[Increase of testosterone-binding protein in severe diseases].
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Biomedical subjects
Publications and source records attributed to R Sapin.
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The existence of a preabsorptive insulin reflex is well known in animals but remains controversial in humans. Glycemia and insulin variations following olfactive and visual presentation of a standard meal were studied in 25 subjects, 10 of them (5 men and 5 women) of normal weight and 15 overweight (7 men and 8 women), after a 15 hour fast. Blood samples were collected continuously, every minute for 16 minutes after the meal was presented. The presentation produced an early blood insulin increment, variable in magnitude and time course and occurring between the 3rd and 9th minute, in both normal and overweight subjects. Glycemia variations were not significant. Our study demonstrated a positive correlation between the reflex insulin release, body weight and a conscious effort to maintain current body weight. However, the differences between overweight and normal subjects remained small. The physiological and psychological determinants of the cephalic phase of insulin secretion are discussed.
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In order to evaluate the relationship between nutritional status and insulin secretion in cirrhosis, the following parameters of caloric (tricipital skin fold, prealbumin) and proteic (arm muscle size, transferrin, 24 h-urinary creatinine excretion) nutritional status were compared in 20 alcoholic cirrhotics and 10 normal subjects. Insulin secretion was evaluated in both groups by insulin and C-peptide response to an intravenous glucose tolerance test and by 24 h urinary excretion of C-peptide. When compared to normals, cirrhotics have lower values for all nutritional status parameters and individually for at least three of those in 14 (70 p. 100) patients. In cirrhotics there is a significant decrease of the 4-min poststimulative response of insulin and C-peptide, contrasting with higher basal and late poststimulative values than in normals. This contrast could be explained by a reduced metabolic clearance rate of insulin (consistent with insulin resistance) and of C-peptide (the urinary clearance of which is 2.5 times lower in cirrhotics than in normals). The 24-h urinary excretion of C-peptide, probably weakly dependent of this reduced clearance, is 50 p. 100 lower in cirrhotics: 12.9 +/- 1.6 nM/24 h than in normals: 26.0 +/- 2.4 nM/24 h (p less than 0.001). In cirrhotics there is a significant linear correlation between 24 h urinary C-peptide excretion and all the nutritional status parameters but one (prealbumin). These results indicate that in cirrhosis: 1) urinary C-peptide excretion rate is a good index of insulin secretion; 2) urinary C-peptide indicates a marked deficit in insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Amiodarone modifies thyroid hormone secretion and hypothyroidism occurs in some cases. The latter diagnosis is often difficult and is of particular importance in these patients as it may have serious consequences for the heart. Early diagnosis is therefore essential but difficult because of the induced hyperthyroxinemia with maintenance of euthyroidism and a hypotriiodothyronemia. The diagnostic performance of an ultrasensitive method of measuring TSH (TSH-U), capable of distinguishing hyper and euthyroidism were compared with standard thyroid function tests and TSH stimulation with TRH in 50 patients treated with amiodarone. Only 6 of the 14 patients with hyperthyroxinaemia had TSH-U values in the hyperthyroid range: only one of these patients had an increased triiodothyronine. In 2 cases the THS-U was low but the T4L was normal. In 4 patients, increased TSH-U allowed diagnosis of latent or patent hypothyroidism. There was a close correlation between results of the TRH stimulation test and those of the TSH-U in all cases. This test may therefore be used as an initial screening test for thyroid dysfunction in patients on amiodarone and is simple, reliable and relatively cheap to perform. It makes it unnecessary to measure all thyroid hormonal parameters and the TRH test simultaneously.
A new ultrasensitive TSH immunoradiometric assay (IRMA) using two monoclonal antibodies is now able to distinguish between euthyroid and hyperthyroid patients. The aim of this study was to compare data given by ultrasensitive basal TSH (IRMA) and by the response of TSH to TRH test considered until now as the more reliable test in case of mild or atypical hyperthyroidism. Basal plasma TSH levels were determined in euthyroid (n = 80), hyperthyroid (n = 30), hypothyroid (n = 14) and pituitary deficient patients (n = 8) before and 30 minutes after a TRH test (250 micrograms i.v.). A close linear correlation was found between basal and post-stimulative TSH levels. Normal TSH response ranged from 2 to 22 uU/ml. The sensibility and the specificity of these two parameters appeared comparable in the case of primary dysthyroidism; on the contrary basal TSH levels were not sufficient for the diagnosis of central hypothyroidism. In conclusion, excepted for pituitary deficiency, basal plasma TSH (IRMA) levels are accurate and sufficient in the evaluation of the thyroid function and make the TRH-test useless.
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The effectiveness of plasmapheresis was evaluated in 8 patients with severe thyrotoxicosis of diverse origin and clinical manifestations, who underwent a total of 22 plasma exchanges. The method proved rapidly effective in controlling the symptoms in 6 cases. No adverse reaction was noted. In all patients plasma exchanges significantly reduced plasma concentrations of total thyroxine and triiodothyronine and of thyroxine-binding globulin, without effect on free thyroxine and triiodothyronine fractions. The satisfactory clinical results obtained can only be explained by displacement of thyroid hormones from the intracellular compartment. The hormonal variations observed were proportional to the initial hormone concentrations, to the amount of thyroxine-binding globulin removed and to the plasma volume purified. It is concluded that plasmapheresis rapidly extracts thyroid hormones and is therefore useful in the treatment of acute severe thyrotoxicosis.
Beta-2-microglobulin was assayed in the plasma and the synovial fluid in 41 subjects with mechanical joint disorders, 27 patients with rheumatoid arthritis and 32 patients with non-rheumatoid arthritis. The plasma beta-2-microglobulin may be raised in all forms of joint disease, especially in the course of rheumatoid arthritis, but its ability to discriminate between rheumatoid arthritis and other forms of inflammatory joint disease is poor. In contrast, for the beta-2-microglobulin level in the synovial fluid, the differences in the means are highly significant between rheumatoid arthritis and non-rheumatoid arthritis. Concentrations of beta-2-microglobulin in the synovial fluid greater than 5.2 micrograms/ml, in this study which excluded patients with renal failure, were 100 per cent specific for rheumatoid arthritis and were found in 52 per cent of cases. However, this result has to be interpreted in the light of the fact that any extra-articular cause for an increased plasma beta-2-microglobulin, particularly renal failure, also causes a rise in the synovial concentration, invalidating the test. For this reason, the authors propose using the value of the beta-2-microglobulin in the synovial fluid minus the plasma beta-2-microglobulin, as a more specific index.
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In order to investigate disturbances in glycoregulation and plasma amino acids and their possible relationship in alcoholic liver diseases, plasma concentrations of insulin, C-peptide, glucagon and branched-chain (valine, leucine, isoleucine) as well as aromatic (phenylalanine, tyrosine) amino acids were measured during an arginine test (i.v infusion of arginine chloride 0.5 g/kg over 30 min) in 21 alcoholic patients: 11 with cirrhosis (group C) and 10 with steatosis (group S). Insulin responses to arginine was reduced in both groups, whereas glucagon response was increased in group C and reduced in group S. Plasma concentrations of branched-chain amino acids were reduced in both groups, irrespective of the degree of hyperinsulinism. Plasma concentrations of aromatic amino acids were increased only in cirrhotic patients; the increase was independent of the degree of hyperglucagonism and of the plasma insulin/glucagon molar ratio. These results suggest that disturbances of glycoregulation in plasma amino acids imbalance do not play a major role in alcoholic cirrhosis and steatosis.
It is well established that glucagon plays an important role in the regulation of fuel supplies as its plasma level increases during the first days of a complete fast. However, it is not certain that glucagon is involved in the adaptation to chronic starvation. In the present study, this problem was investigated by the determination of the changes in the plasma glucagon level elicited by an i.v. glucose tolerance test followed by an i.v. arginine perfusion in 26 self starved patients suffering from anorexia nervosa (AN) and 14 control patients having only minor neurotic disorders. The basal plasma glucagon level tended to be higher in the AN patients than in the controls; but the difference was not statistically significant. Glucagon responses to glucose and arginine observed in the AN patients were not significantly different from those seen in the control patients. In the AN patients, the insulin response to both loads was reduced and the plasma GH level increased paradoxically after the glucose load, whereas it rose normally after the arginine load. It may be concluded that in chronic starvation by AN the regulation of fuel supplies depends mainly on decreased insulin and increased growth hormone secretion. The role of glucagon seems to be of minor importance in this condition.
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Plasma exchanges (PE) have been successfully used in the treatment of thyroid storm. The dramatic results obtained (as in the case reported here) have prompted the authors to evaluate the effects of PE on plasma thyroid hormone (T4, T3 and unbound T4) levels and thyroxine-binding globulin (TBG) levels in 5 euthyroid patients. PE of one blood volume consistently produced a significant decrease in T4, T3 and TBG levels without changes in unbound T4 or TSH. Hormone extraction was proportional to the volume of blood removed and correlated with the amount of TBG extracted. Compared with the estimated total plasma content, the percentage of unbound T4 extracted was superior to that of total T4, which suggests release of free hormones from the intracellular compartment. Repeated PE in the same patient resulted in a transient decrease in T4 without changes in TSH. These results indicate that PE constitutes a fast, simple and effective means of removing thyroid hormones in all emergencies related to thyrotoxicosis. The fact that TSH levels remain stable after PE shows that the thyroid balance in euthyroid subjects is unaffected by this method.
Free plasma thyroxine index (FT4I) and plasma concentrations of triiodothyronine (T3) were routinely determined on admission in 1862 hospital patients without signs or history of thyroid dysfunction. Total thyroxine (T4) and FT4I values were beyond confidence limits in 16.3% and 7.5% respectively of the patients, whereas T3 values were low in 23%. Among the 84 patients with high FT4I, 31 had clinically unsuspected hyperthyroidism confirmed by the TRH test (T3 increased in 66% of the cases). Among the 46 patients with low FT4I, 14 had demonstrable hypothyroidism (low T3 in 65% of the cases). In this population, the prevalence of proven thyroid dysfunction without clinical symptoms was 1.66% for hyperthyroidism and 0.75% for hypothyroidism. The diagnostic value of normal FT4I was estimated at 50%. The persistence of an abnormal FT4I on a second determination indicated the presence of hyperthyroidism in 72% of patients with high FT4I values and of hypothyroidism in 74% of patients with low FT4I values. In doubtful cases, TSH assays or TRH tests led to the concept of "transient" dysthyroidism, and the potential total prevalence of routinely discovered dysthyroidism could be estimated at 3.54% including 2.47% for hyperthyroidism. The latter occurred in 95% of people older than 50, with a sex ratio of 0.94. The cost of diagnosis for each new case clinically unsuspected hyperthyroidism is 1200 Z, but this could be reduced to 450 Z if only patients over 50 years of age were investigated and if FT4I determinations were replaced by free T4 determinations.
The purpose of the present study was to investigate dysfunctions in thyroid gland secretion and regulation among patients with manic-depressive psychosis. Plasma levels of thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH) were measured by radioimmune assays, and TSH responsiveness (delta TSH) to synthetic TSH-releasing hormone (TRH) 250 microgram IV was determined in 20 untreated patients, 19 patients under neuroleptics and 19 patients under antidepressants. Untreated patients were compared with 15 age - and sex-matched controls. They were found to have significantly lower plasma T3 levels than controls (121.0 +/- 6.0 ng/dl as against 144.5 +/- 3.3 ng/dl; p less than 0.01) and blunted TSH response to TRH (delta TSH 4.1 +/- 0.6 instead of 12.6 +/- 2.1). Other thyroid function parameters were unchanged. Under neuroleptic treatment T3 levels tended to increase and delta TSH returned to normal. Manic-depressive psychosis is characterized by hypothalamic-pituitary dysfunction. Thyroid secretion is normal, and the decrease in T3 is probably due to impaired peripheral T4 to T3 conversion.
In common forms of hyperthyroidism serum levels of triiodothyronin (T3) are higher than those of thyroxin (T4) and isolated elevations of serum T3 have even been noted. We report 9 cases of proven hyperthyroidism with normal or low levels of T3 and elevated T4 and reverse T3 (rT3). Most out of the patients were more than seventy years old and had associated diseases. Our data show that the low T3 with elevated rT3 syndrome--which has been noted in many metabolic and pathologic conditions--can coexist in hyperthyroidism. They emphasize the lack of diagnostic discrimination of T3 assays in thyroid dysfunction especially in the older patient or one with associated disease.
In order to investigate the controverted effect of ammonia on insulin and glucagon secretion 3 groups of 55 rats were perfused either by Na+ acetate (controls), either by NH4+ acetate: in the first group plasma insulin (IRI) and glucagon (IRG) levels were compared before and after perfusion; the second group was supplemented by glucose perfusion (1 g/100 g/hour); in the last group an arginine perfusion (1 g/kg/min) was started 15 min after the beginning of NH4+ or Na acetate and IRI and IRG levels were determined in the portal blood. Hyperammonemia, which reached about 500 microgram/dl, reduced significantly the IRI portal level and the IRI secretion induced by glucose or arginine, whereas basal or stimulated IRG levels are not modified. The ratio IRI:IRG is diminished in each group perfused with NH4+ acetate. Our results show that ammonia inhibits insulin without modifications in the glucagon secretion; hyperglucagonemia and hyperinsulinism reported in hepatic encephalopathy with chronic hyperammonemia may not be attributed to an effect of ammonia.