The nature of the resistance in the rat to the development of experimental atherosclerosis is unknown, and its elucidation on mechanisms is vital to further knowledge of the pathogenesis of the disease. The liver is the main organ where cholesterol synthesis predominantly occurs and is also the main source for the plasma cholesterol. One of the factors which regulates the cholesterol metabolism is the thyroid hormone, that is a well known fact. Therefore, with combination of partial hepatectomy and administration of thiouracil, alteration of tissue lipid distribution was studied. 1. Exogenous high cholesterol feeding did not elevate the total serum cholesterol and partial hepatectomized rats, but did cause significant alterations in the tissue lipid distribution. particularly in the adrenal gland, small intestine, liver and kidney. The thyroid gland became hyperplastic. 2. The combined administration of Tapazole and cholesterol caused only a slight elevation of the serum cholesterol level as compared with that of controls, but very significant alterations in the tissue lipid distribution in the adrenal gland and liver. 3. The combined administration of Thyroxine and cholesterol caused only a tendency to minimal decrement of serum cholesterol level as compard with that of controls, but produced a significant inhibition of tissue lipid accumulation in the liver and kidney. 4. Partial hepatectomy caused neither the changes in serum cholesterol level, nor effect of the tissue lipid distribution. 5. Lipid accumulation in the coronary artery and aorta could not be demonstrated, although there was some alteration in the serum cholesterol level and in the tissue lipid distributon. It appears that, in the rats, there was no particular alteration of the intestinal absorption of cholesterol regardless of the thyroid status, and in the pathways of cholesterol metabolism after absorption, partial hepatectomy did not induce particular effect, but changes in the thyroid function did show measurable effects. However, the fact that there were no significant elevations in the serum cholesterol and tissue lipid in the liver suggests that homeostatic mechanisms may have a greater role in the high resistance to the development of atherosclerosis than does an actively functioning thyroid gland.
Animals ; Cholesterol/*metabolism ; *Hepatectomy ; Hypothyroidism/*metabolism ; Lipids/*metabolism ; Male ; Rats

Case-Control Studies ; Child, Preschool ; Congenital Hypothyroidism ; DNA ; genetics ; Female ; Humans ; Hypothyroidism ; genetics ; Infant ; Iodine ; metabolism ; Male ; Mutation ; Polymerase Chain Reaction ; Sodium ; metabolism ; Symporters ; genetics

OBJECTIVETo screen differentially expressed brain proteins with proteomic method in cerebral cortex of neonatal rats with congenital hypothyroidism.

METHODFrom the 13th day of gestation, pregnant Wistar rats from the experimental group were given intragastrically with 2.5 ml of 1% propylthiouracil daily. Cerebral cortex specimens were collected from the control and hypothyroidism neonatal rats. Two-directional electrophoresis (2-DE) was applied to analyze protein expression diversities between the euthyroid and hypothyroidism neonatal rat cerebral cortex. Protein spots with significantly different expression were screened and identified by mass spectrometry. Radioimmunoassay (RIA) was used to analyze serum FT(3), FT(4) levels of each groups.

RESULTThe body weight of hypothyroid neonatal rats were lower than those in the corresponding control group (t = -8.07, P < 0.01). The FT(3) levels of hypothyroid neonatal rats were lower than those in the corresponding control group (t = 5.39, P < 0.01). The FT(4) levels of hypothyroid neonatal rats were lower than those in the corresponding control group (t = 7.62, P < 0.01). Stable 2-DE maps of normal and CH neonatal rat were constantly obtained. The maps were analyzed by software. Seven protein spots with high reproducibility, high resolution and significantly different expression were chosen and identified by mass spectrometry, including collapsing response mediator protein 2, actin related protein 2/3 complex subunit 5, ubiquitin-conjugating enzyme E2-25K, ATP synthase subunit d, Cu-Zn superoxide dismutase, synuclein alpha, and nucleoside diphosphate kinase.

CONCLUSIONThe value of this research is demonstrated here by the identification of several proteins known to be associated with nerve synapse structures formation, cell survival, metabolism, cell signal transduction, neural differentiation and nerve growth in the central nervous system. Furthermore this study identified several proteins except for collapsing response mediator protein 2 and Cu-Zn superoxide dismutase that have not previously been described in the literature and which may play an important role as either sensitive biomarkers of brain dysfunction caused by congenital hypothyroidism. In congenital hypothyroidism, brain development retardation may be related with some important processes, including abnormal synaptic formation, excess ROS production and apoptosis. The above-mentioned proteins may play critical roles in the processes, which provide valuable clues to clarify the pathogenesis of brain developmental disorders induced by congenital hypothyroidism.

Animals ; Animals, Newborn ; metabolism ; Brain ; metabolism ; Cerebral Cortex ; metabolism ; Congenital Hypothyroidism ; metabolism ; Female ; Pregnancy ; Proteome ; analysis ; Proteomics ; Rats

OBJECTIVE: Overt hypothyroidism has been associated with abnormalities of lipid metabolism; however conflicting results regarding the degree of lipid changes in subclinical hypothyroidism (SCH) have been reported. The aim of this study was to assess differences in lipid profile parameters between people with and without SCH in Korean population. METHODS: Serum lipid parameters of 37 patients with SCH and 44 euthyroid control subjects were evaluated in a retrospective cross-sectional study. RESULTS: The mean serum triglycerides (TG) level was significantly higher in patients with SCH than in controls (p < 0.05). The mean serum high-density lipoprotein cholesterol (HDL-C) level was significantly lower in patients with SCH than in controls (p < 0.05). When adjusted by age, the odds ratio for the association of HDL-C with SCH was significant at 0.893 (95% confidence interval 0.809–0.986) compared with that of the euthyroid controls. No association with SCH was found with total cholesterol level, low-density lipoprotein cholesterol level or serum thyroid-stimulating hormone level. In addition, the lipid profile did not differ significantly between premenopausal and postmenopausal women. CONCLUSIONS: We found variations of lipid profiles in patients with SCH, characterized by a significantly lower HDL-C level.
Cholesterol ; Cross-Sectional Studies ; Female ; Humans ; Hypothyroidism* ; Lipid Metabolism ; Lipoproteins ; Odds Ratio ; Retrospective Studies ; Thyrotropin ; Triglycerides

OBJECTIVES: Since 1991, nationwide massive neonatal screen-ing program for phenylketonuria (PKU) and congenital hypothyroidism have been performed in Korea. As in many other countries, efficiency of this program has not been definitely concluded. For the purpose of evaluation of this program, from the perspective of efficiency, a cost-benefit analysis was carried out. METHODS: Costs of the detection and the treatment program were compared with the projected benefit(avoided costs) that results from the prevention of the mental retardation associated with the disorders due to PKU and hypothyroidism. Costs and benefits were discounted at an annual rate of 5 %, and duration of life-long labor was assumed to be 30 years. Cost and benefit were estimated based on the detection rates of one case of PKU per 5,572 and one case of congenital hypothyroidism per 32,554 babies screened during 1991-1997. RESULTS: The benefit-cost ratio was 0.418. The sensitivity analysis for the discount rates and labor durations showed that most cost-benefit ratios were lower than one(1.0) except when discount rate was changed to 3% and detection rate to two- or threefold and/or labor duration to 40 years. CONCLUSIONS: The result of this study suggested that present program of mass screening for PKU and congenital hypothyroidism could not be justified in terms of efficiency. It doesn't coincide with the results of previous studies in major developed countries, presumably because of difference in detection rates and welfare cost for the disabled.
Congenital Hypothyroidism ; Cost-Benefit Analysis* ; Developed Countries ; Hypothyroidism ; Infant, Newborn ; Intellectual Disability ; Korea* ; Mass Screening* ; Metabolism, Inborn Errors* ; Neonatal Screening ; Phenylketonurias

OBJECTIVEDuring the critical period of brain development, insufficiency of thyroid hormone results in severe mental retardation and learning deficit. This study was designed to investigate the effects of hypothyroidism on apoptosis and the expression of Bcl-2 and Bax gene in the developing rat hippocampus neurons and to explore the mechanism of brain development regulated by thyroid hormone.

METHODHypothyroidism was induced by administration of propylthiouracil (PTU, 50 mg/d) solution to the dams from gestational day 15 by gavage. Pups from both hypothyroid and control groups were harvested at postnatal day 1 (P1), P5, P10 and P15, respectively. Blood samples were collected at the time of death for the determination of thyroid hormone. Serum free tri-iodothyronine (FT(3)) and free thyroxine (FT(4)) were measured by using chemoluminescence. Hippocampus collected from the control and hypothyroid pups were examined under light and transmissional electron microscopy. Measurement of DNA fragmentation was carried out by agarose gel electrophoresis. The expression of Bcl-2 and Bax protein in the developing rat hippocampus neurons was performed by Western blotting.

RESULTSSignificantly lower circulating FT(4) and FT(3) levels confirmed the hypothyroid status of the experimental pups. The shrunken and contracted degenerations increased in hippocampus neurons of hypothyroid pups under light microscopy. Enhanced apoptotic cells were found in hippocampus neurons of hypothyroid pups under transmission electron microscopy, especially at P10 and P15. Extensive DNA fragmentation was seen throughout development in hippocampus of hypothyroid pups, but not in the euthyroid controls except for basal level at P10. The expression of Bcl-2 in the hippocampus neurons of hypothyroid pups was significantly lower than that of euthyroid controls at all stages of development (P1: 1.95 +/- 0.27 vs. 2.59 +/- 0.19, P < 0.05, P5: 1.86 +/- 0.24 vs. 2.47 +/- 0.17, P < 0.05, P10: 1.29 +/- 0.22 vs. 1.86 +/- 0.28, P < 0.05 and P15: 1.21 +/- 0.27 vs. 2.18 +/- 0.17, P < 0.01, respectively). The relative amount of expression varied significantly with age in the control pups. The level of Bcl-2 was high in hippocampus neurons of euthyroid at P1, P5, and decreased significantly at P10, and showed a trend of recovery at P15. Similar age-related variation in the expression of Bcl-2 gene was observed in the hypothyroid group at P1, P5 and P10, but the level was maintained low at P15. The expression of Bax in the hippocampus neurons of hypothyroid pups was significantly higher than that of control pups at all stages of development (P1: 1.69 +/- 0.14 vs. 1.24 +/- 0.23, P < 0.05, P5: 1.78 +/- 0.16 vs. 1.29 +/- 0.17, P < 0.05, P10: 1.92 +/- 0.18 vs. 1.45 +/- 0.14, P < 0.05 and P15: 1.86 +/- 0.14 vs. 1.51 +/- 0.12, P < 0.05, respectively). The ratio of Bcl-2/Bax in hippocampus neurons of hypothyroid pups was lower than that of age-matched controls (P1: 1.16 +/- 0.17 vs. 2.12 +/- 0.35, P < 0.05, P5: 1.05 +/- 0.16 vs. 1.94 +/- 0.36, P < 0.05, P10: 0.68 +/- 0.17 vs. 1.29 +/- 0.16, P < 0.05 and P15: 0.67 +/- 0.19 vs. 1.45 +/- 0.22, P < 0.01, respectively).

CONCLUSIONThyroid hormone significantly prevents apoptosis of hippocampus neurons. Congenital hypothyroidism increases not only the extent but also the duration of apoptosis by down-regulation of the anti-apoptotic gene Bcl-2 and maintaining a high level of the pro-apoptotic gene Bax.

Animals ; Animals, Newborn ; Apoptosis ; physiology ; Down-Regulation ; Hippocampus ; metabolism ; Hypothyroidism ; physiopathology ; Neurons ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; bcl-2-Associated X Protein ; metabolism

Metabolic syndrome is a cluster of diseases that include central obesity, hyperglycemia, dyslipidemia, and hypertension. Metabolic syndrome is a risk factor for type 2 diabetes and cardiovascular disease and the key pathophysiology is insulin resistance. Thyroid hormone has been known to play an important role in lipid and glucose metabolism and hypothyroidism causes atherosclerosis and insulin resistance. A number of clinical studies reported overt or subclinical hypothyroidism is associated with metabolic syndrome, and there has been the efforts elucidating a link between these two diseases. Recently, thyroid hormone analogue or thyromimetics has been developed to improve metabolic syndrome including dyslipidemia. I reviewed recently reported mechanisms explaining the association between hypothyroidism and metabolic syndrome, and current status of the development of thyromimetics was also reviewed.
Atherosclerosis ; Cardiovascular Diseases ; Dyslipidemias ; Glucose ; Hyperglycemia ; Hypertension ; Hypothyroidism* ; Insulin Resistance ; Metabolism ; Obesity, Abdominal ; Risk Factors ; Thyroid Gland

PURPOSE: Many inborn errors of metabolism can be completely cured with early detection and early treatment. This is why neonatal screening on inborn errors of metabolism is implemented worldwide. In this study, a cost-benefit analysis was performed on the neonatal screening of phenylketonuria and congenital hypothyroidism in Korea. METHODS: This study included 2,908,231 neonates who took the neonatal screening on phenylketonuria and congenital hypothyroidism in Korea from January 1991 to December 2003. From those neonates, the incidence rates of phenylketonuria and congenital hypothyroidism were measured. Furthermore, based on 495,000 babies born in 2002, were calculated and compared the total costs in case when neonatal screening on phenylketonuria and congenital hypothyroidism is implemented, and when not. RESULTS: If the neonatal screening on phenylketonuria and congenital hypothyroidism is implemented, benefits far exceed costs at a ratio of 1.77:1 in phenylketonuria, and 11.11:1 in congenital hypothyroidism. In terms of wons, the present neonatal screening on phenylketonuria and congenital hypothyroidism will gain us more than 29 billion wons every year. CONCLUSION: This study only concerns the monetary aspects of the neonatal screening. Therefore, the benefits of the neonatal screening is underestimated by ignoring precious but not measurable values such as quality of life. However, the present neonatal screening on phenylketonuria and congenital hypothyroidism is found to be beneficial and should continue for the good of the nation as well as that of the patients.
Congenital Hypothyroidism* ; Cost-Benefit Analysis* ; Humans ; Incidence ; Infant, Newborn ; Korea* ; Metabolism, Inborn Errors ; Neonatal Screening* ; Phenylketonurias* ; Quality of Life

BACKGROUND AND OBJECTIVES: Selenium is an important trace element for thyroid hormone metabolism, and its deficiency can cause hypothyroidism. Serum selenium concentration is the best biomarker to reflect selenium intake and reserve, although other markers can reflect. Therefore, we preliminarily assessed serum and urine selenium concentrations in patients with thyroid disease compared to those of a healthy population. We also investigated the correlation between serum and urine selenium concentration, thyroid hormone and urinary iodine concentration (UIC). MATERIALS AND METHODS: A total of 97 patients (32 men, 65 women, 52.4±14.7 years) with benign thyroid nodules or thyroid dysfunction who visited the Samsung Medical Center between 2008 and 2013 were included. Data for 175 healthy subjects provided by Lee et al. were used as the control. Serum T3, free T4, and thyroid stimulating hormone (TSH) were measured using commercialized RIA or IRMA kits. Serum/urine selenium and UIC were measured by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Median serum selenium concentration was 110 µg/L (95% CI, 73-156). Median urine selenium concentration was 66.3 µg/gCr (95% CI, 28.7-283.5). Compared to 175 healthy subjects (serum 84 µg/L [95% CI, 30-144], urine 34.5 µg/gCr [95% CI, 0.8-107.2]), serum and urine selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects (p<0.001). Serum selenium concentration was significantly correlated with urine selenium concentration after log transformation (r=0.88, p=0.022), but was not significantly correlated with UIC, T3, free T4 and TSH. CONCLUSION: Selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects. Serum selenium concentration was significantly correlated with urine selenium concentration.
Female ; Healthy Volunteers ; Humans ; Hypothyroidism ; Iodine ; Male ; Metabolism ; Selenium* ; Spectrum Analysis ; Thyroid Diseases* ; Thyroid Gland* ; Thyroid Nodule ; Thyrotropin

BACKGROUND AND OBJECTIVES: Selenium is an important trace element for thyroid hormone metabolism, and its deficiency can cause hypothyroidism. Serum selenium concentration is the best biomarker to reflect selenium intake and reserve, although other markers can reflect. Therefore, we preliminarily assessed serum and urine selenium concentrations in patients with thyroid disease compared to those of a healthy population. We also investigated the correlation between serum and urine selenium concentration, thyroid hormone and urinary iodine concentration (UIC). MATERIALS AND METHODS: A total of 97 patients (32 men, 65 women, 52.4±14.7 years) with benign thyroid nodules or thyroid dysfunction who visited the Samsung Medical Center between 2008 and 2013 were included. Data for 175 healthy subjects provided by Lee et al. were used as the control. Serum T3, free T4, and thyroid stimulating hormone (TSH) were measured using commercialized RIA or IRMA kits. Serum/urine selenium and UIC were measured by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Median serum selenium concentration was 110 µg/L (95% CI, 73-156). Median urine selenium concentration was 66.3 µg/gCr (95% CI, 28.7-283.5). Compared to 175 healthy subjects (serum 84 µg/L [95% CI, 30-144], urine 34.5 µg/gCr [95% CI, 0.8-107.2]), serum and urine selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects (p<0.001). Serum selenium concentration was significantly correlated with urine selenium concentration after log transformation (r=0.88, p=0.022), but was not significantly correlated with UIC, T3, free T4 and TSH. CONCLUSION: Selenium concentrations of patients with thyroid disease were significantly higher than those of healthy subjects. Serum selenium concentration was significantly correlated with urine selenium concentration.
Female ; Healthy Volunteers ; Humans ; Hypothyroidism ; Iodine ; Male ; Metabolism ; Selenium* ; Spectrum Analysis ; Thyroid Diseases* ; Thyroid Gland* ; Thyroid Nodule ; Thyrotropin