Benefit of combined triiodothyronine (LT(3)) and thyroxine (LT(4)) treatment in athyreotic patients unresponsive to LT(4) alone.

Despite some reports, the usefulness of levothyroxine (LT(4)) and levotriiodothyronine (LT(3)) combination therapy in hypothyroidism remains controversial. The objective of this paper is to study a benefit of additional LT(3) in athyreotic patients who failed to normalize TSH on LT(4) alone even with hyperthyroid serum T(4) values. In a survey of 200 athyreotic patients treated between 2006 and 2009, about 7% failed to normalize serum TSH levels following treatment with LT(4), though serum T(4) values in the hyperthyroid range were achieved. These patients (characterized by serum T(4)≥160 nmol/L and TSH≥5.0 mIU/L), were additionally treated with 10 µg b. i. d LT(3). LT(3) and LT(4) combination therapy resulted in decreased serum TSH levels into the normal range (12.8 vs. 1.22 mIU/L; p<0.01) and reduced LT(4) dose (153.3 vs. 117.5 µg; p<0.01) required for normalization of serum T(4) values (170.6 vs. 123.3 nmol/L; p<0.01). Serum T(3) values were higher (1.3 vs. 2.26 nmol/L; p<0.01) than those during monotherapy with LT(4). Our results indicate a subpopulation of athyreotic patients that could significantly benefit from combined LT(4) + LT(3) therapy in restoring normal TSH and thyroid hormone patterns. Further research should be undertaken to provide a genetic basis for these findings.

Increased thyroidal T4 to T3 conversion in autonomously functioning thyroid adenoma: from euthyroidism to thyrotoxicosis.

AIM: The aim was to investigate whether the intrathyroid conversion of T4 to T3 in autonomously functioning thyroid adenoma (AFTA) tissue could influence serum T3 levels and suppression of TSH, especially in patients with borderline thyroid function. PATIENTS AND METHODS: In ten patients with AFTA, thyroidal conversion of T4 to T3 was investigated in nodular and paranodular, TSH-suppressed tissue. All patients had normal serum T4 and suppressed TSH. Serum T3 was normal in six, and borderline or slightly increased in four. AFTA and paranodular tissues were surgically removed and frozen at -70°C, then homogenized in a glass homogenizer, centrifuged at 100,000×g, and particulate fraction collected as a pellet. Analysis mixture consisted of thyroid enzyme suspension in 50 µmol/L TRIS buffer with 5 µmol DTT and 200 µL 1.3 µmol T4. Incubation was performed at 37°C and the generation of T3 measured after 5, 10, 20 and 40 minutes respectively. RESULTS: T3 production (pmol/mg protein) was significantly higher in AFTA than in paranodular tissues (8.8 1.2/Mean ± SE/vs. 1.8 ± 0.2; p<0.01), and excessively high (9.8, 14.1, 14.2 and 15.0) in four patients with borderline or slightly supranormal serum T3. A significant correlation was found between serum T3 concentrations and T3 generation (T4 conversion) in AFTA tissues. CONCLUSION: Results suggest that increased thyroidal T4 to T3 conversion in AFTA tissue could be involved in an increased delivery of T3, increased serum T3 and suppressed serum TSH, particularly in patients with the disease evolving from euthyroid to an early hyperthyroid phase.

Structure and expression of Xenopus karyopherin-beta3: definition of a novel synexpression group related to ribosome biogenesis.

Karyopherin-beta3 is a nuclear transport receptor that appears to be involved in nuclear import of ribosomal proteins. Here we report on sequence and expression of karyopherin-beta3 in Xenopus. The differential distribution of karyopherin-beta3 mRNA during Xenopus embryogenesis is similar to that of several other protein import factors and of ribosomal proteins. These genes thus define a novel synexpression group in the context of ribosome biogenesis.

[Children's health and their rights threatened by violence]. / A saúde e o direito da criança ameaçados pela violência.

The purpose of this study is to analyze the follow-up of police reports concerning domestic violence against children aged 0-5, from 1990 to 1995, held in the city of Rio de Janeiro. Based on a descriptive study, initially, on a database, the accusations in general were characterized. Soon after, 18 police stations were visited to analyze the follow-up of the police reports. Out of 105 occurrences, only 25 were regarded as investigatory cases and just 01 was going to be analyzed in court. In sum, violence against child reflects cultural subjects.

Characterization of a subfamily of related winged helix genes, XFD-12/12'/12" (XFLIP), during Xenopus embryogenesis.

The fork head domain family of genes defines a growing group of proteins that serve important regulatory functions in pattern-forming events of both invertebrates and vertebrates. Here we add three closely related, novel members to this family in Xenopus laevis, termed XFD-12, XFD-12' and XFD-12". All three genes reveal indistinguishable expression patterns during Xenopus embryogenesis. During gastrulation, XFD-12 type transcripts are detected exclusively in the superficial layer of cells within the Spemann organizer territory. In the open neural plate, XFD-12 type expression defines a row of cells located along the dorsal midline and destined to become the floor plate of the neural tube. After closure of the neural tube, XFD-12 type encoding mRNAs are only detected in the tailtip and a small area located at the midbrain/hindbrain boundary. Within the Spemann organizer and in the floor plate area, expression of XFD-12 type genes is only partially overlapping with XFD-1 expression.

Exogenous and endogenous suppression of thyroid-stimulating hormone induces similar effects on thyroidal iodothyronines.

Thyroidal concentrations of T4 and T3 and the T4/T3 ratio were analyzed in the nodular and paranodular tissues from two groups of patients with suppressed TSH secretion. The first group consisted of 17 patients with nontoxic nodular goitre (NG), 8 of whom received long-term levothyroxine therapy to suppress TSH, while remaining 9 were untreated. The second group consisted of 10 patients with autonomously functioning thyroid adenoma (AFTA), in whom TSH secretion was suppressed due to the adenoma-induced increase in thyroid hormone concentrations. In nodular tissues of NG patients, thyroidal T4 and the T4/T3 ratio were significantly higher in treated than in untreated patients (0.34 +/- 0.05 vs. 0.15 +/- 0.02 mol T4/mol of thyroglobulin (Tg) and 10.9 +/- 1.2 vs. 5.2 +/- 0.7 respectively). Analysis of paranodular tissues of NG patients also revealed a higher T4/T3 ratio in treated patients (16.0 +/- 2.1 vs. 6.9 +/- 0.9), although thyroidal T3 and T4 concentrations in treated and untreated patients were similar. In AFTA patients, both T3 and T4 concentrations were higher in the adenoma than in paranodular tissues (0.14 +/- 0.04 vs. 0.02 +/- 0.005 mol T3/mol Tg and 1.08 +/- 0.32 vs. 0.26 +/- 0.06 mol T4/mol Tg), whereas the T4/T3 ratio was significantly higher in paranodular tissues (23.2 +/- 5.9 vs. 9.3 +/- 1.8). These results indicate that suppression of TSH induced either exogenously or endogenously results in an increase in the thyroidal T4/T3 ratio that reflects an increase in T4 and/or a decrease in T3 concentrations. These findings also support the notion that TSH preferentially stimulates thyroidal T3 production.

Thyroid hormone economy in response to extreme cold exposure in healthy factory workers.

The effects of cold exposure on serum total T4 (TT4), total T3 (TT3), free T4 (FT4), free T3 (FT3), rT3, TSH, T4-binding globulin (TBG), and T3 resin uptake were investigated in 82 euthyroid factory workers. Twenty-five workers (group 1) were exposed intermittently (approximately 3.5 h daily) to extreme cold (-40 to -20 C) during the 8-h work shift, and 47 (group 2) were exposed to moderate cold (-10 to 8 C) for the entire 8 h. Ten individuals working at room temperature for the same period also were studied. After cold exposure, serum TT4 decreased in group 1 and did not change in group 2, whereas FT4 did not change in group 1 and increased in group 2. After exposure, serum TT3 and rT3 decreased significantly in both groups, while FT3 did not change in either. The basal serum TT4 levels in groups 1 and 2 were significantly lower than those in the control group, whereas those of FT4 and FT3 were higher. Thus, cold exposure had opposite effects on total thyroid hormones and their free fractions, consistent with a cold-induced decrease in thyroid hormone-binding capacity. A postexposure decrease in serum TBG was found in women in group 2, but not in men in either group 2 or group 1, suggesting that factors other than decreased TBG are also involved. The results suggest the possibilities that 1) decreased thyroid hormone-binding capacity is an adaptive response to cold exposure, and/or 2) increased free thyroid hormone levels in response to cold exposure result in a new higher equilibrium between extracellular and intracellular FT4 and FT3.

Relationship between T4, T3 and T4/T3 ratio in thyroid tissue, thyroid and peripheral veins in patients with nontoxic nodular goiter.

The relationship between T4, T3 and T4/T3 ratio in thyroid nodules/paranodular tissues, thyroid and peripheral veins has been investigated in 26 patients with nontoxic nodular goiters; eleven of them were treated with l-thyroxine 150 micrograms daily. A significant correlation between iodothyronine concentrations and T4/T3 [corrected] ratio in paranodular thyroid tissues and thyroid effluents was found in both groups of patients. By contrast, the correlation between these parameters in the nodule and thyroid veins was poor, which implies that the thyroid hormone pattern in the thyroid veins on the side of nodular lesion is predominantly controlled by the release of the hormones from paranodular healthy tissue. A close dependence of the serum T4/T3 ratio on the values of iodothyronines and their ratio in thyroid tissues and thyroid veins was observed in nontreated, but not in treated patients. Conversely, in the latter group, the thyroidal T4/T3 ratio in paranodular tissue, but not in the nodule, was found to be dependent on the serum T4/T3 ratio, suggesting that paranodular thyroid tissue more readily responds to 1-thyroxine-inhibited TSH secretion. The results demonstrate that 1. the serum thyroid hormone pattern under physiological conditions is dependent on the intrathyroidal T4/T3 ratio, and 2. minor alterations in the serum thyroid hormones may secondarily change the thyroidal T4/T3 ratio, presumably by their effect on TSH secretion.

Daily iodine intake in healthy children and adults and in goitrous patients in nonendemic Yugoslav area.

Daily iodine intake has been investigated in 52 healthy children (5-14 years), 112 healthy adults and in 39 patients with nontoxic goiter from the area of Zagreb/Yugoslavia. Fourteen goitrous patients received 1-thyroxine 150 micrograms daily for at least three months before the examination. Iodine intake has been estimated on the basis of urinary iodine excretion (microgram I-/g creatinine) in the first morning specimen. Iodine excretion in nontreated goitrous patients (92 +/- 30; Mean +/- SD) was significantly lower than in healthy adults (112 +/- 38), while the value in treated goitrous patients (165 +/- 69) was significantly higher than that in nontreated goitrous and healthy adult subjects. The results suggest that Zagreb area, although classified as nonendemic, has borderline iodine intake, and that relative iodine deficiency is of importance in goiter formation. The authors plead for increased daily iodine intake through increased table salt iodisation from actual amount of 10 to 20 to 25 mg KI/kg salt in order to provide an average daily intake of 250 micrograms of iodine.

Similar concentrations of thyroidal iodothyronines and T3/T4 ratio in normal thyroids from two Yugoslav districts with different iodine intake.

In spite of different daily iodine intake in two yugoslav districts (littoral-Split 297 +/- 76 (Mean +/- SD) and continental-Zagreb 111 +/- 36 micrograms/g creatinine, p less than 0.001), thyroidal iodothyronine concentrations and T4/T3 ratio in normal post mortem thyroids were comparable. T4 was 260.0 +/- 42.6 micrograms/g w.w. (Mean +/- SE) in Split group vrs. 279.9 +/- 59.4 in Zagreb. T3 was 12.8-2.0 vrs. 12.8 +/- 2.2 and T4/T3 ratio 21.6 +/- 1.9 vrs. 21.1 +/- 2.9 in Split and Zagreb, respectively. It has been concluded that relatively small difference in iodine intake has no effect on thyroidal concentrations of iodothyronines and T4/T3 ratio.

The urinary iodide excretion in subjects on different diets.

The urinary iodide excretion in hospital subjects on regular and different restrictive diets was investigated. In subjects on a regular diet the average urinary iodide (microgram I-/g creatinine; mean +/- SD) was 104.7 +/- 36.7. In subjects on a low caloric diet the urinary iodide content was 101.1 +/- 24.2; in subjects starving for weight-reduction the mean value was 63.2 +/- 23.9, significantly different from the controls (p less than 0.005). In subjects on a high-caloric diet the urinary iodide was 145 +/- 45.4, in those on a hepatoprotective diet 96.8 +/- 18.8, respectively. The iodide excretion in subjects on an ulcer-protective diet was on the average 76.4 +/- 22.3 which was significantly different from those on a regular diet (p less than 0.01).

Increased thyroidal T4/T3 ratio in nodular and paranodular tissues of nontoxic goiter following suppressive treatment with thyroid hormones.

The effect of suppressive treatment with thyroid hormones on thyroidal iodothyronines and T4/T3 ratio in nodular and paranodular tissues was investigated in 12 patients with nontoxic goiter. Results were compared to those from 11 nontreated patients. Continuous thyroid hormone administration produced a significant increase in thyroidal T4 and T4/T3 ratio in nodular tissues while T3 remained unchanged. In paranodular tissues a significant rise of T4/T3 ratio, an insignificant increase in T4 and a decrease in T3 were observed following the administration of thyroid hormones. The results are very similar to those obtained in paranodular tissue of autonomously functioning thyroid nodule, and are probably the consequence of suppressed TSH secretion, as TSH predominantly stimulates the synthesis of T3 and/or thyroidal T4 monodeiodination.

Thyroidal thyroxine and triiodothyronine in autonomously functioning thyroid nodule and paranodular tissue.

Thyroidal thyroxine (T4), triiodothyronine (T3), thyroglobulin (Tg) and T4/T3 ratio were investigated in nodular and paranodular tissue from 16 patients with autonomously functioning thyroid adenomas. The concentration of T4 and T3 in the nodule were 97.7 +/- 20.5 (Mean +/- SE) and 10.2 +/- 2.4 micrograms/g wet weight (w.w.). Both iodothyronines were significantly lower in paranodular tissue (22.6 +/- 4.8 and 1.45 +/- 0.32 micrograms/g w.w., respectively), but with disproportionately decreased T3 which resulted in T4/T3 ratio (25.4 +/- 6.4) higher than in adenoma tissue (11.2 +/- 1.6). In patients with high normal or supranormal serum T3 concentration, thyroidal concentration of T3 in adenoma tissue was higher (15.6 +/- 5.0 vs. 6.3 +/- 1.2 micrograms/g w.w.) and T4/T3 ratio lower (8.05 +/- 2.1 vs. 13.2 +/- 1.9) than in patients with normal serum T3. The results suggest that thyroid release of T3 from adenoma is relatively higher than T4 in patients with autonomously functioning thyroid nodules and increased peripheral T3.