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Throughout the world and particularly in sub-Saharan Africa, deficiencies in trace elements constitute a real public health problem because of the insufficient nutritional quality of food. These trace elements are necessary for many of the body's biochemical reactions. The role of microelements such as vitamin A and zinc has been established in the functioning of the immune system and secretion of inflammatory reaction proteins, but the role of iron in these functions remains to be elucidated. The sample consists of 186 children (3/4) 80 with an iron deficiency and 106 with normal iron status. They range in age from 5 to 15 years and all attend school in the department of Adzope. The study excluded all children with parasites that might affect blood iron, protein and other hematological indicators, in particular, Plasmodium falciparum, Giardia intestinalis, Trichomonas intestinalis, Ascaris lumbricoides, and Ancylostoma. Inflammatory, immune and nutritional proteins were measured by radial immunodiffusion (Mancini's method). Ferritin was measured by a specific immunoenzymatic assay. Hematological indicators were tested by an automatic blood cell counter. Nutritional status was estimated by the weight/height ratio (W/H). This analysis showed that iron deficiency was associated with reduced IgG levels (p0.05), although immunoglobulins A and M remained stable (p0.05. Iron deficiency was also associated with reduced levels of thyroxine-binding prealbumin (TBPA) and albumin (p0.05). Inflammatory proteins did not differ significantly between the two groups (p0.05). Furthermore, the prognostic inflammatory and nutritional index (PINI) did not show any inflammatory, vital or nutritional risk, because it was lower than or equal to 2. Finally, malnutrition was not observed in the iron-deficient children: the difference in the weight/height ratio (W/H = 96.58 +/- 2.4%) between the children with iron deficiency and those with normal iron status (98.7 +/- 4.3%) did not differ significantly. The reduced IgG associated with iron deficiency may be attributed to the role that iron plays in the proliferation and maturation of lymphocytes. Reduced iron levels would thus lead to slowing down the hematopoietic mechanism, resulting in a decrease in B lymphocyte production and thus inevitably a reduction in IgG synthesis. The reduction in albumin and TBPA associated with the iron deficiency but in the absence of any sign of malnutrition (W/H96%) or inflammatory risk (PINI2) in either study group shows that iron may play a dominant role during protein synthesis. Iron deficiency might limit the energy of cellular tissues, leading to a reduction in RNA activity (transcription and translation), which would in turn decrease ribosome activity in tissues and thus reduce amino acid synthesis in cells, resulting in the reduction observed in protein synthesis. The lack of difference between the study groups in inflammatory proteins, notably CRP and alpha1-GPA, indicates that iron deficiency does not appear to be related to an inflammatory process. This study of children without any apparent clinical signs of iron deficiency shows that such a deficiency may be associated with a disruption in protein production. The proteins concerned include IgG, TBPA and albumin. The public authorities should pay particular attention to improving children's diets, especially their micronutrient levels, including for iron, vitamin A and zinc.

Two types of thyroid biochemical abnormalities (TBA) are observed in AIDS. The unspecific TBA are similar to TBA reported in the Euthyroid Sick Syndrome. An increased serum TBG of unknown origin and a decreased circulating rT3 are the most specific TBA of AIDS. The latter abnormality may be in relation with an elevated level of TNF. The frequency of serum antithyroid antibodies seems higher than in control groups. Opportunistic infections of the thyroid gland or destruction of the thyroid by Kaposi's sarcoma are also reported in AIDS.

Prospectively assessment of nutritional status, besides anthropometric parameters measurements, included determination of the following plasma proteins: albumin, transferrin, retinol-binding protein and thyroxine-binding prealbumin, usually regarded as useful indices of protein depletion states. Patients' inflammatory or infectious diseases were investigated by measuring the two most reliable acute-phase reactants (orosomucoid and c-reactive protein). This study was conducted on a group of 56 pediatric patients malnourished and 54 age- and sex-matched healthy subjects as controls. Data showed a higher prevalence of inflammatory process during the course of malnutrition as revealed progressive but severe alteration of the Prognostic Inflammatory and Nutritional Index (PINI) or CRP x a1-GPA/Alb x TBPA. On the other hand, kwashiorkor and marasmus seemed to be a precipitating cause of infectious or/and inflammatory process. We, therefore, conclude that the PINI scoring system should be for the pediatricians, a sensitive and precious tool allowing the correct follow-up of inflammatory pole in nutritional disorders in developing countries.

Simultaneous elevation of thyreostimulin and thyroid hormones values, when associated with clinical hyperthyroidism, raises a dual problem of diagnosis and treatment. We report a case of hyperthyroidism with elevated thyreostimulin in a young adult man. The values of free triiodothyronin and free thyroxin were elevated and the thyroxin binding globulin was normal. A normal pituitary tomodensitometry, the normal values of the alpha sub-unit of thyreostimulin and the dynamic tests of thyreostimulin secretion allowed us to rule out the hypothesis of a pituitary adenoma. Non-tumoral inappropriate secretions of thyreostimulin are at present regarded as syndromes of resistance to thyroid hormones. Their biological translation is a simultaneous elevation of thyreostimulin and thyroid hormones. Peripheral resistance, which is rarely complete, finds its expression in clinical hyperthyroidism or in normal clinical condition, whereas pituitary resistance, which causes the lack of feedback on the secretion of thyreostimulin expresses itself by clinical hyperthyroidism, sometimes with goitre owing to the trophic action of thyreostimulin on the thyroid. Generalized syndromes of resistance are the most common. Our patient had a selective pituitary resistance to thyroid hormones and less than thirty cases are reported in the literature. Treatment with a beta-blocker remains indicated when facing clinical evidence for hyperthyroidism and oral triiodothyronin seems to be able to slow down the inappropriate secretion of thyreostimulin. Regarding our patient who experienced a clinical and biological relapse after the stopping of the treatment, we join many authors who recommend a prolonged treatment.

Amiodarone (A) treatment alters the levels of thyroid hormones. We investigated whether new hormonal assays are also altered by this drug. Thyroid function was determined in 21 patients chronically treated with A and in 30 controls. TSH was determined with a third generation assay. Free T3 and Free T4 levels were determined by 5 different immunoassays. Equilibrium dialysis (E.D.) was considered as the reference assay for FT3 and FT4. With this method FT3 is diminished, reverse T3 ans FT4 are increased whereas TSH remained normal. Only FT3 determined by an assay using a labelled monoclonal antibody (MAB) appears not modified by A. Other methods (chromatography, chemiluminescence and radioisotopic) give results in agreement with E.D. Some of these alterations may be explained by a marked increase in plasma levels of non esterified fatty acids. Hormonal changes induced by A are typically with all but one assays. Whatever the method used the determination of TSH remains necessary to avoid misinterpretation of the thyroid function tests in A-treated patients.

We demonstrate in the mouse serum a hitherto unrecognized major thyroxine binding globulin (TBG), analogous to human TBG or to the recently discovered rat TBG. Our demonstration is based on equilibrium dialysis, electrophoresis, immunoelectrodiffusion and autoradiography techniques. Mouse TBG displays a remarkable ontogenic pattern, with 2-3 times higher activity in foetal than in maternal serum, and a further dramatic increase after birth. Between 1 and 5 days, the T4 binding to serum reaches peak levels 7-10 times more elevated than those measured in normal or pregnant adults. We also present for the first time the ontogenesis of the thyroxine binding prealbumin (TBPA), considered until now as the only specific T4 carrier of the murine species. We show that throughout development it is the TBG, not the TBPA, which crucially governs the level of the T4-serum interactions.

In order to study ligand-protein binding in solution, a dialysis method was used in which the free concentration of ligand can be controlled. The method has certain advantages and was applied to the binding of thyroxine by thyroxine-binding prealbumin, a system about which the results found in the literature are not in good agreement. From the isotherm drawn according to the Scatchard plot, it was found that thyroxine-binding prealbumin only presents a single binding site for thyroxine per molecule, the association constant being 1.7 . 10(8) M-1.

Known since 1967 and usually familial, the syndrome of tissue resistance to thyroid hormones may take one of two different forms, depending on the receptors involved. When resistance affects both peripheral and pituitary receptors, plasma thyroid hormone levels are high despite the lack of thyrotoxicosis, thyroxine and triiodothyronine are ineffective, even in high dosage, and plasma TSH increases to explode under TRH. When resistance only affects pituitary receptors, there is moderate thyrotoxicosis with paradoxical and inappropriate TSH increase. Contrary to expectations, nuclear receptors to triiodothyronine are perturbed in only a few cases. Reduction of thyrotropic hyperfunction, which is the primary purpose of treatment, can be achieved with D-forms of thyroid hormones or with somatostatin and its derivatives.

The authors have set up a thyroxine-binding-globulin radio-immunoassay in blood serum. The standard used has been determined by gravimetry, its maximal thyroxine-binding capacity is 0,96 mole of thyroxine per mole of TBG. Serum concentration of TBG has been measured in 159 euthyroid normals. The mean value of the concentration is 20 mg/l.

Thyroid hormones exert pleiotropic effects at the cell level and several theories to define the initial site of action have been proposed. First mitochondria, nuclei or plasma membrane were considered as the main regulatory step. More recently, evidence of T3 and/or T4 binding sites present in different cellular compartments suggests the existence of more than one initial site of action. Binding sites from cytosol or plasma membrane and endoplasmic reticulum seem to participate either in the storage of thyroid hormones, or in their intracellular transport and metabolism. Mitochondrial and certain plasma membrane binding sites could be responsible for rapid effects of thyroid hormones at their level. Nuclear T3 binding sites located in the chromatin are considered as a true hormone receptor and are more documented in a structural and functional point of view. They may mediate thyroid hormone effects on the regulation of DNA transcription and the synthesis of active proteins. Their mechanism of action is nevertheless not well defined.

It has been reported evidence based on equilibrium binding, electrophoretic, immunoelectrophoretic studies, that the rat possesses a major high affinity thyroid hormone binding protein, with an electrophoretic mobility and binding properties similar to those of the human thyroxine binding globulin (TBG). It is shown that in the sera of postnatal developing animals, between 3 and 21 days, the thyroxine (T4) and the triiodothyronine (T3) binding activities increase up to 10 times over adult or foetal levels, due to a high transient post-natal surge of the rat TBG. In the adult serum, the TBG persists in decreased amounts: it then yields the predominant role as T4 carrier to the thyroid binding prealbumin (TBPA), but retains the major role as binder of T3, i.e. of the biologically active thyroid hormone.

Two kinds of TBG polymorphism are described in human, one found in deglycosylated TBG from individual blood donors, the other is a genetically determined polymorphism. TBG from plasma samples from a patient with toxic goiter, not autoimmune, (p)TBG, from the patient's mother (m)TBG and from individual donors (n)TBG, were labeled with [125I]T4 or [125I]T3 and submitted to isoelectric focusing (IEF), followed by autoradiography. Three faint [125I]T4 radiolabeled bands were detectable in (p)TBG while four strong [125I]T4 radiolabeled bands were detectable in (m)TBG and (n)TBG), respectively. IEF of the [125I]T3 incubated serum samples resulted in no detectable isoelectric radiolabeled band for (p)TBG while a normal pattern was found in (m)TBG and in (n)TBG, respectively. These data suggest a new intraindividual not linked to sexual chromosome X polymorphism characterized by a loss in hormone binding.

The routine T4 determination from filter paper blood spots, with supplementary T.S.H. and T.B.G. determinations on subnormal T4 values, is a reliable method for neonatal hypothyroidism screening. Preliminary results, presently reported, agree with previous studies. However a larger experience is still necessary to decide the best way for mass-screening of congenital hypothyroidism.

The level of TBG in normal adults is 2.21 +/- 0.4 mg/100 ml, without any sex difference. TBG levels are high in the neonatal period (3.26 +/- 0.49 mg/100 ml) and in children under the age of 1 year (2.61 +/- 0.66 mg). Estrogens induce a significant increase (3.96 +/- 1.0 mg) and corticoids a significant decrease of TBG (1.44 +/- 0.32 mg). TBG is also decreased in thyrotoxicosis (1.88 +/- 0.34 mg) but normal in hypothyroidism. There is a strong correlation between T4 and TBG levels, and the T4/TBG ratio appears to be a useful index, which remains constant in normal adults, and under treatment by estrogens and corticoids.

The authors have compared "clinic" and "biology" in order to determine principal tests in vitro in: hyperthyroïdie diagnostic: T3-FT4 rT3; hyperthyroïdie form: TBG; treated greave's disease: FT4-TBG.

Thyroxin binding prealbumin (TBPA) and retinol binding protein (RBP) are associated in a complex responsible for the transport of vitamin A and of about 10% of the thyroid hormones T3 and T4. Both are synthetized in the liver. RBP can be characterized by two essential points: its hepatic secretion depending on the nutritional vitamin A status explains the close relation noted between these two parameters; its catabolism located in the renal tubular cells indicates the important role played by kidney in its metabolism. The concentrations, in serum of normal healthy adults, of TBPA and RBP are respectively 323 mg/l and 63 mg/l for men, 283 mg/l and 52 mg/l for women. In these cases the variations of the two proteins are significantly correlated. In patients with liver diseases and with protein deficiency, there is a lack of synthesis of TBPA and RBP (deficiency in substrate and/or decrease in hepatic synthesis). In vitamin A deficiency and in renal failure, RBP alone is disturbed.

The value of TBG serum concentration for the exploration of thyroid function was studied by radioimmunoassay in 203 patients (133 normals, 62 dysthyroidism, 8 women taking oral contraceptives). The results of the normal patients show important and as of yet unexplained variations of TBG levels, depending on age and sex. In hyperthyroidism, serum TBG was reduced significantly in women and no significantly in men. In hypothyroidism, the levels are significantly high in both sexes. Like the TRH test, the TBG serum concentration determination may be helpful for the diagnosis of a slight hypothyroidism. Moreover, as the serum levels return to normal values with substitutive therapy, TBG assay may be used as a follow-up test during the treatment of hypothyroid patients.

Measurements of thyroxin (T4), thyroxin-binding globulin (TBG) and TSH were carried out in 34 full-term newborns, 21 prematures and 11 neonates with respiratory distress (6 with hyaline membrane disease) at 5 days of age. In cases with neonatal respiratory distress and to a lesser extent in prematures, low T4 due to a decrease of TBG was found, TSH being identical in all groups. The positive correlation between TBG and transferrin suggests a disturbance in hepatic synthesis. The authors conclude that, in cases with neonatal respiratory distress, low T4 does not mean hypothyroidism and does not require a treatment, provided TSH remains within normal limits.

The "euthyroid sick syndrome", representing the changes of thyroid hormone metabolism in disease, embraces the following hormonal changes: 1) A decrease in serum T3 levels which is often accompanied by an increase in rT3 levels. Serum T4 levels remain normal. These changes are extremely frequent in many varied diseases. 2) In very severe disease, serum T4 levels may also decrease. The free T4 index is often decreased and the free T4 may either be normal or decreased. These changes reflect alterations of thyroid hormone metabolism and can be distinguished from primary hypothyroidism by a normal serum TSH level. 3) Occasionally there are transient increases of total and free T4. This disturbance of serum thyroid hormone levels is mostly due to drug interference with thyroid hormone metabolism (amiodarone etc.). Differentiation from hyperthyroidism is difficult. It is important to diagnose the "euthyroid sick syndrome" since this will avoid erroneous diagnosis and treatment or hypo- and hyperthyroidism.

A radioimmunoassay for the accurate measurement of T.B.G., developed by Crouzat-Reynes, was used to perform T.B.G. concentration in sera of euthyroid subjects in different clinical situations, in hypothyroid and hyperthyroid patients. In normal control, the T.B.G. concentration was not different from men and women, from young and old subjects (m = 21,1; sigma = 3,9). On the other hand, in women either pregnant (m = 51,2; sigma = 18,1) or receiving oral contraception (m = 30,1; sigma = 5,7), the T.B.G. levels were significantly higher than euthyro subjects. Cirrhosis of the liver and liver carcinoma were without apparent effect on T.B.G. levels because it was a too few number of patients and the group was too heterogeneous. In the group of hypothyroid (m = 25,9; sigma = 6,5) and hyperthyroid (m = 21,1; sigma = 5,5) patients, the T.B.G. serum concentrations were not significantly different from normal. The ratio T4/T.B.G., as I.T.L. (T4 X T3 uptake) permit to bring back in normal range T4 levels changed by extrathyroidal process; however, this ratio seems to us to be less interesting than standard I.T.L. The T.B.G. assay has not to be considered only as a substitution of T3 uptake because they do not study the same parameters.

Four members of the same family (2 male and 2 female) with normal thyroid function were found to have decreased total T3 and total T4, elevated response to the T3 test and low free thyroxin index. Such biological changes result from a deficiency in carrier protein and should be distinguished from nearly similar abnormalities observed in low T3 syndrome and hypothyroidism. Whilst gonosomal transmission through the X chromosome of thyroxin-binding protein deficiency seems well established, our findings show that another mechanism, i.e. dominant autosomal heredity, is practically certain.

A relationship is proposed for calculating the concentration of free serum thyroxine using the measured values of thyroxine and thyroxine-binding globulin total concentrations. This calculation has been performed on a population of 335 patients. A good discrimination of the different thyroid diseases has been obtained.

An epidemiological study involving 616 subjects carried out in the Man region, Côte d'Ivoire, showed endemic goiter in 54,5% of the group overall and in 80% of females. Thyroid function of subjects chosen at random in the goitrous and non-goitrous group (105 G and 71 NG respectively) was identical. Compared with a French control group T4 was significantly lower but T3 and TSH were higher. TBG level is high with low iodine elimination. High levels of TSH are not necessarily associated with low T3 or T4 levels, or with clinical signs of a hypothyroid condition. They are probably the result of a transient reaction. T4-TSH and T3-TSH correlations for NG subjects were (-0,40) but the T3-TSH correlation for the G subjects was significantly lower (-0,23). These differences could be explained by the simultaneous high levels of T3 and TSH more frequently rencountered in G subjects and by the fact that serious hypothyroid conditions are more frequent in the NG group (6 out of 9). The percentage of hypothyroid conditions is high in both clinical and biological investigations. No anti-thyroglobulin antibodies were found in any of the hypothyroid cases with goitre. The histograms illustrate the clinical and biological heterogeneity of a homogeneous non-medicalised population.

The rT3-binding and human serum proteins was directly studied with tracer doses of radioactive rT3. Polyacrylamide gel electrophoresis showed 125I-rT3 added to human serum was distributed among two proteins: albumin (carrying 57% of tracer rT3) and TBPA )22%). No binding was observed to TBG, protein binding T4.