Iodide supplementation: 200 micrograms daily or 1,500 micrograms weekly?

25 euthyroid volunteers were divided into two groups. Each participant of group A received 200 micrograms iodine in the form of diiodotyrosine per day for a period of eight weeks, i.e. 7 x 200 micrograms iodine/week. Each participant of group B received 1,500 micrograms iodide once a week for a period of eight weeks. In addition to the basal excretion of iodine with the collected urine, the excretion values in group A amounted to 67% of the applied dose in the eighth week. In group B, the excretion values amounted to 65% of the applied dose in the eighth week. Hence, no significant difference between both groups was found.

Hyperthyroidism with or without pyramidal lobe Graves' disease or disseminated autonomously functioning thyroid tissue?

I-123 thyroid scintigrams performed in 349 patients were evaluated with a focus on specific thyroid gland vestiges, namely a pyramidal lobe or a thyroglossal duct. The detection of these vestiges in patients with hyperthyroidiam is indicative of autoimmune hyperthyroidism. In Graves' disease, stimulating thyrotropin (TSH) receptor antibodies cause a significantly more frequent appearance of vestiges of the thyroglossal tract. In contrast, disseminated autonomously functioning thyroid nodules rarely show a pyramidal lobe. The frequency of pyramidal lobe visualization in patients with Graves' disease differed significantly from the frequency in patients with multifocal or disseminated autonomously functioning nodules. In euthyroidism patients, the vestiges may be indicative of the diagnosis of iodine deficiency with or without latent primary hypothyroidism. In thyroid scintigraphy, the pyramidal lobe and the thyroglossal duct can be visualized more easily using I-123 instead of Tc-99m sodium pertechnetate.

Bennhold's analbuminemia: a follow-up study of the first two cases (1953-1992).

A pair of siblings with analbuminemia were followed for 38 years. The female patient received replacement therapy with human serum albumin. Extreme lipodystrophy developed in this patient by the fourth decade of life. She had juvenile osteoporosis, which normalized under albumin replacement. She died from a granulosa cell cancer at age 69. Her brother never received albumin, even though his serum contained only 60 micrograms/ml of an albumin-like protein. He suffered from severe osteoporosis with gibbus formation, and he died from a colon carcinoma at age 59. Despite high cholesterol values and high levels of several blood clotting factors, neither of the patients had severe atherosclerosis or thrombotic events. Laboratory findings before and after infusion of large amounts of albumin into the sister point to a mechanism whereby albumin-bound substances can be passively transported from the bloodstream into the extravascular space and vice versa.

[Iodine content in diet and excretion of iodine in urine]. / Iodgehalt der Nahrung und Ausscheidung von lod im Harn.

The standard food for our volunteers, prepared in the central kitchen of the University Hospital of Tubingen, consisted of breakfast, warm lunch and cold supper and contained, on average, approximately 230 micrograms of iodine/day. It is generally assumed that an equilibrium is established between iodine intake from food and urinary iodine excretion. Hence, the amount of iodine excreted with the urine within 24 h may reflect the daily ingestion of iodine. The fecal iodine losses are considered negligible. The alimentary iodine supply from food of our clinic would meet the WHO recommendations of > 150 micrograms/day to prevent iodine-deficiency goiters. In 27 healthy volunteers the daily uptake of iodine was determined and the urinary excretion of iodine within 24 h was measured. Unexpectedly, only 16% to 18% of the alimentary iodine were excreted with the urine. Hence, the utilization of iodine from the food appears to be limited and therefore cannot prevent goiters in goiter areas. In addition, it was found that the correlation between urinary excretion of iodine and urinary excretion of creatinine is not a reliable parameter for the real daily excretion of iodine and iodine balance.

Inhibitory and disruptive effects of some antirheumatics on antigen-antibody complexes.

Purified antibodies to human serum albumin or to human gamma-globulin were used to study the direct influence of some antirheumatic drugs on the formation and disruption of immunoprecipitates. 125I-labelled human serum albumin and 125I-labelled human IgG served as indicators. The effects of the following drugs were described: diclofenac, monophenylbutazone, diphenylbutazone, ibuprofen, and metamizol. At approximately therapeutic concentrations, the antirheumatics inhibited the formation of complexes of homologous antibodies with human serum albumin and, surprisingly, with human IgG. When the antigens were precipitated with antibodies, subsequent addition of the antirheumatics to the preformed immunoprecipitates caused disruption of [125I]human serum albumin-anti-human serum albumin precipitates but practically no disruption of human [125I]IgG-anti-human IgG precipitates. These new findings may be of relevance for clinical diagnosis and therapy as well as for research in immunochemistry. It is conceivable that, in patients, antirheumatic or other drugs might interfere with immunological determinations of clinico-chemical quantities. Interference of drugs with antigen-antibody reactions might also help to explain some beneficial effects or undesirable side effects of certain drugs.

Oxalic acid in saliva, teeth and tooth tartar.

Oxalic acid was determined in human saliva, teeth, tartar, and in animal teeth. Saliva from dentally healthy male subjects contained 0.10 +/- 0.09 mmol/l (n = 41) and those of dentally healthy female subjects 0.18 +/- 0.17 mmol/l (n = 40). Oxalic acid in tartar from 16 patients was 3.3 +/- 1.2 mmol/kg tartar. In human teeth, oxalic acid was 1.0 +/- 0.3 mmol/kg in milk teeth (n = 12) and 0.9 +/- 0.6 mmol/kg in permanent teeth (n = 60). Human teeth were sorted into age groups and into molars, incisors and premolars. In animal teeth, oxalic acid content varied widely. The formed calcium oxalate is proposed to be a 'physiological' protective mechanism for teeth.

Direct effect of protirelin (TRH) on PB[123I] in autonomous thyroid adenoma.

In a retrospective study of 27 cases of iodine deficiency and/or latent primary hypothyroidism and in 16 cases of thyroid adenoma with hyperthyreosis the routine radioiodine uptake test was combined with a protirelin (TRH) test. After TRH infusion, [PB*I] and TSH increased significantly in all of these 27 patients who served as controls for the hyperthyroid patients. At the same time, the conversion rate Q rose in 14 of the control patients, but it dropped in 13 cases, thus indicating a TSH-induced discharge from the thyroid of radioiodine containing substances that were not bound to serum proteins. In nine of the 16 patients with autonomous adenoma, PB[*I] rose slightly, but Q did not increase significantly. In seven of the 16 adenoma patients, both PB[*I] and Q even dropped slightly in the absence of measurable serum TSH, thus indicating a negative direct effect of TRH on thyroid hormone metabolism.

Oxalate in the human thyroid gland.

Ninety-seven fixed surgical thyroid specimens and 63 unfixed and 40 fixed thyroid specimens from autopsies were examined for their oxalate content. Proteases were used to process the tissue, and the oxalate was determined with an enzymatic assay. The fixed samples were grouped into seven diagnostic categories (diffuse colloid goitre; partially diffuse, partially nodular colloid goitre; nodular colloid goitre; goitre with multifocal functional autonomy; non-functioning adenoma; unifocal functional autonomy; Graves' disease). The oxalate concentrations of the samples were mainly dependent on age and gender, which were distributed unequally among the seven diagnostic groups. In thyroid tissue from cases of Graves' disease, however, the concentration of oxalate was remarkably low and statistically different from those of four of the six other groups.

Isoelectric focussing of human thyroxine binding globulin (thyropexin) and human prealbumin (transthyretin).

Two batches of the highly purified thyroid hormone-binding plasma proteins, human thyropexin and transthyretin, which were prepared in gram quantities for use in animal experiments, were subjected to analysis by isoelectric focussing. Under these conditions, it was observed that human transthyretin was composed of two components. This was presumably due to the use of 8 mol/l urea. The preparations of both human transthyretin and human thyropexin contained some products of decomposition which probably arose in the course of the purification processes and, in addition, possibly also contained some normal genetic variants of human thyropexin. In spite of the alterations, both protein preparations largely retained their thyroid hormone-binding capacity, which is essential for in vivo studies on the re-entry of thyroid hormones from the extravascular space into the circulation. For therapeutic use in thyrotoxicosis, human transthyretin seems to be preferable to human thyropexin.

Direct effects of protirelin (TRH) on cultured porcine thyrocytes.

In several cases of thyroid adenoma in which no TSH was detectable in the serum, a paradoxical decrease of PB123I and its conversion rate Q (PB123I/serum total radioactivity) was observed after infusion of protirelin (TRH). The possibile direct effect of TRH on thyrocytes was therefore studied in vitro. Porcine thyroid cells were cultured in NCTC-135 medium supplemented with a serum substitute and insulin. TRH and some of its analogs enhanced the incorporation of [3H]thymidine into DNA and the uptake of radioiodide into thyrocytes. In the presence of TSH, TRH did not stimulate radioiodine uptake, whereas incorporation of [3H]thymidine into DNA was not antagonized by TSH. Thus, in this culture system, TRH had a direct effect on both growth and metabolism of thyrocytes. TSH can modulate these effects.

Effects of human thyroxine-binding globulin and prealbumin on the reverse flow of thyroid hormones from extravascular space into the bloodstream in rabbits.

A plasma fraction rich in thyroid hormone-binding globulin (hTBG, human thyropexin) was injected iv into rabbits in order to see whether thyroid hormone concentrations in plasma would increase by return of T3 and T4 from the extravascular space. For this purpose, both [125I]T3 and [131I]T4 were simultaneously injected. After 1 h, or after 16 h in another series of experiments, 50 mg hTBG were injected iv. Thereafter, the mean radioactivity of both [125I]T3 and [131I]T4 in the plasma rose, and reached its peak 20-30 min after hTBG injection; [125I]T3 and [131I]T4 returned to the preinjection value slowly, after more than 3 h. When hTBG was injected 15-16 h after the radioactive hormones, the mean radioactivity of [125I]T3 reached its peak about 1 h after hTBG injection and returned to the base value after approximately 5.5 h, [131I]T4 reached its peak about 1 h after hTBG injection and returned to the base value within 12 h. After injection of hTBG, total T4 and T3 concentrations in plasma increased about 3- to 5-fold over the base values. At the same time, the percentage of both, free T4 and free T3 dropped instantly whereas absolute free T4 and free T3 values remained almost constant. After injection of 500 mg transthyretin (hTBPA), a similar flux of [125I]T3 and [131I]T4 was observed, whereas 500 mg human serum albumin were ineffective. These marked effects of injected hTBG and hTBPA on the serum levels of [125I]T3, [131I]T4, and total T3 indicate that reentry of T3 and T4 into the intravascular compartment is an important component of thyroid hormone distribution and transport. As can be anticipated from the animal experiments, the efficiency of plasmapheresis or hemofiltration methods may be improved by previous application of large doses of hTBPA or hTBG in cases of thyrotoxicosis.

Mathematical modelling of intravascular thyroid hormone stimulation by carrier proteins.

A simple mathematical model for the thyroid hormone stimulation in plasma after intravenous administration of pharmacological doses of thyroid hormone binding carrier proteins is described. The model concept is based on the observation of the time course of both radioactive labelled and unlabelled thyroid hormones before and after protein loading in rabbits. All model parameters are derived from experimental measurements in order to guarantee the identifiability with physiological data. The presented initial study could be a theoretical basis for a more effective therapy of thyroid storm by dialysis or plasma exchange methods.