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Biomedical subjects

P Vitti

Publications and source records attributed to P Vitti.

At least 19 recordsLinked to original sources
PubMed1992

Thyroid hypoechogenic pattern at ultrasonography as a tool for predicting recurrence of hyperthyroidism after medical treatment in patients with Graves' disease.

An abnormal thyroid echographic pattern characterized by a diffuse low echogenicity has been described in Hashimoto's thyroiditis and Graves' disease. The aim of the present work was to study the relationship between thyroid hypoechogenicity and the outcome of treatment for hyperthyroidism with antithyroid drugs in patients with Graves' disease. The study group included 105 patients who underwent a course of methimazole treatment. Thyroid ultrasonography was carried out at diagnosis, and autoantibodies to thyrotropin receptor (TR-ab) were measured at the end of treatment. During the follow-up after methimazole treatment, 87/105 (83%) patients had relapse of hyperthyroidism and 18/105 (17%) were in remission. Recurrence of hyperthyroidism occurred in 71/76 (93%) patients with thyroid hypoechogenicity and in 16/29 (55%) of those with normal thyroid echogenicity (chi 2 = 19.0; p less than 0.0001). Positive TR-ab values at the end of methimazole treatment were found in 59/76 (78%) patients with thyroid hypoechogenicity and in 12/29 (41%) patients with normal thyroid echogenicity (chi 2 = 10.9; p less than 0.0001). Sixty-five/87 (74%) patients with relapse of hyperthyroidism and 6/18 (33%) of those who remained euthyroid were TR-ab-positive at the end of methimazole treatment (chi 2 = 9.8; p less than 0.002). The finding of thyroid hypoechogenicity at diagnosis had higher specificity (0.81) and sensitivity (0.72) with respect to TR-ab positivity at the end of methimazole treatment (0.74 and 0.66 respectively) for the prediction of relapse of hyperthyroidism. Therefore, the evaluation of thyroid echographic pattern can be considered a useful prognostic tool in patients with Graves' disease.

Adult↗
PubMed1992

Use of FRTL-5 for the study of thyroid antibodies involved in goitrogenesis.

Some authors have suggested a role of autoimmunity in the pathogenesis of iodine deficiency disorders (IDD). For this purpose we have searched for thyroid adenylate cyclase stimulating antibody (TSAb) and thyroid growth stimulating antibody (TGSAb) in patients with endemic goiter (EG) and endemic cretinism (EC). Immunoglobulins G preparations (IgGs) were tested in FRTL-5 cells. TSAb were calculated as percent of cAMP increase over basal production and TGSAb were expressed as percent of increase of 3H-thymidine incorporation and DNA content in FRTL-5 cells. Our results show that IgGs from goitrous patients were devoid of TSAb and TGSAb activities, while in the same conditions IgGs from patients with Graves' disease had the ability to stimulate cAMP production and 3H-thymidine incorporation in FRTL-5 cells. These data argue against a direct role of TSAb and TGSAb in the pathogenesis of IDD.

Adenylyl Cyclases↗
PubMed1992

Mild iodine deficiency in fetal/neonatal life and neuropsychological performances.

The effects of mild/moderate iodine deficiency during the fetal/neonatal life on neuropsychological performances are still poorly defined. In this research we analyzed some parameters of cognitive performance with sensitive psychometric tests in children living in an area with moderate iodine deficiency. Each subject was submitted to the following neuropsychological tests: 1) a reaction time (RT) session, 2) the block design subtest of the WISC-R, 3) the coding subtest of the WISC-R. No significant difference was found between children with mild iodine deficiency and controls, for block design and coding tests. On the other hand controls had significantly faster RTs. Our data show that exposure to mild iodine deficiency in fetal/neonatal life does not affect general cognitive performance but influences the velocity of motor response to visual stimuli, which may be due to an alteration of the efficiency of the information processing mechanism.

Child↗
PubMed1992

Maturation of pituitary-thyroid function in the anencephalic fetus.

The recent availability of both cordocentesis and ultrasensitive/highly specific immunometric assays for TSH and its subunit determination along with direct "two-step" assays for free thyroid hormone measurement, prompted us to study the maturation of hypothalamic-pituitary-thyroid axis in normal and anencephalic human fetuses from 17 to 26 weeks of gestation. In addition, TSH bioactivity was measured as cAMP accumulation in CHO cells transfected with recombinant human TSH receptor and TSH carbohydrate structure was studied by lectin chromatography. In both normal and anencephalic fetuses, circulating TSH and FT4 levels significantly increased from 17 to 26 weeks of gestation. Circulating FT3 concentrations were very low (0.5-3.1 pmol/l), while alpha-SU levels were very high (20-417 mg/l). Both FT3 and alpha-SU levels did not change from 17 to 26 weeks of gestation and, again, no differences between normal and anencephalic fetuses were recorded. Circulating TSH from both normal and anencephalic fetuses showed an enhanced bioactivity and was more retained on the lectin column than adult TSH, thus indicating that molecules with different carbohydrate structure are circulating during fetal development. In conclusion, the present data demonstrate that the absence of the hypothalamus does not compromise the maturation of pituitary-thyroid function and that the mechanisms underlying the secretion of TSH molecules with elevated bioactivity and different structure of glycosylated chains are not dependent on hypothalamic neuroendocrine control.

Anencephaly↗
PubMed1992

Thyroid autoimmunity and neuropsychological development.

Thyroid autoimmunity may affect neuropsychological development by interfering with the fetal and/or neonatal thyroid status; indeed, both hypo- and hyperthyroidism during the fetal-neonatal life may be associated with a subsequent impairment of intellectual and psychomotor performances. Maternal thyroid status during early pregnancy, and in particular hypothyroidism due to autoimmune thyroiditis, can also affect the fetal neurological development. Finally, anti-thyroid drugs used to control hyperthyroidism in pregnant women with Graves' disease have been widely investigated for their possible effect on the intellectual development of the offspring.

Congenital Hypothyroidism↗
PubMed1991

Thyroid ultrasonography helps to identify patients with diffuse lymphocytic thyroiditis who are prone to develop hypothyroidism.

The clinical usefulness of thyroid ultrasonography in the evaluation of patients with autoimmune thyroiditis has been investigated. Thyroid ultrasonography was performed in 1184 consecutive patients attending our clinic, and the echo density of the thyroid parenchyma was evaluated with respect to that of normal thyroid tissue. Diffuse thyroid hypoechogenicity was found in 44 of 238 (18.5%) patients with autoimmune thyroiditis; the degree of hypoechogenicity was significantly correlated with the levels of circulating thyroid autoantibodies. Thyroid function was normal in all 194 patients with normal thyroid echogenicity, whereas hypothyroidism was found in 28 of 44 (63.6%) with reduced thyroid echogenicity. Included in this group were 8 patients, euthyroid at the first observation, who developed hypothyroidism over an 18-month follow-up period. None of the 133 patients with autoimmune thyroiditis and normal thyroid echogenicity followed for the same period of time became hypothyroid. Evidence of diffuse lymphocytic thyroiditis was obtained by histology after thyroidectomy (n = 10) or multiple fine needle aspiration cytology (n = 15) in 25 of the 44 patients with thyroid hypoechogenicity; on the other hand, focal thyroiditis was shown at histology in 8 patients who had normal thyroid echogenicity. In conclusion, diffuse low thyroid echogenicity was found in about 20% of patients with autoimmune thyroiditis. This echographic pattern is indicative of diffuse autoimmune involvement of the gland and is associated with or may predict the development of hypothyroidism.

Autoantibodies↗
PubMed1990

Incidence of antibodies blocking thyrotropin effect in vitro in patients with euthyroid or hypothyroid autoimmune thyroiditis.

Autoantibodies blocking the TSH-dependent production of cAMP in thyroid cells (TSH-BAb) have been described in atrophic thyroiditis (AT; idiopathic myxedema) and in neonates with transient hypothyroidism, but their incidence in autoimmune thyroiditis in relation to thyroid status remains to be completely established. To this purpose TSH-BAb were evaluated in a group of 140 consecutive patients with autoimmune thyroiditis, which included 26 cases of AT and 114 subjects with goitrous Hashimoto's thyroiditis (HT); among the goitrous group 27 were euthyroid (HT-E), 32 had subclinical hypothyroidism (HT-SH), and 55 had clinical hypothyroidism (HT-H). TSH-BAb were measured in immunoglobulin G prepared by DEAE-Sephadex A-50 by determining their ability to inhibit TSH-dependent cAMP production in a differentiated strain of cultured rat thyroid cells (FRTL-5). Using this sensitive and reproducible method, TSH-BAb were detected in 12 of 26 (46%) patients with AT, in 1 of 27 (3.7%) subjects with HT-E, in 3 of 32 (9.4%) with HT-SH, and in 20 of 55 (36%) with HT-H. The prevalence of TSH-BAb was higher in AT vs. HT-H (P less than 0.001), HT-SH (P less than 0.001), or HT-E (P less than 0.001), and in HT-H vs. HT-SH (P less than 0.001) or HT-E (P less than 0.001). Mean TSH-BAb levels in AT were higher than those in HT-H (P less than 0.005) and HT-SH (P less than 0.025); the difference was not significant between HT-H and HT-SH. An inverse correlation was found between TSH-BAb levels and estimated goiter weight (P less than 0.005). The results of the present study indicate that 1) in autoimmune thyroiditis TSH-BAb are detectable almost exclusively in hypothyroid patients, their prevalence being higher in overt hypothyroidism than in subclinical thyroid failure; 2) the prevalence of TSH-BAb and their mean levels are higher in hypothyroid patients with AT than in those with HT; and 3) therefore, the presence of circulating TSH-BAb appears to be related to the development of hypothyroidism and thyroid atrophy.

Adult↗
PubMed1990

Thyroid autoimmunity and thyroid autonomy.

While it is well established that autoimmune factors are the cause of goiter and hyperthyroidism in Graves' disease, these factors are not yet considered relevant in the development of thyroid autonomy. While an increased overall frequency of anti-Tg and anti-TPO antibodies has been found in moderate iodine-deficient areas, where thyroid autonomy is more frequently observed, there was evidence indicating that thyroid autoimmune phenomena were the consequence rather than the cause of the goiter. Thyroid Stimulating Antibodies (TSAb) have been reported in sera of patients with nodular autonomous goiter, but their pathogenetic relevance is uncertain, since these findings could not be confirmed by others. In our experience TSAb were detected in few cases with multinodular nontoxic goiter and were always associated with anti-TG and anti TPO antibodies, indicating that these patients have the nodular variant of Graves' disease. Besides TSAb, Thyroid Growth Stimulating Antibodies (TGAb) have been detected by different techniques in several goitrous conditions, including Graves' disease and sporadic or endemic nontoxic goiter. The precise nature of TGAb remains to be clarified, and particularly the relationship between TGAb and TSAb is still a matter of controversy. However, data indicating that TGAb cannot be dissociated from TSAb in Graves' sera suggest that these antibodies can be regarded as a sufficient pathogenetic agent for the development of both goiter and thyroid hyperfunction in Graves' disease. The relevance of TGAb in euthyroid goitrous conditions is uncertain, since conflicting results have been reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1989

Recent advances in the understanding of humoral and cellular mechanisms implicated in thyroid autoimmune disorders.

In this review new data are reported indicating that the thyroid microsomal-microvillar antigen can be identified with thyroid peroxidase (TPO). This concept derives from binding studies of monoclonal and polyclonal microsomal antibodies to TPO purified by affinity chromatography or obtained by recombinant DNA technology. Furthermore, immunofluorescence studies performed on cultured thyroid cells have shown the presence of a TPO-related antigen on the surface of the cells. The expression of the TPO antigen is modulated by TSH through the cAMP pathway. The functional activities of TSH receptor autoantibodies have also been characterized. From these studies the following conclusions can be drawn: (i) TSH receptor antibodies possess multiple biological activities, interfering or mimicking TSH actions; (ii) a good correlation is observed between stimulation of adenylate cyclase and of iodide uptake by Graves' IgG. In these IgG preparations, adenylate cyclase- and growth-stimulating activities cannot be separated; (iii) antibodies blocking the TSH-dependent AC are present in patients with autoimmune hypothyroidism; (iv) a mixture of stimulating and blocking antibodies may coexist in the same patient, whose clinical status may result from the sum of the biological activities of these antibodies. Finally, new data are reported on the identification and characterization of T cell clones infiltrating the thyroid tissue of subjects with thyroid autoimmune disorders. The majority of these clones were CD8+ cytolytic T cells with natural killer activity. These latter data may be of importance in the mechanisms of thyroid damage observed in Hashimoto's glands.

Antibody Formation↗
PubMed1989

Thyroid autoantigens and their relevance in the pathogenesis of thyroid autoimmunity.

Humoral and cellular immune responses are both involved in autoimmune disorders of the thyroid gland. In the last five years, new substantial data have been obtained on the nature and the expression of thyroid cell surface autoantigens and on the demonstration of the functional heterogeneity of autoantibodies to the thyroid stimulating hormone (TSH) receptor. In the present report, attention will be mainly focused on recent studies carried out in our laboratory. The main autoantigens so far identified include the 'microsomal' antigen, thyroglobulin and the TSH receptor. For many years the 'microsomal' antigen (M) was considered a poorly characterized constituent of the cytoplasm of the thyroid cell. In the last five years, several lines of evidence were provided indicating that M is also well represented on the surface of the follicular cell and is identical to thyroid peroxidase (TPO). The use of anti-TPO monoclonal antibodies, presently available, have confirmed this antigenic identity. Microsomal (anti-TPO) antibodies are very useful markers of autoimmune thyroid disorders and are generally present in Hashimoto's thyroiditis, idiopathic myxedema and Graves' disease. TSH receptor antibodies (TRAb) are present in the sera of patients with Graves' disease. TRAb are able to stimulate thyroid adenylate cyclase and also to mimic TSH in its thyroid growth stimulation. Thus, these antibodies may have a pathogenetic role in goiter formation and in thyroid hyperfunction in Graves' disease. TRAb were also shown to inhibit both TSH binding to its receptor and TSH-stimulated adenylate cyclase activity. Recently TRAb, which inhibited TSH-stimulated adenylate cyclase activity, were found in idiopathic myxedema patients and may be responsible for impairment of thyroid function.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantigens↗
PubMed1989

Simultaneous assay of thyroid adenylate cyclase- and growth-stimulating antibodies using FRTL-5 cells. Evidence suggesting their identity in patients with Graves' disease.

The relationship between thyroid growth-stimulating antibodies (TGSAb) and thyroid adenylate cyclase-stimulating antibodies (TSAb) in patients with Graves' disease is still a matter of controversy. To investigate this problem, we have developed an assay for the simultaneous measurement of TSAb and TGSAb using FRTL-5 cells. TSAb was detected by its ability to stimulate iodide (I-) uptake and TGSAb by the 3H-thymidine ([3H]-Tdr) incorporation assay. Thirty-four immunoglobulin G (IgG) preparations from patients with active Graves' disease were selected from a previous series in order to include both TSAb-negative IgGs (n = 9) and TSAb-positive IgGs (n = 25) by the cAMP stimulation assay, with a wide range of stimulatory activity. With one exception, the TSAb-positive IgGs produced a significant stimulation of I- uptake; 20 of them were also TGSAb-positive. The nine IgGs negative in the cAMP assay, were also negative in the I-uptake and the [3H]-Tdr incorporation assays. The majority of samples had a similar potency in the two assays and a significant positive correlation was found (r = 0.76; P less than 0.001). Two IgGs previously shown to inhibit TSH-stimulated adenylate cyclase in FRTL-5 cells produced an almost complete inhibition (80-90%) of both TSH- and Graves' IgG-stimulated I- uptake and [3H]-Tdr incorporation. In conclusion, using a simultaneous assay for thyroid growth and adenylate cyclase stimulation, TGSAb in Graves' patients were found only in TSAb-positive IgGs; both Graves' IgG-stimulated activities were inhibited by antibodies blocking the TSH-dependent adenylate cyclase stimulation. Our data strongly suggest that the same antibody may be responsible for both goitre and thyroid hyperfunction of Graves' disease.

Adenylyl Cyclases↗
PubMed1989

The expression of the microsomal/peroxidase autoantigen in human thyroid cells is thyrotrophin-dependent.

In the present report the mechanisms responsible for the expression of the thyroid microsomal autoantigen (M-Ag) were studied in primary cultures of human thyroid cells prepared from Graves' or non-toxic goitres. The indirect immunofluorescence (IFL) technique using human sera positive for anti-microsomal antibody (anti-MAb) was employed to detect M-Ag. Studies were performed to ascertain whether M-Ag recognized by anti-MAb could be identified with thyroid peroxidase (TPO). Preabsorption experiments showed that, similarly to solubilized thyroid microsomes, purified human TPO abolished the binding of anti-MAb to thyrocytes, while no inhibition was obtained with control human tissues. The identity of M-Ag and TPO was also demonstrated using a double layer IFL technique which allowed a simultaneous staining of the antigen(s) recognized by anti-MAb and by a monoclonal anti-TPO antibody. After 5-15 days of TSH withdrawal from the culture medium the M/TPO-Ag disappeared from the surface and the cytoplasm of human thyroid cells. Readdition of TSH (0.1-100 mU/ml) to cells lacking M/TPO-Ag elicited its reappearance within 48-72 h. This effect of TSH was prevented by 10 microM cycloheximide but not by methimazole (0.1-2 mM). Two stimulators of the adenylate cyclase-cAMP system, cholera toxin and forskolin, and 8-bromo-cAMP mimicked TSH in inducing M/TPO-Ag. Thyroid stimulating antibody (TSAb) of Graves' disease also reproduced the effect of TSH on M/TPO-Ag reexpression in human thyroid cells. By contrast, epidermal growth factor, oestradiol or NaI were ineffective in inducing M/TPO-Ag. The present data indicate that: (i) the expression of M/TPO-AG in human thyroid cells is dependent on TSH stimulation, through pathways which involve cAMP production and protein synthesis, (ii) TSAb reproduces this effect of TSH; (iii) oestradiol and NaI have no direct influence on the expression of M/TPO-Ag.

Autoantigens↗
PubMed1988

Measurement of TSAb directly in serum using FRTL-5 cells.

FRTL-5 cells were shown to be suitable for the measurement of thyroid stimulating antibody (TSAb) present in sera of patients with Graves' disease. Current methods for the assay of TSAb require the separation of immunoglobulin G (IgG) from patient sera. In this report the possibility to measure TSAb directly on serum was evaluated using FRTL-5 cells. To this purpose cells were seeded in 96-well plates and cultured for 4 days in medium deprived of TSH. Using this system bovine TSH was able to produce a significant stimulation of cAMP production at 1 microU/ml. Whole normal serum completely inhibited the stimulation of TSH as well as that of TSAb, while diluted serum was devoid of any effect. Heat inactivated sera and IgGs, prepared by DEAE Sephadex separation, were diluted in hypotonic medium and incubated with cells for 1 h at 37 C. After incubation cAMP was measured in the assay medium by RIA. In some experiments the effects of graded dilutions of sera and IgGs with known TSAb activity were compared. Sera as well as IgGs increased the cAMP production, but, at the highest concentrations, an inhibitory effect was evident. For this reason sera were tested after appropriate dilution. Thirteen/27 (48%) sera and 22/27 (81%) IgGs from patients with Graves' disease were TSAb positive. The effect of Graves' sera on adenylate cyclase stimulation was completely inhibited by an anti-human IgG. The results of stimulation produced by Graves' sera and IgGs were highly correlated (r = 0.97, p less than 0.001). In conclusion it is possible to measure TSAb directly in serum using FRTL-5 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Studies on the mechanism responsible for thyrotropin-induced expression of microsomal/peroxidase antigen in FRTL-5 cells.

The expression of the microsomal (M) antigen on the surface and in the cytoplasm of a strain of rat thyroid cells (FRTL-5) is under the regulation of TSH. In the present report the mechanism by which TSH induces such expression was investigated with the use of human microsomal antibody-positive serum and an indirect immunofluorescence technique. Studies were also performed to ascertain whether the M antigen of FRTL-5 cells could be identified with thyroid peroxidase (TPO), as suggested by recent data obtained in human thyroid tissue. Preabsorption experiments showed that, like solubilized human thyroid microsomes, purified human TPO completely abolished the binding of microsomal antibody to FRTL-5 cells. No inhibition was obtained by preabsorption with control human tissues (placenta, liver, and spleen) or human thyroglobulin, indicating that the antigen recognized by microsomal antibody in FRTL-5 cells was TPO. After 72 h of TSH withdrawal from the culture medium the M/TPO antigen disappeared from the surface and the cytoplasm of FRTL-5 cells. Readdition of TSH (250 microU/ml) to the culture medium of cells lacking the M/TPO antigen elicited its reappearance within 24-48 h. This effect of TSH was prevented by 10 microM cycloheximide or 0.5-5 micrograms/ml actinomycin D. Two well known stimulators of the adenylate cyclase-cAMP system, cholera toxin and forskolin, mimicked TSH in inducing the reappearance of the M/TPO antigen. A similar effect was observed with use of the phosphodiesterase inhibitor isobutylmethylxanthine. Reappearance of M/TPO antigen was also produced by the cAMP analog 8-bromo-cAMP. The tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate, which stimulates thyroid cell growth through a cAMP-independent pathway, was ineffective in inducing the M/TPO antigen in FRTL-5 cells. The present data indicate that 1) thyroid peroxidase accounts for most, if not all, of the microsomal antigen of FRTL-5 cells; and 2) TSH modulates the expression of the M/TPO antigen in FRTL-5 cells by a mechanism that involves cAMP production and requires mRNA formation and subsequent protein synthesis.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Interaction of the thyrotropin receptor on rat FRTL-5 thyroid cells with thyrotropin and a thyrotropin-stimulating autoantibody from Graves' patients.

FRTL-5 rat thyroid cells were either surface-labeled with 125I or biosynthetically labeled with [3H]N-acetylglucosamine, solubilized by lithium diiodosalicylate and immunoprecipitated after sequential exposure to bovine thyrotropin and anti-bovine thyrotropin. Autoradiography of polyacrylamide gels run under denaturing conditions and in the presence of a reducing agent revealed two prominent bands with approximate molecular weights of 66-70 kDa and 47 kDa. Immunoprecipitation of the same radiolabeled and solubilized membrane preparations with a Graves' disease IgG having thyroid stimulating but no thyrotropin-binding inhibiting activity revealed only one major band, migrating near the 47 kDa component reactive with thyrotropin. No bands were immunoprecipitated in control incubations using normal human IgG or substituting radiolabeled, solubilized membranes from a rat thyroid cell line with no thyrotropin receptor activity. Thin layer chromatography of Folch extracts of the [3H]-N-acetylglucosamine-labeled immunoprecipitates obtained by either procedure indicated that a specific thyroid ganglioside was coprecipitated with the immunoprecipitated proteins in both cases.

Animals↗
PubMed1987

Detection and characterization of autoantibodies blocking the TSH-dependent cAMP production using FRTL-5 cells.

Autoantibodies blocking the TSH-stimulated cAMP production (TBkAb) were measured in immunoglobulin G (IgG) preparations from 38 patients with primary autoimmune hypothyroidism, using FRTL-5 cells. TBkAb were detectable in 15/23 IgG preparations from patients with untreated idiopathic myxedema, and in 2/15 IgGs from patients under L-thyroxine treatment. None of the IgG from 22 normal subjects or from 10 patients with nonautoimmune hypothyroidism following total thyroidectomy caused any significant effect on the TSH-stimulated cAMP production. No correlation was found between TBkAb and the thyroid microsomal antibody. Antibodies inhibiting the 125I-TSH binding to TSH receptor were detectable in only 3/20 patients; IgGs from these 3 patients were also positive in the TBkAb assay. One IgG with potent TBkAb activity inhibited the TSH-stimulated adenylate cyclase in a competitive manner, while it had no effect on the forskolin-stimulated cAMP production. The inhibiting action of this IgG was almost completely lost after preabsorption with human thyroid membranes. In conclusion, we describe a new practical and sensitive method for the measurement of TBkAb; TBkAb are distinct from the microsomal antibody, and are probably directed to the TSH receptor.

Adenylyl Cyclases↗