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Biomedical subjects

A Pinchera

Publications and source records attributed to A Pinchera.

At least 271 records · Page 15Linked to original sources
PubMed1989

Treatment of hyperthyroidism due to inappropriate secretion of thyrotropin with the somatostatin analog SMS 201-995.

The management of hyperthyroidism due to inappropriate secretion of TSH (IST) includes agents that selectively suppress TSH hypersecretion both in patients with TSH-secreting tumor [neoplastic IST (nIST)] in whom pituitary surgery was unsuccessful and in those with selective pituitary resistance to thyroid hormone action [nonneoplastic IST (nnIST)]. Among such agents, somatostatin administration has proven to be effective in blocking TSH hypersecretion, but its short plasma half-life prevented its use in long term therapeutic trials. The recent availability of a potent and long-acting analog of somatostatin (SMS 201-995, Sandostatin) prompted us to study its effects on serum TSH, alpha-subunit, and free thyroid hormone (FT4 and FT3) concentrations in five patients with nIST and three patients with nnIST. During short term SMS 201-995 administration (100 micrograms, sc, three times daily for 5 days) both serum TSH and alpha-subunit levels decreased in all patients with nIST (mean decrements, -86% and -85%, respectively), with concomitant normalization of serum FT4 and FT3 concentrations. In the three patients with nnIST, this treatment lowered serum TSH levels less well (mean decrement, -47%), although serum FT4 and FT3 levels normalized in one patient. Chronic SMS 201-995 (100 micrograms, sc, every 12 h for 1-7 months) treatment in four hyperthyroid patients (two with nIST and two with nnIST) resulted in a steady euthyroid state in both patients with nIST, with restoration of normal visual fields in one patient. In contrast, in both patients with nnIST, escape occurred after 2 weeks of therapy. We conclude that SMS 201-995 administration is effective treatment for patients with nIST, able to suppress TSH hypersecretion from the adenomatous thyrotrophs and, consequently, to restore clinical and biochemical euthyroidism in such patients. On the contrary, the inhibitory effects of SMS 201-995 on TSH secretion in patients with nnIST are weaker and transient.

Adult↗
PubMed1989

Antibodies to human thyroid peroxidase in autoimmune thyroid disease: studies with a cloned recombinant complementary deoxyribonucleic acid epitope.

Previous studies carried out by screening a lambda gt11 human thyroid cDNA library with serum samples from selected patients with Hashimoto's thyroiditis and a polyclonal antibody to porcine thyroid peroxidase (TPO) confirmed, at the molecular level, that TPO is a major component of the thyroid microsomal antigen (M). That investigation led to the isolation of a clone (C2) which encodes an 85-amino acid segment of TPO and harbors a major epitope recognized by serum from several patients with autoimmune thyroid disease that contained anti-M autoantibodies (MAb). In this study, C2 antigen that was produced as a beta-galactosidase fusion protein was used to establish an enzyme-linked immunoabsorbent assay for the detection of anti-C2 autoantibodies (C2Ab). C2Ab then were assayed in 191 patients with different autoimmune and nonautoimmune thyroid disorders, and 50 patients with nonthyroidal autoimmune diseases. The results were compared with the titers of anti-TPO antibodies (TPOAb; as detected by monoclonal antibody-assisted RIA) and MAb (as detected by passive hemagglutination). Positive C2Ab was found in the serum of 85 of 136 (63%) patients whose serum contained TPOAb and/or MAb. A significant positive correlation was found between the levels of C2Ab and those of TPOAb (r = 0.76; P less than 0.001) or MAb (r = 0.69; P less than 0.001), which was independent of the type of underlying autoimmune thyroid disorder. Low levels of C2Ab also were found in 10 of 105 (9%) serum samples that did not contain TPOAb. Western blot analysis carried out on the latter samples showed that in 2 samples the apparent C2Ab reactivity was due to the presence of antibodies reacting with beta-galactosidase. In conclusion, we confirmed the validity of screening lambda gt11 cDNA human thyroid libraries to better characterize thyroid autoantigens and demonstrated the feasibility of using recombinant proteins to establish diagnostic assays for autoantibodies.

Antibodies↗
PubMed1989

Studies on the occurrence of ophthalmopathy in Graves' disease.

Eye disease was associated with hyperthyroidism in 202 of 221 patients with active Graves' ophthalmopathy (91.4%) and was not accompanied by thyroid hyperfunction (euthyroid Graves' disease) in the remaining 19 (8.6%). All the latter patients had some mild thyroid abnormalities (thyroid autoantibodies, negative TRH test, negative T3 suppression test, goitre). Sex distribution analysis evidenced a higher prevalence in females with a female/male ratio of 2.1 which was, however, significantly lower (P less than 0.05) than that observed in control (Graves' disease patients without overt ophthalmopathy (female/male ratio = 3.4]. Patients with euthyroid Graves' disease showed a female/male ratio of 0.7. Age distribution revealed a peak prevalence in the 5th decade of life, identical to that of Graves' disease without ophthalmopathy. A close temporal relationship between the onset of hyperthyroidism and the onset of ophthalmopathy was found, since in about 85% of the patients the first ocular manifestations occurred within +/-18 months around the onset of hyperthyroidism.

Adolescent↗
PubMed1989

High potential to tumor necrosis factor alpha (TNF-alpha) production of thyroid infiltrating T lymphocytes in Hashimoto's thyroiditis: a peculiar feature of destructive thyroid autoimmunity.

T lymphocytes present in thyroid infiltrates of 6 patients with Hashimoto's thyroiditis (HT) and of 4 patients with Graves' disease (GD) were analyzed at clonal level and their profiles of mitogen-induced lymphokine secretion were characterized. Production of interleukin-2 (IL-2), interleukin-4 (IL-4), interferon-gamma (IFN-gamma) was measured in culture supernatants of a total number of 332 T cell clones (TCC) from HT, of 269 TCC from GD infiltrates and of 266 control TCC derived from normal lymphoid tissues. No significant difference was found in the ability to produce IL-2 between TCC from HT or GD infiltrates and control TCC. The proportion of HT- or GD-derived TCC able to produce IL-4 was extremely low (4 and 5%, respectively) in comparison with controls (19%). In contrast, the proportion of interferon-gamma (IFN-gamma)-producing (IFN-P) TCC derived from either HT (87%) or GD (80%) infiltrates was much higher (p less than 0.0005) than that found in controls (59%). In addition, most of IFN-P TCC from either HT or GD usually released higher amounts (p less than 0.002) of IFN-gamma than did control clones. No significant difference was found between GD infiltrates and controls in the proportions of TCC able to secrete TNF-alpha (39% and 47%, respectively), whereas the proportion of TNF-alpha-producing (TNF-P) TCC derived from HT (78%) was significantly higher (p less than 0.0001). In addition, most of both CD8 and CD4 TCC from HT released higher amounts of TNF-alpha than did TNF-P clones from controls or GD. These data suggest that T cells present in autoimmune thyroid infiltrates share a number of functions, such as high production of IFN-gamma, but differ with regard to their ability to secrete TNF-alpha, which is peculiar of most T cells present in the thyroid of HT patients.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Assays of TSH-receptor antibodies in 576 patients with various thyroid disorders: their incidence, significance and clinical usefulness.

UNLABELLED: The incidence and the significance of TSH-receptor antibodies in Graves' disease and in various thyroid disorders have been evaluated. TSH-binding inhibiting antibodies (TBIAb) and thyroid stimulating antibodies (TSAb) were detected in a large proportion of Graves' disease patients (TBIAb in 68.8% and TSAb in 77.8%), in a small number of patients with idiopathic myxoedema or Hashimoto's thyroiditis, and were not detected in patients with endemic euthyroid goitre, differentiated thyroid carcinoma and toxic adenoma. Furthermore, TSH-receptor antibodies were present in some patients with toxic multinodular goitre (TBIAb in 12.7% and TSAb in 15.9%). When TSH-receptor and other thyroid autoantibodies were compared, it was found that 13 of the 15 Graves' patients with negative tests for thyroglobulin and thyroid microsomal antibodies were positive for TSH-receptor antibodies. On the other hand, 9 of the 11 patients with toxic multinodular goitre who had positive TSH-receptor antibody tests, also had serum thyroglobulin and/or thyroid microsomal antibodies. No significant differences in the prevalence of TSH-receptor antibodies were found in Graves' patients irrespective of the presence of ophthalmopathy or pretibial myxoedema. Elevated TBIAb activity at the end of anti-thyroid drug treatment was found in 52.9% of Graves' patients who subsequently relapsed, while in Graves' patients in remission TBIAb was always negative. TSH-receptor antibody results were not predictive of the outcome of radioiodine treatment in Graves' disease. Finally no correlation could be found between TBIAb and TSAb in Graves' disease and Hashimoto's thyroiditis. IN CONCLUSION: the high incidence of TSH-receptor antibodies in Graves' disease confirms their pathogenetic role in the development of hyperthyroidism; TSH-receptor antibodies in Graves' disease are not significantly associated with the presence of ophthalmopathy or pretibial myxoedema; TSH-receptor antibody assays may be useful for the diagnosis of Graves' disease in the absence of other signs of autoimmunity. TBIAb seems to be a good predictor of relapse in Graves' patients treated with anti-thyroid drugs; a fraction of toxic multinodular goitre could be a nodular variant of Graves' disease.

Autoantibodies↗
PubMed1989

Clinical and biologic behavior of bone metastases from differentiated thyroid carcinoma.

Thirty (3.8%) of 780 patients with differentiated thyroid cancer seen between 1970 and 1987 had bone metastases. The primary tumor was follicular in 26 patients and papillary in four. Mean age at diagnosis was 61 years. The manifestation of bone metastases was the presenting symptom in 18 patients (60%). Treatment included total thyroidectomy, levothyroxine sodium therapy, and radioactive iodine treatments. Twenty-seven patients had bone metastases from the initial observation, with 44 sites involved. Of the sites, 27 (61%) were shown both on iodine 131 whole-body scan (WBS) and on x-ray film, 11 (25%) only on WBS, and six (14%) only on x-ray film. Multiple involvement was observed in 11 patients. The radiologic appearance was invariably osteolytic. Serum thyroglobulin was elevated in all patients. After radioactive iodine, no WBS+/X-ray+ metastases showed a complete response, although a sclerotic border was noted in several cases, whereas six WBS+/X-ray- lesions were no longer detectable by WBS. Treatment with radioactive iodine and bone surgery resulted in a complete cure in three patients and in a reduction of tumor mass in three. Twenty-one (70%) of the patients died of thyroid cancer after a mean survival of 86 months. Of the nine patients still alive, two are free of disease, three have a good quality of life, and four have severe disability.

Bone Neoplasms↗
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↗
PubMed1989

Methodological approach and diagnostic usefulness of a new assay for anti-thyroid peroxidase autoantibodies.

Although thyroid microsomal antibodies (anti-MAb) have been recently proven to be directly to thyroid peroxidase (TPO), current methods for MAb detection still employ unpurified microsomal fractions. The authors have therefore developed and evaluated a specific radioimmunoassay (RIA) for autoantibodies to TPO (anti-TPO Ab) based on competitive inhibition of 125I-TPO to an anti-TPO monoclonal antibody coated on plastic microtiter wells (RIA-1) or tubes (RIA-2). Preliminary experiments showed that both assays were able to specifically detect anti-TPO Ab, while negative results were obtained with normal sera and with sera containing other organ- and non-organ-specific autoantibodies including anti-thyroglobulin antibodies (anti-TgAb). No significant difference in sensitivity, specificity and reproducibility was found between RIA-1 and RIA-2, and the results obtained with the two techniques were therefore pooled together. Anti-TPO Ab were then assayed in 110 normal controls and in 441 patients with different autoimmune (AITD) or non-autoimmune (N-AITD) thyroid diseases and compared to anti-M Ab as assessed by passive hemagglutination (PH). Positive anti-TPO Ab were observed in 4/110 (3.6 p. cent) normal controls, 88/117 (80 p. cent) patients with Graves' disease, 122/123 with Hashimoto's thyroiditis or idiopathic myxedema and 21/201 (10.4 p. cent) with miscellaneous N-AITD. A highly significant positive correlation (r = 0.91, p less than 0.0001) was found between anti-MAb by PH and anti-TPO Ab by RIA ;discrepant results were limited to sera with negative or low (1/100-1/400) anti-M Ab titers.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1988

Relationship between progesterone receptor and productive fibrosis as an index of tumor differentiation in breast cancer.

We studied the relationship between steroid receptors (SR) and various stromal parameters in 100 breast cancers. Each specimen was submitted to SR determination by the dextran-coated charcoal assay and to histologic examination. No relationship was found between the presence of SR and necrosis or fibroblastic cell content. There was an inverse correlation between SR positivity and the extent of lymphocyte infiltration (p less than 0.05). ER + PR + status was strongly correlated with marked productive fibrosis (PF) (p less than 0.005). When SR were separately assayed, only the presence of PR was correlated with PF (p less than 0.005); similar results were obtained for PR levels (p less than 0.01). PF was also associated with a higher nuclear grade (p less than 0.001). In conclusion, in this study a strong correlation between PR positivity or concentration and extent of PF was demonstrated in breast cancer. Since PR synthesis is an expression of an intact regulatory pathway, our data suggest that stromal production in breast cancer is related to the degree of differentiation of malignant epithelial cells.

Adult↗
PubMed1988

Thyroid carcinoma in thyrotoxic patients treated by surgery.

We report the incidence of thyroid cancer in a series of 1832 consecutive patients seen for thyrotoxicosis of any etiology during 1970 and 1985 in our department. Surgical treatment for thyrotoxicosis was selected as the treatment of choice in 179 patients (9.8%), 86 with toxic diffuse goiter (TDG), 21 with toxic nodular goiter (TNG) and 40 with toxic adenoma (TA). The presence of thyroid cancer was found in 11 patients for a total incidence of 6.1%. Six patients had TDG (percent incidence in this group 6.9%), 4 patients had TNG (7.5%) and 1 had TA (2.5%). While the presence of thyroid cancer was totally unsuspected in TNG and TA, in TDG 4 out of 6 patients found to have a cancer, had been suspected before surgery. When a thyroid nodule was present in a toxic diffuse goiter the possibility to face with a malignant lesion reached 22.2% of the cases (4 out of 18 cases), while only 2 out of 68 patients (2.9%) with TDG and no nodule had thyroid cancer. These results confirm recent other series reporting the frequent association of hyperthyroidism and thyroid cancer and suggest that in thyrotoxic patients any nodule must be screened carefully to rule out malignancy.

Adenoma↗
PubMed1988

Comparison of complement fixation and radioassay techniques to detect solubilized human thyroid microsomal antigenic activity.

Although recently the human thyroid microsomal antigen (M-Ag) has been possibly identified as the thyroid peroxidase, its nature remained unknown over almost three decades. One of the difficulties encountered in the identification of M-Ag derived from the conflicting data obtained in the attempts to solubilize active antigenic material from thyroid subcellular fractions. In particular, following detergent treatment, M-Ag could not be detected by complement fixation, while a full recovery of the antigen has been observed using a radioassay technique. In the present investigation, the antigenic activity of Triton X-100 solubilized thyroid microsomes was assessed in parallel by complement fixation and radioassay methods employing the same anti-microsomal antibody (anti-M Ab) preparation for antigen detection. In untreated microsomes antigenic activity was detected by both methods. In contrast, detergent solubilized M-Ag was detected by radioassay, but could not be detected by complement fixation. These data indicate that detergent solubilization diminishes the complement fixing capacity of M-Ag, while the solubilized antigen can still be fully detected by its binding reaction with the autoantibody, and explain the discrepant results obtained in previous studies.

Autoantibodies↗
PubMed1988

The different types of hyperthyroidism in Europe. Results of a prospective survey of 924 patients.

In a prospective multicentric study, 924 untreated hyperthyroid patients were investigated, coming consecutively within one year into 17 thyroid centers of 6 European countries. With the aid of clinical information, evaluation of thyroid scan and centrally assayed thyroid hormones, thyroid antibodies, TSH-binding inhibiting immunoglobulins (TBII), and urinary iodine, different types of hyperthyroidism could be shown. Two types of hyperthyroidism could be defined directly: autonomous adenoma in cases of hot nodules in thyroid scan and Graves' disease, defined as hyperthyroidism with eye symptoms, and/or measurable TBII levels. The remainder, called "non-classifiable", included TBII negative Graves' patients, comprising of Hashitoxicosis, toxic nodular goiter, and other multifocal autonomies. 9.2% of the patients had an autonomous adenoma, 59.6% Graves' disease, and 31.2% unclassified hyperthyroidism. The main and significant difference between these types were mean age, goiter size, nodularity, and severity of the disease, being especially expressed in Graves' disease. Graves' patients had significantly increased T3/T4 ratios. Using as additional criteria diffuse regular uptake and/or increased T3/T4 ratios for immunogenic types of hyperthyroidism at least half of the 31.2% unclassified hyperthyroidism are probably Graves' disease. Forming two groups of iodine-deficient areas (IDA) and iodine-sufficient areas (ISA) according to the urinary iodine, it was possible to elucidate some characteristics independently of local factors. Autonomous adenoma was more frequent in IDA (10.1%) than in ISA (3.2%). Differences in iodine supply are reflected in the three types of hyperthyroidism by a significant higher prevalence of goiter, thyroid nodularity, lower thyroid hormone concentrations, and a higher rate of T3 toxicosis in IDA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Thyroxine uptake by human hepatoma cells from serum of patients submitted to long-term thyroxine suppressive therapy.

The significance of thyroxine (T4) uptake from serum in the assessment of thyroid status was evaluated, using human hepatoma (Hep G2) cells, in 30 euthyroid subjects, 6 hypothyroid and 19 hyperthyroid patients, and in 23 athyreotic cancer patients under T4 suppressive therapy. Cellular thyroxine (CT4) was determined according to Sarne and Refetoff, J. Clin. Endocrinol. Metab. 61: 1046, 1985. CT4 averaged 9.9 +/- 2.8 pg/well (mean +/- SD, range 5.7-15.3) in euthyroid subjects, 1.5 +/- 1.0 pg/well (range 0.05-4.2) in hypothyroid patients, 40.5 +/- 18.8 pg/well (range 18.3 +/- 104.7) in hyperthyroid patients, and 23.7 +/- 7.2 pg/well (range 14.2-40.2) in T4-treated patients. In eu-, hypo- and hyperthyroid patients, a significant correlation was observed between CT4 and free T4 index (FT4I), free T4 (FT4) or Sex Hormone Binding Globulin (SHBG) values. In T4-treated patients, CT4 values were correlated with FT4I values, but not with FT4 or SHBG levels. All T4-treated patients with elevated SHBG levels had elevated FT4, FT4I and CT4 values. In contrast, of the 16 T4-treated subjects with normal serum SHBG concentrations, all but one had normal FT3, 3 (19%) had elevated FT4, 10 (62%) elevated FT4I and 13 (81%) elevated CT4, but all (100%) had undetectable TSH levels. Thus, considering serum SHBG concentrations as a parameter of hepatic tissue response to thyroid hormone, CT4 values, at least in T4-treated patients, do not accurately reflect the liver responsiveness to thyroid hormone action.

Carcinoma, Hepatocellular↗
PubMed1988

Free thyroxine and free triiodothyronine measurement in dried blood spots on filter paper by column adsorption chromatography followed by radioimmunoassay.

Free thyroxine (FT4) and free triiodothyronine (FT3) were measured by column adsorption chromatography followed by radioimmunoassay in dried blood spots on filter paper in euthyroid subjects, hyperthyroid and hypothyroid patients, and in subjects with TBG excess. The sensitivity (B/T% = 95%) was 1.5 pg/ml (working range 1.5-46.4 pg/ml) for FT4 and 1.5 pg/ml (working range 1.5-32.0 pg/ml) for FT3. Intraassay coefficient of variations (CVs) ranged 4.4-8.8% for FT4, 8.7-10.1% for FT3; interassay CVs varied from 8.9-9.0% for FT4, 9.3-10.4% for FT3. FT4 and FT3 values found in dried blood spots were highly correlated with the corresponding values in serum (r = 0.97, P less than 0.001 for FT4; r = 0.96, P less than 0.001 for FT3). FT4 concentrations in dried blood spots ranged 8.1-20 pg/ml in euthyroid subjects, 19.4-60.0 pg/ml in hyperthyroid patients, less than 1.5-7.1 pg/ml in hypothyroid patients, 7.8-18.8 pg/ml in euthyroid subjects with TBG excess. FT3 values in dried blood spots ranged 2.5-5.8 pg/ml in euthyroid subjects, 7.1-30.0 pg/ml in hyperthyroid patients, less than 1.5-2.8 pg/ml in hypothyroid patients, 2.5-5.2 in euthyroid subjects with TBG excess. The results of the present study, while confirming previous data on FT4 determination in dried blood spots, represent the first report on FT3 measurement in the same system, thus allowing a more complete assessment of thyroid status made by mail at the expense of few drops of blood.

Adolescent↗
PubMed1988

An unusual case of a false-positive iodine-131 whole body scan in a patient with papillary thyroid cancer.

A false-positive I-131 whole body scan (WBS) for lung uptake in a patient with papillary thyroid cancer, with replacement of his infiltrated esophagus with a left colon graft, is presented. The I-131 image, seen in the upper right lung field, was due to the contaminated colon graft lacking normal peristaltic movements, which was located in the right paramediastinal region. This finding was demonstrated by imaging the upper digestive tract with orally administered Tc-99m DTPA and by a barium x-ray.

Aged↗