low in the remaining 26. In the group with huge goiters, serum T3 levels were low in 9, normal in 20, and elevated in only one. T3 values in the groups with big and huge goiters were significantly higher than those of the non-goitrous group. As mentioned above, there was a negative correlation between serum T4 and T3 in subjects with goiters, and relative hypersecretion of T3 occurred in the goitrous groups in contrast to the non-goitrous group. The result of our study confirms that preferential secretion of T3 by the thyroid occurs in goitrous subjects and may represent an important homeostatic mechanism to combat against iodine deficiency.Serum TSH levels in 28 non-goitrous subjects were all within the normal range, and there were elevated serum TSH levels in only 19 out of the 135 goitrous subjects. Although serum log TSH levels do not significantly correlate with the degree of goiter, the mean serum log TSH of the goitrous groups was higher than that of the non-goitrous group, the mean of which was higher than that of the control subjects.Following TRH infusion, 7 non-goitrous subjects showed normal serum TSH response to TRH. In 34 goitrous subjects, there were various serum TSH responses, which included a normal response in 17, delayed in 6, hypo in 4, non in 5 and hyper in 2. According to our results of the TRH test, the secretion of TSH by the pituitary in goitrous subjects following TRH infusion may be different from that in a normal control. There were two inverse relations between basal TSH and T4 (r=-0.43, P<0.01) and peak TSH and T4 (r=-0.44, P<0.01) following TRH infusion. There was, however, no significant relation between serum TSH and T3. Since serum TSH correlated with serum T4 in the TRH test, the TSH secretion of the pituitary may be partially controlled by the serum T4 level. There was no positive case in the thyroid test and only one positive case in the microsome test.Many of the subjects with goiter have hypothyroidism, if judged by serum T4, T3 and PBI.

Placento-thyroidal relationship in normal pregnancy.

Estimations of serum HCT, HTSH, T4, T3, PBI, ETR, Triosorb, TBG-binding capacity, BMR and urinary total estrogen were made simultaneously in 160 women in normal pregnancy. TRH stimulation tests were made in 20 cases in each trimester of pregnancy. HCT was detectable even in early pregnancy, tending to increase gradually toward the terminal stage of pregnancy as serum thyrotrophin bioactivity showed. On the other hand, serum TSH level measured by radio-immunoassay remained essentially the same throughout the course of pregnancy as in the nonpregnant state, moreover, it was suggested by the TRH stimulation test that pituitary TSH secreting function of pregnant women was similar to that of the non-pregnant. These findings suggest that thyroid hyperfunction during pregnancy which is shown by progressively increased T3, T4, and PBI may not be due to high estrogen-high TBG binding capacity-low free thyroxinenegative feed back-high TSH secretion but to HCT originating from placenta. In spite of thyroid hormone increase, it is true that the clinical picture of hyperthyroidism is not manifest among normal pregnant women, and ETR remained within the non-pregnant range throughout the course of pregnancy. We have also demonstrated that Triosorb decreased progressively. This may be interpreted to be due to the increase of TBG binding capacity which is increased progressively and binds more of free thyroxine during pregnancy. Such a change in TBG binding capacity is well known to be caused by the effect of estrogen which is progressively increased during pregnancy. In a word, it is possible to say that there is a placento-thyroidal system in pregnancy; HCT elevates thyroid function and TBG increased by estrogen carries thyroid hormone to target organ.

Serum triiodothyronine 7-15 years after fractionated low dose radioiodine therapy of thyrotoxicosis.

In 189 of 334 patients, who had been treated with fractionated doses of radioiodine for Graves' disease 7-15 years ago, the serum concentrations of triiodothyronine have been estimated in additition to the following parameters: Protein bound 127-iodine (PB-127-I), free thyroxine index, cholesterol- and TSH-level in serum, tendon reflex time and clinical index according to Billewitz et al. (1969). In forty-one of the 189 sera the free T4 (AFT4) and free T3 (AFT3) concentrations were measured as well. The following hormonal and clinical patterns were observed: (1) Euthyroidism, with all parameters within the normal range in 148 patients (equals 78-4%). (2) Hypothyroidism with low serum T3, PBI, AFT4, AFT3 and elevated TSH six subjects (equals 3-2%). (3) Persistent hyperthyroidism with increased thyroid hormone concentrations and low TSH in seven cases (equals 3-7%). (4) In twenty-eight clinically euthyroid patients (equals 14-8%) TSH was elevated with normal PBI and AFT4. Twenty of these subjects had a low normal T3 and in nine the T3 was clearly in the hypothyroid range (40 plus or minus 12 mug/dl). (5) The constellation of normal T3, low T4 and elevated TSH, which has been frequently found after radioiodine therapy, has been seen in only moderate form in ten cases.

Effects of a polychlorinated biphenyl mixture (aroclor 1254) and DDT on biliary thyroxine excretion in rats.

Treatment of rats with a polychlorinated biphenyl mixture (Aroclor 1254; PCB) causeda 4- to 5-fold increase in the 3-hr biliary excretion of 125I-thyroxine (T4). In treated rats bile flow was increased and the 125I-T4 bile:plasma ratios (B/Pratios) and biliary clearance rate of plasma 125I-T4 were greatly elevated. The proportion of biliary 125I present as T4-glucuronide was larger in PCB-treated rats. PCB also elevated thyroid 13II uptake andreduced serum PBI concentrations. DDT did not affect the biliary excretion of 125I-T4, but did increase bile flow and the biliary clearance rate of plasma 125I-T4. It also caused a marginal elevation of B/P ratios and increased the proportion of biliary 125I present as T4-glucuronide slightly but significantly. DDT did not affect thyroid 13II uptake or serum PBI concentrations. The effects of PCB were similar to those of the polycyclic hydrocarbon-type of enzyme inducers. The results of DDT-treatment were similar to those produced by the phenobarbital type of inducer...

The transplacental passage of thyroxine and foetal thyroid function in the rat.

ABSTRACT A study has been made of the transplacental passage of thyroxine (T4) in rats when the hormone is present in physiological concentrations, and of the activity of the foetal thyroid gland in the perinatal period. Several aspects of foetal thyroid function were assessed in intact and thyroid-ectomized (TX) pregnant rats maintained with graded doses of T4. A daily dose of 2 μg T4/100 g body weight yielded near normal maternal and foetal serum PBI levels; with a dose of 1 μg the values were slightly low. Both these doses resulted in a decrease in the total and T4 iodine content of the foetal thyroid; an even greater decrease occurred in rats maintained with 5 μg/100 g body weight/day. The rate of uptake of iodine by the foetal gland was significantly depressed by the 2 but not the 1 μg dose. Serum PBI levels in the foetus were related directly to the dose of T4 and inversely with the degree of depression of the thyroid gland. Both maternal and foetal serum PBI levels in the unsupplemented TX rats were at least 60 % of normal and there was evidence of increased secretion of T4 by the foetal thyroid. The data indicate that the placenta is readily permeable to T4 when the hormone is present in maternal serum in doses that are close to physiological. However it was not possible to estimate the extent of the placental transfer of endogenous hormone. Significant foetal thyroid function was evident near term. It is suggested that both the foetal and maternal thyroids contribute to the maintenance of serum T4 levels in the foetus.

Iodine metabolism in spotted munia, Lonchura punctulata

Radioactive iodine metabolism was studied in both sexes of Spotted Munia, Lonchura punctulata, during different periods of the year. A characteristic “avian pattern” of thyroidal radioiodine retention was observed, which appeared to be due to a rapid turnover, as evident from a high uptake, rapid thyroxinogenesis, and release of hormone into blood. Monoiodotyrosine (MIT), diiodotyrosine (DIT), and thyroxine (T 4) were the three iodoamino acids identified. Triiodothyronine (T 2) was never detected. Thyroxinogenesis was of the typical vertebrate type. With time MIT:DIT ratio, which was always less than one, registered a decline, indicating a precursor-product relationship with the hormone. A pronounced seasonal variation was demonstrated in thyroidal 131I uptake, thyroxine production, and serum PBI, which were all minimal during the peak phase of reproductive activity in this bird. Effect of starvation, exogenous iodide (KI), thyrotropin (TSH), and propylthiouracil (PTU) was also studied. Starvation increased 131I uptake and favored high MIT formation, resulting in MIT:DIT ratios greater than one, indicating economic handling of iodine. KI drastically depressed 131I uptake and favored rapid conversion of MIT to DIT. But T 4 production was not markedly altered by these two treatments. TSH stimulated 131I uptake, organification of iodide, conversion of MIT to DIT and thyroxine production, pointing toward an active pituitarythyroid axis. PTU led to increase in DIT and a 5-fold decrease in T 4, indicating that in wild birds, as in mammals, the DIT to T 4-step may be the most sensitive to PTU treatment. The annual fluctuations in thyroid activity, which do not coincide with natural fluctuations in temperature and daylength, may be influenced by extra intake of iodide, by contributing to the extrathyroidal pool, and endogenous thyrotropin secretion.

IODINE METABOLISM IN AUTONOMOUS HOT NODULES OF THE THYROID

SUMMARYThe thyroidal iodide clearance rate, the plasma inorganic iodine (PII), the absolute iodine uptake (AIU) by the thyroid, the serum PBI, the intrathyroidal exchangeable iodine pool, the renal iodide clearance rate and the urinary iodine excretion were measured in twenty‐one cases of autonomous hot thyroid nodule with suppression of the normal parenchyma (toxic adenoma, TA), in eight cases of autonomous hot nodule without such suppression (subtoxic adenoma, STA), and in eighteen controls; the 131 I uptake and PB131 I were measured in 390 cases of TA and 111 of STA compared with eighty‐one controls.The most striking finding was a greatly reduced pool of intrathyroidal exchangeable iodine in the TA group. This explained the high PB131 I values (out of proportion to the degree of hyperthyroidism) and the short biological half‐life of radioiodine within the gland. There was no evidence of iodine deficiency, either from the PII or the urinary iodine measurements. Otherwise the patients with TA showed evidence of mild hyperfunction: increased 131I uptake, AIU and PBI, but with a considerable overlap with the normal range. The patients with STA had, in general, laboratory values intermediate between the TA group and the controls. The intrathyroidal exchangeable iodine pool was not significantly reduced, probably because in STA the normal parenchyma surrounding the nodule was still actively taking part in the exchange, whereas in the TA the normal parenchyma constituted a practically dormant iodine pool.

Long-acting thyroid stimulator and thyroid function in relatives of patients with Graves' disease.

SUMMARYIn ten families, fifty relatives and seven husbands of ten patients with untreated Graves’disease were submitted to clinical examination, biological and immunological investigations. They were compared with fifty control subjects. In the relatives, thyroid diseases were found in 26%, positive LATS‐IgG responses in 30%, thyroid antibodies in 23% and abnormal NBEI in 30%. The mean LATS response was significantly greater than in controls. With one exception no overt hyperthyroidism was found in the relatives on the basis of serum PBI, T3 resin uptake test, total T4 and TSH level. From the analysis of the pedigrees, no definite mode of inheritance can be found for LATS and NBEI. These data suggest the existence of a thyroid metabolic anomaly in the families of patients with thyrotoxicosis and argue against LATS as the cause of the hyperthyroidism of Graves’disease.

The Effect of Amprolium and of Payzone on the Functional State of the Thyroid in Growing Chickens

Amprolium fed to growing chickens in a concentration of 125 p.p.m. in a commercial diet was accompanied by a small but significant decrease in thyroid activity compared with the results for untreated chickens, judged by serum PBI values. The epithelium : colloid relation was lowered. This was presumed to be a consequence of the antagonistic effect of amprolium on thiamine. Payzone feeding, 10 p.p.m. in commercial feed, caused a more pronounced retardation of thyroid activity, judged by the same criteria. A possible connection between the depressed thyroid function and the well-established improvement in weight gain and feed conversion in connection with payzone feeding is discussed.

Rod myopathy: Beta globulin peak and increased complement

A distinct beta globulin peak was consistently present on paper electropherograms of sera from three brothers with nemaline, i.e., rod myopathy. The C3 component complement was elevated in each of them; other constituents of the beta peak were not increased. Laboratory indices other than the serum creatinine levels, including serum cholesterol, triglycerides, PBI and insulin and growth hormone responses, blood cell karyotype, and plasma 11(OH)corticosteroids and urinary 17-ketosteroids, 11-desoxycortisol metabolites and Porter-Silber chromogens were unchanged. Serum creatinine was low.

Thyroid hormone-binding in opossum serum: evidence for polymorphism and relationship to haptoglobin polymorphism.

Thyroid hormone—binding in the serum of the opossum (Didelphys marsupialis virginiana Kerr) is limited to a postalbumin (PtA1), the major carrier of radiothyroxine in the common phenotype of T4 distribution, and serum albumin. In 6 of 177 individual sera surveyed in a polyacrylamide gel electrophoresis system a more cathodal postalbumin (PtA2) was found. PtA2 is stable at 4 C unless mixed with PtA1 serum when an additional postalbumin develops whose electrophoretic mobility is between those of PtA1 and PtA2. Unlike PtA1( the slower postalbumin has little or no affinity for triiodothyronine (T3). Both postalbumins can be quantitated by saturation techniques, with binding curve plateaus achieved at T4 concentrations in serum of 100 μg/100 ml, and binding capacities ranging from 12 to 35 M-g T4/100 ml serum. There is no correlation between serum PBI and postalbumin binding capacity. The low serum PBIs in this species (mean = less than 1.5 μg/100 ml) are in agreement with total serum T4 measured by the competitive protein binding technique and may reflect affinity of binding proteins for T4 which is somewhat lower than in human serum. Dialyzable fraction T4 measured in pooled PtAx sera was.04%. The binding protein pattern in this American marsupial contrasts sharply with that of an Australasian marsupial, the kangaroo (Macropus giganteus), which shows prealbumin, albumin and postalbumin binding of T4 and in which prealbumin is the major carrier. The serum haptoglobin (Hp) phenotypes in the opossum have also been defined. Of 4 phenotypes described in this study from 65 sera, 3 phenotypes occurred only in PtA1 sera. The fourth Hp phenotype, designated 3–1, was observed only in PtA2 sera. The invariable association of Hp 3–1 and PtA2 phenotypes suggests linkage of traits, or, possibly, that a single protein (PtA2) may have haptoglobin and T4-transport functions. (Endocrinology92: 822, 1973)

Comparative Study of Thyroxine Assays Employing Kit Radio-Ligand Reagents

A comparative study of some ‘kit’ radiometric procedures for the determination of thyroxine in serum is reported. Four manufacturers' competitive-binding reagents and methods—three incorporating prior extraction and one employing column elution—are examined. Considerable discrepancies exist between the manufacturers' ‘standards’ which, in the main, account for the differences in results obtained by the different methods. Other deficiencies include susceptibility to metal ion interference, variation (up to 8%) in thyroxine extraction and non-specific, i.e. ‘mimic T-4’, measurement. Radio-ligand reagent ‘kits’ need to be critically assessed before being used routinely. Separation of hypo-and hyperthyroid from euthyroid patients is achieved as well with some competitive protein-binding T-4 methods as with serum PBI.