Screening for risk of delivery of a hypothyroid baby.
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Animals↗
Biomedical subjects
A Pinchera
Publications and source records attributed to A Pinchera.
L-thyroxine therapy induces a fall of thyroid microsomal and thyroglobulin antibodies in idiopathic myxedema and in hypothyroid, but not in euthyroid Hashimoto's thyroiditis.
Thyroid microsomal (MAb) and thyroglobulin (TgAb) antibodies were sequentially measured by sensitive and quantitative radioassays in 17 patients with goitrous Hashimoto's thyroiditis (9 hypothyroid, 8 euthyroid) and in 19 patients with idiopathic myxedema before and at various time intervals up to 24-48 months after the institution of L-thyroxine therapy. Thyroid antibodies were also determined in 5 euthyroid subjects with Hashimoto's thyroiditis maintained without treatment for a similar period. During L-thyroxine administration a reduction of MAb with respect to the pretreatment level was found in 6 of the 9 (67%) hypothyroid patients with Hashimoto's thyroiditis and in 16 of the 19 (84%) patients with idiopathic myxedema. The decrease of MAb was highly significant in both groups (p less than 0.001 and p less than 0.0001, respectively). A fall of TgAb occurred in 2 of the 3 patients (75%) with hypothyroid Hashimoto's thyroiditis and in 9 of the 10 (90%, p less than 0.001) patients with idiopathic myxedema having abnormally elevated pretreatment TgAB levels. No consistent pattern of MAb and TgAb changes was observed in the euthyroid subjects with Hashimoto's thyroiditis, whether treated or untreated. In the hypothyroid patients with Hashimoto's thyroiditis a significant association was found between the decrease of MAb and the reduction of goiter size (p less than 0.05) occurring during L-thyroxine administration. Moreover, the decrease of MAb and TgAb in idiopathic myxedema was greater (p less than 0.05) in the patients with normalized serum TSH (less than or equal to 4 microU/ml) than in those showing only a partial reduction of serum TSH (greater than 4 microU/ml) under L-thyroxine.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Serum free thyroid hormones in subclinical hypothyroidism.
Serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations were measured in a group of 52 patients with subclinical hypothyroidism (SH) and in an equal group of age and sex-matched normal controls. SH was defined by normal total T4 (TT4) and total T3 (TT3) concentrations, normal FT4 and FT3 indices, raised TSH levels, in the absence of signs and symptoms of hypothyroidism. Serum FT4 levels averaged 6.1 +/- 1.6 pg/ml (mean +/- SD, p less than 0.001 vs controls), with values below lower normal limits in 33/52 patients; mean FT3 concentrations averaged 3.1 +/- 0.7 pg/ml (p less than 0.001 vs controls), with values below lower normal limits in 8/52 patients. The analysis of results by the Galen and Gambino predictive value model demonstrated a higher sensitivity, but a lower specificity of FT4 as compared to FT3 in the diagnosis of SH. These results indicate that FT4 should be measured in addition to TSH for the diagnosis of impending thyroid failure, thus showing that in many cases patients with so-called subclinical hypothyroidism are actually already mild hypothyroid.
Adult↗
Serum thyrotropin by ultrasensitive immunoradiometric assay and serum free thyroid hormones in pregnancy.
Variations of serum TSH, measured by an ultrasensitive immunoradiometric assay, of serum total and free thyroid hormones and of thyroxine-binding globulin (TBG) and sex hormone-binding globulin (SHBG) were investigated in a group of 18 normal women before and during pregnancy. A gradual increase of total thyroid hormones, TBG and SHBG was observed, while mean serum free thyroxine and free triiodothyronine progressively decreased. Serum TSH concentrations were comprised within the normal range throughout pregnancy, although a small but significant increase was found in the 2nd and 3rd trimester. These changes may represent a compensatory mechanism to meet the increased demand for thyroid hormones in pregnancy and must be taken into account for a correct evaluation of thyroid function during gestation.
Adult↗
Treatment of amiodarone associated thyrotoxicosis by simultaneous administration of potassium perchlorate and methimazole.
Amiodarone iodine induced thyrotoxicosis occurs frequently in patients residing in areas of mild iodine deficiency and in patients with preexisting goiter. Drug therapy of the hyperthyroidism is often unsuccessful. Twenty-three patients with amiodarone induced thyrotoxicosis were either not treated, treated with 40 mg methimazole daily or with methimazole and 1 gm potassium perchlorate daily for up to 40 days and then with methimazole alone. Thyrotoxicosis was more likely to spontaneously remit in patients without goiter. Therapy with methimazole alone was unsuccessful in inducing euthyroidism in 5 patients with goiter. However, combined therapy with methimazole and potassium perchlorate rapidly alleviated hyperthyroidism in almost all patients with goiter. This drug combination is successful because perchlorate inhibits the active transport of iodine into the thyroid and methimazole blocks the intrathyroidal synthesis of thyroid hormones.
Adult↗
Effects of amiodarone and desethylamiodarone on pituitary deiodinase activity and thyrotropin secretion in the rat.
The effect of acute administration of amiodarone, its major metabolite desethylamiodarone and iodine in an amount equal to that contained in amiodarone on serum thyroid hormone and thyrotropin (TSH) concentrations and hepatic and pituitary 5' deiodination of thyroxine (T4) in the euthyroid and hypothyroid rat was evaluated. Amiodarone, desethylamiodarone and iodine all caused a decrease in serum T4 and triiodothyronine (T3) concentrations in euthyroid rats, while serum TSH concentrations and pituitary and hepatic 5' deiodinase activities were decreased only in the amiodarone and desethylamiodarone-treated animals. Serum TSH was increased in the iodine treated rats. Amiodarone, but not iodine, decreased serum T3 and TSH concentrations and pituitary and hepatic 5' deiodinase activities in hypothyroid rats. Inhibition of hepatic 5' deiodinase activity was also observed by the addition of amiodarone in vitro in the absence of dithiothreitol (DTT) but not in the presence of DTT. The decrease in the serum T4 concentration observed with amiodarone and desethylamiodarone administration is probably secondary to the inhibitory effect of iodine released from the drugs on thyroidal T4 synthesis and secretion. Iodine inhibition of thyroidal T3 synthesis and secretion, decreased T4 substrate for a peripheral generation of T3 and inhibition of T4 to T3 conversion all contribute to the decrease in serum T3 observed. The decrease in the serum TSH concentration, despite low serum T4 and T3 concentrations and inhibition of pituitary 5' deiodinase, suggest that amiodarone may function as a thyroid hormone agonist in the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)
Amiodarone↗
Human serum thyrotrophin measurement by ultrasensitive immunoradiometric assay as a first-line test in the evaluation of thyroid function.
An ultrasensitive immunoradiometric assay (IRMA) using two monoclonal anti-TSH antibodies has been used for TSH measurements in basal conditions and after TRH stimulation. The results have been compared with those obtained by conventional radioimmunoassay (RIA). The IRMA method had very high sensitivity (0.07 microU/ml). Detectable serum TSH concentrations were found in all normal subjects by IRMA, but in only 76% by RIA. No overlap was observed with the results obtained by IRMA in untreated overtly hyperthyroid patients, in whom serum TSH was below the limit of detection. The relationship between basal and TRH-stimulated serum TSH concentrations by IRMA and RIA was evaluated in 176 subjects including normals and patients with untreated and treated hyperthyroidism, functioning thyroid adenoma, nontoxic goitre and patients on L-thyroxine therapy. A normal TSH response to TRH was observed in virtually all patients with detectable basal serum TSH by both methods. When patients with undetectable basal serum TSH levels were considered, all but one (98%) had no TSH response to TRH by IRMA. On the contrary using RIA, an absent response was found only in 47% of subjects, a blunted responses in 10% and a normal response in 42%. These data indicate that basal serum TSH measurements by IRMA allows a complete discrimination of normal from hyperthyroid patients and can avoid the need for TRH stimulation tests.
Adenoma↗
Is humoral thyroid autoimmunity relevant in amiodarone iodine-induced thyrotoxicosis (AIIT)?
Amiodarone, an iodine containing drug, may induce thyrotoxicosis by an uncertain mechanism. In this study the role of thyroid autoimmunity was evaluated in 28 consecutive patients referred to us because they had become hyperthyroid during long-term amiodarone administration. Titres of thyroglobulin and thyroid microsomal antibodies, TSH binding-inhibitory and thyroid stimulating antibodies were evaluated. Underlying thyroid disorders were demonstrated in 20 patients (9 of them had toxic diffuse goitre, seven toxic multinodular goitre and four toxic adenoma), while eight patients did not show any apparent thyroid gland abnormality. Circulating thyroid autoantibodies could be found in all amiodarone iodine-induced hyperthyroid patients with toxic diffuse goitre and in one with toxic multinodular goitre, whilst they were absent in the other patients. These studies suggest that thyroid autoimmunity has little if any role in the development of thyrotoxicosis in amiodarone treated patients without underlying thyroid disorders. Furthermore, in amiodarone-iodine-induced thyrotoxicosis associated with various thyroid diseases, the humoral markers of thyroid autoimmunity show an incidence similar to that observed in spontaneous hyperthyroidism.
Adult↗
Ontogeny of nyctohemeral variations of thyrotropin-releasing hormone in rat hypothalamus.
The ontogeny of nyctohemeral variations of hypothalamic TRH content was determined in male rats from 7-45 days after birth, exposed to a daily 12-h light, 12-h dark cycle (0600-1800 h light; 1800-0600 h dark) or maintained in complete darkness until 45 days. TRH was extracted from whole hypothalami with 90% methanol and assayed by specific RIA. Hypothalamic TRH extracted from rats at different ages showed immunological, chromatographic, and biological properties identical to those of synthetic TRH. No significant variations in hypothalamic TRH content during the day were observed in 7-, 10-, and 17-day-old rats; a significant change, with a maximal value at 1800 h, was observed in 23-day-old rats, while an adult pattern with a maximal value at 1200 h and a minimal value at 2400 h was found in rats of 31 days of age and became more evident in 45-day-old rats. In animals maintained in complete darkness for 45 days after birth, no significant changes in hypothalamic TRH content at 1200 and 2400 h were observed. These findings indicate that environmental cyclic light-dark exposure is required for the development of diurnal changes in hypothalamic TRH content. Furthermore, any study involving hypothalamic TRH determination should take into account the age of animals and the diurnal variations of TRH.
Age Factors↗
Effect of the antileukemic agent L-asparaginase on thyroxine-binding globulin and albumin synthesis in cultured human hepatoma (HEP G2) cells.
L-Asparaginase (ASNase), a drug widely used in the treatment of acute lymphoblastic leukemia, has been reported to decrease serum T4-binding globulin (TBG) levels, while results of serum albumin determinations were conflicting. This effect in vivo has been attributed to depressed liver protein synthesis, but this hypothesis has not been proved. To investigate this problem, human hepatoma (Hep G2) cells were continuously labeled for 4 h with 100 microCi/ml [35S]methionine in the absence or presence of graded amounts of ASNase (from 0.1 nM to 0.1 mM). Media and cell lysates were collected, immunoprecipitated with antialbumin or anti-TBG serum and protein A, and submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Gels were sliced, and the radioactivity was counted in a beta-counter. A dose-dependent inhibition of TBG and albumin biosynthesis (as well as of total protein synthesis) was demonstrable, but TBG appeared to be more sensitive to the action of the drug. In fact, TBG biosynthesis was reduced by 8% with 0.1 nM ASNase, while an effect on albumin was observed only at 1 nM ASNase; 50% inhibition was obtained with 30 nM ASNase in the case of TBG and with 800 nM in the case of albumin. At the highest concentration (0.1 mM), TBG biosynthesis was reduced by 94%, and albumin biosynthesis by 75%. ASNase also proved to have a time-dependent effect, as assessed by the measurement of radioimmunoassayable TBG in the media from Hep G2 cells grown in the presence of 10 nM ASNase for 1-4 days. The TBG concentration was progressively reduced, by 40% after 1 day to 85% after 4 days. In pulse-chase experiments, a reduction of total (intracellular plus secreted) immunoprecipitable TBG and, to a lesser extent, albumin was observed, suggesting that the drug also affected the catabolism of newly synthesized proteins. These results provide the first in vitro evidence that ASNase actually inhibits TBG biosynthesis. This effect is not specific for TBG, but this protein appears to be more susceptible than albumin to ASNase action. This can explain why in patients treated with ASNase for leukemia, a decrease in serum TBG concentrations has not always been associated with a reduction in serum albumin levels.
Asparaginase↗
Cytolytic T lymphocytes with natural killer activity in thyroid infiltrate of patients with Hashimoto's thyroiditis: analysis at clonal level.
T Lymphocytes from thyroid infiltrates and peripheral blood (PB) of 3 patients with Hashimoto's thyroiditis (HT) were cloned using a microculture system previously shown to allow the clonal expansion of virtually all PB T lymphocytes from normal individuals. The phenotypic and functional features of a total number of 153 clones from thyroid infiltrates and 206 clones from PB were examined and compared with those of 272 clones derived from normal PB and spleens. The majority of clones derived from thyroid infiltrates of patients with HT had the cytotoxic/suppressor (T8+) phenotype, whereas the majority of clones from PB expressed the helper/inducer (T4+) phenotype. In addition, a consistent proportion (25%) of clones derived from PB of one patient had a phenotype (T3+T4-T8-) that was only occasionally found on clones obtained from PB or spleens of normal subjects. Most clones derived from both PB and thyroid infiltrates of the patients with HT had cytolytic activity, assessed by a lectin-dependent cytolytic assay against the murine P815 tumor cell line. The high frequency of cytotoxic T cells in thyroid infiltrates was related to the increased proportion of T8+ cells, whereas enhanced percentages of cytotoxic cell precursors with T4+ and T3+T4-T8- phenotypes primarily accounted for the high frequency of cytolytic T cells in the PB of the same patients. Many cytolytic T cell clones derived from thyroid infiltrates also had natural killer activity against human K562 and MOLT-4 target cells. These data provide the first functional analysis of T lymphocytes infiltrating the thyroid gland in patients with HT and suggest that the high proportions of cytolytic T cell precursors found in both thyroid infiltrates and PB of these patients may be of importance in determining the tissue damage in thyroid autoimmune disease.
Antibodies, Monoclonal↗
Thyroid function modulates thymic endocrine activity.
The thymus produces humoral factors that induce proliferation and differentiation of T-cells, which are responsible for cell-mediated immunity. Recent data in animals suggest that such thymic hormone activity is modulated by the neuroendocrine network and, in particular, by thyroid hormones, but no information is presently available in humans. To study this question, we measured the circulating thymic factor called thymulin (Zn-FTS) in hyperthyroid and hypothyroid patients. Thymulin levels were higher in hyperthyroid patients than in normal subjects, whereas hypothyroid patients had lower thymulin levels than normal subjects. A significant correlation was found between circulating thymulin and serum T4 and T3 levels. Thymulin changes could be reversed by appropriate treatment in both groups of patients. Recent data indicate that zinc is required to confer biological activity on thymic hormone molecules. This raised the question of whether the influence of thyroid status on thymulin activity could be mediated by changes in serum zinc concentrations. No support for such an explanation was obtained by thymulin measurements by a modified bioassay using an optimal zinc concentration in the assay system. In conclusion, thyroid status modulates thymic endocrine function in humans. Whether and to what extent such modulation is relevant to the function of the immune system remain to be established.
Adolescent↗
Thyroid-stimulating antibody mimics thyrotropin in its ability to desensitize the adenosine 3',5'-monophosphate response to acute stimulation in continuously cultured rat thyroid cells (FRT-L5).
TSH preincubation induces refractoriness to further stimulation of cAMP accumulation by the hormone in cultured thyroid cells. The question of whether the thyroid-stimulating antibodies (TSAb) present in sera of patients with Graves' disease have the same desensitizing effect as TSH was evaluated in this study using a differentiated strain of rat thyroid cells (FRT-L5) which requires TSH for growth and develops refractoriness to acute TSH stimulation of cAMP accumulation. Cells cultured for 4-5 days in medium deprived of TSH recovered responsiveness to TSH and TSAb. Refractoriness to TSH was reinduced in these cells by a 24-h preincubation with 250 microU/ml TSH. The addition of 100 microM KI or 100 microM methimazole to the medium together with TSH did not modify TSH-induced refractoriness. Four different TSAb preparations all induced refractoriness to TSH-stimulated cAMP accumulation. TSAb preincubation induced refractoriness to acute TSAb as well as TSH-stimulated cAMP accumulation. TSAb-induced desensitization was dose dependent and required prolonged (8-24 h) exposure to TSAb. Furthermore, the desensitization induced by TSAb as well as that caused by TSH were significantly inhibited by cycloheximide, indicating the need for de novo protein synthesis. In conclusion, TSAb mimics TSH in the induction of refractoriness in FRT-L5 cells.
Animals↗
Short term administration of potassium perchlorate restores euthyroidism in amiodarone iodine-induced hypothyroidism.
We studied the effect of potassium perchlorate (KClO4) in patients with hypothyroidism due to amiodarone. The short term administration of KClO4 to six such patients led to prompt restoration of euthyroidism, while the three untreated patients remained hypothyroid for 2-6 months. Since KClO4 inhibits thyroid iodide transport, thereby blocking further entrance of iodide into the thyroid and decreasing intrathyroidal iodide content, amiodarone-associated hypothyroidism is probably secondary to the inhibitory effect of excess intrathyroidal iodine on thyroid hormone synthesis.
Adult↗
Ontogenetic development of pancreatic thyrotropin-releasing hormone in human foetuses and in infants.
The ontogeny of thyrotropin-releasing hormone (TRH) in pancreata of human foetuses from 15-36 weeks of gestation and of infants has been studied. TRH was detectable in the pancreas of a 15 week old foetus; a progressive increase of pancreatic TRH content was observed until the 34th week of gestation, whereas a progressive decrease was found in the late period of pregnancy and in 1 year old infants. In contrast, the pancreatic insulin content showed a progressive increase during the entire pregnancy and in the first year after birth. These data indicate that TRH and insulin have different ontogenetic patterns in the human pancreas.
Female↗
Serum thyroid autoantibodies as a risk factor for development of hypothyroidism after radioactive iodine therapy for single thyroid 'hot' nodule.
Hypothyroidism is often observed after radioiodine treatment in Graves' disease, but it is considered a rare complication in single hyperfunctioning thyroid nodule ('hot' nodule). This concept has been recently challenged, but the available data are conflicting. In the present study we therefore assessed the development of permanent hypothyroidism in 126 patients with thyroid hot nodule treated with 131I (180 muCi/g of estimated nodule weight, total dose 5.5-28.9 mCi). Follow-up ranged between 1 to 11 years. Hypothyroidism was observed in 5 (4%) patients, corresponding to a cumulative incidence by life-table analysis of 4.8% ten years after treatment. No relationship was found between the development of hypothyroidism and the size of the nodule or the total amount of administered dose. Fifty-six patients with euthyroid hot nodule at the time of treatment had higher cumulative incidence of hypothyroidism after 10 years (9.7%) than those with toxic adenoma (1.5%) (0.1 greater than P greater than 0.05 by logrank test). When the patients were analyzed according to the presence or absence of serum antithyroglobulin and/or antithyroid microsomal autoantibodies, the prevalence of hypothyroidism after 131I treatment was higher (4/25 = 16%) in patients with significant serum antibody titres (greater than or equal to 1/400 by passive haemagglutination), when compared to that observed in subjects with negative antibody tests (1/101 = 1.0%). Life-table analysis showed in antibody positive patients a cumulative incidence of hypothyroidism after 10 years of 18.0% vs 1.4% in antibody negative patients (P less than 0.001 by logrank test).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Hyperthyroidism in Europe: clinical and laboratory data of a prospective multicentric survey.
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Adenoma↗
In vivo activated cytotoxic T cells in the thyroid infiltrate of patients with Hashimoto's thyroiditis.
High proportions of T8+ cells with inverted T4/T8 ratio were found in freshly isolated thyroid lymphocytes from patients with Hashimoto's thyroiditis. In addition, about one third of thyroid infiltrating cells expressed the TAC antigen, whereas in patient peripheral blood (PB) or normal lymphocytes from PB or lymphoid organs the percentage of TAC-positive cells was consistently lower than 10%. Following negative selection with OKT4 or OKT8 monoclonal antibodies and complement, TAC+ T cells were enriched in the T8+ cell population. Thyroid infiltrating T cells from two patients underwent two different cloning procedures. In the first, single T cells were initially activated with phytohaemagglutinin (PHA) and interleukin 2 (IL-2), in the other with recombinant IL-2 (rIL-2) alone. The majority of T cell clones obtained by initial PHA-stimulation (55-65%) had the T8+ phenotype, but the frequency of T8+ clones obtained by stimulating T cells with rIL-2 alone was even higher (78 & 71%, respectively). The majority of T8+ clones elicited by PHA (35/37 & 36/38) and all the T8+ clones (36/36 & 22/22) obtained from thyroid infiltrates with initial stimulation by rIL-2 displayed cytolytic activity. Most of cytolytic T8+ clones obtained from thyroid infiltrates with both cloning procedures, displayed NK activity against human K562 and MOLT-4 target cells, but not against a NK-resistant target, such as Raji cells. These data suggest that in Hashimoto's disease a considerable proportion of thyroid infiltrating T cells are in vivo activated T8+ cytolytic T cells with NK activity, which may be of importance in determining or maintaining the tissue damage of the target gland.
Adult↗