Protein-bound Iodine Research Articles

The Influence of Fatty Acids on Serum Thyroxine Determination by Competitive Protein-Binding Radioassay

Thyroxine concentration, determined by competitive protein-binding radioassay (T4(D)), increased in serum stored at 20 degrees C and 37 degrees C. The increase correlated well with the increase in nonesterified fatty acids (NEFA). In vitro addition of NEFA to serum and in vivo increase in NEFA induced by post-prandial heparin injection resulted in a proportional increase in T4(D) values. Protein-bound iodine and thyroxine concentration, as determined by radioimmunoassay, were not influenced by storage and changes in NEFA concentration. NEFA interfere with T4(D), leading to elevated results.

The automatic determination of iodide or iodate in solution by catalytic spectrophotometry, with particular reference to river water

A catalytic procedure, in which a Technicon AutoAnalyzer(I) is used, for determining iodide or iodate (50 µg l–1) added to river water (during river-flow gauging operations by the dilution method) is described. The maximum error of the analytical procedure, as determined by replicate analysis of six sets of eleven samples, is ± 0·36 per cent. in the range 20–100 µg l–1. The setting up of the procedure is described in detail, according to Mark's (1973) recommendations. The shape of the most appropriate calibration graph is considered. Also, the effects of changes in temperature, reaction period and spectrophotometric variables are discussed. This information could be used directly in the development of methods for determining iodine in other types of sample, e.g., protein-bound iodine in blood or urine and iodate or iodide in sea water, etc. Further, it could also be used in developing other automatic procedures that rely upon catalytic reactions that follow a pseudo-first-order behaviour.

Thyroid function during erythrosine ingestion in doses encountered in therapy with conventional antibiotics.

Six euthyroid patients without clinical or biochemical evidence of any renal or thyroid disorder received a diet of fixed composition. They were given no drugs. Urine was collected quantitatively throughout the whole investigation for determination of iodine and creatinine. After 5 days on diet they received 1.91 mumol of erythrosine, corresponding to approximately 7.88 mumol of iodine daily for 10 days. Thyroidal radioiodine studies were performed, levels of plasma inorganic iodine were calculated, and thyroxine, protein-bound iodine, and total iodine in serum were determined before and during erythrosine ingestion. A statistically significant increase in plasma inorganic iodine or in urinary iodine excretion was not found. The other test results of thyroid function remained virtually unchanged. Based on clinical aspects of thyroidal iodine metabolism we conclude that at most 7.8 per cent of the iodine content of the ingested erythrosine could have supplemented the iodine space.

A comparative study of avian and rat patterns in thyroid function—II. plasma protein-bound iodine and thyroid hormone secretion

1. PB 127I is lower in the duck than in the rat (1·90 ± 0·06 μg/100 ml vs 4·95 ± 0·04 μg/100 ml), and 127I/PB 127I plasma ratio is greater in the duck. 2. PB *I in ducks, hens, pigeons or quail, is not a whole hormonal fraction as it is in the rats and most mammals. 3. A non-hormonal iodinated and organic fraction appears early in the plasma after radioiodine injection (3–6 hr) largely before hormonal iodine, and represents 98 to 100% of the PB *I. This fraction is TCA precipitable but not extractable with n-butanol. 4. Biological half life of radiolabelled T4 ( 125I) in duck plasma is always shorter when it is evaluated from PBI than from total plasma radioactivity. 5. TSR in the duck is greater than in the rat (1·88 ± 0·11 μg T4/day per 100 g body weight vs 1·25 ± 0·05). Iodine deficiency greatly diminishes PB 127I and TSR in the duck.

Response of the thyroid gland to changes in the blood plasmin concentration

In experiments on rabbits, plasmin (fibrinolysin), in a dose of 2000 units/kg modified the hormone-excreting function of the thyroid gland: 5 min after injection of the preparation the blood protein-bound iodine level was lowered, but 1 h after injection it was raised. In rabbits with depressed thyroid function fibrinolysin also inhibited the hormone-excretory function of the gland. If plasmin activity was reduced by e-aminocaproic acid, the protein-bound iodine level rose. Heated fibrinolysin did not affect thyroid function.

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 < 0.05) more feed and grew significantly (P < 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 > 0.05). After 70 days on trial, weight gain was less (P < 0.05) on the 20% RF diet compared with the 0 and 6.5% diets. There was a significant (P < 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 < 0.05) thyroid hypertrophy, but at slaughter serum protein-bound iodine level was the same (P > 0.05) for all groups. There was little difference among groups with respect to pelt size and pelt quality.

Binding of thyroid hormone in rabbit serum: definition of a prealbumin and effects of strain variation on binding.

SUMMARY Sera from inbred rabbit strains have been studied to determine radio-thyroxine distribution after electrophoresis, to measure protein binding capacity for thyroxine (T4) and to examine possible interrelationships of binding capacity and serum protein-bound iodine (PBI). In electrophoretic studies at pH 7·4, serum albumin and prealbumin, the latter a previously unrecognized carrier of T4 in the rabbit, are the principal transport proteins. At pH 9·0, prealbumin is the major carrier (61% of tracer). Prealbumin also binds significant quantities of tri-iodothyronine. The mean binding capacity of serum prealbumin for T4 in 12 rabbit strains was 500 μg/100 ml. Protein-bound iodine levels are known to be strain-dependent in the rabbit. In the current studies, however, there was no strain-specificity of prealbumin binding capacity, and no correlation between PBI and binding capacity of prealbumin, the principal T4-specific transport protein. These observations suggest that factors other than the capacity of binding proteins for T4 may be primary determinants of hormone levels (PBI) in blood in the rabbit.

Thyroidal iodopriteins in Pendred's syndrome.

Radiation Medicine Centre, Bio-Medical Group, Bhabha Atomic Research Centre, Tata Memorial Hospital, Parel, Bombay-12, India (Received 25 March 1974) Pendred's syndrome is characterized by familial goitre, nerve deafness and a partial release of radio-iodine from the thyroid on perchlorate administration. This last was thought to be due to impaired activity of peroxidase enzymes or to some abnormality of receptor proteins where iodination occurs. Burrow, Spaulding, Alexander & Bower (1973) reported that peroxidase activity in such patients is normal but studies on thyroidal iodoproteins have shown variable results (Medeiros-Neto, Nicolau, Kieffer & Ulhoa-Cintra, 1968; Milutinovic et al. 1969). A 22-year-old deaf-mute woman (N.G.) with a goitre which had progressively increased in size from infancy was euthyroid in all respects: basal metabolic rate, 10·0%; serum cholesterol concn, 174·3 mg/100 ml; tri-iodothyronine (T3) red blood cell uptake, 14·6%; stable protein-bound iodine levels, 5·7 μg/100 ml. Radioactive iodine uptake by the thyroid was 65·7%

RELEASE OF THYROXINE FROM THE LIVER DURING ANAESTHESIA AND SURGERY

During relatively minor surgical procedures under halothane anaesthesia, an increase in plasma protein-bound iodine concentration was observed. In patients previously given thyroxine labelled with radio-iodine, plasma radioactivity concentrations also increased. There was a concomitant decrease in radioactivity in the liver. The results suggest that anaesthesia leads to a progressive discharge of protein-bound thyroxine from the liver into the plasma. The effect is believed to be reversible.

THE RADIOIMMUNOASSAY OF THYROXINE IN UNEXTRACTED HUMAN SERUM

A specific, accurate, precise and simple radioimmunoassay for thyroxine (T4) in small volumes of unextracted serum is described. It discriminates well between levels found in different states of thyroid function. Levels in euthyroid subjects range between 4.3 and 11.2 μg/100 ml (mean 7.7); in untreated hyperthyroid subjects, 13.2‐25.6 μg/100 ml (mean 19.2); and in untreated hypothyroid subjects undetectable to 2.6 μg/100 ml (mean 1.4). There is satisfactory correlation with competitive protein binding and protein bound iodine methods. Because of its advantages over previous techniques, it is suggested that T4 radioimmunoassay will become the routine method of assessing thyroid status.The measurement of serum thyroxine (T4) is the single most important test in the routine laboratory assessment of thyroid status. Ideally the T4 assay should be specific, cheap, simple and have a high sample capacity. Thyroxine is determined most commonly in serum extracts by competitive protein binding (CPB) methods (Murphy & Pattee, 1964; Ekins et al., 1969) or, indirectly, by estimation of serum protein bound iodine (PBI). Both techniques require the processing of relatively large volumes of serum before assay. The PBI method has the added disadvantage of measuring iodine‐containing compounds other than thyroxine (Acland, 1971).We report here a specific, precise and simple radioimmunoassay for thyroxine in unextracted human serum and its application to the assessment of thyroid status. It has significant advantages over CPB, PBI and previous radioimmunoassay methods.

Thyroid activity and (Hemidactylus flaviviridis Rüppell) in relation to sex hormones.

SUMMARY Orchidectomy in Hemidactylus flaviviridis led to significant reduction of thyroidal 131I uptake, thyroidal content of thyroxine, plasma protein-bound iodine and oxygen consumption of isolated liver and skeletal muscle (at 30 °C). Administration of testosterone to orchidectomized lizards restored these parameters to normal levels. Dependence of thyroid function and oxidative metabolism on male hormone may be a general feature in reptiles. This hormone may, therefore, be of greater physiological importance in these animals than in other vertebrates. Since reptiles occupy a crucial phylogenetic position in the animal kingdom these findings are important from the point of view of evolution of the functional aspects of hormones in vertebrates. The results also show that thyroid function is inhibited by oestrogen(s) in this lizard. This may be an adaptive compensatory measure to control (through effects of the thyroid on metabolic activities) the extra expenditure of energy usually associated with such energy-consuming functions as ovulation and egg-laying.

Metabolic Aspects of Spontaneous Rewarming in Accidental Hypothermia and Hypothermic Myxoedema

The metabolic background to spontaneous rewarming has been studied in 70 euthyroid patients with accidental hypothermia and in 18 patients with hypothermic myxoedema by correlating their rates of rewarming with their initial serum protein bound iodine (PBI), blood glucose, plasma free fatty acid (FFA), plasma 11-hydroxycorticosteroid (11-OHCS), and arterial PO2 levels. In the hypothyroid group, the rates of spontaneous rewarming correlated significantly with only the PBI levels (P < 0.05). In the euthyroid group, there may be an inverse correlation between the rate of spontaneous rewarming and age (P < 0.10). The roles played in the rewarming process by the other parameters measured are discussed, particularly in relation to individual clinical situations.

Skin Pigmentation and Acute Renal Failure in a Patient Receiving Phenazopyridine Therapy

ACUTE renal failure and skin pigmentation secondary to phenazopyridine hydrochloride therapy have been previously described in patients with preexisting renal dysfunction.¹The present report concerns a patient with apparently reasonable prior renal function who, while receiving usual doses of the phenazopyridine, developed yellowish-orange pigmentation of the skin and of urinary casts, and acute renal insufficiency. <h3>Report of a Case</h3> An 85-year-old white woman was admitted to the hospital in December 1970 because of atrial fibrillation, angina pectoris, and left ventricular failure. Her medications included pentaerythritol tetranitrate and sublingual nitroglycerine (Nitrol tablets). On physical examination, apart from her cardiopulmonary manifestations, she was also found to have suprapubic and bilateral costovertebral angle tenderness. Laboratory determinations included the following: hemogram, serum electrolytes, bilirubin, protein electrophoresis, glutamic oxaloacetic and glutamic pyruvic transaminases, alkaline phosphatase, and protein-bound iodine. All were within normal limits. Serum urea nitrogen and creatinine values were 10 mg/100 ml and

The effect of lithium on thyroid functioning: A controlled study

THE EFFECTS of lithium on thyroid function have recently been reviewed by SHOPSIN.~ Anecdotal reports of hypothyroidism and goiter are described. Controlled human studies have been done by SEDVALL et aL2 and COOPER and SIMPSON.~ SEDVALL et al.2 gave lithium to 14 manic-depressives and used 11 patients receiving phenothiazines, with other diagnoses as controls. The lithium treatment was begun, “about one week after admission to the hospital. . . . Tests of thyroid function were performed during the first week after admission to hospital and 10 to 14 days later. At the latter time lithium treatment in the manic-depressive patients had been maintained for 7 to 20 days.” A personal communication from the senior author indicates that the initial thyroid function tests were all done prior to initiation of lithium, and the second series of tests were done 7 -20 days after lithium was begun, and not 10-14 days as published. Compared to the first test, there was a significant decrease in protein bound iodine (PBI) and a significant increase in the percentage of orally administered radioactive iodine (24 hr RAIl”l) in the thyroid after 24 hr, in the lithium treated manic-depressed patients. There were no changes in the control patients. It is difficult to evaluate the significance of these results because the control group had different diagnoses and received an active drug that may affect thyroid function tests.4 COOPER and SIMPSON~ compared PBI and free thyroxine in 25 manic-depressives two weeks after initiating lithium treatment to 139 other psychiatric admissions (excluding organic psychoses) who had blood drawn while drug free. The PBI and free thyroxine were significantly reduced in the lithium group. They also compared RAIU (24 hr) before, and 12-16 weeks after lithium treatment in 12 manic-depressives and found a significant increase following lithium treatment. BURROW et aL5 studied 9 patients before and after 3-4 weeks of lithium therapy. Some patients received concomitant psychotropic drugs and perhaps diphenylhydantoin or oral contraceptives. The patients were hospitalized and diagnosed as having “mood disorders” although one patient may have been hospitalized for a seizure disorder. They found that *We wish to acknowledge the help we received in the statistical computations from Mrs. Dolores Millan

Role of the thyroid in the development of the obese-hyperglycemic syndrome in mice ( [formula omitted

Some aspects of thyroid activity in obese mice were investigated. Protein-bound iodine (PBI), hormonal iodine (HI), total thyroxin (TT 4) in plasma, 131I uptake and release from the thyroid and apical cell width, and nuclear volume of the thyroid epithelial cells were determined in various age groups in obese and nonobese mice. On the basis of the results of the comparison between the obese and nonobese mice, it was concluded that the genetically obese mouse is hypothyroid. This conclusion is supported by the finding that body temperature that is low in obese mice, can be raised by thyroxin injections to normal values. An increased sensitivity for exogenous thyroxin can be shown also in the induction of liver mitochondrial α-glycerophosphate dehydrogenase. The possibility that hypothyroidism is one of the causes of the obese-hyperglycemic syndrome is discussed.

Effect of Synthetic Salmon Calcitonin on Iodine Metabolism in Rabbits

SummaryLong-term administration of synthetic salmon calcitonin to rabbits markedly decreases the radioiodine (131I) uptake in the thyroid gland as well as in the plasma. Protein-bound iodine and thyroxine serum levels are also decreased. In contrast, the renal iodine clearance is much increased in calcitonin-treated rabbits as compared to controls or to vehicle alone. This ioduric effect of salmon calcitonin can explain its role in goiter induction.This study was supported in part by NIH-General Grant, and Detroit General Research Corporation. We thank the Armour Pharmaceutical Company for the kind supply of synthetic salmon calcitonin used in this study.

The frequency distributions of commonly determined blood constituents in healthy blood donors

The frequency distributions of 19 biochemical variables in blood have been studied on 1000 blood donors. The distributions within age/sex groups of calcium, CO 2 capacity, chloride, ions difference, inorganic phosphate, potassium, sodium and total protein values did not differ significantly from Gaussian form; those of alkaline phosphatase, cholesterol, creatinine, glucose, glutamic oxaloacetic transaminase, iron, protein-bound iodine, urea and urate could be converted to close agreement with Gaussian distributions by logarithmic transformations, although the glucose distribution remained significantly long-tailed. Albumin and globulin were slightly skew in opposite directions. There was no evidence that distributional shape was affected by age or sex.

Augmentation of the peripheral metabolism of L-triiodothyronine and L-thyroxine after acclimation to cold. Multifocal stimulation of the binding of iodothyronines by tissues.

Increased metabolism of thyroid hormones was observed in rats adapted to an ambient temperature of 4 degrees C. The increased hormonal degradation was manifested in enhanced metabolic, urinary deiodinative, biliary, and fecal clearances of iodothyronines. Increased metabolic clearances were due to stimulation of cellular hormonal disposition, evidenced by elevated intrinsic cellular clearances. After adaptation, the concentration of protein-bound iodine in plasma was decreased, and the binding of the hormones by plasma proteins was increased. The enhanced rate of metabolism of iodothyronines was associated with stimulation of the binding of these hormones by diverse tissues, suggesting the participation of extrahepatic degradative foci in the increased hormonal deiodination observed in vivo. Increased hepatocellular binding and a significantly enlarged hepatic distribution space of thyroxine were noted. Hepatocellular binding of triiodothyronine was similarly augmented, and a smaller but significant increase in the hepatic space of this iodothyronine was detected. Analysis of the hepatic subcellular partition of iodothyronines 35 min after the intravenous administration of isotopically labeled thyroid hormones disclosed increased hormonal binding by the microsomal fraction in cold-adapted animals and an attendant increase in the microsomal protein concentration. Partial microsomal subfractionation in a discontinuous sucrose gradient indicated that the observed stimulation of microsomal hormonal binding was associated with proliferation of the smooth endoplasmic reticulum.

Iodine contamination of the serum protein-bound iodine: incidence and clinical significance.

Iodine contamination as defined by the combination of a raised (PBI-T(4)I) difference and low (131)I neck uptake was found in 38 (17.5%) of 217 euthyroid patients. Of these, 17 had PBI levels of greater than 20 mug/dl but in the remainder levels were clinically feasible. In only 21 was there a history of exposure to iodine. Two of 12 hypothyroid patients had PBI levels well within normal limits. False elevation of the PBI is thus shown to be common. It is neither always obvious nor can it be easily avoided. The PBI is not an acceptable alternative to T(4) estimation by other methods.

Chemical and Immunological Properties of Iodocompounds Associated with Particulate Fractions of Hog Thyroid Cells

Iodocompounds bound with various particulate components in hog thyroid cells were analyzed quantitatively with their chemical and immunological properties based on the iodine analysis of the particulate components and their detergent extracts. Almost all the particle-bound iodine was found to be protein-bound and distributed among various sized particulate components. Sodium deoxycholate (0.26% to 1%) solubilized about 80% of the iodoprotein from either microsomal or lysosomal fraction and about 60% of that from either mitochondrial or nuclear fraction. Addition of 0.5% sodium dodecyl sulfate into 1% sodium deoxycholate caused the solubilization of particle-bound iodoprotein (s) remaining after the sodium deoxycholate treatment. Sixty percent of the microsomal or of the lysosomal iodoproteins solubilized with sodium deoxycholate was precipitated with anti-hog thyroglobulin serum in a “double” immunoprecipitation system, while 40% of the mitochondrial or the nuclear iodoproteins was precipitated. From these analyses, it was concluded that at least 80% of thyroglobulin-related iodoproteins in the particulate fractions was associated with rather small particulate components in the cell homogenate. Analysis by sucrose density gradient centrifugation showed that 50% of the protein-bound iodine solubilized from the microsomal pellet was recovered in 19 S region, suggesting the presence of an appreciable amount of particle-bound thyroglobulin with similar sedimentation property to “soluble” thyroglobulin.