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Biomedical subjects

A Pinchera

Publications and source records attributed to A Pinchera.

At least 307 records · Page 17Linked to original sources
PubMed1987

Clinical usefulness and limitations of serum thyrotropin measurement by 'ultrasensitive' methods. Comparisons of five kits.

Five different ultrasensitive thyrotropin (TSH) assay kits (Boots-Celltech, Immunotech, ORIS-CIS, Travenol and Boehringer) have been used for TSH measurements in various conditions. All the kits were based on an immunometric method but differed with regard to components and procedure. The sensitivity appeared essentially the same for the five kits (0.10 microU/ml) as well as the intraassay precision (coefficient of variation less than 12%). In contrast, the interassay coefficients of variation in the low TSH range varied from 12.8 to 21.3%. Discrepancies from kit to kit were observed and accounted for by differences in the components and procedure of the kits. Basal serum TSH was determined in normal subjects (n = 261) and in patients with thyroid dysfunction (n = 392). No overlap was shown between normals and patients with overt hypothyroidism. In contrast, an overlap existed between normals and hyperthyroids for all the kits but one. Measurements in patients with nontoxic goiter showed that TSH may be undetectable in clinically euthyroid patients, whatever the kit used. After TRH stimulation, 95% of the 375 patients tested associated either an absence of response to TRH with undetectable basal TSH values, or a blunted response with low basal TSH levels or normal response with normal basal TSH concentrations. However, 9 patients with suppressed TSH showed a response to TRH and 7 patients with normal basal TSH levels presented an exaggerated response to TRH. Taken together, these results demonstrate that even though ultrasensitive measurements of TSH do not meet the expectation of completely discriminating euthyroid from hyperthyroid patients, ultrasensitive TSH assay kits represent a powerful tool in the diagnosis of thyroid dysfunction, which would eliminate, in most instances, the need for TRH test and diminish thyroid hormone assay requests.

Adolescent↗
PubMed1987

Amiodarone: a common source of iodine-induced thyrotoxicosis.

Amiodarone, a iodine-rich drug widely used in the treatment of tachyarrhythmias, represents one of the most common sources of iodine-induced thyrotoxicosis. The data concerning 58 patients with amiodarone-iodine-induced thyrotoxicosis (AIIT) were analyzed in the present study. Prevalence of AIIT was higher in males than in females (M/F = 1.23/l). Thyrotoxicosis occurred either during treatment with or at various intervals after withdrawal of amiodarone. AIIT developed not only in patients with underlying thyroid disorders, but also in subjects with apparently normal thyroid gland. Classical symptoms of thyrotoxicosis were often lacking, the main clinical feature being a worsening of cardiac disorders. Biochemical diagnosis of AIIT was established by the finding of elevated serum total and free triiodothyronine levels, since elevated serum total and free thyroxine could be found also in euthyroid amiodarone-treated subjects. Twenty-four-hour thyroid radioiodine uptake was very low or undetectable in AIIT patients with apparently normal thyroid glands, while it was inappropriately elevated in patients with underlying thyroid disorders, despite iodine contamination. The role of autoimmune phenomena in the pathogenesis of AIIT appeared to be limited, because circulating thyroid autoantibodies were undetectable in AIIT patients without underlying thyroid disorders or with nodular goiter. Conversely, humoral features of thyroid autoimmunity were mostly found in AIIT patients with diffuse goiter. Treatment of AIIT appeared to be a difficult challenge. Among the 11 patients given no treatment, thyrotoxicosis spontaneously subsided in the 5 patients with apparently normal thyroid gland, whereas the 6 patients with nodular or diffuse goiter were still hyperthyroid 6-9 months after discontinuation of the drug. The administration of high doses (40 mg/day) of methimazole alone proved to be ineffective in most (14/16) patients given this treatment. Twenty-seven patients were treated by methimazole combined with potassium perchlorate (1 g/day). With one exception, euthyroidism was restored within 15-90 days in all cases with underlying thyroid abnormalities, and within 6-55 days in subjects with apparently normal thyroid gland. Thus, the combined treatment appears to be the most effective one, but, due to the potential toxicity of potassium perchlorate, it should be reserved to patients with severe thyrotoxicosis and should be carefully monitored.

Adult↗
PubMed1987

Orbital cobalt radiotherapy and systemic or retrobulbar corticosteroids for Graves' ophthalmopathy.

Orbital radiotherapy and corticosteroids are two well-established medical treatments for severe Graves' ophthalmopathy. In this report we analyze the results obtained by the combination of orbital radiotherapy and systemic or retrobulbar corticosteroids in patients with severe Graves' ophthalmopathy. Orbital cobalt radiotherapy was carried out by a cobalt unit, delivering a total of 2,000 rads to each eye in 10 daily doses. Systemic corticosteroid treatment was started with 70-80 mg methylprednisolone/day for 2-3 weeks with subsequent progressive reduction of the dose until discontinuation of the drug after 5-6 months. Retrobulbar corticosteroid therapy was performed by 14 bilateral injections of 40 mg methylprednisolone acetate at 20- to 30-day intervals. Results were evaluated both on clinical grounds and by numerical scoring (ophthalmopathy index, OI). Excellent or good responses were obtained in the majority of 72 patients by combined treatment with orbital cobalt radiotherapy and systemic corticosteroids. Soft tissue changes, newly developed eye muscle dysfunction and optic neuropathy showed the most beneficial effects from treatment, whereas proptosis, corneal lesions and long-standing eye muscle abnormalities responded to a lesser extent. The results of a controlled clinical trial showed that the combined treatment was more effective than the administration of systemic methylprednisolone alone. Because relevant side effects of systemic corticosteroid therapy were observed in 4 cases, the clinical validity of retrobulbar corticosteroids in substitution for systemic corticosteroids was evaluated in 44 patients. Excellent or good responses were observed in 25% of these patients, slight responses being obtained in 55% and no change in 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Modality Therapy↗
PubMed1987

Further studies on the role of glycosylation in thyroxine-binding globulin secretion by human hepatoma (HEP G2) cells.

To investigate the role of glycosylation of T4-binding globulin (TBG) in the secretion of the protein, human hepatoma (Hep G2) cells were continuously labeled with [35S] methionine or [3H]mannose or pulse-chase labeled with [35S] methionine in the absence or presence of 1 microgram/ml swainsonine, an inhibitor of Golgi alpha-mannosidase II and lysosomal alpha-mannosidase. In the presence of this alkaloid, TBG was released into the medium at a faster rate than in control cells (50% being secreted after 35 min and 47 min, respectively), owing to accelerated intracellular transport of the newly synthesized protein. TBG secreted from swainsonine-treated cultures moved faster in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, probably because of the reduced sialylation of TBG consequent to the perturbed processing of the oligosaccharide units. Furthermore, secreted TBG was sensitive to endo-beta-N-acetylglucosaminidase H digestion as shown by the shift in the apparent molecular size in sodium dodecyl sulfate-polyacrylamide gel electro-phoresis from 50,000 to 45,000 daltons. Sensitivity to endo H indicated the presence of hybrid-type oligosaccharide chains with high mannose structures. This was also suggested by the higher incorporation of [3H]mannose in swainsonine-treated cultures. In conclusion, the results of the present study demonstrate that swainsonine accelerates the release of TBG from Hep G2 cells and that complete processing of oligosaccharide moieties is not required for TBG secretion.

Alkaloids↗
PubMed1987

Factors affecting suppression of endogenous thyrotropin secretion by thyroxine treatment: retrospective analysis in athyreotic and goitrous patients.

UNLABELLED: Factors affecting TSH suppression by L-T4 administration were retrospectively evaluated in 452 patients: 180 who were athyreotic after total thyroidectomy and remnant radioiodine ablation for differentiated thyroid carcinoma and 272 with nontoxic diffuse or nodular goiter. All patients were considered clinically euthyroid. TSH secretion was assessed by iv TRH stimulation testing. The T4 dose associated with an undetectable basal serum TSH level and no increase in serum TSH after TRH administration (suppressive dose) averaged 2.7 +/- 0.4 (SD) micrograms/kg body weight (BW)/day in athyreotic patients and 2.1 +/- 0.3 micrograms/kg BW/day in goitrous patients (P less than 0.001). The 25th-75th percentile intervals were 2.5-2.9 micrograms/kg BW/day for athyreotic patients and 1.9-2.3 micrograms/kg BW/day for goitrous patients. The suppressive dose of T4 was dependent in both groups on patient age, younger patients needing higher doses than older patients. The duration of treatment also proved to be an important parameter, since in both groups the percentage of patients with suppressed TSH secretion increased if TRH testing was carried out after at least 6 months after the initiation of therapy. Serum total T4, total T3, free T3 (FT3), free T4 (FT4) index, and FT3 index values did not differ in the two groups and were significantly higher (P less than 0.001) than in normal subjects. Mean serum FT4 was significantly higher in athyreotic patients than in goitrous patients with suppressed TSH secretion. Among athyreotic patients with suppressed TSH secretion, 24% had elevated serum FT4 and FT3, and 47% had elevated serum FT4 alone. Of goitrous patients with suppressed TSH secretion, 20% had elevated serum FT4 and FT3, and 27% had elevated serum FT4 alone. On the other hand, 35% of athyreotic patients and 14% of goitrous patients whose TSH secretion was not suppressed had elevated serum FT4. Serum sex hormone-binding globulin concentrations were measured in 3 groups of goitrous women. Values above normal limits were found in 13/26 patients (50%) with high serum FT4 and FT3, in 4/30 patients (13%) with elevated serum FT4 alone, and in 1/25 patients (4%) with normal FT4 and FT3. IN CONCLUSION: TSH suppression requires daily doses of T4 between 2.5 and 2.9 micrograms/kg BW in athyreotic patients and between 1.9 and 2.3 micrograms/kg BW in goitrous patients, with appropriate adjustments in relation to the age of the patient; Assessment of the adequacy of treatment should not be carried out before 6 months after the institution of therapy.

Adolescent↗
PubMed1987

Thymulin deficiency and low 3,5,3'-triiodothyronine syndrome in infants with low birth weight syndromes.

Experimental and clinical evidence indicates that thymic endocrine function is under neuroendocrine control. Recently, a positive correlation was found between plasma thymulin (a major endocrine product of thymus) and serum thyroid hormone concentrations. Low serum thyroid hormone concentrations are frequently found in premature newborn infants. In this study we measured plasma thymulin by bioassay and serum T3 and T4 in a series of healthy fullterm newborns and in premature infants with various disorders. The study subjects were 26 healthy fullterm infants, 23 fullterm small for gestational age infants, 30 preterm appropriate for gestational age (AGA) infants, 22 preterm small for gestational age infants and 30 infants with respiratory distress syndrome, of whom 15 were fullterm and 15 were preterm AGA. Blood samples were obtained 3, 5, 10, 20, and 40 days after delivery. In the healthy fullterm infants plasma thymulin concentrations were low during the first days of life and subsequently increased, reaching normal values for children aged 1-12 months by the 10th day after birth. Persistently low plasma thymulin and serum T3 levels were found in the majority of infants with pathological conditions; the lowest values for both hormones were found in infants with respiratory distress syndrome. A highly significant positive correlation was present in all groups between mean plasma thymulin and serum T3, but not T4. Short term T3 administration in 6 additional preterm AGA infants caused a significant increase in plasma thymulin titers compared to those in 6 untreated infants. We conclude that plasma thymulin is decreased in premature newborns with the low T3 syndrome and that this abnormality may be reversed by administration of T3. These findings indicate that thymic endocrine activity is modulated by thyroid function in early postnatal life.

Euthyroid Sick Syndromes↗
PubMed1987

Comparison of serum thyroid microsomal and thyroid peroxidase autoantibodies in thyroid diseases.

Recent evidence indicates that human thyroid peroxidase (TPO) has most of the characteristics of the thyroid microsomal antigen. The question of whether TPO accounts for part or all of the antigenic activity recognized by circulating anti-microsomal antigen autoantibody (anti-M Ab) remains to be determined. The availability of an anti-TPO monoclonal antibody and of a highly purified TPO preparation allowed the development of specific and sensitive radioassays for anti-TPO autoantibody (anti-TPO Ab). In this study we compared anti-M Ab and anti-TPO Ab levels in serum from 128 subjects, including patients with Hashimoto's thyroiditis (n = 31), idiopathic myxedema (n = 11), hyperthyroid Graves' disease (n = 45), miscellaneous nonautoimmune thyroid disorders (n = 9), and normal subjects (n = 32). Anti-M Ab and anti-TPO Ab were measured by radioimmunological methods employing two different assay designs: 1) competitive radioassay (CR), based on the inhibition of radioiodinated antibody binding to human thyroid microsomes coated on microtiter wells, using a) [125I]immunoglobulin G (IgG) containing a high anti-M Ab titer (for anti-M Ab determinations), or b) [125I]anti-TPO monoclonal antibody (for anti-TPO Ab); and 2) sandwich immunoradiometric assay (IRMA) using microtiter wells coated with thyroid microsomes (for anti-M Ab determinations) or immunoaffinity-purified TPO (for anti-TPO Ab determinations) and [125I]anti-human IgG antibody. Anti-M Ab also was measured by passive hemagglutination. Anti-M Ab titers by PH closely correlated with anti-TPO Ab levels whether assayed by IRMA (r = 0.905; P less than 0.00001) or CR (r = 0.922; P less than 0.00001). Even closer correlations were found when anti-M Ab and anti-TPO Ab both were measured by the same type of radioassay procedure (IRMA, r = 0.945 and P less than 0.00001; CR, r = 0.957 and P less than 0.00001). No differences in the correlation between anti-M Ab and anti-TPO Ab results were found when the data in patients with different autoimmune thyroid disorders were analyzed separately. Further and more direct evidence for the identity of anti-M Ab and anti-TPO Ab was provided by the ability of purified TPO to completely inhibit the binding to thyroid microsomes of radioiodinated IgG preparations containing high anti-M Ab titers. In conclusion, our results provide strong support for the concept that TPO accounts for virtually all of the antigenic determinants reacting with the autoantibodies commonly termed anti-M antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens↗
PubMed1987

Evaluation of the nocturnal serum thyrotropin (TSH) surge, as assessed by TSH ultrasensitive assay, in patients receiving long term L-thyroxine suppression therapy and in patients with various thyroid disorders.

Circadian variations of serum TSH concentrations have been reported, with higher values occurring in the late evening or early morning. In patients receiving long term L-T4 suppression therapy, it may be important to achieve suppression of TSH secretion throughout the day. To investigate whether undetectable serum TSH values in the morning are associated with undetectable serum TSH levels at night, serum TSH concentrations were measured by an ultrasensitive immunoradiometric assay in 16 normal subjects, 20 hyperthyroid patients, 10 patients with primary hypothyroidism (either untreated or inadequately treated with L-T4), 1 patient with central hypothyroidism, 10 patients with nontoxic nodular goiter, 5 patients with functioning thyroid adenoma, 20 patients receiving L-T4 replacement therapy, and 30 patients receiving L-T4 suppression. In 6 subjects blood was drawn at hourly intervals for 24 h; in 2 normal subjects a major TSH surge occurred between 2300-0100 h, with other minor peaks, and the same pattern was found in two patients receiving L-T4 replacement, whereas in 2 patients receiving L-T4 suppression, serum TSH was constantly below the limit of detection of the assay (i.e. less than 0.07 mU/L). In the remaining patients blood was drawn at hourly intervals between 2300-0200 h and on the next morning before (0830-0900 h) and 30 min after iv TRH administration. In normal subjects, in patients receiving L-T4 replacement therapy, and in hypothyroid patients, serum TSH values at night were higher than in the morning, with normal responses to TRH in the first 2 groups and exaggerated responses in the latter. The patient with central hypothyroidism had no nocturnal TSH surge and no TSH response to TRH. In all hyperthyroid patients, serum TSH was undetectable both at night and during the day, and none had a serum TSH response to TRH. Among patients with nontoxic goiter, 7 had detectable serum TSH in the morning, with higher values at night, and a normal response to TRH; the remainder had undetectable serum TSH both at night and in the morning, and subnormal or absent TSH responses to TRH. All 5 patients with a functioning thyroid adenoma had undetectable serum TSH levels in the morning and during the night, and subnormal or absent TSH responses to TRH. Of the 30 patients receiving long term (greater than 6 months) L-T4 suppression therapy, 28 had undetectable serum TSH both during the night and in the morning and unresponsiveness to TRH.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗
PubMed1987

Cellular localization of the microsomal antigen and the thyroid peroxidase antigen.

Evidence has been accumulated that human thyroid microsomal/microvillar autoantigen (M) is expressed both in the cytoplasm and on the surface of thyroid follicular cells. The availability of this autoantigen to the immune system, possibly associated with abnormally expressed HLA-DR antigens may be relevant both to the triggering and to maintenance of thyroid autoimmune reactions. Preliminary biochemical characterization of M suggested that it was a glycoprotein with a mol. wt. of about 100-110 kD. recent studies carried out in our laboratories taking advantage of monoclonal antibodies provided evidence that the structure presently referred as M-Ag is represented by thyroid peroxidase (TPO). The identity between TPO and M is further supported by four-layer immunofluorescence analysis showing a complete overlap of the two antigens both in the surface and in the cytoplasm of thyroid cells and by the observation that the expression of M and TPO is similarly modulated by TSH, possibly through a cAMP-dependent mechanism.

Cells, Cultured↗
PubMed1987

Enhanced production of gamma-interferon by thyroid-derived T cell clones from patients with Hashimoto's thyroiditis.

T lymphocytes from thyroid infiltrate and peripheral blood (PB) of four patients with Hashimoto's thyroiditis (HT) were analysed at clonal level for their ability to secrete interleukin 2 (IL-2) and gamma-interferon (gamma-IFN). As controls, T cell clones from PB of four normal donors and from spleen of two trauma victims were used. While no abnormality was found in the capacity to produce IL-2, the proportion of gamma-IFN-producing (IFN-P) T cell clones derived from HT infiltrates was significantly higher (P less than 0.0005) than that of IFN-P clones derived from normal or patient PB. Most of CD4+ and CD8+ IFN-P clones from thyroid infiltrates, as well as a proportion of CD4+ PB-derived clones of patients with HT, released higher amounts of gamma-IFN than control clones. A relationship could be demonstrated between high gamma-IFN production and natural killer (NK) activity in T cell clones from thyroid and PB of HT patients. In fact, the percentage of IFN-P clones with NK potential (NK+) was remarkably higher (P less than 0.0005) in thyroid infiltrates than in normal spleen or PB. The proportion of IFN-P NK+ clones from patient PB was also significantly increased (P less than 0.02) but, unlike thyroid-derived clones in which the majority of IFN-P NK+ clones were CD8+, most PB-derived IFN-P NK+ clones from the same patients expressed the CD4+ phenotype. Almost all thyroid NK+ clones could be triggered to produce more gamma-IFN, while gamma-IFN synthesis by NK-negative thyroid clones was comparable to that of control clones. In view of the multiple effects ascribed to gamma-IFN in the cascade of events leading to immune responses, the abnormal potential to gamma-IFN secretion shown by intrathyroidal T lymphocytes may be of importance in the pathogenesis of autoimmune thyroiditis.

Adult↗
PubMed1987

Serum sex hormone-binding globulin in amiodarone-treated patients. A marker for tissue thyrotoxicosis.

The lodinated antiarrhythmic drug amiodarone frequently causes an elevation of the serum thyroxine (T4) level in patients who remain clinically euthyroid. Less frequently, true iodine-induced hyperthyroidism may occur. The clinical and laboratory distinction between these two conditions is often difficult. Since the serum sex hormone-binding globulin (SHBG) concentration is elevated in hyperthyroidism, this study was carried out to evaluate the serum SHBG concentration as a possible marker of hyperthyroidism in patients receiving amiodarone. Patients treated with amiodarone were divided into three groups: clinically euthyroid with normal serum T4 and triiodothyronine (T3) concentrations, clinically euthyroid with elevated serum T4 and normal T3 concentrations, and clinically hyperthyroid with elevated serum T4 and T3 concentrations. The mean serum SHBG concentration was significantly elevated in amiodarone-induced hyperthyroid patients, while it was normal in euthyroid patients treated with amiodarone who had normal or elevated serum T4 concentrations. The results suggest that the hyperthyroxinemia induced by amiodarone is not associated with excess thyroid hormone action in the liver unless the serum T3 concentration is also elevated.

Aged↗
PubMed1987

Therapeutic doses of iodine-131 reveal undiagnosed metastases in thyroid cancer patients with detectable serum thyroglobulin levels.

Serum thyroglobulin (Tg) measurements in patients with treated differentiated thyroid cancer are usually well correlated with the presence or absence of residual or metastatic thyroid tissue. However, it is not rare to find a patient with detectable serum Tg levels but negative 131I whole-body scan (WBS) and no evidence of disease activity. To clarify the reason for this discrepancy, we decided to perform the WBS after the administration of a therapeutic dose of 131I in 17 consecutive patients in whom serum Tg was detectable while the WBS performed with a 5 mCi tracer dose was negative (12.6% of 135 patients studied with both WBS and serum Tg). The result of this study demonstrated that after this procedure the WBS became positive for significant residual or metastatic areas of radioiodine uptake in all patients but one. Such data indicate that in our patients the presence of circulating Tg is not a false-positive Tg result, but is due to the presence of residual or metastatic tissue that is not detected in the conventional WBS, that can be visualized using therapeutic doses. Preliminary follow-up data indicate that this procedure may also have therapeutic effect, although the relevance of this aspect remains to be established.

Adolescent↗