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Biomedical subjects

D Glinoer

Publications and source records attributed to D Glinoer.

At least 91 records · Page 5Linked to original sources
PubMed1985

Absence of circulating desialylated thyroxine-binding globulin in patients with hepatobiliary disease.

Thyroxine-binding globulin (TBG) is the major thyroid hormone carrier protein. The molecule contains approximately 10 sialic acid residues which play a key role in the peripheral metabolism of TBG. Since the serum of patients with liver disease often contains large amounts of several desialylated glycoproteins, the aim of the present studies was to characterize circulating TBG and to examine the possible presence of desialylated TBG (dTBG) in 24 patients with a variety of hepatobiliary diseases and selected on the basis of elevated serum levels of desialylated glycoproteins. Using 4 immunochemical techniques applied for the measurement of TBG, for the detection of dTBG and for the characterization of TBG microheterogeneity, the results indicated: a) a wide scatter of serum TBG levels between 4 and 23 mg/l; b) the absence of detectable amounts of dTBG in any of the sera tested; and c) a close similarity between the microheterogeneity of TBG in patients with liver disease with that of control sera or of purified TBG. In conclusion, in patients with acute and chronic liver disease, TBG, although quantitatively modified, remains qualitatively unaltered, suggesting that diseased liver produces fully sialylated TBG and that its catabolism is not impaired.

Adult↗
PubMed1984

Increased risk of primary hypothyroidism in preterm infants.

Serum levels of thyroid stimulating hormone, thyroxine, triiodothyronine, free T4, thyroxine-binding globulin, reverse T3, and the TSH secretory areas and peak T3 after intravenous injection of 40 micrograms thyrotropin-releasing hormone were determined weekly from day 5 to 6 to 11 weeks of age in 42 unselected full-term and 61 preterm Belgian infants. The results on day 5 indicated a progressive deficit of thyroid function related to the degree of prematurity. In 92 infants this deficit progressively decreased with age and disappeared at 5 to 7 weeks. However, 11 infants developed biochemical evidence of overt but transient hypothyroidism. Belgian neonates are relatively iodine deficient, and this factor affects the constitution of iodine stores within the thyroid gland: (1) the urinary concentrations of iodine in the 103 infants studied in Belgium were markedly lower than in 30 infants from California; and (2) The iodine concentration of the thyroid gland in preterm infants who died during the 10 first days of life was almost three times lower in Brussels than in Toronto. The results indicate that, in Belgium, the effects of relative iodine deficiency on thyroid function are superimposed on and mask the physiologic state of tertiary hypothyroidism in prematurity.

Belgium↗
PubMed1983

Comparison of human thyroxine-binding globulin purification by affinity chromatography procedures.

Three procedures for the isolation of thyroxine-binding globulin from human serum, using affinity chromatography on triiodothyronine (T3) linked to Sepharose (A), thyroxine (T4) linked to Sepharose (B) or T3 linked to epoxy-Sepharose (C) as the first purification step, were compared. With the use of additional purification steps, the three procedures yielded pure thyroxine-binding globulin without desialylation. With procedure A, the initial binding of T4-binding globulin to T3-Sepharose was very low, yielding a poor final recovery (17%). Procedure B gave the highest yield (35%) after a three-step purification, with a low T4 content (0.15-0.30 mol/mol). Procedure C also gave a high yield (28%) after only two purification steps, with a T4 content greater than 0.7 mol/mol. The microheterogeneity of T4-binding globulin obtained with these three procedures was demonstrated by isoelectric focusing: five major bands were observed between pH 4.1 and 4.6, and intermediate faint bands (often doublets) in the same pH range. However, with procedures A and C, the most acidic bands (pH 4.10-4.20) were always absent. Thyroxine-binding globulin was preincubated with radioactively labelled T3 or T4 and the hormone-protein complex was analyzed by isoelectric focusing. The binding of T3--compared to that of T4--was reduced in the most acidic protein subspecies. These results suggest differences in the thyroid hormone binding properties of the various subspecies of human T4-binding globulin.

Chromatography, Affinity↗
PubMed1983

Thyroidal release after oral administration of TRH in normal subjects.

The oral administration of 40 mg TRH to 17 normal volunteers induced a greater TSH response in females than in males, contrasting with an identical pattern of total T3 and T4 (TT3, TT4) and of free T3 and T4 (FT3, FT4). TSH peaked at 180 min while thyroid hormones (total and free) reached their maximum at 360 min. The drop in the T4 to T3 ratio (total and free hormones) observed at 360 min is consistent with an initial preferential T3 secretion. At 360 min the thyroglobulin (Tg) levels were still in the basal range while at 24 h a significant increase was observed, essentially in female subjects. Thus T3, T4 and Tg seem to be sequentially secreted by the thyroid in response to a prolonged TSH stimulus.

Administration, Oral↗
PubMed1981

Alterations in circulating thyroid hormones and thyroxine binding globulin in chronic alcoholism.

The present study concerns eighteen chronic alcoholics with minimal liver damage. A significant reduction in total serum T4 with an accompanying drop in circulating TBG was observed in these otherwise euthyroid patients. During alcohol withdrawal, we observed a rapid increase in T4 and TBG into the normal range. We suggest that the fall in the level of circulating thyroxine-binding globulin is related to a defect in its synthesis or secretion by the liver due to ethanol consumption. Caution is recommended in the interpretation of thyroid function tests in chronic alcoholics.

Adult↗
PubMed1981

[Use of plasmapheresis in a case of Graves' disease with malignant ophthalmopathy (author's transl)].

A short trial with high doses of prednisolone to treat a 62 year-old woman with malignant ophthalmopathy due to Graves disease yielded an unsatisfactory improvement after 5-6 days. The authors decided therefore to use plasmapheresis, 4 plasma exchanges of 2.5 liters each associated with prednisolone (80 ng/day) and azathioprine (100 mg/day). This therapeutic approach resulted in a spectacular improvement obtained after less than 2 weeks: normalization of thyroid function, improvement of all ophthalmological indices confirmed by radiology (C.A.T.) of the retroocular region. The rapid and important improvement obtained after such a short period of time is in favor or the major role of plasmapheresis in this combined therapy of malignant Graves' ophthalmopathy.

Azathioprine↗
PubMed1981

[Fine-needle aspiration (F.N.A.) of thyroid cold nodules (author's transl)].

In a retrospective study of 100 patients operated on between 1974 and 1979 in our institution for thyroid cold nodules, an 8% incidence of thyroid cancer was found at surgery. Since 1979, F.N.A. was performed in 160 patients with thyroid cold nodules. Adequate cytological material was aspirated in 90% (144) of the cases; of those, a benign cytological lesion was diagnosed in 128 (89%) and suspicion of cancer in 16 (11%). To date fifty-one patients were operated: 41 with benign cytology and 10 with cancer suspicion; benignity was confirmed in 39/41 cases with benign cytology and malignity in 5/10 with suspect cytology. In conclusion, clinical diagnosis of thyroid cold nodules is greatly improved by the use of F.N.A. Despite the limitations of the technique, preoperative suspicion of cancer was increased 7-fold. Caution is recommended in the follow-up cases with benign cytology since, in these preliminary results, 2 false-negatives were found.

Biopsy, Needle↗
PubMed1978

[Hormonal control of thyroxine-binding globulin synthesis and metabolism (author's transl)].

Serum thyroxine-binding globulin (TBG), the major plasma transport protein for thyroid hormones in man, was shown to be altered under the influence of estrogen and in hypothyroidism. In order to study these alterations, we used an animal model. Synthesis of TBG was demonstrated in hepatocytes isolated from adult Rhesus monkeys, and in a monkey hepatocarcinoma continuous cell culture line (NCLP-6-E). When the hepatocytes were obtained from monkeys pretreated with beta-estradiol (E2), a specific 2.5-2.9 fold increase of TBG synthesis and secretion was shown; similar data were obtained with the tumor line. Furthermore, an increased TBG production was shown with these cells when T4 (from 10(-14) to 10(-11) M) was added to the culture medium. The in vitro results were correlated with in vivo data obtained by investigating the metabolism of TBG after iv injection of tracer doses of purified, radiolabelled TBG to normal, E2-treated and thyroidectomized monkeys. The main effect of estrogen administration was a marked increase of the production rate. During hypothyroidism, the catabolism and the production rate of TBG were decreased. In both conditions, there were significant changes in the distribution volume of TBG, the physiologic relevance of which remains to be investigated.

Animals↗
PubMed1977

Effects of estrogen on thyroxine-binding globulin metabolism in rhesus monkeys.

To investigate the effects of estrogen on thyroxine-binding globulin (TBG) metabolism, 4 female Rhesus monkeys were studied before and 3-4 weeks after implantation of beta-estradiol (E2)-containing capsules. In addition, 2 of the animals were also studied for the first 7 days after the start of E2. Serum E2 increased 10-fold from 20 +/- 7 to 212 +/- 41 pg/ml. Serum TBG, initially 20.2 +/- 6 mug/ml, was elevated by 24 h after E2 implantation, and reached a steady level of 46.8 +/- 5.0 mug/ml by 7-10 days. For the turnover studies, highly purified [125I]iodo-TBG was injected iv and serum [125I]PBI and urinary 125I excretion were measured daily. TBG kinetics were evaluated by use of a compartmental model. Although a 2-compartment model was sufficient to fit the control and late E2 data, a 3-compartment model was developed in order to account for the modifications observed during the early E2 period. The final decay rate (k) of TBG was 0.26 +/- 0.01/day during the control period and was slightly lower after E2 (0.23 +/- 0.01/day). In the 2 monkeys studied during the early E2 period, the major effect of E2 was a stimulation of the TBG production rate. This was simulated in the model by a stepwise increase occurring in the last quarter of the first day after E2. There was also an abrupt redistribution of TBG in the compartments defined by the model. The total distribution or serum equivalent volume of TBG after 3-4 weeks of E2 increased 1.4-fold, from 338 +/- 37 ml to 458 +/- 22 ml, and the metabolic clearance rate increased 1.3-fold, from 90 +/- 10 ml/d to 113 +/- 12 ml/d. The increase in the final TBG production rate (2.9-fold) was only slightly greater than the rate calculated for the early E2 period, and was similar to the increase we have recently found in monkey hepatocytes studied in vitro after isolation from E2-treated animals. It appears that stimulation of hepatic synthesis of TBG accounts for the elevated serum levels of TBG observed after estrogen.

Animals↗
PubMed1977

Stimulation of thyroxine-binding globulin synthesis by isolated rhesus monkey hepatocytes after in vivo beta-estradiol administration.

The rate of in vitro production of thyroxine-binding globulin (TBG) was studied in hepatocytes isolated from 6 control rhesus monkeys (serum TBG: 19.6 +/- 0.5 micrograms/ml; mean +/- SE) and 6 monkeys treated for 4-5 weeks with beta-estradiol (E2) (serum TBG: 45.1 +/- 1.8 micrograms/ml). Incorporation of [3H]leucine into intracellular soluble and particle-bound TBG, and into secreted TBG was determined for incubation periods up to 9 h. TBG was purified by affinity chromatography and measured by specific immunoprecipitation. The absolute amount of [3H]TBG and the ratio of [3H]TBG to total labeled protein in the same fraction were 3-fold higher in the particulate fraction and in the incubation medium of hepatocytes isolated from E2-treated monkeys. In separate experiments, TBG accumulation in the medium was measured for periods up to 19 h by radioimmunoassay. A 2.4-fold increase was observed with hepatocytes from E2-treated monkeys (3.48 ng TBG/h/10(7) cells, compared to 1.46 in controls). Correction of the production rates for the number of cells surviving during the incubation, and assuming 10.2 x 10(9) cells per liver, gave TBG production rates of 250 micrograms/liver/day in hepatocytes from E2-treated monkeys and 104 micrograms/day in hepatocytes from control monkeys. These experiments demonstrate that estrogen increases in vitro synthesis and secretion of TBG by isolated hepatocytes. The observed 2.4 to 3-fold increase was similar to the 2.9-fold increase in TBG production measured in vivo by kinetic analysis of TBG metabolism.

Animals↗