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Biomedical subjects

A Pinchera

Publications and source records attributed to A Pinchera.

At least 343 records · Page 19Linked to original sources

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↗

In vitro studies on TSH secretion and adenylate cyclase activity in a human TSH-secreting pituitary adenoma. Effects of somatostatin and dopamine.

We have studied the in vitro TSH secretion and the adenylate cyclase (AC) activity of a human pituitary adenoma surgically removed from a hyperthyroid patient showing high serum TSH levels. The tumor appeared almost homogeneously constituted by cells positive for an anti-TSH-beta antiserum and showing the ultrastructural characteristics of the adenomatous thyrotrophs. Adenoma fragments released in vitro a large amount of TSH (148.4 microU/mg prot/30 min), alpha-subunit (35.5 ng/mg prot/30 min) and TSH-beta (10.1 ng/mg prot/30 min). The effects of somatostatin (GHRIH) and dopamine (DA) on the hormone release have been tested in vitro. Both agents markedly inhibited the release of intact TSH and TSH-beta whereas the release of alpha-subunit was less affected. The two agents were effective at concentrations higher than 10(-8)M. The ability of GHRIH and DA in modulating the AC activity was investigated in membrane fraction preparations. GHRIH inhibited AC at concentrations higher than 10(-7)M. The maximal inhibition was 32% at 10(-5)M. Conversely, DA slightly stimulated AC activity. This effects was not mimicked by the dopaminergic ergot CH 29-717, which was completely ineffective on the enzyme. These results suggest that: 1) in this TSH-secreting pituitary adenoma a normal secretory response to the inhibiting agents (GHRIH and DA) is present; 2) different mechanisms of transduction of the GHRIH and DA signals (cAMP dependent and cAMP independent) could be operating in this tumor.

Adenoma↗

Impaired ventilatory drive in short-term primary hypothyroidism and its reversal by L-triiodothyronine.

Alveolar hypoventilation is known to occur in myxedema. Reduction of hypercapnic ventilatory drive has not been reported, up to now, in patients with short-term hypothyroidism. Eleven patients with short-term hypothyroidism, before and after L-triiodothyronine (L-T3) replacement therapy, and 10 normal controls were studied. Hypercapnic ventilatory drive was assessed by the evaluation of the relation between the response of ventilation and mean expiratory flow to CO2 rebreathing and by the evaluation of ventilation and mean expiratory flow at a fixed level of carbon dioxide. In patients with short-term hypothyroidism these parameters were reduced as compared with normal controls and returned to normal after L-T3 replacement. We conclude that hypercapnic ventilatory drive is blunted by short-term hypothyroidism and normalizes following replacement therapy.

Adult↗

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↗

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↗

Diagnostic value of a single serum thyroglobulin determination on and off thyroid suppressive therapy in the follow-up of patients with differentiated thyroid cancer.

To assess the significance of a single serum thyroglobulin (Tg) determination on and off thyroid suppressive therapy, serum Tg measurements have been performed in 349 serum samples from 82 patients with differentiated thyroid cancer. All samples were collected after total thyroidectomy with or without subsequent ablation of residual thyroid tissue by radioiodine. One hundred and fifty-three samples were obtained while the patients were on thyroid suppressive therapy and 196 after withdrawal of medication. The results of serum Tg assays were analysed in relation to the presence or absence of residual or metastatic thyroid tissue, as assessed by clinical and laboratory evaluation, including 131I whole body scan. In patients with thyroid residue but no metastases, undetectable serum Tg (false negative results) occurred in 45% of cases off therapy and in 92.9% of cases during therapy. In the presence of metastases no undetectable serum Tg result was found in patients off therapy, while four (6.9%) out of 58 samples from patients with bone and/or lung metastases and seven (31.8%) out of 22 samples from patients with lymph node metastases alone were undetectable (falsely negative) during suppressive therapy. Serum Tg was undetectable in sera from patients with no evidence of thyroid residue or metastatic disease in all but one (1.7%) of 59 samples on and three (5.4%) of 56 samples off suppressive therapy. These Tg results were confirmed to be truly rather than falsely positive, since evidence of metastatic disease was obtained by whole body scan after the administration of therapeutic doses of 131I.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Expression of the microsomal antigen on the surface of continuously cultured rat thyroid cells is modulated by thyrotropin.

The thyroid microsomal antigen, commonly implicated in thyroid autoimmune diseases, is not confined to cytoplasm, but is also present on the surface of human thyroid cells in primary culture. In this study, a strain of differentiated rat thyroid cells (FRTL5) grown in continuous culture was used to investigate the relationship between functional status of the thyroid cell and expression of microsomal antigen on its surface. Sera from eight patients with Hashimoto's thyroiditis, one with idiopathic hypothyroidism, and three with hyperthyroid Graves' disease were selected for the presence of microsomal antibody, but undetectable thyroglobulin antibody. One additional serum sample from a patient with Graves' disease, which was negative for both thyroid antibodies was used. Sera from eight normal subjects were used as controls. Indirect immunofluorescence was applied to FRTL5 cells that were viable or fixed with acetone in order to expose intracellular antigens. When FRTL5 cells were cultured in Coon's medium containing TSH (300 microU/ml), positive indirect immunofluorescence surface staining was observed with sera containing microsomal antibody, but not with control sera or with the Graves' serum negative for microsomal antibody. A rough correlation was found between the intensity of the surface fluorescence and microsomal antibody titer. After acetone treatment, microsomal antibody-positive sera produced typical cytoplasmic staining. When FRTL5 cells were cultured in the absence of TSH, disappearance of the surface fluorescence and reduction of the cytoplasmic microsomal antigen occurred. Readdition of TSH progressively restored both the surface and cytoplasmic microsomal antigen. The present data indicate that the thyroid microsomal antigen is represented on the surface of FRTL5 cells, and its expression is modulated by TSH.

Animals↗

Serum free thyroxine in patients with T3-toxicosis.

The serum free thyroxine concentration was measured by direct radioimmunoassay in 38 untreated T3-thyrotoxic patients with elevated serum total and free triiodothyronine, normal serum thyroxine and free thyroxine index, no TSH response to TRH, and with clinical evidence of hyperthyroidism. An elevation of circulating free thyroxine values was observed in 58% of the patients, whereas total serum thyroxine concentration was within the normal range. It is suggested, therefore, that T3-thyrotoxicosis should be reserved for patients with elevated serum total T3 and free T3 concentrations and normal serum total T4 and free T4 concentrations. Serum thyroxine-binding globulin concentrations were significantly lower (P less than 0.025) in patients with an elevated serum free thyroxine (18.7 +/- 3.6 micrograms/ml: mean +/- SD) as compared with those in patients with a normal free thyroxine concentration (23.4 +/- 2.6 micrograms/ml). In addition, no daily fluctuations in total and free thyroxine concentration were observed in 6 patients over a 4-8 day period.

Adult↗

Humoral markers for thyroid carcinoma.

We investigated the usefulness and limits of serum thyroglobulin, serum calcitonin, and serum tissue polypeptide antigen as humoral markers for thyroid carcinoma in 364 patients with papillary, follicular, medullary, and undifferentiated types of thyroid cancer. In agreement with other studies we found that serum thyroglobulin was a specific and sensitive marker for well-differentiated thyroid cancer after total thyroidectomy. Lymph node, lung, and bone metastases were associated with high serum thyroglobulin concentrations, both during and after thyroid-suppressive therapy with L-thyroxine. Serum thyroglobulin determination was superior to whole body scanning in predicting the presence of differentiated metastases, because patients with nonfunctioning metastases and negative whole body scan also had high levels of serum thyroglobulin. Serum calcitonin levels were increased in all patients with active medullary thyroid cancer, confirming the specificity of this marker in detecting tumors arising from parafollicular C-cells. Furthermore, in medullary thyroid cancer serum tissue polypeptide antigen levels were also increased in most patients. This last substance was found to be increased also in undifferentiated thyroid cancer. Of particular interest was the finding of increased serum tissue polypeptide antigen levels in 15 cases of differentiated thyroid cancer, whose metastases underwent a progressive process of "dedifferentiation."

Calcitonin↗

Twenty-four hour radioactive iodine uptake in 35 patients with amiodarone associated thyrotoxicosis.

Amiodarone associated thyrotoxicosis (AAT) occurs in approximately 10% of patients treated with this iodine rich drug in areas of mild iodine deficiency. The thyroid radioactive iodine uptake (RAIU) is usually undetectable or very low in iodine-induced thyrotoxicosis. In the present study, 35 patients with AAT were evaluated. Twelve patients had no thyroid abnormalities by physical exam and all had 24-hr RAIU less than or equal to 4%. In contrast, nine of 11 patients with AAT and diffuse goiters and eight of 12 patients with AAT and nodular goiters had RAIU values greater than 8%. In patients with AAT and goiter it appears possible that the thyroid fails to adapt normally to the excess iodide load, resulting in an inappropriately high RAIU in the presence of excess plasma iodine.

Adult↗

Metastatic medullary and undifferentiated thyroid cancers are not associated with elevated levels of serum thyroglobulin.

It is now well accepted that serum thyroglobulin (Tg) determination is a specific marker of disease activity in well-differentiated thyroid cancer after total thyroidectomy. In this study we examined 15 thyroidectomized patients with metastases from medullary thyroid cancer and 10 patients with metastases from undifferentiated thyroid cancer, to determine whether serum Tg measurement could be useful also in these types of thyroid tumors. In contrast with differentiated thyroid cancer, which had high levels of circulating serum Tg, patients with medullary and undifferentiated thyroid cancer had undetectable or low levels of serum Tg. Thus, serum Tg measurements are not useful in the diagnosis of metastatic disease in these patients.

Calcitonin↗

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↗

Serum tissue polypeptide antigen (TPA) in thyroid cancer.

Serum tissue polypeptide antigen, (TPA), carcinoembryonic antigen (CEA), calcitonin (CT) and thyroglobulin (Tg) have been measured by specific radioimmunoassays in 174 patients with various types of thyroid cancer previously submitted to thyroidectomy. Elevated serum TPA concentrations were found in 12 of 13 patients with local invasion or distant metastases from undifferentiated thyroid cancer or thyroid lymphosarcoma, while serum Tg and CEA values were normal or undetectable. In 123 patients with well differentiated thyroid cancer serum TPA was usually normal regardless of the presence or absence of functioning metastases. On the contrary, 14 of 15 patients with "dedifferentiated" metastases from previously differentiated thyroid cancer had elevated serum TPA values, while serum CEA was normal and serum Tg variable. Serum CT was confirmed as the most sensitive marker of metastatic medullary thyroid carcinoma, but elevated serum TPA values were also found in most of these cases. The present data indicate that serum TPA provides a new humoral marker in the follow-up of undifferentiated and "dedifferentiated" thyroid carcinoma and may also be usefully employed as an additional marker for medullary thyroid carcinoma.

Adolescent↗

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↗