Biomedical subjects
G Pineda
Publications and source records attributed to G Pineda.
[Determination of antibody antireceptor of TSH, experience in patients with thyroid disorders and controls].
In order to measure TSH receptor antibodies (TRAb) we tried to set up a radioreceptor assay using human thyroid membranes. Due to lack of appropriate binding activity of the material obtained, we decided to use a kit which provides solubilized porcine membrane-receptors to TSH instead of human membranes, as well as calibrators that have been standardized in a receptor assay against MRC LATS std B. With these reactives we have measured TRAb in sera from 7 normal controls (C), 54 thyrotoxic patients (43 diffuse goiters [BDH], 8 multinodular goiters [BHM] and 3 Subacute Thyroiditis [TSA]), 3 patients with Hashimoto's Thyroiditis (TH) and in 6 non-hyperthyroid Graves ophthalmopathy patients. Measurement were initially performed using calibrators and the results expressed as U/L; since a very good correlation between the expression U/L and the calculated Inhibition Index (I.I.) was found (r = 0.99, n = 15, p < 0.001), results are shown using latter. In C mean +/- SD value for I.I. was 3.4 +/- 2.37%, so we decided to use, as cut off criteria for differentiating between normal and abnormal results, the figure 11%, which represents the mean +/- 3 SD. According to this, 93% of BDH had elevated TRAb activity while only slightly more than one third of MBH had elevated values, this difference being highly significant (p < 0.0001); both TSA and TH patients showed low TRAb activity while all Graves ophthalmopathy pts had elevated values, thus suggesting that they had a latent disease. We concluded that the methodology that is adequate and practical for clinical purposes.(ABSTRACT TRUNCATED AT 250 WORDS)
[Effect of insulin-like growth factor I on HLA-DR antigen expression in cultured human thyrocytes: a component of the autoimmune process?].
The aim of this study was to determine whether IGF-1 and INS are able to induce HLA-DR antigen expression (AgHLA-DR) in cultured human thyrocytes. Cytotoxicity assay in thyroid epithelial cells (cultured for 7 days to avoid spontaneous antigen expression) from 14 patients operated due to different thyroidal diseases, was used to assess HLA-DR expression. AgHLA-DR was reinduced adding IFN-delta, IGF-1 or INS to the culture media, alone, combined or associated with TSH or TBII. Both IGF-1 and INS induced HLA-DR expression in a similar way as IFN-delta did, and the response was enhanced with their combination, suggesting that they have different sites of action. Their association with TSH or TBII further augmented the response. To determine if IGF-1 acts via lymphocyte IFN-delta secretion, peripheral lymphocytes from 5 normal subjects were cultured with and without IGF-1 and the supernatant was used as stimulator, observing a stimulation similar to that induced by IFN-delta. This finding supports the hypothesis that IGF-1 acts stimulating a specific tyrosine kinase protein (p56 1ck) which is located in T lymphocyte receptors. According to our results we can conclude that, at least in vitro, both IGF-1 and INS play a role in the immune process, probably exerting a paracrine effect on autoimmunity, acting as perpetuating factors.
[Intrathyroidal lymphocytes in autoimmune thyroid diseases].
Aiming to assess the autoimmune origin of certain thyroid diseases, we studied the phenotypic composition and the ability of intrathyroidal lymphocytes to a re-induce HLA-DR expression on autologous thyrocytes coming from patients with graves's disease, nodular goiter and papillary thyroid carcinoma. Lymphocytes coming only from graves's disease patients were capable of reinduce HLA-DR expression on autologous thyrocytes (24.1 +/- 13.6 vs 1.5 +/- 2.54% in nodular goiter and carcinoma), as interferon gamma did (17.4 +/- 8.34%). Phenotypic characterization showed a significant decrease of T-CD3 (total lymphocytes) and T-CD4 (helper) in lymphocytes coming from patients with nodular goiter and carcinoma, and a marked reduction of T-CD8 (suppressor) in lymphocytes coming from patients with graves disease. Thus the T-CD4/T-CD8 ratio varies according to the etiology of the thyroidal disease. The lack of suppressor activity would explain why cells coming only from patients with graves disease, show marked HLA-DR expression. These findings give little support to the autoimmune origin hypothesis for nodular goiter and thyroid carcinoma.
[Lack of in vitro effect of antithyroid drugs upon peroxidase antigen expression in autoimmune thyroid disease].
The aim of this study is to determine whether antithyroid drugs (ATD) act via inhibiting thyroid hormone synthesis or by interfering with the immune process which leads to autoimmune disease. Previously we had demonstrated that ATD do not affect HLA-DR and TPO antigen expressions induced by appropriate stimulus in normal thyrocytes, so we decided to study what happens when the same experiments are performed using autoimmune thyrocytes. Cultured thyroid tissue from patients operated on for Graves' Disease or Hashimoto's Thyroiditis were stimulated with TSH or TBII alone or associated with ATD; TPO antigen expression was evaluated by the Cytotoxicity Assay using human monoclonal antiTPO. When autoimmune thyrocytes were cultured and no stimulus was used or with the addition of MMI or PTU alone, very low values of TPO expression were noted (8.6 +/- 6.7, 5.0 +/- 7.1 and 4.2% +/- 2.3% respectively); if they were stimulated with TSH or TBII, a sharp rise of TPO antigen expression was detected (54.4 +/- 23.3 and 62.6 +/- 16.5%), these figures being significantly different from unstimulated cells (p < 0.001). If both stimulus were used associated with ATD, the high TPO antigen expression was unaffected. It is concluded that, at least in vitro, ATD have no effect upon induced-antigen expression in autoimmune thyrocytes. Since they do not alter antigen presentation, a primary step in the immune process, it is difficult to accept that their mechanism of action is through interference with the immune response.
[Experimental evidence that endogenous TSH modulates microsomal antigen expression: clinical implications].
The purpose of this work was to study if TSH has a role in TPO antigen expression in vivo. Using the cytotoxicity assay we measured TPO expression and correlated it with TSH serum levels in 3 groups of rats: control, hypothyroid and hypothyroid supplemented with thyroxine. For comparative purposes, in the cytotoxicity assay we used rat monoclonal antiTPO or human sera with high titles for antiTPO antibodies. Hypothyroid rats showed marked elevations of TSH serum levels and TPO antigen expression in their thyrocytes when compared to the control and supplemented group. A positive correlation between TPO antigen and TSH levels was observed (r = 0.69, p < 0.001). There was an excellent correlation between TPO results using rat monoclonal or human sera antibodies (r = 0.94 p < 0.0001). It is concluded that TSH modulates TPO antigen expression. These data are of clinical relevance considering that TSH modulates the expression of other antigens that can maintain the immune response and perpetuate the immune disease in patients with Graves disease treated with antithyroid drugs. Thus, the avoidance of TSH hypersecretion with administration of thyroxine could be useful to treat these patients.
[Importance of gamma-interferon and DR expression in autoimmune thyroid disease].
The purpose of this paper is to study some of the mechanisms by which antigen presentation, one of the first steps in the immune process, is modulated. Three different experiments are performed: a) Using thyroid tissue from patients operated on for Graves' Disease, spontaneous HLA-DR and TPO antigen expressions were measured through the Cytotoxicity Assay; these findings were correlated with the presence of antiTPO in the sera of these patients. It was found that only patients whose thyroid tissue spontaneously expressed both antigens had circulating antiTPO in their sera, thus demonstrating that dual expression is basic for antibody production. b) Blood samples from other Graves' patients were obtained; peripheral lymphocytes were isolated and cultured in complete media for 5 days, then supernatant was separated and IFN-g concentration was measured by a sandwich type RIA; the same procedure was done in 12 normal controls in order to compare the results. It was found that lymphocytes from Graves' patients secreted significantly more IFN-g than normal controls (20.9 +/- 13.54 U/ml vs 3.7 +/- 3.22 U/ml respectively, p < 0.001) confirming that they were sensitized, so this determination could be used as a marker of immune process, if other infectious conditions are excluded; also it was found that IFN-g hypersecretion persists once hyperthyroidism has been treated, pointing out that the immune abnormality is still present.(ABSTRACT TRUNCATED AT 250 WORDS)
[Thyroid profile in normal pregnancy].
The aim of this study was to update the thyroid hormone profile in normal pregnant women with adequate iodine nutrition, to analyze the physiological changes that occur during pregnancy and to know the role that TBG and bHCG exert on these changes. One hundred six pregnant women without goiter, former thyroid diseases or positive antimicrosomal antibodies were studied. Fifty three of them were prospectively followed during the gestational period. Thirty age matched non pregnant women were studied as a control group. Serum T3t, T4t, T41, conventional and IRMA TSH, rT3, TBG, bHCG, antimicrosomal antibodies and urinary iodine content were measured. Median urinary iodine content was 18.9 ug/ml in pregnant women, discarding iodine deficiency, the main observed changes occurred between weeks 6 and 14 with significant elevations of T3t, T4t, T41, rT3, TBG and bHCG and TSH decrease. There was a positive correlation between TBG and T3t and T4t indicating a causal relationship. There was a negative correlation between T41 and TSH and between TSH and bHCG and a positive correlation between T41 and bHCG, suggesting a thyroid stimulator effect of bHCG which would raise T41 and thus inhibit TSH secretion.
[Treatment of hyperthyroidism during pregnancy: experience with 19 cases].
Untreated hyperthyroidism in pregnant women is associated with a high incidence of maternal and fetal complications. Thus, its treatment is mandatory, ideally using PTU because it has lesser transplacental passage. From 1987 and 1991 we have attended 19 hyperthyroid pregnant women. Of these, 18 had diffuse and 1 nodular goiter and in 10, thyrotoxicosis preceded pregnancy. PTU was used in 17 women (7 received it along the whole pregnancy), five had to be operated due to poor response, one received propranolol and one patient was not treated due to lack of attendance. Cesarean section was performed in 12 women, 5 had vaginal delivery, one had a miscarriage at the 20th week of pregnancy due to a neurological malformation and one patient was lost from control before delivery. The newborn of the untreated woman had a neonatal thyrotoxicosis and the resting 16 did not show evidence of thyroid disfunction. Newborns from mothers receiving PTU until delivery had significantly lower rT3 levels and non significant changes in T4 and T3. At the end of the observation period, 8 patients were euthyroid, 3 hypothyroid (2 after 131-l and 1 after surgery), 4 continued on PTU and 4 were lost from control. It is concluded that the outcome of pregnancy may be uneventful in hyperthyroid women provided that there is a close and adequate follow up.
Rapid preoperative preparation in hyperthyroidism.
OBJECTIVE: We have evaluated an alternative method of preparation of hyperthyroid patients for surgery, using betamethasone, iopanoic acid and propranolol. DESIGN: Betamethasone (0.5 mg every 6 hours), iopanoic acid (500 mg every 6 hours) and propranolol (40 mg every 8 hours) were given orally for 5 days; thyroidectomy was performed on the 6th day. We analysed patient acceptability, clinical and hormonal effects, ease of surgery and final outcome. PATIENTS: Thirteen females and 1 male, aged 16-59 years, ten with diffuse goitre and four with nodular goitre were submitted to subtotal thyroidectomy because antithyroid drugs had failed to control thyrotoxicosis or because hyperthyroidism coexisted with other conditions (pregnancy, hypertensive disease). MEASUREMENTS: Daily clinical assessments were made together with T3, T4 and rT3 serum concentrations before and while on drug treatment, during the surgical procedure and post-operatively. RESULTS: Daily assessment showed progressive clinical improvement so that on day 5 the patients were considered clinically euthyroid. Serum levels of T3 (mean +/- SD) showed significant decrease (by 38.2 +/- 24.9%, P less than 0.01) as early as 24 hours after medication was started, reaching almost euthyroid levels on day 3; on the day of operation T3 had diminished by 64.5 +/- 16.6% (P less than 0.0001). Serum T4 concentration showed a slight but significant decrement only from day 4 on and never reached euthyroid levels. Serum rT3 values exhibited a brisk increment at 24 hours (+333 +/- 194%, P less than 0.0001) and remained elevated between 8 and 10 nmol/l until medication was stopped. Drug tolerance was considered as excellent since no serious side-effects were noted, even in pregnant patients. There were no anaesthetic incidents or postoperative complications and patients were discharged 48-72 hours after operation. The final outcome has been satisfactory and pregnant patients continued their pregnancies without incident, bearing normal children. CONCLUSIONS: Pharmacological combination of betamethasone, iopanoic acid and propranolol has proved to be safe and effective and is of low cost. Provided there is adequate supervision of the patients, it may be used in patients requiring urgent thyroidectomy or in those who for reasons of non-compliance need a short preoperative regime.
[Spontaneous expression of class II (HLA-DR) molecules in thyroid pathology].
The spontaneous expression of Class II molecules (HLA-DR) was studied in cultured thyrocytes obtained from patients with Graves Disease (n = 7), Hashimoto's Thyroiditis (n = 5), euthyroid nodular goiter, (n = 12), papillary carcinoma (n = 5), and laryngeal carcinoma (3 normal thyroid glands). If nodular goiters and papillary carcinoma are of autoimmune origin, as Graves Disease and Hashimoto's Thyroiditis, they should spontaneously express HLA-DR antigen on their cell surface as this has been considered one of the initial steps of autoimmunity. The study was performed using the cytotoxicity assay. Immediately after the thyroid glands were obtained, thyrocytes were labelled with 51-Cr and incubated overnight; the cells were destroyed by adding monoclonal antiHLA-DR antibody and rabbit complement. The cytotoxicity index (CI% + SD) which reflects 51-Cr release from lyzed cells was used to measure antigen expression. While Graves Disease's and Hashimoto's Disease's thyrocytes expressed HLA-DR in high proportion, normal thyrocytes and thyroid cells from other diseases did so in minimal proportion (28.12 +/- 10.71 vs 2.26 +/- 2.32, p < 0.001). These findings strongly suggest that nodular goiters and papillary carcinoma are not of autoimmune origin since they are unable to express HLA-DR on their cell surface. It is postulated that HLA-DR expression is the result of the influence of T lymphocytes previously sensitized to thyroid antigens.
[Thyroid disease in progressive systemic sclerosis].
There is no agreement wither thyroid disease is a common feature of progressive systemic sclerosis (PSS). We evaluated 28 patients with proven PSS with determinations of T3, T4, TSH and Tg as well as antimicrosomal autoantibodies. Radioactive I uptake, thyroid scintigraphy, TRH test and fine needle biopsy were performed in selected patients. Twelve (43%) patients had clinical or laboratory evidence of thyroid dysfunction. Four patients had euthyroid goiter, 3 had evidence of autoimmune disease, 2 had chronic Hashimoto's thyroiditis, 1 was hypothyroid, 1 hyperthyroid and one has subacute thyroiditis. The CREST variant of PSS was most commonly associated with thyroid pathology. Our results indicated that thyroid disease is frequently associated to PSS. A complete clinical and laboratory evaluation is needed to confirm its presence.
[Problems in the diagnosis of thyroid dysfunction of the elderly adult].
Thyroid disfunction in the aged is often misdiagnosed either due to scanty symptoms, masking by other ailments or because function tests can be altered by extrathyroid causes such as chronic diseases, drugs or undernutrition. We surveyed 93 patients from 60 to 104 years old (73 females) living in geriatric homes. Most received at least 2 drugs for control of hypertension, coronary artery disease, diabetes, parkinsonism or psycho-organic deterioration. No clinical evidence of thyroid disfunction was found in 75 patients. T3 was 73.6 +/- 25.5 ng/dl, T4 7.3 +/- 1.8 micrograms/dl, TSH 2.8 +/- 0.9 uU/ml and rT3 32.2 +/- 16.3 ng/dl. Antimicrosomal antibodies were negative in all. Significant differences were found comparing these values with those obtained in 26 normal adults with mean age 39.9 years: T3 was lower and TSH and rT3 were higher in the elderly (p less than 0.0001). T3 decreased and rT3 increased in relation to age and males had significantly lower values of T3, T4 and TSH than females. Some evidence of thyroid disfunction was present in the remaining 18 patients: 9 had multinodular and/or positive antimicrosomal antibodies with euthyroid hormone levels; 6 had elevated T3, T4 and fT4 so hyperthyroidism was suspected; the remaining 3 patients had TSH levels above 20 uU/ml indicating the presence of hypothyroidism of which only one had some clinical manifestation. Thus, thyroid disfunction in the elderly + is not uncommon (3.2% of hyperthyroidism and 2.6% hypothyroidism in this series) in the absence of clinical manifestation. Treatment may improve the quality of life in these patients.
[Efficacy of propylthiouracil in the treatment of amiodarone-induced hyperthyroidism].
Amiodarone is a benzofuranic derivative widely used in cardiologic practice because of its excellent antiarrhythmic properties. Due to its high iodine content, it interferes with thyroid physiology and can cause either hyper or hypothyroidism. Amiodarone-induced hyperthyroidism should be considered as a serious complication since it develops in cardiac patients, the clinical diagnosis can be difficult and because conventional methods of therapy are said to be often ineffective. We analyze the outcome of 10 pts, chronically treated with Amiodarone (16-60 mo, mean 37.6 mo) who develop hyperthyroidism during the antiarrhythmic therapy. All patients had multinodular goiter. Overt clinical picture for thyrotoxicosis was seen in 7 of them and lab tests showed: rT3 = 101.1 +/- 14.9 ng/dl; T3 = 220.2 +/- 25 ng/dl; T4 = 15.6 +/- 1.9 micrograms/dl, TSH = 0.8 +/- 0.2 microU/ml and TRH response 0.0 microU/ml. Thyroid microsomal antibodies were negative in 3 pts studied. After Amiodarone was discontinued, patients were followed-up monthly. In 2, normalization of clinical and laboratory indexes were obtained at 40-60 d and no other medication was given. In the remaining, due to the intensity of clinical manifestations, PTU treatment was started (300 mg/d) After 4 mo, euthyroidism was achieved in 6 and it persisted after discontinuation of PTU has patient failed to respond to PTU, 131I was administered with excellent results. Patients have been followed-up up to 3 years after therapy without observing thyrotoxic relapses nor deterioration of their cardiological condition.2+ conventional therapies (PTU or 131I) have been, very effective.
[Thyroid microsomal autoantibodies in thyroid disease: their value as an antigenic marker].
An autoimmune disease can be the cause of thyroid disfunction. Determination of autoantibodies titers is the best way of demonstrating its existence. We studied 172 thyroid patients (146 females, 26 males) with ages ranging from 15 to 81 years. Thyroid microsomal autoantibodies (TMA) were detected by a modified agglutination test (SERA-TEK kit, Ames Div); a dilution greater than or equal to 1/1600 was considered as diagnostic of autoimmune disease. Patients were classified according to morphological and functional status in 3 groups: GI = non toxic goiter, n = 98 (71 diffuse, 20 multi and 7 uninodular); GII = toxic goiter, n = 62 (52 diffuse, 4 multi, 2 uninodular and 4 subacute thyroiditis); G III = hypothyroidism, n = 12 (5 primary hypothyroidism and 7 chronic thyroiditis). A control group of 30 normal individuals, ages ranging from 19 to 85 years was also studied. Diagnostic titers of TMA were found in 30.8% of group I, 88.5% of group II, 91.6% of group III and only in 6.6% of controls. The high incidence of positive TMA in toxic diffuse goiter (96.1%) as well as in hypothyroid patients was expected since these are typical examples of thyroid autoimmune disease. In the non toxic goiter group, positive TMA were present in 50% of multinodular, 28% of uninodular and 25% of diffuse goiters and the incidence of positive TMA varied according to age, being higher over the age of 40 years and lower under the age of 20 years. We postulate that this unexpected high incidence of positive TMA in non toxic goiter is due to amelioration of chronic iodine deficiency inducing the expression of latent autoimmune disease.(ABSTRACT TRUNCATED AT 250 WORDS)
[Hyperthyroidism and pregnancy: a diagnostic and therapeutic problem].
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[Influence of maternal thyroid pathology on pregnancy].
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[Pursued objectives with the use of 131I for the treatment of hypothyroidism: analysis of 2 series receiving different doses].
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