Biomedical subjects

G F Fenzi

Publications and source records attributed to G F Fenzi.

At least 37 records · Page 2Linked to original sources

PubMed1986

Is humoral thyroid autoimmunity relevant in amiodarone iodine-induced thyrotoxicosis (AIIT)?

Amiodarone, an iodine containing drug, may induce thyrotoxicosis by an uncertain mechanism. In this study the role of thyroid autoimmunity was evaluated in 28 consecutive patients referred to us because they had become hyperthyroid during long-term amiodarone administration. Titres of thyroglobulin and thyroid microsomal antibodies, TSH binding-inhibitory and thyroid stimulating antibodies were evaluated. Underlying thyroid disorders were demonstrated in 20 patients (9 of them had toxic diffuse goitre, seven toxic multinodular goitre and four toxic adenoma), while eight patients did not show any apparent thyroid gland abnormality. Circulating thyroid autoantibodies could be found in all amiodarone iodine-induced hyperthyroid patients with toxic diffuse goitre and in one with toxic multinodular goitre, whilst they were absent in the other patients. These studies suggest that thyroid autoimmunity has little if any role in the development of thyrotoxicosis in amiodarone treated patients without underlying thyroid disorders. Furthermore, in amiodarone-iodine-induced thyrotoxicosis associated with various thyroid diseases, the humoral markers of thyroid autoimmunity show an incidence similar to that observed in spontaneous hyperthyroidism.

Adult↗

PubMed1986

Thyroid-stimulating antibody mimics thyrotropin in its ability to desensitize the adenosine 3',5'-monophosphate response to acute stimulation in continuously cultured rat thyroid cells (FRT-L5).

TSH preincubation induces refractoriness to further stimulation of cAMP accumulation by the hormone in cultured thyroid cells. The question of whether the thyroid-stimulating antibodies (TSAb) present in sera of patients with Graves' disease have the same desensitizing effect as TSH was evaluated in this study using a differentiated strain of rat thyroid cells (FRT-L5) which requires TSH for growth and develops refractoriness to acute TSH stimulation of cAMP accumulation. Cells cultured for 4-5 days in medium deprived of TSH recovered responsiveness to TSH and TSAb. Refractoriness to TSH was reinduced in these cells by a 24-h preincubation with 250 microU/ml TSH. The addition of 100 microM KI or 100 microM methimazole to the medium together with TSH did not modify TSH-induced refractoriness. Four different TSAb preparations all induced refractoriness to TSH-stimulated cAMP accumulation. TSAb preincubation induced refractoriness to acute TSAb as well as TSH-stimulated cAMP accumulation. TSAb-induced desensitization was dose dependent and required prolonged (8-24 h) exposure to TSAb. Furthermore, the desensitization induced by TSAb as well as that caused by TSH were significantly inhibited by cycloheximide, indicating the need for de novo protein synthesis. In conclusion, TSAb mimics TSH in the induction of refractoriness in FRT-L5 cells.

Animals↗

PubMed1986

Thyroid autoimmunity and endemic goiter.

The goitrogenic role of autoimmune phenomena in endemic goiter is still uncertain. Scanty and discrepant results have been reported in different areas of the world. This prompted us to evaluate the prevalence of circulating thyroid antibodies in an area of northwestern Tuscany during a survey for endemic goiter. The survey was carried out according to the P.A.H.O. criteria in a stable community. In all schoolchildren (n = 142; age range 7-15 years) and in most of their parents (n = 159), thyroid size was evaluated and urine was collected for iodine determination. Blood was drawn for determination of circulating thyroid microsomal (MAb) and thyroglobulin antibodies (TgAb). TSH binding-inhibiting (TBIAb) and thyroid growth-stimulating antibodies (TGSAb), TT3, TT4 and TSH. Prevalence of goiter in schoolchildren was 77.9% and 94.8% in their parents. Mean (+/- S.D.) urinary iodine excretion was 55.0 +/- 2.1 micrograms/24 h. The overall frequency of TgAB and MAB in the adult population was 14.4, statistically higher than of control subjects matched for sex and age. The frequency in schoolchildren was 4.3%. TBIAb and TGSAb were undetectable in all tested cases. The presence of goiter in children was unrelated with the presence of thyroid antibodies in parents, whether goitrous or non-goitrois. A higher prevalence of goiter was found in children with goitrous parents as compared to children with non-goitrous parents (P less than less than 0.005). In conclusion, the frequency of thyroid autoantibodies in the adult population of the endemic area studies was increased, but showed no relation with the presence of goiter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1985

Can the inhibition of prostaglandin synthesis affect the adenylate cyclase response to thyroid stimulating antibodies?

The majority of Graves' immunoglobulins have the capacity to stimulate thyroid adenylate cyclase (AC) activity in vitro. So far, the exact events leading to AC activity stimulation by thyroid stimulating antibody (TSAb) are not known. It has been suggested that TSAb activates thyroid AC through prostaglandin (PG) synthesis, implying the concept that TSH and TSAb stimulate AC in different ways. If this is so, the inhibition of PG synthesis should notably reduce the response of thyroid plasma membrane to TSAb. We have, therefore, investigated the effect of 2 inhibitors of PG synthesis on the TSAb-stimulated AC activity in a crude human thyroid plasma membrane preparation. Neither indomethacin, nor hydrocortisone, even at concentrations able to completely inhibit PG synthesis, had any significant effect on the thyroid plasma membrane response to TSAb. The results suggest, therefore, that, at least under our experimental conditions, PG does not mediate the AC activation by TSAb. Consequently, the aforementioned suggestion should not be used to claim that TSH and TSAb activate thyroid AC through different pathways. The data, however, do not exclude that TSAb may determine PG synthesis in thyroid cells through the phosphatidylinositol signal system (Pl system).

Adenylyl Cyclases↗

PubMed1985

Reciprocal changes of serum thyroglobulin and TSH in residents of a moderate endemic goitre area.

Subjects living in iodine deficient areas were reported to have elevated serum thyroglobulin (Tg) concentrations. This finding was interpreted as related to thyroid stimulation. Discrepant results, however, were found when serum Tg concentrations were correlated either with serum TSH or with goitre size. In this study we investigated the relationships between goitre size, serum Tg and serum TSH in 488 unselected adult subjects living in an endemic area of North-Western Tuscany (Garfagnana district). The control group comprised 352 subjects residing in a non-endemic area. In the endemic area a high prevalence of goitre was found (80.1%), thyroid enlargement being slight to moderate in the majority of cases and very large only in six subjects. Serum Tg concentrations increased and serum TSH levels decreased with the size of goitre. Statistical analysis by the chi-square cross correlation test showed that the converse changes of serum Tg and serum TSH in relation to goitre size were highly significant. These findings indicate that the increase of serum Tg occurring in endemic goitrous subjects may be related to factors other than TSH stimulation. Functional autonomy of the thyroid may account for the finding of low serum TSH and elevated serum Tg values in patients with large goitres. The present data do not exclude the possibility that the release of Tg is influenced by TSH stimulation, but indicate that other factors may be responsible for the increased levels of Tg found in endemic goitre.

Adult↗

PubMed1984

Serum thyroglobulin determinations in the differential diagnosis of congenital hypothyroidism.

The value of serum thyroglobulin (Tg) determination in the differential diagnosis of congenital hypothyroidism was assessed by serum Tg measurements in 14 patients with proven congenital hypothyroidism, in 3 subjects with transient perinatal hypothyroidism, in 3 newborns with congenital thyroxine binding globulin (TBG) deficiency and in 34 normal controls. Serum Tg was undetectable in all 6 cases with thyroid agenesis, normal or moderately elevated in the 4 cases with ectopic thyroid, markedly increased in the 4 cases with dyshormonogenic goiter and normal in the 3 cases with transient hypothyroidism and in the 3 with TBG deficiency. The present data indicate that serum Tg measurements may be useful in the differentiation of athyreotic hypothyroidism from other conditions of congenital hypothyroidism.

Adolescent↗

PubMed1984

Serum thyroglobulin in newborns' cord blood, in childhood and adolescence: a physiological indicator of thyroidal status.

Serum thyroglobulin (Tg) was measured in the cord blood of 635 newborns and serum thyroxine (T4) reverse triiodothyronine (rT3), TSH and T3 were measured in about 200 of them. Cord Tg was detectable in all newborns with a mean +/- SE value (50 +/- 1.3 ng/ml) higher than that found in the serum of adult subjects (n = 144; Tg = 13 +/- 1.1; p less than 0.0001). Cord Tg had a log-normal distribution. A low, but positive correlation was found between cord Tg and cord TSH (n = 242; r = 0.17; p less than 0.05) but not with cord T4 or cord rT3. Gestational age was negatively correlated with cord Tg or cord rT3 (rS = 0.97; p less than 0.01; rS = -0.89; p less than 0.02, respectively) while was positively correlated with cord T4 or cord TSH (rS = 0.85; p less than 0.05; rS = 0.86; p less than 0.01, respectively). Birth weight, maternal diabetes, induction of labor with oxitocin, cesarian section and newborns' illness showed no influence on cord Tg levels when considered alone, but decreased cord Tg levels were found in ill newborns delivered by cesarian section. On the contrary, increased cord Tg levels were present in cord blood of newborns who developed hypoglycemia soon after birth and in small for gestational age newborns. In 24 newborns studied daily for the first 6 days of life, serum Tg was always detectable with mean values not different from those found in the cord blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1983

TSH-displacing activity versus TSH-binding inhibiting activity of immunoglobulins from patients with Graves' disease.

Inhibition of binding of TSH to thyroid plasma membranes by immunoglobulins G (IgG) from patients with Graves' disease has been interpreted as evidence of an interaction with the TSH receptor, but other explanations may account for this phenomenon. Displacement of receptor-bound TSH might be a more direct index of such an interaction. The aim of the present study was to assess TSH-displacing activity (TDA) of Graves' IgG by a newly developed assay and compare TDA to TSH-binding inhibiting activity (TBIA) and thyroid-stimulating antibody (TSAb) activity. TDA was assessed by preincubating 125I-TSH with thyroid plasma membranes and by measuring residual bound 125I-TSH after addition of IgG. TBIA was evaluated by determining binding of 125I-TSH to thyroid plasma membranes preincubated with IgG. Results were expressed as % TSH-displacing or binding inhibition activities of test IgG with respect to normal control IgG. The percent of TDA positive Graves' IgG preparations (72.7%) was greater than that of TBIA positive (48.5%). There was no correlation between TDA and TBIA results, since 11 Graves' IgG preparations were TDA positive but TBIA negative, and 6 were TDA negative but TBIA positive. Hashimoto's or idiopathic myxedema IgG preparations were positive in 2/7 in the TDA and in 1/7 in the TBIA assays, respectively. Neither TDA nor TBIA correlated with TSAb determined by cAMP accumulation in thyroid plasma membrane. The TDA assay developed in this study appeared to be more sensitive than the more widely used TBIA assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

PubMed1983

A sensitive method for assaying thyroid stimulating immunoglobulins of Graves' disease: use of the guanyl nucleotide-amplified thyroid adenylate cyclase assay.

The purpose of this study was to develop and validate a sensitive method for evaluating adenylate cyclase stimulation by thyroid-stimulating antibodies (TSAb), based on the measurement of thyroid membrane adenylate cyclase activity in the presence of a non-hydrolyzable GTP analogue, guanyl-5'-yl imidodiphosphate (Gpp(NH)p). The addition of Gpp(NH)p (10(-5)M) produced a 10-fold increase of the sensitivity of the system for both TSH and TSAb. Immunoglobulin G preparations from sera of 30 patients with Graves' disease were tested for the adenylate cyclase stimulation either in the presence or in the absence of Gpp(NH)p: a significant stimulation was observed in 27/30 patients when the GTP analogue was added to the system, while only 20/30 patients were positive in the absence of the nucleotide. The advantage of Gpp(NH)p addition was also evident in a large series which included 57 patients with Graves' disease, 15 with Hashimoto's thyroiditis or primary myxoedema and 22 normal subjects. In fact, 88% of patients with Graves' disease resulted positive, while no significant stimulation was elicited by Hashimoto's thyroiditis, primary myxoedema and by normal immunoglobulins. The sensitivity achieved in our system which employs thyroid plasma membranes was similar to that obtained by other investigators with the use of thyroid slices or thyroid cells in primary culture. Furthermore, methods based on thyroid plasma membranes are supposed to have a better reproducibility, since the same tissue preparation, if appropriately stored, may be used in several different tests.

Adenylyl Cyclases↗

PubMed1982

Thyroid-stimulating immunoglobulins.

The presence of thyroid-stimulating immunoglobulins in patients with Graves' disease is well established. Considerable evidence has accumulated that these immunoglobulins are antibodies to a thyroid plasma membrane antigen whose precise nature remains to be identified. The question whether the antigen is related to the TSH receptor is still debated. The causative role of thyroid-stimulating immunoglobulins in the hyperthyroidism of Graves' disease is widely recognized. The use of human specific stimulation assays has circumvented the objection of the relatively low frequency of long-acting-thyroid-stimulator-(LATS)-positive patients. Individual variations in the thyroid response may account for the lack of correlation between the levels of thyroid-stimulating immunoglobulins and most parameters of thyroid function. In this respect, the interference of nonstimulatory thyroid antibodies and of other autoimmune mechanisms may be of importance. An important clinical implication of thyroid-stimulating immunoglobulin determinations is their value in predicting the relapse of hyperthyroidism in treated patients. This clinical application has been so far limited by the technical difficulties of the assays. This emphasizes the need for a simple and reliable test, which can be used for routine measurements of thyroid-stimulating immunoglobulins.

Graves Disease↗

PubMed1982

[Thyroid-stimulating immunoglobulins. The related antigens].

The presence of thyroid stimulating antibodies (TSAb) in patients with Graves' disease is well established. Considerable evidence has accumulated that these are antibodies to thyroid plasma membrane components related to the TSH receptor. The question of whether thyroid stimulation is mediated by a direct interaction with the TSH binding site is still debated. Recent data obtained by the use of monoclonal antibodies to the TSH receptor are consistent with the view that Graves' immunoglobulins comprise antibodies to at least two different components of the TSH receptor complex, one of which is more strictly related to the binding of TSH and the other to the transmission of the hormonal effect. The causative role of TSAb in the hyperthyroidism of Graves' disease is widely recognized. The use of human specific stimulation assays has circumvented the objection of the relatively low frequency of LATS-positive patients. Individual variations in the thyroid response may account for the lack of correlation between levels of thyroid stimulating immunoglobulins and most parameters of thyroid function. In this respect, the interference of non-stimulatory thyroid antibody and of other autoimmune mechanisms may be of importance. An important clinical implication of TSAb and TSH-binding inhibiting antibody determinations is their prognostic value in predicting the relapse of hyperthyroidism in treated patients. This clinical application has been so far limited by the technical difficulty of the assays. This emphasizes the need for a simple and reliable test, which can be used for routine measurements of TSAb.

Antibodies, Monoclonal↗

PubMed1982

Studies on thyroid cell surface antigens using cultured human thyroid cells.

Human thyroid cells in primary culture were used for studies of thyroid cell surface antibodies in patients with thyroid autoimmune disorders. Radioiodinated IgG preparations containing thyroid microsomal antibody (TMAb), thyroid stimulating antibody (TSAb) and/or thyroglobulin antibody (TgAb) were tested for binding to thyroid cells. Binding was observed with radioiodinated IgG from patients with Graves' disease, Hashimoto's thyroiditis and idiopathic myxoedema containing TMAb, irrespective of the presence of TSAb and TgAb, while negative results were obtained with normal IgG. A dose-dependent inhibition of binding to thyroid cells was produced by the addition of the corresponding unlabelled IgG preparations. Evidence for tissue specificity was provided by the absence of binding to human skin fibroblasts used as controls. Preabsorption with human thyroid microsomes completely abolished the binding to thyroid cells of a radioiodinated TMAb positive IgG preparation, while only incomplete removal of the reactivity to thyroid microsomes was produced by preabsorption with thyroid cells. These data suggest that some but not all microsomal antigenic determinants are expressed on the thyroid cell surface. Binding to thyroid cells was also observed with purified TgAb, indicating that thyroglobulin antigenic determinants are present on the surface of thyroid cells. No evidence of binding was obtained with a TSAb positive Graves' IgG preparation with undetectable TMAb and TgAb. Unlabelled IgG preparations containing TMAb from patients with either Hashimoto's thyroiditis or idiopathic myxoedema were shown to inhibit the binding to thyroid cells of radioiodinated TMAb positive Graves' IgG and vice versa. These data indicate that antibodies present in these thyroid autoimmune disorders share common thyroid cell surface antigens. However, the binding of radioiodinated IgG from a patient with idiopathic myxoedema was only partially inhibited by Graves' or Hashimoto's IgG, suggesting that some of the thyroid cell surface antibodies of idiopathic myxoedema may not be detectable in other thyroid autoimmune disorders.

Antibodies↗

PubMed1981

Comparison between thyroid stimulating and tsh-binding inhibiting immunoglobulins of Graves' disease.

In the sera of patients with Graves' disease abnormal thyroid 'stimulating' immunoglobulins have been demonstrated by in vivo and in vitro assay systems. Conflicting results have been reported when thyroid stimulating and thyrotrophin (TSH)-binding inhibiting activities have been compared. The present study was performed in forty-nine hyperthyroid Graves' patients to ascertain the relationships among TsH-binding inhibiting immunoglobulins (TBII), measured by a radio-receptor assay, thyroid stimulating antibody(TSAb), assayed by stimulation of adenylate cyclase-cAMP system in human thyroid plasma membranes, and LATS, measured by McKenzie's mouse bioassay.TBII was detected in twenty-one of forty-nine (42.9%), TSAb in thirty-five of forty-nine (71.4%) and LATS in nineteen of forty-nine (38.8%).TBII was also present in four of sixteen (25%) patients with other thyroid autoimmune disorders. When the results obtained with the different techniques were compared, correlation was found between LATS response and TSAb activity ( =0.53, P less than 0.001), while there was no correlation between TSAb and TBII activities and between LATS response and TBII activity. These data conform that TSAb is specific and sensitive marker of Graves' disease and suggest that TBII activity is not necessarily synonymous with thyroid stimulation, and could reflect a different phenomenon concomitantly produced.

Animals↗

PubMed1978