Radiation dose to the testes after 131I therapy for ablation of postsurgical thyroid remnants in patients with differentiated thyroid cancer.

UNLABELLED: Radioiodine-131 is used in differentiated thyroid cancer (DTC) for ablation of postsurgical thyroid remnants and destruction of metastases. The question may be raised of whether 131I treatment of DTC in male patients may give an irradiation dose to the testes that could impair fertility. Few data in the literature concern the dose absorbed by the testes after 1311 therapy for DTC. Because 131I kinetics may be altered by the hypothyroid condition commonly present at the time of treatment and by the radioiodinated iodoproteins released by the damaged thyroid tissue, the dose values reported in the International Commission on Radiological Protection (ICRP) tables for euthyroid men may not be appropriate. To clarify this problem, three male subjects undergoing 131I therapy for ablation of thyroid remnants shortly after thyroidectomy for DTC were studied. METHODS: The mean administered activity was 1256 MBq, and the duration of the study was 2 wk. The gamma dose was measured by thermoluminescent dosimeters (TLDs) applied to the lower poles of the testes. Correction factors were calculated for the distance of the TLD from the center of the testes and for attenuation by the testes of the gamma rays reaching the TLD. After correction, the gamma dose to the testes ranged from 21 to 29 mGy. The gamma dose calculated by the Medical Internal Radiation Dose (MIRD) method from blood and urine samples was similar (18-20 mGy) to that measured by TLDs. The beta dose was estimated by the MIRD method from blood activity and testicular volume and ranged between 14 and 31 mGy. RESULTS: The total (beta and gamma) doses to testes were 30, 33 and 43 microGy/MBq in the three subjects. CONCLUSION: These values are close to those derived from the ICRP tables (26-37 microGy/MBq 131I) for euthyroid subjects. The present data indicate that significant irradiation is delivered to the testes after the administration of the 131I ablative dose to thyroidectomized patients. The relevance of the radiation absorbed by testes on fertility remains to be established.

Unusual calcified goiter associated with increased iodoprotein in serum.

For 30 years we have followed the case of a euthyroid patient who had a goiter diagnosed at age 15. It was originally diffuse and did not shrink during treatment, first with desiccated thyroid extract and then with triiodothyronine. After treatment was stopped, the goiter gradually became nodular and calcified when the patient was in her late teens or early 20s; it then shrank. She remains clinically and chemically euthyroid, with a calcified, multinodular goiter and persistent elevation of the serum PBI concentration which, early in the course of the disease was shown to include a substantial fraction of butanol-insoluble iodine. In a euthyroid patient, the association of an elevated serum PBI concentration (with an abnormally large butanol-insoluble iodine fraction) with a diffuse goiter that became nodular and calcified may be unique.

Release of thyroid hormone from circulating thyroglobulin in the rat.

Under normal conditions, a small amount of thyroglobulin (Tg) exists in peripheral blood. However, the fate of circulating Tg is unclear. In the present study, in vivo labelled rat Tg was injected iv into rats whose thyroids had been blocked with KI to determine whether circulating Tg released thyroid hormone by hydrolysis in extrathyroidal tissues. Radiolabelled Tg was obtained from thyroid of rats injected with 125I 24h before sacrifice, and subsequently purified by ammonium sulphate precipitation. The plasma samples were obtained from tail veins or by cardiac punctures at various times following injection of [125I]rat Tg. The radioactive samples were separated into iodoprotein, iodoaminoacid and iodide fractions using columns of anion and cation exchange resins. The per cent radioactivity of the iodoprotein, iodoaminoacid an iodide fractions, respectively, was 91.2, 3.8 and 5.2 at 15 min and 66.9, 17.4 and 15.4 at 20 h after injection. In the iodoaminoacid fractions, the presence of T4, T3, MIT and DIT was defined by further fractionation using a Sephadex G-25 column. At 20 h after injection, more than 75% of the radioactivity of the iodoaminoacid fraction was found to be incorporated in T4 and T3. It is concluded that circulating Tg is hydrolyzed in extrathyroidal tissues and that thyroid hormone is released into the circulation, but the amounts of T4 and T3 released are not physiologically significant.

Valoración metodológica, diagnóstica y económica de los principales parámetros de laboratorio empleados en nuestro medio para evaluar la función tiroidea / Methodologic, diagnostic and economic assessment of the main laboratory parameters used in Cuba for the thyroid function assessment

Se introduce, desarrolla y valora diversos procedimientos para el diagnóstico funcional tiroideo como son el Iodo unido a proteínas séricas, la captación tiroidea de I131 (CI131) y el aquilograma, los cuales tienen limitaciones metodológicas y diagnósticas. También se emplearon los radioinmunoanálisis de tiroxina (T4), tirotropina (TSH) y el índice de tiroxina libre (IT4L) los cuales poseen mayor especificidad, sensibilidad y precisión por lo que permiten obtener resultados con valor diagnóstico más elevados. El valor diagnóstico de los radioinmunoanálisis fue mayor (especialmente el IT4L) que el obtenido para el Iodo unidos a proteínas séricas, CI131 y aquilograma, aunque el valor económico de estos últimos fue más bajo. Se recomienda la inclusión de los radioinmunoanálisis y técnicas relacionadas en el Sistema Nacional de Salud, dadas las ventajas metodológicas y diagnósticas que poseen, de modo que sustituyan paulatinamente al Iodo unido a proteínas séricas, CI131 y aquilograma en el diagnóstico funcional tiroideo

Low molecular weight thyroglobulin leading to a goiter in a 12-year-old girl.

We characterized the abnormal thyroglobulin (TG) in the thyroid and serum of a 12-yr-old girl with a large sporadic multinodular goiter first noted at age 4 yr. She developed normally and had no clinical evidence of hypothyroidism. However, her serum T4 was less than 1.0 microgram/dl, T3 was 125 ng/dl, and TSH was 155 microU/ml. Serum PBI was 9.7 micrograms/dl, and more than 90% was not extractable with butanol. The 24-h radioactive iodine uptake was 55%, not dischargeable by perchlorate. Hormone formation was tested by the administration of 131I before surgery. [131I]T4 and [131I]T3, but not 131I-labeled iodotyrosines, were present in the thyroidal venous blood. Hydrolysis of 10,000 X g supernatants from three randomly obtained samples of the goiter revealed 66-77% of the 131I as iodotyrosines, 2-4% as iodothyronines, and 10-12% as undigestable material; the MIT to DIT ratio ranged from 3.1-8.7, and the T4 to T3 ratio ranged from 2.3-8.3. The TG level was 2.5 mg/g in the goiter and 9.4 micrograms/ml in the serum. The RIA displacement curves for the goiter and serum TG levels were both identical to the curve produced by normal human TG. The iodine contents of goiter and serum TG were 0.49% and 0.47% (wt/wt), respectively. The T4 to T3 ratio was lower in the goiter (approximately 5) than in the serum iodoprotein (approximately 45), whereas the calculation of the T4 to T3 ratio in the thyroidal secretion was less than 1. The goiter and serum TG bound normally to Concanavalin A, indicating that they contained carbohydrate. When either serum- or goiter-soluble proteins were gel-filtered (Bio-Gel A-5m), TG immunoreactivity and stable iodine elution profiles were the same, suggesting that no significant amounts of other iodoproteins were present in the thyroid or circulation. Both serum and goiter TG elution volumes corresponded to mol wt of approximately 9 X 10(4). A sedimentation rate of 10-11 S was found for both goiter and serum TG. An abnormally low mol wt of 8.5-9.0 X 10(4) was determined by sodium dodecyl sulfate-electrophoresis, in good agreement with the estimates from gel filtration studies. A single band was present on sodium dodecyl sulfate-electrophoresis regardless of whether the TG was reduced before the analysis. Thus, it is very unlikely that the low molecular weight was due to partial hydrolysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Respuesta de tirotropina (TSH) e iodo unido a proteína (PBI) a stress emocional / Thyrotropin (TSH) and protein bound iodine (PBI) response to emotional stress

Se estudió el efecto de dos tipos diferentes de estrés emocional inducido por estimulación audiovisual sobre las concentraciones de TSH y PBI en sujetos sanos. Con este fin se utilizaron 2 grupos experimentales de 15 y 12 sujetos, con los cuales se efectuaron dos experimentos de metodologías similares y con diferentes estímulos emocionales. En el experimento 1 el estrés se producía por material fílmico inductor de reacciones emocionales negativas y en el experimento II se inducía excitación emocional agradable por estimulación musical. El PBI aumentó significativamente p<0,05 en ambos experimentos y la TSH aumentó significativamente en el primero p<0,05 y no así en el segundo. No se obtuvo correlación significativa entre los incrementos de TSH y sus respectivos incrementos de PBI en el experimento I. Se discute la posibilidad de que las respuesta inespecífica de aumento de PBI sea debida a excitación del sistema nervioso simpático a través de su inervación en los folículos del tiroides, y que la TSH sea susceptible de liberarse selectivamente ante estímulos emocionales específicos(AU)

Characterization of iodoproteins secreted by phagocytosing human polymorphonuclear leukocytes.

Several proteins, glycoproteins, and iodoproteins are secreted from human polymorphonuclear leukocytes during phagocytosis of inert latex particles. The amount of 125I-labeled proteins increases during 10 to 60 min of incubation. The 125I-iodoproteins secreted into the incubation medium during the phagocytosis were first separated on Sephadex G-150 column and then characterized by column chromatography on Sepharose 4B, Sephadex G-200, and G-100. Three 125I-iodoproteins were found with the molecular weights of 580,000, 100,000, and 22,000. The molecular mass of 15 protein subunits calculated after sodium dodecyl sulfate-polyacrylamide gel electrophoresis ranged from 11,000 to 86,000 daltons. Four of the protein subunits were labeled with 125I. Their molecular weights were 63,000 to 69,000, 44,000 to 49,000, 22,000, and 11,000. In addition to iodoproteins, several 125I-labeled peptides and compounds were found by column chromatography on Bio-Gel P-2 and P-10. The 125I-iodoproteins are not secreted from resting or boiled granulocytes, and their production is 92 to 98% inhibited by 1 mM KCN or 1 mM sodium azide. The double-labeling technique with [125I]- and [131I]-iodine suggests that the iodoproteins formed in the phagocytosing granulocytes or secreted into the incubation medium are not identical.

Circadian rhythms in the concentration of plasma thyroxine in vitamin A-deprived calves.

Over a period of approximately 11 months, a total of 57 24 hour experiments was performed on 5 calves. The animals were fed a vitamin A-free diet and showed the common signs of vitamin A deficiency. During each experiment blood samples were taken hourly and the plasma iodoprotein content of each sample was determined. Each set of 24 values was subjected to Fourier analysis in an attempt to elucidate 24 hour, sinusoidal rhythms in iodoprotein concentration. A rhythm was deemed to be present where the chance of random sampling producing the observed pattern of concentration was less than or equal to 0.05. 25 such rhythms were detected. As the probability of random sampling giving rise to 25 rhythms in 57 tests is extremely small, circadian rhythms are assumed to exist in vitamin A-deficient, as in normal, calves. Rhythms, the characteristics of which are described here, were observed under natural conditions of day and night, and with controlled light and darkness. It is suggested that the occurrence of the rhythms, in relation to the environmental patterns of light and darkness, is better related to other aspects of brain activity than to those concerned with vision.

The metabolism in man of intravenously injected iodine-labelled trascobalamin I not saturated with cobalamin.

Transcobalamin I not saturated with cobalamin was purified. After iodine-labelling, a fraction of approximately 0.6 retained its cobalamin-binding capacity. Iodinated protein was used for turnover studies in three healthy subjects. The plasma curves obtained were identical to those of iodinated transcobalamin I saturated with cyanocobalamin. The cobalamin-binding capacity of the iodinated protein was determined on microcolumns containing insolubilized cobalamin. The binding capacity decreased rapidly, only 50% of the initial unsaturated cobalamin-binding capacity remaining after 0.2 to 0.3 days. It is concluded that the turnover of transcobalamin I not saturated with cobalamin does not differ from the turnover of transcobalamin I saturated with cyanocobalamin, and that transcobalamin I saturated with cobalamin in vivo is metabolized at the same rate as is transcobalamin I saturated with cyanocobalamin in vitro.

Low density and high density lipoprotein turnover following portacaval shunt in swine.

Turnover of 125I-low density lipoprotein (LDL) and of 131I-high density lipoprotein (HDL) was determined before and after end-to-side portacaval shunt in eight swine. LDL (d 1.019-1.063) and HDL (d.1.09-1.21) were isolated by ultracentrifugation and iodinated by the iodine monochloride technique. Immediately postoperatively there was no consistent change in the fractional catabolic rate (FCR) of LDL compared to preoperative control values, while in all animals FCR of HDL was significantly increased (by as much as 300%). After recovery from surgery, neither LDL nor HDL catabolic rates were significantly elevated above control values in four swine. However, plasma levels of LDL and HDL protein, and of LDL and HDL cholesterol were significantly reduced 10-12 weeks after the portacaval shunt. The reduced levels of LDL and HDL associated with normal fractional clearance rates imply a reduction in synthesis of LDL and HDL following portal diversion.

Separation of labelled iodide, iodoprotein, iodotyrosines, and iodothronines in serum from patients treated with iodine-131, using an improved chromatographic method.

A method is described for complete separation of iodoprotein, 3-iodotyrosine (MIT), 3,5-diiodotyrosine (DIT), 3,5,3-triiodo-L-thyronine (T3), and L-throxine (T4) on a single column run on Sephadex G-25 superfine in alkaline solution. Sera from patients treated with 131I- have been analysed by this method after removal of I- by resin dialysis.

Transferrin uptake and release by reticulocytes treated with proteolytic enzymes and neuraminidase.

The mechanism of transferrin uptake by reticulocytes was investigated using rabbit transferrin labelled with 125I and 59Fe and rabbit reticulocytes which had been treated with trypsin, Pronase or neuraminidase. Low concentrations of the proteolytic enzymes produced a small increase in transferrin and iron uptake by the cells. However, higher concentrations or incubation of the cells with the enzymes for longer periods caused a marked fall in transferrin and iron uptake. This fall was associated with a reduction in the proportion of cellular transferrin which was bound to a cell membrane component solubilized with the non-ionic detergent, Teric 12A9. The effect of trypsin and Pronase on transferrin release from the cells was investigated in the absence and in the presence of N-ethylmaleimide which inhibits the normal process of transferrin release. It was found that only a small proportion of transferrin which had been taken up by reticulocytes at 37 degrees C but nearly all that taken up 4 degrees C was released when the cells were subsequently incubated with trypsin plus N-ethylmaleimide, despite the fact that about 80% of the 59Fe in the cells was released in both instances. Neuraminidase produced no change in transferrin and iron uptake by the cells. These experiments provide evidence that transferrin uptake by reticulocytes requires interaction with a receptor which is protein in nature and that following uptake at 37 degrees C, most of the transferrin is located at a site unavailable to the action of proteolytic enzymes. The results support the hypothesis that transferrin enters reticulocytes by endocytosis.

Thyroid hormone regulation of extrathyroidal iodoproteins.

The effect of thyroid status on plasma and tissue levels of labeled nonextractable iodine (NEI) derived from the metabolism of radioiodothyronines was examined in the rat. Concentrations of radioiodoprotein were substantially elevated in plasma, kidney, and liver in thyroidectomized animals 72 h postinjection of [125I]triiodothytonine ([125I]T3). Similarly, total rat concentrations of radioactive NEI were increased (52%) 72 h after injection of [125I]T3. NE125I concentrations from [125I]T3 in plasma, kidney, and liver were diminished progressively in thyroidectomized animals maintained on increasing doses of thyroxine replacement, demonstrating that iodoprotein levels were inversely related to thyroid state. The plasma disappearance rate of radioiodoprotein from [125I]T3 was markedly slowed in hypothyroid animals and accelerated in intact controls rendered hyperthyroid with daily injections of T4, 8 mug/100 g BW. Propylthiouracil (PTU) treatment of thyroidectomized rats maintained on T4, 2 mug/100 g BW per day resulted in increased NE125I from [125E]T3 in plasma, kidney, and liver. The results of the foregoing investigations suggest that thyroid hormone regulates levels of iodothyronine-derived iodoproteins by influencing the rate of degradation of iodoproteins. Moreover, the observed elevation of iodoprotein levels in T4-maintained thyroidectomized animals after PTU administration appears consistent with the modification of thyroid status due to the peripheral antithyroxine effect of PTU.

The fate of circulating lactate dehydrogenase-5 in the rabbit.

1. In an attempt to determine the mechanism whereby enzymes are removed from the circulating plasma, purified rabbit-muscle lactate dehydrogenase-5 was labelled with 125I and injected intravenously into rabbits. During the first hour after injection enzyme activity and radioactivity disappeared from the plasma at comparable fast rates, which are attributed mainly to distribution of the enzyme throughout the extracellular fluid. This was followed by a phase lasting about 7 h during which enzyme activity disappeared at a faster rate than the radioactivity, an observation indicating either intravascular breakdown of the enzyme protein or its degradation in the tissues, followed by release of labelled fragments into the circulation. Enzyme activity then reached a constant value and the plasma radioactivity continued to decrease at a slower exponential rate; it is suggested that this is due to removal of breakdown products. 2. The radioactivity of the tissues was measured at various time-intervals after injection. After 2 h and 8 h highest concentrations were found in the spleen, liver, jejunum and duodenum. Relatively high concentrations were also found in the intestinal juices throughout the period of study, an observation which suggests that discharge via the small intestine is a major route whereby inactivated enzyme fragments are removed from the circulation. 3. About 5% of the injected radioactivity was recovered in the faeces during the first 3 days, and the urine accounted for 73% during the same period. About 35% of the urinary radioactivity was shown by silver nitrate precipitation and by chromatography to consist of free iodide and the remainder appeared to consist of radio-iodinated amino acids or peptides. Free mono- and di-iodotyrosine were identified among the products. These results suggest that further breakdown in the intestine is followed by absorption of the products, which are excreted in the urine.