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Biomedical subjects

G A Medeiros-Neto

Publications and source records attributed to G A Medeiros-Neto.

At least 19 recordsLinked to original sources
PubMed1990

Thyroid peroxidase in endemic goiter tissue.

Thyroid peroxidase (TPO) activity and TPO protein were analyzed in endemic goiter tissue under iodine deficiency and after iodine supplement. TPO was prepared from 9 endemic goiter tissues and 4 normal thyroid tissues by solubilizing enzyme with detergent. Four patients with endemic goiter received iodized oil injection 12 months before surgery. All patients had normal serum thyrotropin (TSH) and thyroid hormone levels before surgery. TPO activity was measured by iodinase assay and guaiacol assay. Endemic goiter TPO showed greater iodination activity than that of normal TPO (p less than 0.01). The guaiacol assay showed greater TPO activity in 6 of the 9 endemic goiter tissues than that of the normal tissue. Iodized oil treatment did not affect TPO activity or TPO proteins when compared with those in untreated endemic goiter tissues. TPO activity in endemic goiter tissue correlated with thyroid T4 5'-deiodinase activity and not with thyroid hormone content in thyroglobulin. Since thyroid T4 5'-deiodinase and TPO are under control of TSH, an increase in TPO activity in the presence of normal serum TSH may be explained by the increased sensitivity of endemic goiter tissue to TSH-one of the possible adaptation mechanisms of endemic goiter.

Adult↗
PubMed1990

Dyshormonogenetic goiter: presence of an inhibitor of normal human thyroid peroxidase.

A dialyzable, thermostable inhibitor of normal thyroid peroxidase (TPO), with UV absorption maximum at 250-260 nm, was found in the digitonized, washed particulate fraction of two dyshormonogenetic goiters. No intrinsic TPO iodide-oxidation activity was detectable in either of these goiters, and their TPO iodination activity was below the method sensitivity threshold, even after dialysis. These findings could be explained by an absent or abnormal TPO associated with the synthesis of a TPO-inhibitor, or by the irreversible inhibition of a normal enzyme by the inhibitor.

Dialysis↗
PubMed1988

Deficiency of superoxide dismutase in endemic goiter tissue.

Superoxide dismutase (SOD) activity and its concentration were measured in thyroid tissues obtained from patients with Graves' disease, Hashimoto's thyroiditis, differentiated thyroid cancer, and endemic goiter (before and after iodine supplementation) as well as in normal thyroid tissue (paranodular tissue) from patients with follicular adenomas. SOD activity was measured by pyrogallol assay in ethanol-chloroform extracts of the thyroid homogenates. The SOD concentration in the thyroid extract was measured as immunoreactive SOD by electroimmunoassay. Endemic goiter tissues (n = 10) contained significantly lower SOD activity [mean, 1.9 +/- 1.9 (+/- SD) vs. 7.5 +/- 3.9 ng purified SOD/micrograms DNA; P less than 0.02] and concentration (mean, 0.2 +/- 0.1 vs. 0.8 +/- 0.5 ng SOD/microgram DNA; P less than 0.01) compared with those of normal tissues. No other pathological thyroid tissues had such consistently low SOD levels. Lactate dehydrogenase activity, a marker of cytosolic enzyme, was not lower in endemic goiter tissues than in normal tissues, suggesting that both tissues possessed functioning cells capable of producing cytosolic enzyme. Thyroid tissue from endemic goiter patients previously treated with iodized oil injection also had low SOD activity and concentration. Western blot analysis indicated that SOD protein in the endemic goiter tissue did not differ from that in normal thyroid tissue. We conclude that there is deficiency of cytosolic SOD in endemic goiter tissue. Since the deficiency of cytosolic SOD causes more prolonged exposure to oxygen free radicals, the decrease in SOD might contribute to the degenerative changes frequently found in these tissues.

Blotting, Western↗
PubMed1988

Towards the eradication of iodine-deficiency disorders in Brazil through a salt iodination programme.

Iodine-deficiency disorders have been a serious public health problem in Brazil because of the failure of a salt iodination programme established in 1953. The reasons for this failure were logistical, e.g., potassium iodide was not supplied to all salt-producers, iodination of salt was largely erratic, and part of the population at risk used only non-refined salt, which was not iodinated. In 1978 a task force was therefore formed to implement measures to eliminate iodine-deficiency disorders from the country. For this purpose, potassium iodate was distributed, free-of-charge, to all salt mills and an iodate dosing spray was supplied without cost to small salt producers. Also, regional laboratories for determining iodine in salt were set up, inspectors made regular visits to the salt mills, and samples of salt from commerce and from the producers were analysed. More than 90% of the samples contained 10-30 mg iodine per kg. In three typical areas of the country with endemic goitre the urinary excretion of iodine increased from an average of less than 40 mug iodine to 125 +/- 38 mug iodine per g creatinine. In conclusion, the salt iodination programme was a complete success and could serve as a model for other countries with a high prevalence of iodine-deficiency disorders.

Brazil↗
PubMed1986

Thyroid growth immunoglobulins in large multinodular endemic goiters: effect of iodized oil.

Iodized oil (IO) was administered to 10 goitrous patients recently emigrated to São Paulo (SP) from iodine deficiency areas and to 42 goitrous patients from 2 Brazilian chronic iodine deficiency regions, Loreto and Luziania (L). Thyroid growth-promoting immunoglobulin G (IgG) thyroid-stimulating antibody, serum thyroglobulin (Tg), TSH, and thyroid hormones were measured before and 1 yr after IO administration. In all patients there was a remarkable reduction of gland mass associated with a significant decrease (P less than 0.01) in both basal serum Tg and peak Tg levels after bovine TSH administration. The mean percent Tg increase after bovine TSH treatment was reduced to 82% above basal levels compared with 224% before IO. Mean serum TSH levels, elevated only in the L group [7.3 +/- 11 (+/- SD) microU/ml] decreased to the normal range after IO (2.5 +/- 2.1 microU/ml). Serum T3 and T4 concentrations did not change greatly. Tests for microsomal antibodies were negative before and after IO. IgG concentrates of serum obtained before and after IO were tested for their ability to stimulate incorporation of [3H]thymidine into DNA or to increase intracellular generation of cAMP in FRTL-5 cells. Thymidine incorporation activity was found in 8 of 10 patients from SP [316 +/- 37% (+/- SEM); range, 140-480%] and 25 of 42 patients in the L group (mean, 206 +/- 14; range, 120-500%) before IO. Stimulation of thymidine incorporation reflected true growth-promoting activity, as confirmed by experiments measuring cell number, was not accounted for by TSH in the preparation, and reflected IgG action because it was abolished by absorption with antihuman IgG. IgG from only 1 patient in group SP and 4 patients in group L stimulated intracellular production of cAMP in FRTL-5 cells. All patients except 1 in both groups had no IgG stimulation (less than 120%) of growth-promoting activity 1 yr after IO treatment. There was a significant positive correlation between thyroid growth-promoting activity and serum Tg concentrations (r = 0.58; P less than 0.001), but no significant correlation was found with other parameters (TSH, T4, and T3). We conclude that growth-promoting IgGs lacking ability to stimulate cAMP production may play a role in the large multinodular goiters due to chronic iodine deficiency.

Adenylyl Cyclases↗
PubMed1985

Persistent pituitary resistance to thyroid hormone in congenital versus later-onset hypothyroidism.

The pituitary and peripheral responses to L-T4 and L-T3 therapy were studied in 12 patients with congenital goitrous hypothyroidism, in 10 patients with an ectopic thyroid and onset of hypothyroidism at 3-8 years of age, and in 6 patients with adult-onset hypothyroidism, after they had had their chronic thyroid hormone replacement therapy discontinued for 30 days. They were first treated with increasing L-T4 (0.1, 0.2 and 0.4 mg daily) followed by L-T3 (0.05 and 0.2 mg daily) after stopping thyroid medication for another month. Ten normal subjects were treated identically. In normal individuals the peak TSH, alpha, and TSH-beta response to TRH was significantly decreased with 0.1 mg L-T4 or 0.05 mg L-T3 daily and was suppressed with 0.2 and 0.4 mg L-T4 or 0.2 mg L-T3 daily; serum cholesterol and triglyceride decreased significantly with 0.2 or 0.4 mg L-T4 or 0.2 mg L-T3 daily; testosterone-estradiol binding globulin (TeBG) increased significantly at the same doses. In congenitally hypothyroid patients receiving 0.2 mg L-T4 daily, the mean peak TSH after TRH was 24 +/- 17 microU/ml, whereas in patients with an ectopic thyroid or adult-onset hypothyroidism the peak TSH was significantly less at 5.9 +/- 8.8 and 5.5 +/- 5.7 microU/ml, respectively. Only at the highest doses of L-T4 (0.4 mg/day) or L-T3 (0.2 mg/day) was the TSH response to TRH suppressed in the congenitally hypothyroid group. The alpha and TSH-beta subunit levels followed those of TSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Serum thyroglobulin (Tg) stimulation with bovine TSH: a useful test for diagnosis of congenital goitrous hypothyroidism due to defective Tg synthesis.

Sixteen patients with congenital goitre were submitted to a bovine TSH stimulation test (bTSH), and serum thyroid hormones (T3, T4), TSH and thyroglobulin (Tg) were measured before and after bTSH injection. In 9 patients with an organification defect basal levels of Tg were normal (19.4 +/- 3.1 micrograms/l) rising after bTSH to a mean level +/- SEM of 37.3 +/- 4.1 micrograms/l. Six patients with defective Tg synthesis or release had a mean basal level of serum Tg of 8.7 +/- 1.9 microgram/l (mean +/- SEM) and failed to raise serum Tg concentrations after bTSH (mean +/- SEM: 10.4 +/- 2.1 micrograms/l). In both groups a modest although significant (P less than 0.05) change in serum thyroid hormones after bTSH was noted. We conclude that the bTSH test may be used to distinguish the group with defective Tg synthesis or release from other types of congenital goitre.

Adolescent↗
PubMed1979

Congenital goitre and hypothyroidism with impaired iodide organification and high thyroid peroxidase concentration.

A sibship of thirteen subjects whose parents were first cousins was studied for a defect in thyroid hormone synthesis. Five sibs were goitrous and had congenital hypothyroidism. All but one showed a positive perchlorate discharge test (PDT). Three other subjects were goitrous and euthyroid (one with a positive PDT), and the remaining five sibs were euthyroid with a presumably normal thyroid. However, an abnormally exaggerated TSH response to TRH was observed not only in the hypothyroid patients but also in six of the other subjects, indicating a decreased thyroid feedback at the pituitary level in the presence of a normal serum concentration of thyroid hormones. In two hypothyroid patients a normal serum T3, low serum T4 and a low reverse T3 were observed. Microscopic studies of thyroid tissue from three of the sibs disclosed marked cellular hyperplasia with no lymphocytic infiltration anywhere in the tissue. Peroxidase activity was determined on tissue from three sibs by three different assay procedures. It was within the normal range in one patient and was significantly elevated in the other two. There was no evidence for a qualitatively defective peroxidase. The defect in thyroid function in this family does not appear to involve a peroxidase deficiency. Thyroglobulin isolated from the thyroid glands of two of the goitrous, hypothyroid subjects was poorly iodinated but was judged to be normal by immunoreactive and ultracentrifugation procedures. Although the nature of the thyroid metabolic defect in this family was not elucidated, the evidence suggests a genetic defect, probably involving a recessive gene.

Adolescent↗
PubMed1979

Imparied cyclic-AMP response to thyrotrophin in congenital hypothyroidism with thyroglobulin deficiency.

A 19 year old man had congenital hypothyroidism and severely retarded development. His thyroid gland was not enlarged and laboratory findings included low serum concentration of T4 (2.8 microgram/100 ml) and T3 (16 ng/100 ml) with a high level of TSH (52 microU/ml) that rose to 192 microU/ml after TRH. 131I uptake by the thyroid was normal (41.5% at 24 h) and did not show a normal increase after exogenous TSH administration (49.5% at 24 h). The perchlorate discharge test was negative and no antibodies against thyroid antigens were found. Studies on the biopsy specimen revealed low iodide trapping by the thyroid slices and no formation of cyclic AMP after TSH was added to the medium. The endogenous TSH of the patient was biologically active increasing cyclic adenosine monophosphate c-AMP concentration in normal thyroid slices. No thyroglobulin was found in the thyroid tissue either by immunological or ultracentrifugational methods. An increased proportion of iodoalbumin was present in the serum. We postulate that the fundamental defect in this gland is an impaired generation of c-AMP by the defective thyroid cell and deficiency of thyroglobulin formation resulting in inadequate thyroxine and triiodothyronine synthesis.

Adult↗
PubMed1978

Effects of iodides on the hypothalamic-pituitary-thyroid axis in neurological endemic cretinism: evidence for compensated thyroidal failure in adult life.

Thyroid function studies, performed after iodide administration to five patients with neurological endemic cretinism, were indicative of hypothyroidism. All five subjects had either a low serum thyroxine (T4) or a high basal thyrotrophin (TSH) level and a clearly exaggerated TSH response to thyrotrophin releasing hormone (TRH). These findings are in sharp contrast with those we have previously described in goitrous patients without cretinism from the same geographical area. One interpretation of our observations is that there is an underlying mild defect in thyroid hormone synthesis in endemic cretinism predisposing to iodine induced hypothyroidism.

Adult↗
PubMed1978

3,3',5'-triiodothyronine, thyroxine, triiodothyronine, and thyrotropin levels in maternal and cord blood sera from endemic goiter regions of Brazil.

T4, T3, rT3, and TSH were measured in cord blood of infants born in mild to severe endemic goiter areas and nonendemic urban areas in South and North America. A significantly high rT3 concentration was found in newborns living in the urban area of South America as compared to a Canadian newborn population. There were no differences among the various thyroid parameters in the groups of newborns studied. Blood from goitrous mothers showed significantly higher concentrations of T3 and TSH than nongoitrous mothers. However, these changes did not affect the concentrations of thyroid hormones, rT3, or TSH in the fetal circulation.

Brazil↗
PubMed1977

Familial goitre with partial iodine organification defect, lack of thyroglobulin, and high levels of thyroid peroxidase.

From a sibship of three sisters having congenital goitre and normal hearing, two had impairment of organification of iodine. S1 (4 years old) had goitre since birth, euthyroidism, and a negative perchlorate test. S2 (15 years old) and S3 (13 years old) were hypothyroid, and had radioiodide discharge after potassium perchlorate administration of 19.8% and 26.1%, respectively. Thyroid tissue was obtained at thyroidectomy. Peroxidase activity, in the thyroidal subcellular particles, was found to be qualitatively normal, but quantitatively increased. In the triiodide assay, the activity was: S1 6912 u, S2 2590 u, and S3 3844 u (normal values 900-1700 u). In the tyrosine-iodinase assay, the activities, expressed as nmoles of iodide incorporation per gram of tissue, were S1 1046, S2 471 (normal values 220-410). The activity of the thyroidal NADPH-cytochrome c reductase, an enzyme possibly involved in hydrogen peroxide generation, was: S1 0.084, S2 0.047, and S3 0.005 (normal values 0.018 muEq/min/mg). No thyroglobulin was detected by analytical ultracentrifugation, polyacrylamide gel electrophoresis, or double immunodiffusion in agar of the supernatant fractions. In patient S2, whose gland was labelled in vivo with 125I, 60% of the total radioactivity of the gland (pooled nodular and paranodular specimens) was in a particulate iodoprotein that was solublilized by trypsin, deoxycholate or digitonin. In the soluble fraction there were two iodoproteins: iodalbumin, and a second iodoprotein similar to the solubilized particulate iodoprotein. It is postulated that absence of the normal thyroidal receptor protein might be in some cases a cause of iodine organification defect.

Adolescent↗
PubMed1975

The effect of iodized oil on the TSH response to TRH in endemic goiter patients.

The TSH and T3 response to synthetic TRH was evaluated in 4 groups of patients: normal controls and goitrous subjects from the urban area of Sao Paulo (urinary iodine excretion: 172.2 +/- 48.3 mug I/g creatinine) and nongoitrous and goitrous subjects from the endemic areas of Sao Bento (urinary iodine excretion: 53.8 +/- 17.1 mug I/g). Plasma T4 and T3 were within our normal range in all groups of patients. The mean plasma TSH was significantly higher (5.2 +/- 3.3 muU/ml) in goitrous subjects living in Sao Bento as compared to normal control groups both in urban or endemic areas, and after TRH these patients had an exaggerated and sustained TSH response with a significantly higher peak level (21.1 +/- 7.9 muU/ml). T3 concentration rose in all subjects following TRH and all patients from the Sao Bento endemic areas had a significantly higher proportionate increase in plasma T3 at 120 min. After an injection of iodized oil basal plasma TSH returned to the normal range in the goitrous subjects from Sao Bento. The mean peak TSH response to TRH was 9.1 +/- 3.8 muU/ml at 3 months after the iodized oil injection, and only at 6 months after the iodized oil TSH response was significantly reduced (peak level: 6.1 +/- 2.4 muU/ml). It is confirmed that plasma TSH levels are increased in endemic goitrous patients but not in normal controls living in the same endemic area and it is suggested that the pituitary threshold for inhibition of secretion of TSH by T4 and T3 has been reset in these goitrous subjects to achieve a persistently higher secretion rate of TSH.

Brazil↗
PubMed1975

Effect of iodized oil on iodine content, thyroglobulin maturation and on biochemical constituents of endemic goitre in brazil.

The biochemical and morphological changes in thyroid glands were studied in 5 patients with endemic goitre in the region before and one year after the administration of iodized oil. Each patient received a tracer dose of 125-I 3-5 weeks before the biopsy and another tracer of 131-I 12 h before surgery. It was observed that: 1. Iodine deficient goitrous glands had more protein per gram of tissue and that this was corrected by iodination. 2. The goitrous glands exhibited a higher relative proportion of particulate iodoprotein that incorporates more labelled iodine in relation to time of labelling. This abnormal situation is reverted to normal by iodination. 3. A significantly higher proportion of T3 + T4 is synthetized by the glands treated with iodized oil. 4. The increased amount of 127-I per gram of tissue is followed by an increased iodination level of thyroglobulin. 5. The ultracentrifugal pattern of proteins observed for iodine deficient glands differed from the iodinated glands, indicating a failure of maturation of thyroglobulin and possibly a greater than normal degree of heterogeneity. 6. The shift in sedimentation pattern was clearly induced by the increased degree of iodination, as shown by the iodized oil injection. 7. The increased cellularity and the higher rate of protein synthesis in the goitrous glands are reverted to normal after the iodized oil injection.

Biopsy↗