Indices of thyroid function were measured in 229 healthy term neonates at birth and at 5, 10, and 15 days of age. Results were analysed to assess whether maternal diabetes mellitus, toxaemia of pregnancy, intrapartum fetal distress, duration of labour, method of delivery, asphyxia at birth, race, sex, birthweight, birth length, head circumference, or method of feeding influenced any index. Thyroxine, the free thyroxine index, and free thyroxine concentrations at birth correlated with birthweight. Method of delivery influenced mean thyroxine and free thyroxine index values at birth and at age 5 days. Mean values of triiodothyronine, reverse triiodothyronine, thyroxine binding globulin, and thyroid stimulating hormone were not affected by any of the perinatal factors studied. Birthweight and perhaps method of delivery should be taken into account when interpreting neonatal thyroxine parameters but determination of thyroid stimulating hormone as a screen for congenital hypothyroidism in healthy term neonates circumvents these considerations.

For hormonal deficiency caused by endocrine organ diseases, continuous oral hormone administration is indispensable to supplement the shortage of hormones. In this study, as a more effective therapy, we have tried to reconstruct the three-dimensional thyroid tissue by the cell sheet technology, a novel tissue engineering approach. The cell suspension obtained from rat thyroid gland was cultured on temperature-responsive culture dishes, from which confluent cells detach as a cell sheet simply by reducing temperature without any enzymatic treatment. The 8-week-old Lewis rats were exposed to total thyroidectomy as hypothyroidism models and received thyroid cell sheet transplantation 1 week after total thyroidectomy. Serum levels of free triiodothyronine (fT(3)) and free thyroxine (fT(4)) significantly decreased 1 week after total thyroidectomy. On the other hand, transplantation of the thyroid cell sheets was able to restore the thyroid function 1 week after the cell sheet transplantation, and improvement was maintained for 4 weeks. Moreover, morphological analyses showed typical thyroid follicle organization, and anti-thyroid-transcription-factor-1 antibody staining demonstrated the presence of follicle epithelial cells. The presence of functional microvessels was also detected within the engineered thyroid tissues. In conclusion, our results indicate that thyroid cell sheets transplanted in a model of total thyroidectomy can reorganize histologically to resemble a typical thyroid gland and restore thyroid function in vivo. In this study, we are the first to confirm that engineered thyroid tissue can repair hypothyroidism models in rats and, therefore, cell sheet transplantation of endocrine organs may be suitable for the therapy of hormonal deficiency.

Glial cells were isolated from 1-week-old rat brain and cultured in a serum-free medium supplemented with the hormones insulin, hydrocortisone, and triiodothyronine. After 1 week in culture the cell population consisted mainly of galactocerebroside-positive cells (GC+; oligodendrocytes), the remainder of the cells being positive for glial fibrillary acidic protein (GFAP+; astrocytes). Oligodendrocytes were selectively removed from the cultures by complement-mediated cytolysis. The activities of glutamine synthetase and of various marker enzymes were measured in the nonlysed cells remaining after complement treatment of the cultures and in the culture medium containing proteins of the lysed cells. We found that the cellular activity of glutamine synthetase decreased in parallel with the lysis of GC+ cells and that the activity of glutamine synthetase in the supernatant increased. The activity of glycerol-3-phosphate dehydrogenase, a marker enzyme for oligodendrocytes, was no longer detectable in complement-treated cultures and the activity of glutamine synthetase was markedly lowered, whereas the activity of lactate dehydrogenase was as high as in untreated cultures. The location of glutamine synthetase both in oligodendrocytes and in astrocytes was confirmed by double-label immunocytochemistry with antisera against glutamine synthetase, GC, and GFAP. We conclude that in this culture system glutamine synthetase is expressed in both types of glial cells and that the activity of lactate dehydrogenase is at least one order of magnitude higher in astrocytes than in oligodendrocytes.

Graves' disease (GD) is one of the most common thyroid diseases that cause hyperthyroidism. Gestational transient thyrotoxicosis (GTT) is nonautoimmune hyperthyroidism that occurs in women with a normal pregnancy. Postpartum transient thyroiditis (PTT) is a destructive thyroiditis induced by autoimmune mechanism in the postpartum period. Hyperthyroidism due to GD usually tends to improve during the course of gestation and exacerbate after delivery. When the patient with treated GD presents with thyrotoxicosis in the early pregnancy or in the postpartum period, differential diagnosis of exacerbation of GD with GTT or PTT is important because the latter disorders are fundamentally transient. To evaluate the incidence of GTT and PTT in a GD population, we investigated the thyroid functions, thyrotropin receptor antibodies (TRAb), and human chorionic gonadotropin (hCG) during pregnancy and for 1 year after delivery for 39 pregnancies in 34 women with GD. The incidence of GTT was 26% (10/39) of pregnancies. The peak value of hCG in the GTT group ([23.7 +/- 14.5] x 10(4) IU/mL, n = 9) was significantly higher than that in the non-GTT group ([13.3 +/- 4.7] x 10(4) IU/mL, n = 19). The incidence of PTT was 44% (17/39) of deliveries. The free triiodothyronine (FT(3))/free thyroxine (FT(4)) ratio of the exacerbation group of GD (3.1 +/- 1.0, n = 10) at the time of thyrotoxicosis after delivery was significantly higher than that of the PTT group (2.5 +/- 0.4, n = 16). The peak TRAb value of the exacerbation group of GD (72.5 +/- 121.7 IU/L, n = 10) at the time of thyrotoxicosis after delivery was also significantly higher than that of the PTT group (1.4 +/- 0.8 IU/L, n = 16). In conclusion, the high peak value of hCG is valuable for suspecting GTT, and the high FT(3)/FT(4) ratio is valuable for suspecting recurrence in the patients with GD. In both situations, changes of TRAb were also valuable in differentiating the recurrence of GD from GTT or PTT.

BACKGROUND

The impact of subclinical hyperthyroidism (sHT) on the cardiovascular system still needs to be elucidated. The aim of the study was to prospectively assess blood pressure (BP), variability in heart rate, and the prevalence of arrhythmias in patients with sHT, both before and after they are restored to the euthyroid state.

METHODS

The study group consisted of 44 normotensive patients (37 women, 7 men), aged 22-65 years (mean±SD: 45.9±11.0) with sHT. Enrolled patients were drawn from 1080 patients referred to our department for treatment of hyperthyroidism. Study patients were treated with radioiodine treatment to restore the euthyroid state. Ambulatory BP monitoring and Holter electrocardiography were performed (i) when sHT was diagnosed and (ii) at least 6 months after they became euthyroid.

RESULTS

sHT in comparison to the euthyroid state was associated with higher (109.3±7.1 vs. 107.1±7.7 mmHg) nocturnal systolic mean BP (p=0.035) and BP load (14.8 vs. 10.2%, p=0.033), mean diastolic BP (66.4±6.6 vs. 64.8±6.6 mmHg, p=0.047), and mean arterial pressure (80.8±43.1 vs. 79.3±43.6 mmHg, p=0.049). Moreover, significant changes in both the time and frequency domain measures of heart rate variability (HRV) were observed: decrease of the square root of the mean squared differences of successive NN intervals (rMSSD) (45.68±34.1 vs. 65.09±50.6 ms, p=0.03) and the low frequency power (LF) (5.71±0.99 vs. 6.0±1.01 ms(2), p=0.049) as well as increase of QT interval dispersion (58.25±28.5 vs. 46.90±12.1 ms, p=0.020). This was accompanied by a clinically insignificant increase in the frequency of ventricular extrasystoles (VES) (3.1±7.4 vs. 0.6±1.2 per hour, p=0.048) and increased mean heart rate (78.4±6.8 vs. 76.0±8.0 beats/min, p=0.004). Some of the parameters correlated positively with thyroid hormones: nocturnal diastolic BP with free triiodothyronine (FT(3)) (r=0.397, p=0.008), rMSSD with free thyroxine (FT(4)) (r=0.389, p=0.013), and QT interval dispersion with FT(4) (r=0.450, p=0.004).

CONCLUSIONS

The study suggests that sHT in comparison to euthyroid status may be associated with a statistically significant but probably clinically insignificant increase of QT interval dispersion, prevalence of VES, elevated nocturnal arterial BP, and changes in HRV. These findings broaden our understanding of the cardiovascular effects of sHT.

The causes of hyperprolactinemia, the correlation between serum levels of PRL and thyroid function and magnetic resonance imaging (MRI) of the pituitary were studied in patients with chronic thyroiditis. Seventy-four female patients and 15 normal control women participated in this clinical survey. Fourteen of 74 patients with various thyroid conditions had increased serum PRL. The incidence of hyperprolactinemia in the overt primary hypothyroid group was 42.4% and was significantly higher than in any other group with normal serum thyroxine. There was a close association between the increment in serum PRL and of free triiodothyronine above the basal level after TRH administration. There were 14 patients with hyperprolactinemia in three of which serum PRL was over 60 micrograms/L. PRL producing tumor, severe primary hypothyroidism and liver cirrhosis were detected in these three patients, respectively. These results indicate that the pathogenesis of increased serum PRL was not uniform in patients with Hashimoto's thyroiditis, although there was a correlation between hyperprolactinemia and impaired thyroid function. It is proposed, therefore, to measure and follow serum levels of PRL and MRI of the pituitary in patients with chronic thyroiditis, especially with impaired thyroid function.

OBJECTIVE

This study was undertaken to evaluate the effect of triiodothyronine replacement on the early postoperative course of neonates undergoing aortic arch reconstruction.

METHODS

We performed a randomized, double-blind, placebo-controlled trial of triiodothyronine supplementation in neonates undergoing either a Norwood procedure or two-ventricle repair of interrupted aortic arch and ventricular septal defect. Patients were assigned to receive a continuous infusion of triiodothyronine (0.05 micro/kg/h) or placebo for 72 hours after cardiopulmonary bypass. Primary end points were a composite clinical outcome score and cardiac index at 48 postoperative hours.

RESULTS

We enrolled 42 patients (triiodothyronine n = 22, placebo n = 20). Baseline characteristics were similar in the treatment groups. Study drug was discontinued prematurely because of hypertension (n = 1) and ectopic atrial tachycardia (n = 1), both cases in the triiodothyronine group. Free and total triiodothyronine levels were higher in the triiodothyronine group than in the placebo group at 24, 48, and 72 postoperative hours (P < .001). The median clinical outcome scores were 2.0 (range 0-4) with triiodothyronine and 2.0 (range 0-7) with placebo (P = .046). Compared with those in the placebo group, neonates assigned to triiodothyronine had shorter median time to negative fluid balance (2.0 vs 2.5 days, P = .027). Cardiac index values were 2.11 +/- 0.64 L/min x m2 with triiodothyronine and 2.05 +/- 0.72 L/min x m2 with placebo (P = .81). Heart rate and diastolic blood pressure were not influenced by triiodothyronine supplementation, but systolic blood pressure was higher in the triiodothyronine group (P < .001). No serious adverse events were attributed to triiodothyronine administration.

CONCLUSIONS

Triiodothyronine supplementation was safe and resulted in more rapid achievement of negative fluid balance after aortic arch reconstruction. Cardiac index at 48 hours was not significantly improved.

Selenium (Se) is an essential trace element for animals and humans. Its biological role was established following the discovery that Se is a structural component of the active center of the enzyme glutathione peroxidase (GSH-Px). During the last decade remarkable progress has been made in the recognition of the structure and function of several selenoproteins. Cellular GSH-Px was the first enzyme recognized as a selenoprotein. In it Se was found in the form of selenocysteine. The enzyme is a tetrameric protein and is composed of four apparently identical subunits each containing one gram atom of Se. Plasma GSH-Px also has a tetrameric form with identical subunits and with one atom of Se per subunit. It is, however, a glycosylated protein, and is distinct from cellular enzyme. Both enzymes catalyze the reduction of hydrogen peroxide and a variety of organic hydroperoxides by glutathione. A third GSH-Px, called phospholipid hydroperoxide glutathione peroxidase (PHGSH-Px), is a monomeric, membrane-associated enzyme containing one atom of Se per mole of protein. This enzyme destroys esterified lipid hydroperoxides. The fourth known mammalian selenoenzyme is a type I iodothyronine 5'-deiodinase that catalyzes the deiodination of L-thyroxine to the biologically active hormone 3,3',5-triiodothyronine. It is a monomeric enzyme and contains one atom of Se per mole of protein. Selenoprotein P, a fifth known selenoprotein, is a glycosylated, monomeric protein containing ten atoms of Se per molecule. The function of this protein is not known, but it may play a role in Se transport or be connected with a protective activity against free radicals. In all these selenoproteins the Se is incorporated into the protein molecule via the selenocysteinyl-tRNA which recognizes the specific UGA codons in mRNAs to insert selenocysteine into the primary structure of selenoproteins.

Thyroid hormones influence growth and differentiation of bone cells. In vivo and in vitro data indicate their importance for development and maintenance of the skeleton. Triiodothyronine (T3) inhibits proliferation and accelerates differentiation of osteoblasts. We studied the regulatory effect of T3 on markers of proliferation as well as on specific markers of the osteoblastic phenotype in cultured MC3T3-E1 cells at different time points. In parallel to the inhibitory effect on proliferation, T3 down-regulated histone H4 mRNA expression. Early genes (c-fos/c-jun) are highly expressed in proliferating cells and are down-regulated when the cells switch to differentiation. When MC3T3-E1 cells are cultured under serum-free conditions, basal c-fos/c-jun expressions are nearly undetectable. Under these conditions, c-fos/c-jun mRNAs can be stimulated by EGF, the effect of which is attenuated to about 46% by T3. In addition, T3 stimulated the expression at the mRNA and protein level of osteocalcin, a marker of mature osteoblasts and alkaline phosphatase activity. All these effects were more pronounced when cells were cultured for more than 6 days. These data indicate that T3 acts as a differentiation factor in osteoblasts by influencing the expression of cell cycle-regulated, of cell growth-regulated, and of phenotypic genes.

We tested the ability of a serum-free medium containing insulin, transferrin, 17 beta-estradiol, dexamethasone, triiodothyronine, prostaglandin F2 alpha, and fibronectin (HBCA medium) to support the continuous growth and passage of five human breast carcinoma cell lines on a collagen matrix. Doubling times of the cell lines (20 to 44 hr) were similar in HBCA and serum-supplemented media. The gross morphology of the cell lines was not altered in the serum-free medium. Insulin, transferrin, and the collagen matrix were the most essential factors required for optimal growth of the cell lines. Estradiol appeared to stimulate the growth of cell lines, both with and without estrogen receptors. HBCA medium supplemented with low concentrations of bovine serum albumin, Fraction V (0.5%, v/v), supported the clonal growth of three cell lines in soft agarose with colony-forming efficiencies superior to that observed with standard serum-supplemented medium. Deleting estradiol from HBCA medium reduced the colony-forming efficiency of the three cell lines. HBCA medium may be useful in studying hormonal regulation and improving the in vitro growth of human breast cancer.

BACKGROUND

Familial dysalbuminemic hyperthyroxinemia (FDH) is a common cause of euthyroid hyperthyroxinemia. Clinical recognition of FDH is crucial for preventing unnecessary therapy in clinically euthyroid patients with abnormal thyroid function tests. Our goal was to identify the cause of abnormal serum tests of thyroid function in a Canadian family of Bangladeshi extraction.

METHODS

The proposita was found to have elevated free thyroxine (fT4) and free triiodothyronine (fT3) with nonsuppressed thyrotropin (TSH) on screening blood work. After detailed studies excluding hyperthyroidism and resistance to thyroid hormone, blood was obtained from all members of her immediate family for further investigation.

METHODS

We conducted laboratory analyses and sequencing of candidate genes.

RESULTS

Two members of this family have FDH, caused by a not previously identified mutation in the albumin gene. This mutation, located in exon 7 of the gene (652A>C), produces a single amino acid substitution in the protein molecule (R218S). The mutant albumin is associated with a ninefold increase in serum total T4 and a twofold increase in serum total reverse T3 compared to patients with normal albumin. Modeling data for the R218S variant are compatible with the increased binding affinity of this variant albumin for T4.

CONCLUSIONS

The R218S substitution reported here causes FDH that, in terms of the magnitude of serum iodothyronine elevation, is intermediate to the two previously reported mutations at codon 218 FDH: R218H being more mild and R218P more severe.

The transport of [(125)I]thyroxine (T(4)) and [(125)I]triiodothyronine (T(3)) into liver was investigated with a tissue sampling-portal vein injection technique in the anesthetized rat. The method allows the investigation of the effects of plasma proteins in human serum on the unidirectional influx of T(4) or T(3) into liver cells. The percent extraction of unidirectional clearance of T(3) and T(4) was 77+/-2% and 43+/-2%, respectively, after portal injection of a bolus of Ringer's solution. Cell membrane transport of T(4) or T(3) was nonsaturable because 50-muM concentrations of unlabeled hormone had no effect on transport. The addition of bovine albumin in concentrations of 1, 5, or 10 g/100 ml bound >98% of T(4) or T(3) in vitro, but had no significant effect on T(3) or T(4) transport in vivo. Conversely, 10% rabbit antisera specific for T(3) or T(4), completely abolished the intracellular distribution of thyroid hormone into liver. In the presence of rat serum, which contains albumin and thyroid hormone binding pre-albumin (TBPA), 18 and 81% of total plasma T(4) and T(3), respectively, were available for transport in vivo. The fraction of hormone available for transport in the presence of normal human serum, which contains albumin, TBPA, and thyroid hormone binding globulin (TBG) was 11% for T(4) and 72% for T(3). The fraction of hormone transported into liver after injection of serum obtained from pregnant or birth control pilltreated volunteers was 4% for T(4) (but this was not significantly different from zero) and 54% for T(3). THESE DATA SUGGEST: (a) The mechanism by which T(4) and T(3) traverse the liver cell membrane is probably free diffusion. (b) Albumin-bound T(4) or T(3) is freely cleared by liver, approximately 50% of TBG-bound T(3) is transported, but little, if any, of TBPA-bound T(4) or TBG-bound T(4) is cleared by liver cells. (c) Although the albumin-bound fraction of T(4) greatly exceeds the free (dialyzable) moiety, the two fractions are both inversely related to the existing TBA or TBG level; therefore, in vitro measurements of free T(4) would be expected to accurately reflect what is available for transport in vivo. Conversely, TBG-bound T(3) is readily transported in vivo; therefore, it is proposed that in vitro measurements of free T(3) do not reliably predict the fraction of T(3) available for transport into liver in vivo.

Isolated proximal tubular (PT) and distal tubular (DT) cells from rat kidney were cultured for up to 9 days under serum-free, hormonally-defined conditions on 35-mm polystyrene culture dishes. Several hormonal and growth factor supplements were assessed for their ability to promote growth (increased protein and DNA content) and stability of differentiated phenotype (high activities of gamma-glutamyltransferase and alkaline phosphatase as brush-border membrane markers in PT cells; maintenance of high activities of glutamate dehydrogenase as a mitochondrial marker in both PT and DT cells; maintenance of low and high activities of lactate dehydrogenase in PT and DT cells, respectively; expression of cytokeratins). Basal supplemented media (DMEM/F12, 1:1 v/v) contained insulin, hydrocortisone, epidermal growth factor, sodium selenite and transferrin as supplements. Additionally, triiodothyronine selectively promoted growth and stability of differentiated phenotype in PT cells and thyrocalcitonin selectively promoted growth and stability of differentiated phenotype in DT cells. On Day 3 of primary culture, PT and DT cells were incubated for up to 8 h with either tert-butyl hydroperoxide (tBH; 0.5-10 mM), methyl vinyl ketone (MVK; 1-10 mM), or p-aminophenol (PAP; 1-10 mM) and cellular injury, as assessed by cellular release of lactate dehydrogenase, was determined. DT cells were significantly more susceptible to injury from both tBH and MVK, but the two cell populations were equally susceptible to injury from PAP, which is the same susceptibility pattern seen in freshly isolated cells. These results suggest that primary cultures of rat renal PT and DT cells reflect similar biochemical properties as freshly isolated cells and are, therefore, useful models for study of chemically induced injury.

In euthyroid rats fed a high carbohydrate fat-free diet for 10 days, the mass of cellular malic enzyme mRNA in liver is increased 7- to 8-fold above the basal level. Malic enzyme activity is stimulated to the same extent. This effect does not result from an increase either in the transcriptional activity of the malic enzyme gene, as determined by nuclear run-off transcription assay, or in the content of intranuclear malic enzyme RNA sequences. Mathematical modeling shows that this increase in cytoplasmic mRNA is compatible with retarded degradation of cytoplasmic mRNA. Regulation of malic enzyme by carbohydrates is liver-specific, since no response is observed in the following nonhepatic tissues: brain, heart, spleen, kidney, testis, and lung. Furthermore, the amplitude of the response in liver depends on the thyroid state of the animals, being lower (by a factor of approximately 4) in hypothyroidism and higher (12- to 15-fold) when normal animals are injected simultaneously with a daily dose of 15 micrograms of triiodothyronine per 100 g of body weight for 10 days. Since thyroid hormones regulate liver malic enzyme synthesis predominantly at the nuclear level and carbohydrates at the cytoplasmic level, the additive effect of triiodothyronine and a high carbohydrate diet on the activity of malic enzyme is readily explicable.

The recommendations for the dietary allowance of iodine are 150 micrograms per day for adolescents and adults. Thyrotropin (TSH) and thyroglobulin (Tg) can be used as surveillance indicators for assessing iodine deficiency disorders. We compared the relation between TSH and Tg, free triiodothyronine, and thyroxine serum levels with urinary iodine excretion in 2311 untreated euthyroid patients using our modified cericarsenite method. An adequate iodine intake may be assumed when TSH and Tg values are at the lower end of the normal range. Patients were grouped according to urinary iodine excretion and goiter size. In the group with an iodine excretion between 201 and 300 micrograms of iodine per gram of creatinine, the lowest TSH values and even low Tg levels could be shown. We conclude that an iodine intake of approximately 250 micrograms/day is associated with the lowest TSH stimulation to thyrocytes. In the groups separated according to thyroid size, significantly higher Tg levels were found in the patients with uninodular and multinodular goiter as a result of longstanding iodine deficiency, whereas actual urinary iodine excretion did not differ significantly. Additionally, iodine excretion of 39,913 euthyroid patients between 1984 was 1996 was examined. In Austria iodized salt (10 mg KI/kg) was introduced by law in 1963 and increased to 20 mg KI/kg salt in 1990. An initial increase of iodine excretion until 1993 was followed by a decrease in 1994 and 1995 without further changes in 1996. These results show that iodine intake has improved since 1984; however, in 1996 iodine excretion in one-third of the investigated patients was under 100 micrograms per gram of creatinine and more than 80% had less than 200 micrograms per gram of creatinine.

We evaluated the incidence of thyroid cancer in patients with adenomatous goiter and investigated the clinical factors distinguishing patients with occult thyroid cancer, defined as a tumor size smaller than or equal to 10 mm, from those with clinical thyroid cancer, defined as a tumor size larger than 10 mm. Of 835 patients with histologically confirmed adenomatous goiter, 256 (30.7%) also had thyroid cancer, being occult in 137 patients and clinical in 119 patients. There was no correlation between the maximum size of the thyroid cancer tumor and the age of the patient, and the percentage of patients with thyroid cancer in each group was not influenced by age. There were no significant differences in age, sex, the serum concentrations of free triiodothyronine, free thyroxine, thyrotropin, and thyroglobulin, or the urinary iodine creatinine ratio. The frequency of calcified lesions being detected by ultrasonography (US) and/or neck X-ray in the patients with clinical thyroid cancer was significantly greater than that in those with occult cancer at 83% vs 57%, respectively (P < 0.0001). This study disclosed a high prevalence of thyroid cancer associated with adenomatous goiter, and the results suggest that a considerable number of associated carcinomas remain occult. The detection of calcification in the thyroid gland is one of the surgical indications for patients with adenomatous goiter.

OBJECTIVE

Hypothyroidism is associated with changes in appetite and body weight. Ghrelin is an orexigenic peptide, and it stimulates appetite and increases food intake. However, the potential relationship between circulating ghrelin levels, hypothyroidism, and thyroid antibodies has not been adequately studied.

METHODS

Forty-seven patients with hypothyroidism due to Hashimoto's thyroiditis and 48 euthyroid subjects were enrolled in the study. Thyroid hormones and antibodies, insulin, glucose, ghrelin levels, and lipid parameters were measured in all the subjects.

RESULTS

Hypothyroid group showed significantly decreased serum levels of ghrelin and ghrelin=body mass index (BMI) compared to euthyroid group (31.9 +/- 21.5 pg/mL vs. 50.5 +/- 34.8 pg/mL, p < 0.001; and 1.24 +/- 0.93 vs. 2.12 +/- 1.53, p < 0.0001). In hypothyroid group, 6 months after treatment, ghrelin levels and ghrelin/BMI remained lower than euthyroid group (33.2 +/- 21.1 pg/mL vs. 50.5 +/- 34.8 pg/mL, p < 0.001; and 1.27 +/- 0.86 vs. 2.12 +/- 1.53, p < 0.0001). Ghrelin levels were decreased in hypothyroid patients with high thyroid peroxidase antibody (TPOAb) titre compared to hypothyroid patients with low TPOAb titre (19.1 +/- 23.1 pg/ mL vs. 35.3 +/- 17.4 pg/mL, p < 0.01). Ghrelin levels correlated positively with free triiodothyronine (FT3) and free thyroxine (FT4), and negatively with age, thyroglobulin antibody (TAb), TPOAb, total cholesterol (T-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TG) in hypothyroid group. In euthyroid group, circulating ghrelin levels correlated negatively with age, FT3, FT4, TG, and VLDL-C levels. No significant correlation was observed between ghrelin and homeostasis model assessment for insulin resistance (HOMA-IR) and between ghrelin and quantitative insulin sensitivity check index (QUICKI) in both groups. Regression analysis revealed that FT3 level is the most important predictor of ghrelin levels.

CONCLUSIONS

Thyroid hormones and antibodies seem to have a potential effect on serum ghrelin levels in patients with hypothyroidism.

OBJECTIVE

To evaluate the relationship between serum total testosterone (TT) level and lipid profile after adjusting for some traditional confounding factors, free thyroid hormones and TSH in Chinese men.

METHODS

This was a retrospective study based on an epidemiological investigation including 11 000 subjects. Bivariate and partial correlation analysis, multiple linear regression analysis, and a general linear model were used to assess the influence of TT on the lipid profile. Additionally, the odds ratios (ORs) (95% CIs) for hypertriglyceridemia and low HDL-C in relation to TT categories were calculated using logistic regression analysis.

RESULTS

A total of 4114 subjects whose mean age was 56.04±8.75 years were finally analyzed. There was a significant linear trend toward lower total cholesterol (TC), lower triglycerides (TG), and higher HDL-C with increasing serum TT, which remained significant after adjusting for age, BMI, fasting blood glucose, systolic blood pressure, free triiodothyronine, free thyroxine, and TSH. Compared with the bottom quartile of TT, the adjusted OR (95% CI) for hypertriglyceridemia and low HDL-C was 0.082 (0.048-0.138, P=0.000) and 0.669 (0.503-0.891, P=0.006) respectively in the top quartile of TT.

CONCLUSIONS

TT was correlated negatively and linearly with TC, TG, and LDL-C and positively and linearly with HDL-C. Low TT might have adverse effects on the lipid profile and thus represent a risk factor for hypercholesterolemia, hypertriglyceridemia, high LDL-C, and low HDL-C, suggesting the importance of maintaining an appropriate TT level in men.

Thyroid hormone-responsive tissues contain chromatin "receptor" proteins that are concentrated in chromatin subfractions enriched in DNA. These receptors appear to be DNA-binding proteins. In the present study, we utilized a DNA-cellulose binding assay to further examine the interactions of solubilized receptors with DNA. [125I]Triiodothyronine associates with receptors bound to DNA-cellulose, whereas free [I]triiodothyronine and [125I]triiodothyronine associated with other proteins does not. The DNA-receptor interactions appear to be strong enough to exist at physiological ionic strength since binding is 50% maximal ag 0.175 M NaCl and is only partly inhibited by Ca2+ and Mg2+ in the 1 to 5 mM range. Most, if not all, of the receptors are capable of DNA binding, and there are at least 80,000 receptor binding sites/diploid DNA (assuming one triiodothyronine binding site/receptor). Binding of the receptor-[125I]triiodothyronine complexes to other DNAs and analogs was examined using a competition assay. There is similar binding by native and denatured DNA, gy eukaryotic DNA from different species and by prokaryotic DNA (Bacillus subtilis). Binding by natural DNAs is more avid than by cytoplasmic RNA, nuclear RNA, poly(dA-dT)-poly(dA-dT), or poly(dG-dC)-poly(dG-dC). Under these conditions, binding by tRNA and poly(dA) is insignificant, and the nucleotide monomers ATP and GTP have no detectable binding. These studies support the idea that the thyroid hormone receptor is a DNA-binding protein and that the interaction is a major determinant for receptor localization in chromatin. The competition studies suggest that the polynucleotide composition and/or conformation can have marked influences on the binding, and that multiple orders of binding affinity can exist. The presence of specific sequences cannot be excluded. However, the finding that receptors bind extensively and tightly to DNA suggests that receptors in chromatin may randomly bind to any available DNA, resulting in some of the receptors being at physiologically unimportant sites. If so, the several thousand hormone receptors present in each target cell may be required to enhance the possibility that some of the receptors are present at the actual sites of action.

Since the treatment of postmenopausal breast cancer patients with aminoglutethimide caused hypothyroidism with an unexpectedly high frequency previous treatment was suspected to contribute to hypofunction of the thyroid. Serum thyrotropin, triiodothyronine and free thyroxine index were compared between breast cancer patients who had undergone irradiation of regional lymph nodes and non-irradiated breast cancer patients, as well as patients having endometrial or colorectal carcinoma. Subclinical and clinical primary hypothyroidism was significantly more frequent in breast cancer patients who had previously received irradiation on supraclavicular lymph nodes comprising a minor part of the thyroid. Testing for the presence of autoantibodies against thyroid tissue components gave no evidence for radiation-induced autoimmune thyroiditis. Drugs suppressing thyroid hormone synthesis like aminoglutethimide may frequently cause myxedema in such irradiated women, especially at postmenopausal age.

OBJECTIVE

The underlying mechanisms of reduced pain perception in anorexia nervosa (AN) are unknown. To gain more insight into the pathology, the authors investigated pain perception, autonomic function, and endocrine parameters before and during successful treatment of adolescent AN patients.

METHODS

Heat pain perception was assessed in 15 female adolescent AN patients and matched controls. Results were correlated with autonomic and endocrine parameters (free triiodothyronine, free cortisol). Autonomic function was studied using heart rate variability and pupillary light reflex assessment. To investigate the influence of therapy on these parameters, data were obtained at three different time points.

RESULTS

Heat pain thresholds were significantly increased in the acute state and decreased after weight had been regained for 6 months. Similarly, an increased parasympathetic tone was present in the acute state only. The relative amplitude of the pupillary light reflex showed a positive correlation to pain thresholds over time and predicted disease progression. In addition, the authors found a negative correlation between increased pain thresholds and low free cortisol.

CONCLUSIONS

Increased pain thresholds are associated with increased parasympathetic tone and a hypothyroid state in AN. This may either indicate common central mechanisms or suggest a causative interaction.

Bromocriptine, a dopamine D2 agonist, inhibits seasonal fattening and improves seasonal insulin resistance in Syrian hamsters. Alterations in daily rhythms of neuroendocrine activities are involved in the regulation of seasonal metabolic changes. Changes in circadian neuroendocrine activities that regulate metabolism are believed to be modulated by central circadian oscillators within the hypothalamic suprachiasmatic nuclei (SCN) of seasonal animals. We examined the association of metabolic responses to bromocriptine with its effects on the daily rhythms of metabolic hormones and daily monoamine profiles within the SCN, a primary circadian pacemaker known to regulate metabolism, in Syrian hamsters. Obese glucose-intolerant male Syrian hamsters (body weight [BW] 185 +/- 10 g) held on 14h daily photoperiods were treated at light onset with bromocriptine (800 microg/animal/day, ip) or vehicle for 2 weeks. Animals were then subjected to a glucose tolerance test (GTT) (3 g/kg BW, ip). Different subsets of animals (n = 6) from each treatment group were sacrificed at 0h/24h, 5h, 10h, 15h, or 20h after light onset for analyses of SCN monoamines, plasma insulin, prolactin, cortisol, thyroxin (T4), triiodothyronine (T3), glucose, and free fatty acids (FFAs). Compared with control values, bromocriptine treatment significantly reduced weight gain (14.9 vs. -2.9 g, p < .01) and the areas under the GTT glucose and insulin curves by 29% and 48%, respectively (p < .05). Basal plasma insulin concentration was markedly reduced throughout the day in bromocriptine-treated animals without influencing plasma glucose levels. Bromocriptine reduced the daily peak in FFA by 26% during the late light span (p < .05). Bromocriptine significantly shifted the daily plasma cortisol peak from the early dark to the light period of the day, reduced the plasma prolactin (mean 1.8 vs. 39.4 ng/dL) and T4 throughout the day (mean 1.6 vs. 3.8 microg/dL), and selectively reduced T3 during the dark period of the day (p < .01). Concurrently, bromocriptine treatment significantly reduced SCN dopamine turnover during the light period and shifted daily peaks of SCN serotonin and 5-hydroxy-indoleacetic acid (5-HIAA) content by 12h from the light to the dark period of the day (p < .05). This was confirmed by a further in vivo microdialysis study in which bromocriptine increased SCN extracellular 5-HIAA of glucose-intolerant hamsters during the dark phase (47% increase, p < .05) toward levels observed in normal glucose-tolerant hamsters. Thus, bromocriptine-induced resetting of daily patterns of SCN neurotransmitter metabolism is associated with the effects of bromocriptine on attenuation of the obese insulin-resistant and glucose-intolerant condition. A large body of corroborating evidence suggests that such bromocriptine-induced changes in SCN monoamine metabolism may be functional in its effects on metabolism.

OBJECTIVE

Thyroid dysfunction is a known finding in alcoholism. Most studies have reported the reduction in peripheral thyroid hormones in acute withdrawal and long-term abstinence periods of alcohol dependence. The aim of the present study was to investigate the alterations of free thyroid hormones in early and late withdrawal and their association with aggression, age of onset, and family history of alcoholism.

METHODS

Male inpatients (n = 39; mean age +/- SD: 42.55 +/- 8.02 years) in alcohol withdrawal were compared with healthy men (n = 28; mean age +/- SD: 38.31 +/- 9.26 years). Levels of free thyroxine (fT4), free triiodothyronine, (fT3) and thyrothrophin (TSH) were measured in early (first day) and late (28th day) withdrawal in the patients and only once in the controls.

RESULTS

In early withdrawal, levels of thyroid hormones did not differ from those in the controls. In late withdrawal, fT3 and fT4 levels (2.71 +/- 0.56 and 10.80 +/- 1.86 pg/ml) were lower than those of both controls (3.32 +/- 0.41 and 11.95 +/- 1.49 pg/ml, respectively, P < 0.05 in both cases) and patients in early withdrawal (3.18 +/- 0.72 and 12.68 +/- 2.50 pg/ml, respectively, P < 0.05 in both cases). Patients were divided into subgroups according to aggression level, onset age of alcoholism, and family history. While the high-aggression group had lower serum levels of fT3 and fT4 in late withdrawal (2.49 +/- 0.41 and 10.44 +/- 2.15 pg/ml) compared with those of controls (P < 0.05 in both cases), the low-aggression group only had lower serum levels of fT3 in late withdrawal (2.90 +/- 0.62 pg/ml) compared with those of controls (P < 0.05). fT3 and fT4 values in the family history-negative group (2.67 +/- 0.56 and 10.75 +/- 1.88 pg/ml) were lower than those of controls in late withdrawal (P < 0.05 in both cases). Both fT3 and fT4 levels in late withdrawal (2.69 +/- 0.54 and 10.83 +/- 1.96 pg/ml) were decreased in early-onset group compared with those of controls (P < 0.05 in both cases).

CONCLUSIONS

Decreased free thyroid hormone levels may be a result of heavy alcohol consumption or a trait marker of alcoholism, especially in high-aggressive, early-onset and family history-negative patients.

OBJECTIVE

The present study was to compare the efficacy of a single daily dose of methimazole (MMI) and propylthiouracil (PTU) in the treatment of Graves' hyperthyroidism.

BACKGROUND

Antithyroid drugs, MMI and PTU, are widely used in the treatment of hyperthyroidism. Previous studies in the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a more favourable result with MMI. However, the efficacy of a single daily dose of PTU was inconsistent. In this study, we examined the therapeutic efficacy of single daily doses of MMI and PTU on the change of thyroid hormones and thyrotropin receptor antibodies (TRAb) levels.

METHODS

Thirty patients with newly diagnosed Graves' hyperthyroidism were randomly divided into two groups, each receiving a single dose of either 15 mg MMI or 150 mg PTU daily for 12 weeks. The therapeutic efficacy was determined by serum total triiodothyronine (TT3), total thyroxine (TT4), thyrotropin (TSH), free thyroxine (FT4), and TRAb levels at baseline and at the end of 4, 8 and 12 weeks during the study period.

RESULTS

There was no significant difference in baseline thyroid function parameters. Serum TT3, TT4 and FT4 levels in the MMI-treated group were significantly lower than those of the PTU-treated group after 4 weeks and through the end of the study. MMI also has superior effect on reducing serum TRAb levels than PTU after 8 weeks and at the end of the study.

CONCLUSIONS

During the 12-week treatment of Graves' hyperthyroidism, a single daily dose of 15 mg MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of Graves' hyperthyroidism.