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Biomedical subjects

G Medeiros-Neto

Publications and source records attributed to G Medeiros-Neto.

70 records · Page 4Linked to original sources
PubMed1989

Qualitative and quantitative defects of thyroglobulin resulting in congenital goiter. Absence of gross gene deletion of coding sequences in the TG gene structure.

Seven subjects belonging to three families (ME, MA, MO), with congenital goiter and various degrees of thyroid hypofunction, were investigated from the standpoints of clinical, biochemical, and molecular biology. In two of these families (ME, MA), 6 individuals had low serum levels of Tg-related antigens with a minor increase after bovine TSH (bTSH) stimulation. A large proportion of the tracer was incorporated into serum albumin, and Tg antigens in the thyroid extracts were barely detectable by RIA. (0.19 mg/g tissue; normal, 70-90 mg/g). Gel filtration (CL6B Sepharose gel) showed absence of a normal Tg peak, and SDS agarose gel electrophoresis indicated complete absence of Tg dimer and monomer. Immunoelectrophoresis confirmed the absence of Tg-related antigens. Thus, in these patients a quantitative defect of Tg gene expression was characterized. By contrast, in the MO family a high basal serum concentration of immunoreactive Tg was present, with an exaggerated response to bTSH. Thyroid extracts revealed elevated TPO activity and normal levels of Tg-related antigens. Tg was also eluted in the gel filtration columns with the same mobility as standard 19S Tg. Immunoelectrophoresis against rabbit and human Tg was abnormal, with two precipitin arcs being detected. The Tg molecule after hydrolysis yielded only DIT and MIT, with poor formation of iodothyronines. Microscopic studies revealed a pronounced lack of colloid in the follicular lumina, and overdistended endoplasmic reticulum cisternae.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Low levels of thyroglobulin messenger ribonucleic acid in congenital goitrous hypothyroidism with defective thyroglobulin synthesis.

We characterized the virtual absence of immunoassayable thyroglobulin (Tg) in the serum and thyroid gland of two siblings (MA, JNA) and one nephew (RSS) from a family without inbreeding or familial goiter. Diagnosis of defective Tg gene expression was based on findings of normal PBI and low serum T4, low or normal serum T3, negative perchlorate discharge test, and virtual absence of the serum Tg response to challenge by bovine TSH. This conclusion was confirmed by analysis of proteins in the goiter extracts. Only minute amounts of immunoassayable Tg were detected by RIA (MA, 0.11; JNA, 0.19 mg/g tissue; compared to 70-90 mg/g in normal thyroid tissue). Gel filtration in Sephacryl S300 showed the absence of a normal Tg peak at 280 nm and concentration of label mostly on albumin. A minor intermediate peak of radioactivity was also detected, with the size of, approximately, normal Tg. Sodium dodecyl sulfate-agarose gel electrophoresis indicated the absence of Tg dimer and monomer, and Western blotting and immunoelectrophoresis confirmed this finding. Dot blot quantification of Tg and thyroid peroxidase mRNA indicated decreased hybridization of the patients' mRNA (MA, 44%; JNA, 63%) with phTgM2 (Tg probe) and increased hybridization (MA, 191%; JNA, 182%) with the pM5 (thyroid peroxidase probe) compared with control thyroid tissue. Dot blot analysis of Tg mRNA from the two siblings weakly hybridized with 3' and 5' Tg probes. RNA analysis by means of Northern transfer showed a clear signal of hybridization with Tg probe (phTgM1) in the 8- to 9-kilobase range, corresponding to the normal size Tg mRNA. No major polymorphisms were noted in Southern blotting, using seven restriction endonucleases. We conclude that no gross alteration of the 5' region of Tg gene was present in these patients. Ultrastructural examination of the thyroid tissue indicated that the rough endoplasmic reticulum was not augmented, nor were the cisternae of rough endoplasmic reticulum dilated. The defect observed in these goiters is diminished tissue concentration of Tg mRNA with defective translation. However, small amounts of functionally active Tg could be synthesized, iodinated, and immediately hydrolized, yielding mostly T3, owing to the intense tissue stimulation by TSH.

Adult↗
PubMed1987

Reduced serum thyroglobulin response to bovine TSH in malignant hypofunctioning solid thyroid nodules: comparison to benign nodular disease.

Forty-three euthyroid patients with a single, solid, nonfunctioning thyroid nodule were submitted to fine needle aspiration biopsy and serum thyroglobulin (Tg) was measured before and after (48h) 10 U of bovine TSH. Twenty-two normal subjects were also submitted to the bTSH test. Patients with nonfunctioning nodules were divided in two groups: (I) Benign or Suspicious Cytology (n = 32), (II) Malignant tissue (n = 11). In the latter group all patients underwent surgery and the pathology findings confirmed the presence of thyroid carcinoma. Twenty-one patients with benign or suspicious cytology were also operated upon and the diagnosis was colloid goiter (n = 16) and follicular adenoma (n = 5). In eleven other patients the nodule reduced significantly in size (8) or was no longer palpable after suppressive therapy (3). Normal individuals had a basal serum Tg mean +/- SD value of 12 +/- 7.2 ng/ml and a peak Tg value of 44 +/- 47 ng/ml. Serum Tg values were significantly higher (p less than 0.01) in patients with benign and malignant nodules. However the mean absolute increment (delta Tg) after bTSH was significantly lower (p less than 0.01) in patients with malignant nodules (7.2 +/- 4.8 ng/ml) as compared with normal subjects (22 +/- 16 ng/ml) or subjects with benign nodules (31 +/- 30 ng/ml). The relative (%) serum Tg increment was also significantly lower in patients with malignant tissues (14 +/- 11) as compared to those with benign nodules (77 +/- 86) or normal subjects (247 +/- 173).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Effect of thyroid hormone therapy on plasma insulin-like growth factor I levels in normal subjects, hypothyroid patients and endemic cretins.

The effect of thyroid hormone therapy (L-T4 or L-T3) on plasma immunoreactive insulin-like growth factor I (somatomedin C, Sm-C) concentrations was studied in 8 normal controls, 14 primary hypothyroid subjects and in 7 patients with endemic cretinism. In normals basal levels of Sm-C (1.56 +/- 0.77 U/ml) increased to (2.46 +/- 1.0 U/ml; L-T4) and to (2.9 +/- 0.95 U/ml; L-T3). Plasma Sm-C basal levels were significantly lower in primary hypothyroid subjects (0.81 +/- 0.48 U/ml) and increased to 2.54 +/- 1.43 U/ml (L-T4) and to 2.16 +/- 0.83 U/ml (L-T3). A significant and positive correlation (r = 0.56) was found between Sm-C and serum T4 and T3 concentrations. Plasma Sm-C concentrations in endemic cretinism were initially normal in 4 patients, but low in the remaining 3 (mean +/- SD: 1.18 +/- 0.63 U/ml) and did not increase after 12 months (1.34 +/- 0.61 U/ml) or 18 months (1.01 +/- 0.43 U/ml) of L-T4 and L-T3 therapy. Plasma T4 levels and free T4 increased considerably in EC after therapy with a significant decrease in the previously elevated plasma TSH concentrations. The subnormal response of plasma Sm-C during effective thyroid thyroid hormone therapy could be an additional factor involved in growth failure of endemic cretins.

Adolescent↗
PubMed1986

Iodized oil treatment for endemic goiter does not induce the surge of positive serum concentrations of anti-thyroglobulin or anti-microsomal autoantibodies.

Forty-three goitrous patients (grade II and III, WHO classification), living in areas of chronic iodine deficiency, were treated with an injection of iodized oil (470 mg iodine). Serial measurements of serum thyroid hormone levels after the therapy revealed increasing concentrations of both hormones, with a significantly lower serum T3/T4 ratio, and progressively significantly lower serum TSH mean values. Serum Tg mean value, initially elevated (58 +/- 9 ng/ml), decreased after 6 months and returned to the normal range at 36 months of therapy. In none of the examined patients (except for one subject with positive autoantibodies before therapy), it was observed the surge of positive anti-thyroglobulin or anti-microsomal autoantibodies after the iodized oil. We conclude that iodized oil therapy does not induce an abnormal autoimmune reaction in endemic goiter patients.

Adolescent↗
PubMed1986

Serum immunoreactive somatomedin-C levels in growth failure and delayed puberty associated with chronic hepatosplenic schistosomiasis.

Eleven patients, five males, six females, aged 14-20 years with hepatosplenic schistosomiasis (HSS), growth failure and delayed puberty were submitted to endocrine evaluation. All patients had well preserved parenchymal liver function although several changes were present in the portal system, showing a poorly vascularized liver. Bone age was retarded, thyroid function was normal, the human growth hormone response to hypoglycaemia was within the normal limits and the prolactin response to TRH was normal. LH and FSH basal levels were normal and a normal rise was observed after a provocative test with LHRH. Gonadal function, expressed as serum testosterone or oestradiol levels, was abnormally low for the chronological age. Serum somatomedin-C levels were also low (range 0.11-2.10 U/ml) for the respective Tanner stage or bone age of each individual patient. One year after a splenorenal shunting in the three patients that returned for follow-up, it was observed that sexual maturation reached Tanner stage III, linear growth increment ranged from 9.0 to 11.5 cm and serum somatomedin-C levels increased to 4.3-5.6 U/ml. We concluded that a combination of undernutrition and marked vascular changes in the liver, present in HSS, are associated with decreased serum sex steroids and somatomedin-C concentrations, resulting in growth failure and delayed puberty in these patients.

Adolescent↗
PubMed1986

Long-term effect of iodized oil on serum thyroglobulin levels in endemic goitre patients.

Serum thyroglobulin (Tg) response to bovine TSH (bTSH) was evaluated in 44 goitrous patients (grades III and IV) living in conditions of chronic iodine (I) deficiency (iodine urinary excretion less than 40 micrograms I/g) and in 26 normal subjects. After the initial clinical evaluation and laboratory tests (bTSH test, T4, T3, anti-Tg and anti-microsomal antibodies) all goitrous patients received 1 ml i.m. of iodized oil (I-oil) and were followed up for 30 months. The bTSH test was repeated at 6, 12, 20 and 30 months after I-oil in 21 subjects. A marked reduction in goitre size was observed in 85% of the patients with a concomitant significant increase in the mean serum T4 and T3 concentrations, a significant fall in the mean serum TSH level and a significant decrease in the T3/T4 ratio. Goitrous patients had elevated serum basal Tg levels (55 +/- 8 SEM micrograms/l) and a significantly mean higher peak Tg value after bTSH (200 +/- 65 micrograms/l) as compared with normal subjects (respectively, 11 +/- 1.4 and 32 +/- 3.4 micrograms/l). Larger goitres (grade IV) had a significantly higher mean peak Tg response as compared with grade III goitres. Treatment with I-oil significantly reduced the mean peak Tg response to bTSH after 6 months (59 +/- 10 micrograms/l) but at 12 and 20 months the peak Tg response after the injection rose, respectively, to 110 +/- 19 micrograms/l and 92 +/- 14 micrograms/l (P less than 0.02 as compared with 6 months), returning to the normal range only at 30 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Transient thyrotoxicosis in endemic goitre patients following exposure to a normal iodine intake.

Twenty-three endemic goitrous subjects (goitre grade: III and IV) that were living in a chronic iodine-deficient area (iodine intake: less than 40 micrograms I/d) were submitted to clinical and laboratory evaluation within 3-8 weeks of arrival at the metropolitan area of São Paulo, where daily iodine intake is estimated to be 150-200 micrograms I/d. Eight patients developed a mild thyrotoxic state (T4 = 14.7 +/- 2.3 micrograms/dl, T3 = 279 +/- 55 ng/dl, no TSH response to TRH). Five additional subjects, although euthyroid, had a blunted TSH-response to TRH, and the remaining ten patients were euthyroid and had a normal TSH response to TRH. Thyrotoxicosis was associated with larger goitres (mean thyroid weight: 133 +/- 46 g), with high thyroid uptake of RAI (mean 24 h 131I uptake: 40 +/- 15%) but not with increased urinary iodine excretion. Serum Tg levels were more elevated in the first two groups of patients (respectively, geometric means 68 and 72 ng/ml), than in the euthyroid, TRH-responsive group (52 ng/ml). Thyrotoxicosis resolved spontaneously after three to six months without the need for any specific medication. It was concluded that a relatively small and normal iodide intake due to regular consumption of iodized salt and industrialized foods may induce a transient form of thyrotoxicosis in endemic goitre patients arriving into urban areas.

Adult↗
PubMed1983

TSH secretion and regulation in endemic goiter and endemic cretinism.

In endemic goiter patients living in a chronic iodide deficiency area (less than 50ug/day) TSH basal levels and the TSH response to TRH is significantly higher (31 +/- 8uU/ml) than in normal controls (10 +/- 4uU/ml). There is a negative correlation between levels of iodine intake and serum TSH concentration and thyrotropin is thus increased when iodine decreased. Also it was shown that serum TSH levels correlate inversely with the serum concentration of T4 (r=0.69) but not with the usually normal or elevated serum concentration of T3 in endemic goiter patients. It has been postulated that in the absence of appropriate serum levels of T4 the pituitary thyrotrophs have an abnormally low T4 to T3 conversion and the pituitary-nuclear/serum T3 ratio does not increase sufficiently to compensate this phenomenon. On the other hand nuclear receptor saturation of T3 in tissues such as liver and kidney would remain at euthyroid levels due to the higher serum T3 concentrations. Endemic goiter patients when moving to an urban area where iodine intake is higher (greater than 150ug/day) than in the rural villages, had a blunted TSH response to TRH (15/23 subjects) or developed a mild clinical and laboratory picture of hyperthyroidism (7/23 individuals). Serum TSH levels and the TSH response to TRH is abnormally elevated in the myxedematous type of endemic cretinism but more than one third of the neurological goitrous cretins (euthyroid) have an exaggerated and sustained TSH response to TRH. This has been considered as a decreased thyroid reserve. Measurement of alpha subunits and TSH-beta in both types of endemic cretinism demonstrated that although these patients have a marked enlargement of the sella turcica the alpha subunits, although higher than normal (1.7-3.4 ng/ml) were not suggestive of a pituitary tumour. The pituitary enlargement was probably secondary to the long standing untreated thyroid failure.

Adult↗
PubMed1980

Triac (3,5,3'-triiodothyroacetic acid) partially inhibits the thyrotropin response to synthetic thyrotropin-releasing hormone in normal and thyroidectomized hypothyroid patients.

The effects of a daily oral dose (1.4 mg) of 3,5,3'-Triiodothyroacetic acid (Triac) on thyroid hormone levels (T4, T3 and rT3) and on the TSH and PRL responses to TRH were studied in 15 normal subjects and 5 hypothyroid patients. There were no significant changes in weight, heart rate, reflex time, or serum concentration of either cholesterol or triglycerides after 6 weeks of Triac administration. However, T4 was significantly reduced to a lower mean level (mean +/- SEM, 7.3 +/- 0.7 to 4.3 +/- 0.6 microgram/dl) in the control group. T3 and rT3 concentrations increased, possibly due to a cross-reaction with Triac in their respective RIAs. The peak TSH response to TRH in the normal subjects was 17.6 +/- 3.4 muU/ml and fell significantly to 2.0 +/- 0.8 muU/ml after Triac administration. In the hypothyroid subjects the mean serum TSH level was significantly reduced from 136 +/- 66 to 12.6, 10.5, and 11.6 muU/ml in the weeks after Triac administration. The mean peak response of both TSH and PRL after TRH (206 muU and 44.8 ng/ml, respectively) declined significantly to 63.4 muU/ml and 24 ng/ml. It was concluded that this dose of Triac partially inhibits the synthesis and secretion of TSH and PRL without any major peripheral metabolic effects.

Adult↗
PubMedDate not supplied

Serum levels of total testosterone and sex hormone binding globulin in hypothyroid patients and normal subjects treated with incremental doses of L-T4 or L-T3.

Plasma testosterone (T) and sex hormone binding globulin (SHBG) were assayed in normal controls (N = 9) and hypothyroid patients (N = 17) receiving increasing doses of L-T4 (0.2 mg, 0.4 mg for 30 days), followed first by 30 days without medication and then by 30 days each of 0.05 mg L-T3 and 0.2 mg L-T3. Normal male controls showed a significant increase in plasma T only at high doses of either L-T4 (0.4 mg) or L-T3 (0.2 mg). A small but significant increase in plasma T levels was observed in normal female subjects at 0.4 mg of T4. In both men and women, plasma SHBG increased in a dose-dependent manner with L-T4 or L-T3 and correlated positively and significantly with serum thyroid hormone levels. Hypothyroid male subjects had significantly lower levels of plasma T (mean +/- SD) of 279 +/- 131 ng/dl as compared with normal males (431 +/- 118 ng/dl), which reached the normal range only at a relatively high dose of either L-T4 (0.4 mg) or L-T3 (0.2 mg). No significant changes in plasma T were seen in the hypothyroid female group. Basal plasma SHBG levels were significantly lower in both hypothyroid men and women and increased towards normal levels during L-T4 and L-T3 therapy, although the response to thyroid hormones was significantly lower than that of normal controls. These results indicate that thyroid hormone therapy increases plasma SHBG levels in both normal and hypothyroid patients and that this increase precedes the expected elevation of plasma T in males.

Adolescent↗
PubMedDate not supplied

Decreased growth hormone (GH) response to oral clonidine in endemic cretinism: effect of L-T3 therapy.

As GH secretion is dependent upon thyroid hormone availability, the GH responses to clonidine (150 micrograms/m2) and the TSH and PRL response to TRH were studied in eight endemic (EC) cretins (3 hypothyroid, 5 with a low thyroid reserve) before and after 4 days of 100 micrograms of L-T3. Five normal controls (N) were also treated in similar conditions. Both groups presented a marked increase in serum T3 after therapy (N = 515 +/- 89 ng/dl; EC = 647 +/- 149 ng/dl) followed by a decrease in basal and peak TSH response to TRH. However, in the EC patients an increase in serum T4 levels and in basal PRL and peak PRL response to TRH after L-T3 therapy was observed. One hypothyroid EC had a markedly elevated PRL peak response to TRH (330 ng/dl). There were no significant changes in basal or peak GH values to treatment with L-T3 in normal subjects. In the EC group the mean basal plasma GH (2.3 +/- 1.9 ng/ml) significantly rose to 8.8 +/- 3.2 ng/ml and the mean peak response to clonidine (12.7 +/- 7.7 ng/ml) increased to 36.9 +/- 3.1 ng/ml after L-T3. Plasma SM-C levels significantly increased in N from 1.79 +/- 0.50 U/ml to 2.42 +/- 0.40 U/ml after L-T3 (p less than 0.01) and this latter value was significantly higher (p less than 0.05) than mean Sm-C levels attained after L-T3 in the EC group (respectively: 1.14 +/- 0.59 and 1.78 +/- 0.68 U/ml). These data indicate that in EC the impaired GH response to a central nervous system mediated stimulus, the relatively low plasma Sm-C concentrations, and the presence of clinical or subclinical hypothyroidism may contribute to the severity of growth retardation present in this syndrome.

Administration, Oral↗
PubMedDate not supplied

[Molecular biology of the genetic defects of synthesis, transport and peripheral action of the thyroid gland hormones].

Recent advances in molecular biology and the use of modern techniques made possible the identification and cloning of DNA portions of the human genome encoding proteins that are important for the synthesis, storage, transport and action of thyroid hormones. These achievements have led to the diagnosis of the basic defects at the DNA level and the understanding of the biochemical disturbance in the genetic disorders of thyroid metabolism. In patients with defective expression of thyroid peroxidase (TPO) the presence of polymorphism (RFLP) associated with Bgl-I segregates with the affected individual with goiter, hypothyroidism and positive perchlorate discharge test. Defects in the thyroglobulin are either quantitative (no Tg is synthetized) or qualitative (an abnormal Tg is expressed). Low messenger RNA codifying for Tg was present in one of the families with virtual absence of Tg in serum and thyroid tissue. In another family absence of sialic acid incorporation into the Tg molecule produced a Tg with structural defect, incapable of T3 and T4 generation. A point mutation in the nucleotide 281 of exon 5 has been claimed as the mutation producing a defective TBG. Finally, the resistance to thyroid hormone action is linked to a mutation in the c-erb-A beta, detected by the presence of a polymorphism EcoRV, that will encode a defective protein or will produce a protein that might block the T3 binding to the receptor.

Animals↗