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Biomedical subjects

A Pinchera

Publications and source records attributed to A Pinchera.

At least 289 records · Page 16Linked to original sources
PubMed1988

Demonstration of blocking immunoglobulins G, having a heterogeneous behaviour, in sera of patients with Graves' disease: possible coexistence of different autoantibodies directed to the TSH receptor.

Previous studies by us and others have shown that Graves' immunoglobulins G (IgGs) behaved as agonists or even antagonists of TSH. In this paper we have looked for the existence of IgG preparations without any thyroid stimulatory activity but able to significantly block the action of TSH in 128 hyperthyroid Graves' patients. The presence of TSH-binding inhibiting antibodies (TBIAb) and that of thyroid stimulating antibodies (TSAb) was evaluated by a radioreceptor assay using solubilized thyroid plasma membranes and by assaying the adenylate cyclase (AC) function of thyroid plasma membranes, respectively. Seventeen IgGs were negative for TSAb but positive for TBIAb in the screening, using only one concentration of IgG. Three kinds of activity were investigated in these IgGs at different doses: (1) TSH-binding inhibiting activity; (2) thyroid AC stimulating activity; and (3) the inhibition of TSH-induced AC stimulation. The results showed that the level of activity was not always dose-dependent. A significant (greater than 20%) inhibition of the TSH-dependent AC stimulation was present in 15 of the 17 IgGs examined: this inhibition was more elevated at lower than at higher doses in two preparations. No significant correlation was found between the three activities. In short, we have been able to demonstrate the existence of 'blocking' antibodies, apparently without any stimulatory activity, in some patients with Graves' disease. The diphasic pattern of the dose-response curves of some IgGs and the lack of correlation between the different activities can be explained by the co-existence in the sera of Graves' patients of different autoantibodies varying in concentration, binding affinity constant and intrinsic biological activity.

Adenylyl Cyclases↗
PubMed1988

Treatment of inappropriate secretion of thyrotropin with somatostatin analog SMS 201-995.

Inappropriate thyrotropin secretion (IST) may originate from either neoplastic disease (nIST) or non-neoplastic resistance to thyroid hormone (nnIST). An inhibitory effect of somatostatin on TSH secretion has been documented. In an attempt to elucidate the possible therapeutic effect of this peptide on nIST and nnIST, a study was conducted in 7 such patients. Sandostatin (SMS 201-995) was administered in daily doses of 100 micrograms for several days to 1 month. Four patients with nIST responded with a fall in circulating TSH as well as alpha-subunit with concomitant normalization of free thyroxine and clear symptomatic improvement. In the 3 nnIST patients this effect was considerably less apparent and a partial TSH escape was observed on long-term treatment in 2 cases. The importance of somatostatin and its analogs in the management of thyroid malignancy is stressed.

Antineoplastic Agents↗
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↗
PubMed1988

Thyroid autoantibodies in thyroid cancer: incidence and relationship with tumour outcome.

In the present investigation we studied serum anti-thyroglobulin and anti-thyroid microsomal autoantibodies, measured by hemagglutination technique, in 600 patients with thyroid cancer seen by us from 1975 to 1985 (mean follow-up 46 months). Positive thyroglobulin antibodies and/or microsomal antibodies were found in 138 (23%) patients (23.9% with papillary, 25% with follicular, 16.1% with anaplastic, and 4.1% with medullary thyroid carcinomas). The incidence of positive tests was similar in each decade of life (ranging between 21.9% and 27.9%), whereas in a normal sex-matched population with no evidence of thyroid disease, the frequency of positive tests was very low in young people and increased to 23% in people older than 60. In 64 patients with no evidence of residual or metastasic thyroid tissue after surgery and radioiodine, initially positive antibody titres became negative in 54.6%, decreased in 32.8%, did not change in 3.1%, and increased in 9.3%. On the contrary, antibody titres of patients with persistent disease became undetectable in 8.3%, decreased in 16.6%, remained unchanged in 25%, and increased in 50%. The clinical course of differentiated thyroid cancer was unaffected by the presence of thyroid antibodies and no difference was found in the death rate between antibody-positive and antibody-negative patients (11.5% and 13.6%, respectively). In conclusion, our data indicate that: 1) autoimmune phenomena are not an infrequent finding in thyroid cancer; 2) as in non-malignant thyroid diseases, positive-antibody tests are more frequently observed in females than in males; 3) at variance with normal controls, no age-dependent increase in serum anti-thyroid antibodies was found in thyroid cancer; 4) the presence of metastatic thyroid tissue seems to be necessary to perpetuate the autoantibody synthesis, and 5) anti-thyroid autoantibodies are not a protective or worsening factor in the tumour outcome.

Adolescent↗
PubMed1988

Thyroid cancer in children and adolescents.

We report on 49 patients younger than 18 years at diagnosis, of 776 patients with thyroid cancer, seen in our institution in the last 17 years. Female/male ratio was 2.2:1. Histologic type was papillary in 44, follicular in 4, and medullary in 1. Initial treatment was near-total thyroidectomy with or without neck dissection. Surgical complications (vocal cord palsy, permanent hypoparathyroidism, or both) were found in 25 patients and were usually associated with more advanced primary tumors. At surgery, node metastases were present in 73% of the patients and lung metastases, detected by chest x ray films, in 6%. Patients were treated with thyroid suppressive therapy and, except the one with medullary cancer, with radioiodine (131I) therapy. After a mean follow-up of 7.7 +/- 4.4 years (range, 1 to 17 years), one patient with lung metastases died of respiratory failure. Of 36 patients who have been followed up more than 4 years, 22 (61.1%) are now cured, and 14 have metastases (to lymph nodes, 2; to nodes and lung, 10; and to lung, 2). Since 1977 serum thyroglobulin (Tg) was used routinely as a tumor marker for differentiated thyroid cancer. After operation, Tg was elevated in all patients both not receiving (mean +/- SE, 902 +/- 380 ng/ml) and receiving (44 +/- 15 ng/ml) suppressive therapy; after 131I treatment, serum Tg dropped to 104 +/- 50 and 7.3 +/- 1.7 ng/ml, without and with suppressive therapy, respectively. Of 11 patients with lung metastases treated with 131I, respiratory function, as assessed by means of spirometry, was normal in three, mildly reduced in six, and severely impaired in two (including the one who died). In conclusion, our study indicates that thyroid cancer in young patients is rather advanced at initial examination and usually associated with node and, less frequently, lung metastases. Total thyroidectomy, radioiodine treatment, and thyroid suppressive therapy represent an effective combination of treatments for this disease and allow a good quality of life. The most serious adverse effect is represented by the high incidence of surgical complications and by pulmonary restrictive disease in relation to lung metastases.

Adolescent↗
PubMed1987

[Clinical aspects of hyperthyroidism in areas of different supplies of iodine. Results of a European prospective study].

Clinical aspects of 924 unselected patients with hyperthyroidism from 17 thyroid centres of 6 European countries were investigated in a prospective study for exactly 1 year. Serum samples were centrally assayed for thyroid hormones, thyroid autoantibodies and TSH-binding inhibiting immunoglobulins (TBII), and urine samples for iodine. 26 items of information per patient were computerized and evaluated. Forming 2 groups from iodine-deficient areas (IDA) and iodine-sufficient (ISA) according to the urinary iodine, it was possible to elucidate some characteristics independently of local factors. The most important findings were: 1. Three types of hyperthyroidism were described: Graves' disease was defined as hyperthyroidism with eye symptoms and/or the presence of measurable TBII; autonomous adenomas were defined by a single hot nodule in the thyroid scan; the remainder included TBII negative hyperthyroid patients as well as non-immunogenic forms of hyperthyroidism (toxic multinodular goiter and other multifocal autonomies). These were termed "non-classifiable" patients. Graves' patients, representing an average of 60% of the patients, have an age peak between 40 and 49 years; they are 10 years younger than unclassified hyperthyroid patients and 20 years younger than patients with autonomous adenoma, who represented 9.2% of the patients. Surprisingly, there was no difference in the prevalence of Graves' disease between IDA and ISA. 2. An unexpectedly high rate of 10.5% of hyperthyroid patients (Graves' disease 8.5%, non-Graves' disease 14.2%) had no goiter, a figure increasing in the elderly to almost 17%. In IDA the thyroid was larger and the goiter more often nodular than in ISA. IDA are characterized by significantly higher rates (11.3%) of autonomous adenoma than ISA (3.2%). 3. 59.4% of 507 patients with Graves' disease had eye symptoms, 44.6% of at least grade II or higher using the Werner classification. There was no difference between patients from ISA and IDA. We found unilateral ophthalmopathy in 6.7% of Graves' patients. 4. The median iodine excretion was calculated from urinary iodine after exclusion of values over 250 micrograms iodine/g creatinine, arbitrarily defined as iodine contamination. In IDA the median iodine excretion was 63.6, and in ISA 105 micrograms/g of creatinine. 5. Surprisingly, proven iodine contamination was as frequent in IDA (14.5%) as in ISA (15.2%). In the survey protocol, however, this was noticed less often by physicians in ISA.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
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

Increased level of thyroglobulin mRNA in a human familial goiter.

Thyroglobulin (Tg) and its specific mRNA were analyzed in the thyroid gland of two cases of familial goiter. A three-fold increase in the level of stable protein and functional Tg mRNA was found in the goiter of one of the two patients in whom a desiodase defect was demonstrated. Normal concentrations of both Tg and its mRNA were found in the other goiter in which no enzymatic defect could be shown. Our results suggest that the increase of Tg mRNA levels found in the goiter with a desiodase defect was due to a chronic stimulation of the gland by TSH.

Adolescent↗
PubMed1987

High prevalence of subacute thyroiditis during summer season in Italy.

Eighty consecutive patients with typical subacute thyroiditis were evaluated. Sex distribution showed a higher incidence in females (F/M 3.2/1), with a mean age of 44 yr. In the majority of patients (51/80 = 66%) the onset of the disease was between June and September (46% in July and August). The remaining cases were distributed in the other months without a clear monthly prevalence. These results indicate that the seasonal distribution of subacute thyroiditis is almost superimposable to that of established infections due to some enteroviruses (Echovirus, Coxsackie A and B viruses), suggesting that summer enterovirus infections may be responsible for a large proportion of cases of subacute thyroiditis.

Acute Disease↗
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↗
PubMed1987

McCune-Albright syndrome with gigantism and hyperprolactinemia.

We describe the case of a 38-year-old man with typical Mc Cune-Albright syndrome and the unusual combination of both growth-hormone and prolactin hypersecretion. The patient was extremely tall, which is unusual in Mc Cune-Albright syndrome, suggesting that he did not have precocious fusion of the epiphysis, a common finding in this syndrome. Unfortunately the patient refused any treatment for his disease. A similar case has been previously described only in a 14-year-old boy.

Adult↗
PubMed1987

Serum TSH measurements by a sensitive enzyme immunoassay discriminate euthyroid from hyperthyroid subjects and avoid the need for TRH test during suppressive therapy with L-thyroxine.

Serum TSH was determined photometrically by a recently developed enzyme immunoassay (EIA) based on the use of a monoclonal antihuman TSH-beta antibody and a polyclonal antiTSH antibody coupled to horseradish peroxidase. The results obtained in patients with various thyroid disorders and in normal controls were compared with those achieved by conventional double antibody radioimmunoassay (RIA). In normal subjects, serum TSH was detectable in all cases by EIA (values ranging from 0.27 to 5.1 mU/L), but only in 76% by RIA. Ninety-two percent of hyperthyroids had undetectable serum TSH by EIA and the remaining 8% had values between 0.2 and 0.4 mU/L. In clinically euthyroid patients with nontoxic goiter, 9% had undetectable serum TSH by EIA, suggesting the presence of autonomously functioning areas within the thyroid. Serum TSH under basal conditions and after TRH stimulation was measured in 45 patients on L-thyroxine suppressive therapy. Undetectable basal serum TSH by EIA was associated with a lack of TSH response to TRH in 95% of cases. Conversely, 37.5% of patients with undetectable basal serum TSH by RIA had a normal or blunted response to TRH. Detectable basal values were predictive of a normal response to TRH by both methods. These data indicate that basal serum TSH measurement by EIA allows an almost complete differentiation of normal from thyrotoxic patients and can avoid the need of the TRH stimulation test.

Adolescent↗
PubMed1987

Amiodarone iodine-induced hypothyroidism: risk factors and follow-up in 28 cases.

Amiodarone, an iodine-rich drug widely used for the treatment of cardiac tachyarrhythmias, may induce either hyperthyroidism or hypothyroidism. Of 467 patients chronically treated with this drug referred to our institution, amiodarone iodine-induced hypothyroidism (AIIH) developed in 28 patients (6%). AIIH patients were subdivided into two groups according to the presence (group A) or absence (group B) of underlying thyroid abnormalities. Thyroid autoantibodies were present in 10 of 19 patients from group A and 0 of 9 patients from group B. The thyroid 24-h radioiodine uptake (RAIU) was evaluated in 15 patients: low values (less than 4%) were found in three patients and detectable values (7-50%) were observed in 12. Perchlorate discharge tests were positive in all four patients tested. Follow-up data were available in 20 patients (16 in group A and four in group B). Hypothyroidism was transient in 12 (60%) and persistent for several months after amiodarone withdrawal in eight (40%). While all patients in group B had transient hypothyroidism, 50% of patients with underlying thyroid abnormalities (group A) had persistent hypothyroidism. Thyroid autoantibodies were found in seven of eight patients with persistent hypothyroidism and in only three of 12 patients with transient hypothyroidism. Conversely, seven of 10 patients with positive thyroid autoantibodies had persistent hypothyroidism and 9 of 10 patients with undetectable thyroid autoantibodies had transient hypothyroidism. These data indicate that: (i) AIIH may develop in patients with or without underlying thyroid abnormalities; (ii) RAIU is inappropriately elevated in many patients with AIIH; (iii) intrathyroidal iodine is not organified; (iv) serum thyroid autoantibodies represent a risk factor for the development of AIIH; (v) AIIH spontaneously remits after amiodarone withdrawal in patients without thyroid abnormalities, but may persist in patients with concomitant thyroid disorders, especially those with circulating thyroid autoantibodies.

Adult↗
PubMed1987

Orbital cobalt irradiation combined with retrobulbar or systemic corticosteroids for Graves' ophthalmopathy: a comparative study.

Combined therapy with systemic corticosteroids and orbital cobalt radiotherapy has been shown to be an effective treatment of severe Graves' ophthalmopathy. The potentially serious side-effects of large doses of systemic corticosteroids prompted us to evaluate the use of retrobulbar corticosteroids instead of systemic corticosteroids. Forty-four patients with active Graves' ophthalmopathy were given orbital cobalt irradiation (total dose 2000 rads) and retrobulbar methylprednisolone acetate (14 bilateral injections at 20-30 d intervals). The degree of ocular involvement and responses to treatment were evaluated by numerical scoring (ophthalmopathy index, OI) and clinical assessment. Excellent or good responses were observed in 11 out of 44 patients (25%), 24 (55%) showed slight responses, and no change was found in 9 patients (20%). The initial OI mean score was 5.9; the final score was 3.2, with a change of -2.7 (P less than 0.001). Regression or partial improvement was observed in most cases (35/44, 80%) with soft tissue changes, and in all 9 cases with sight loss due to optic neuropathy. Proptosis, corneal lesions and extra-ocular muscle involvement were less responsive, since regression or partial improvement was observed in 39% (12/31), 50% (8/16) and 31% (13/42), respectively. No major side-effects were observed. The effects of this type of therapy and those obtained by combined therapy with systemic corticosteroids and orbital radiotherapy were compared in two groups of 30 patients each, randomly assigned to either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗