Severe hypothyroxinemia in a young adult with Carbimazole-TreatedT3-Predominant Graves’ hyperthyroidism, Reversed with L-Thyroxine Loading Immediately Post-Total Thyroidectomy / Journal of the ASEAN Federation of Endocrine Societies

@#Patients with triiodothyronine (T3)-predominant Graves’ hyperthyroidism with markedly elevated serum thyroid stimulating immunoglobulin (TSI) levels and massive goitre may display discordant hypothyroxinemia with eutriiodothyroninemia or hypertriiodothyroninemia while on anti-thyroid drug therapy. A 25-year-old female with the above was started on oral carbimazole therapy for 9 months before total thyroidectomy. Preoperatively, her serum free T4 was reduced to below detection limit, and total T4 reduced to 11% of lower limit of normal, while T3 levels remained normal, and TSH remained largely suppressed. Immediately after total-thyroidectomy, a loading dose of L-thyroxine (L-T4) was administered intravenously. She was extubated without any postoperative complications. Serum free and total T4, and TSH normalized within the next 24 hours. The peculiar thyroid axis dynamics and use of L-T4 postoperative loading in such a rare clinical scenario are discussed.

Comparative study of lipid profile between clinical and subclinical hypothyroidism

Background: Subclinical hypothyroidism (SH) is characterized by elevated levels of serum thyroid stimulating hormone in the presence of normal thyroxin levels. Subclinical hypothyroidism is often associated with elevated total cholesterol and other lipid profile parameters. This study was done to evaluate the lipid metabolism in subclinical hypothyroidism.Methods: This case control study was done to compare the lipid profile parameters between subclinical and overt hypothyroidism cases attending the outpatient facility of our tertiary care hospital of our medical college in Puducherry. Newly diagnosed cases of hypothyroidism were selected by convenient sampling. A total of 37 SH cases and 31 overt hypothyroidism cases were included. Blood samples were drawn to measure lipid profile. A 2D echocardiogram was done to evaluate cardiac function. Ultrasonogram was done to evaluate fatty liver.Results: The mean age of the participants in the subclinical hypothyroidism group was 34.2±12.2 years while in the clinical hypothyroidism group was 35.7±9.8 years. About 13.5% of the participants in subclinical hypothyroidism group and 12.9% of the participants in clinical hypothyroidism had fatty liver in ultrasound. A significant difference was observed in the mean values of total cholesterol, triglycerides and LDL levels between clinical and subclinical hypothyroidism.Conclusions: This study highlights the need for screening of subclinical hypothyroidism in order to prevent the incidences of cardiovascular complications and other diseases like metabolic syndrome.

Association of low levels of free thyroxin within normal range with the severity of coronary artery disease and carotid atherosclerosis / 西安交通大学学报(医学版)

Objective To investigate the association of low level of free thyroxin (FT4)within normal range with the severity of coronary artery disease (CAD)and carotid atherosclerosis.Methods We enrolled 312 consecutive patients who underwent coronary angiography (CAG)and divided them into CAD group (196 cases)and non-CAD group (116 cases)according to CAG results.We calculated Gensini score and divided CAD group into≤10 Gensini score group (n=65),10-30 Gensini score group (n=67)and ＞30 Gensini score group (n=64).Thyroid hormone level,carotid intima-media thickness (CIMT)and other clinical data were measured and compared between the groups,and the correlation analysis was used to find the relationship of FT4 level with Gensini score.By taking CIMT reference value of 0.9 mm as the standard,we divided the patients into thickened IMT group (IMT≥0.9 mm)and normal IMT group (IMT＜0.9 mm).Results The level of FT4 was significantly lower in CAD group and subgroups than in non-CAD group (P＜0.05).The level of FT4 was negatively correlated with Gensini score (P＜0.05).The levels of FT4 and TT4 were significantly lower in thickened CIMT group than in normal CIMT group (P＜0.05).Conclusion Low level of FT4 within normal range is significantly related to the severity of CAD,and low level of FT4 can be used as an independent risk factor for the severity of CAD.Low levels of FT4 and TT4 are significantly related to carotid atherosclerosis.

Effects of excess maternal thyroxin on the bones of rat offspring from birth to the post-weaning period

ABSTRACT Objective To evaluate, in rat offspring, bone changes induced by excess maternal thyroxin during pregnancy and lactation, and to assess the reversibility of these changes after weaning. Material and methods Twenty Wistar rats were distributed in two groups, hyperthyroid and control, that were treated daily with L-thyroxin (50 mcg/animal) and placebo, respectively. The treatment was initiated seven days before mating and continued throughout pregnancy and lactation. From every female of each of the two groups, two offspring were euthanized after birth, two at 21 days of age (weaning), and two at 42 days of age (21 days after weaning). In newborns, the length of pelvic and thoracic limbs were measured, and in the other animals, the length and width of the femur and humerus were measured. Bones were dissected, decalcified, embedded in paraffin, and analyzed histomorphometrically. Results Excess maternal thyroxin significantly reduced the length of the pelvic limb in neonates. In 21-day-old individuals, excess maternal thyroxine reduced the length and the width of the femur and the humerus. It also increased thickness of the epiphyseal plate and the percentage of trabecular bone tissue. In 42-day-old individuals, there were no significant differences between groups in relation to the parameters evaluated in the previous periods. Conclusion Excess maternal thyroxine reduced growth in suckling rats both at birth and at weaning, and it also increased the percentage of trabecular bone tissue in 21-day-old animals. These changes, however, were reversible at 42 days, i.e., 21 days after weaning. Arch Endocrinol Metab. 2016;60(2):130-7.

Effect of Levothyroxine Replacement Therapy on Improving Diffused Left Ventricular Myocardial Lesions in Patients With Hypothyroidism / 中国循环杂志

Objective: To study the effect of levothyroxine replacement therapy on improving diffused left ventricular myocardial lesions and cardiac function in patients with hypothyroidism. Methods: Our research included 2 groups: Hypothyroidism group,n=20 newly diagnosed patients and Control group, n=17 normal healthy subjects. Diffused left ventricular myocardial lesions were quantitatively evaluated by non-invasive cardiac MRI T1 mapping technique. Left ventricular myocardial T1 value and left ventricular function before and after levothyroxine replacement therapy were compared; the relationship between T1 value and thyroid function and the relationship between T1 value and the indicators of left ventricular function were analyzed. Results:①Compared with Control group, Hypothyroidism group had increased left ventricular myocardial T1 value, P<0.01, while decreased cardiac index (CI) and left ventricular peak filling rate (PFR), allP<0.05.②In patients with hypothyroidism, left ventricular myocardial T1 value was negatively related to serum FT3 level (r=-0.52,P=0.0006) and PFR (r=-0.43,P=0.0085).③Compared with pre-therapeutic condition, the patients with recovered normal thyroid function showed obviously decreased left ventricular myocardial T1 value and improved CI, PFR. Conclusion: Levothyroxine replacement therapy may improve diffused left ventricular myocardial lesions in patients with hypothyroidism, and therefore improve the cardiac function.

Comparison of therapeutic effects of L-Thyroxin, apelin and a combination of both on antioxidant enzymes in the heart of PTU-induced hypothyroid rats

Atherosclerosis is one of the common disorders among hypothyroidism, which, increased the risk of cardiovascular diseases. Reactive oxygen species are associated with atherosclerosis development. Antioxidant defense systems are the scavenger for free radicals. Apelin is an endogenous ligand for the APJ receptor (apelin receptor) that exists in most tissues, acts as an adiponectin. It has been identified that apelin administration, improve the antioxidant capacity (TAC). Therefore, this study was conducted to assess, therapeutic effects of apelin, T4 (L-Thyroxin) or both on antioxidant capacity in 6-propyl-2-thiouracil (PTU)-induced hypothyroid rats. Forty male Wistar rats were randomly assigned into five groups: C: control group; P group (hypothyroid): PTU (0.05 %) administration for six weeks; P+A, P+T and P+A+T groups: after 4 weeks of PTU administration, animals treated with Apelin (200 μg/kg/day, ip) T4 (0.02 µg/g/day, gavage) and apelin+T4; for two weeks respectively accompanied by PTU administration. Aplein administration in P+A group and P+A+T group had beneficial effect to lowering of malondialdehyde (MDA) content as compared to hypothyroid group (8.52±0.64 and 8.53±1 vs. 13.67±1.64 nmol/g tissue, P<0.05) and also had increasing effect on Superoxide dismutase (SOD) and glutathion peroxidase (GPx) activity and the total antioxidant capacity (TAC) content compared to the hypothyroid group. This study showed that apelin was able to improve the oxidant-antioxidant balance in the heart tissue of the hypothyroid rats by elevating of antioxidant enzyme activity.

Study on effect and correlation of thyroid hormone level changes in peritoneal dialysis patients by thyroxin tablet / 中国生化药物杂志

Objective To investigate the changes of thyroid hormone in peritoneal dialysis patients and analyse its impact factors, as well as the therapeutic effects of small dose of thyroxine.Methods 150 uremic patients in Hunan Provincial People’s Hospital from December 2013 to December 2014 were selected, 70 cases of uremia non-dialysis patients were divided into group A, while 80 uremia peritoneal dialysis for more than half a year were divided into group B.70 cases healthy examinees during the same period in our hospital were selected as control group ( group C ) . The total triiodothyronine (T3), total thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), hemoglobin (Hb), serum albumin (ALB), total cholesterol (TC), triglyceride (TG), serum creatinine (SCr), C reactive protein (CRP) and left ventricular ejection fraction ( LVEF) , subjective global assessment of nutritional act ( SGA) and other indicators were detected in three groups.Patients in group B were divided into two sub-groups according to thyroid hormone levels: B1 group had normal thyroid level while B2 abnormal.And the administration of small dose of thyroid hormone was given to patients in group B2, and the effect of the administration was evaluated by the above indexes.Results The FT3 in group A and B were significantly lower than that in group C (P<0.01).There were significant differences of levels of ALB, CRP, SGA between group B1 and group B2, and the FT3 level in group B was significant correlated with SGA, ALB, LVEF(r=0.815,P<0.001;r=0.780,P<0.001;r=0.953,P<0.001).After treated with small dose of thyroid hormone, FT3 and LVEF were improved while FT4, TSH, ALB, SGA, CRP were not improved in group B2.Conclusion The thyroid hormone level in patients with continuous ambulatory peritoneal dialysis decreases which is dominated with FT3.The decreased thyroid level is significantly correlated with nutrition ( ALB, SGA) and left ventricular function.The administration of small dose of thyroid hormone can improve the left ventricular systolic function.

Binding pattern of 125Iodine thyroxine and tri-iodothyronine in skin and liver tissues of spotted munia, Lonchura punctulata: Co-relation to seasonal cycles of breeding and molting.

Prevalent notion about thyroid hormones is that thyroxine (T4) is a mere precursor and physiological effects of thyroid hormones are elicited by tri-iodothyronine (T3) after mono-deiodination of T4. Earlier studies on feather regeneration and molt done on spotted munia L. punctulata suggest that T4 (mono-deiodination suppressed by iopanoic acid and thyroidectomized birds) is more effective than T3 in inducing feather regeneration. The binding pattern of 125I labeled T4 and T3 has been investigated in the nuclei prepared from skin and liver tissues (samples obtained during different months) of spotted munia using scatchard plot analysis. The results show that binding capacity (Bmax – pmole/80 µgm DNA) of 125I-T3 to nuclei of skin was significantly higher in November as compared to April and June, whereas the binding affinity (Kd-10-9M-1) was significantly lower in November as compared to April and June. During November, Bmax for binding of T3 and T4 did not vary in liver and skin nuclei but Kd varied significantly. Binding capacity of 125I- T3 to skin and liver did not vary but binding affinity of 125I- T4 to skin was approximately 7 times higher than that of liver. The results suggest that T4 does show a variation in binding pattern that co-relates to the molting pattern of spotted munia. These variations might play important role in different physiological phenomenon in this tropical bird. The experiments do point towards the possibility of independent role of T4 as a hormone, however, further experiments need to be done to ascertain the role of T4 in this model and work out the exact molecular mechanism of action.

Study of Hypothyroid Related Atrioventricular Block in Elderly Hypothyroid Patients and Assessment of Any Reversal After L-Thyroxin Therapy.

We intend to study the pattern of atrioventricular conduction blockage in hypothyroidism in elderly population and assessment of any reversal after Lthyroxin therapy. Aims : 1) To detect hypothyroid related AV block in elderly hypothyroid patients. 2) To supplement L-thyroxin for 6 weeksand check whether the AV conduction is restored or not. Settings and design : The proposed study is a hospital based case control study followed by interventional one. Hypothyroid elderly subjects attending OPD over a period of one year were considered for the purposes of observation. Age and gender matched controls were selected simultaneously. Methods and materials : 42 elderly (>60 years) hypothyroid patients were selected as case and 45euthyroid sage and gender matched subjects as control. ECG was done to asses the degree of AV block. Any degree of AV conduction block noted, was supplemented with L-thyroxin for 6 weeks and later resting ECG was done to assess whether the normal AV conduction was restored or not. Statistical analysis : Chi square test done between the case and control group and paired T test done before and after L-thyroxin supplementation. Results : Chi square test revealed that out of 42 cases, a significant proportion of 62% had increased P-R interval (P<.001), whereas 76% out of 45 control had normal P-R interval.After L-thyroxin supplementation in 69% of the cases, normal P-R interval was restored (P< .001, paired T test value 13.484). Conclusion : In hypothyroid patients AV block detected in resting ECG should be a matter of concern, because if the conduction block is reversed to normal sinus rhythm by thyroxin supplementation, unnecessary pacemaker implantation can be avoided.

Relationship between thyroid hormone level and the change of left ventricular function in septic patients / 中华急诊医学杂志

Objective To investigate the occurrence of thyroid disorders in septic patients and the relationship between thyroid hormone level and the change of left ventricular function.Methods A total of 63 septic patients,43 male and 20 female,aged 50 to 88 years with mean 63.3 ± 18.5,were included in the present study.The thyroid hormone levels and C-reactive protein (CRP) levels were detected in all patients on the next day of admission.Clinical information of each patient was recorded including demographics and co-existed disease,APACHE Ⅱ score at admission and the incidence of shock and subsequent multiple organ dysfunction syndrome (MODS).At 24 hours,the second week and the third week after admission,a serial trans-thoracic echocardiography were performed in all patients to observe changes of left ventricular end diastolic dimension,left ventricular eject fraction and E/A (the ratio between maximal velocity of blood flow at mitral valve orifice in the early diastolic phase and maximal velocity of blood flow of atrium in systolic phase).Another 38 patients with ordinary infections,21 male and 17 female,with mean age 58.6 ± 16.8 (48-84 years) were selected as controls for comparison.The difference in thyroid function between sepsis group and control group was analyzed.The levels of serum thyroid hormone associated with the incidence of shock and MODS were studied among different types of the left ventricular structure and function in sepsis group.Results The levels of serum free tri-iodothyronine (FT3) and free tetra-iodothyronine (FT4) in sepsis group were significantly lower than those in control group (P ＜ 0.05),but there was no difference in level of thyroid stimulating hormone (TSH) between these two groups.The patients with sepsis had three types of the left ventricular dysfunction:diastolic dysfunction without the enlargement of left ventricular (type Ⅰ) in 31 patients,the enlargement of left ventricular with diastolic dysfunction (type Ⅱ) in 18 patients and the enlargement of left ventricular with both systolic and diastolic dysfunction (type Ⅲ) in 14 patients.Compared with the other two types,the type Ⅲ patients had significantly lower levels of FT3 and FT4 and higher incidences of shock and MODS (P ＜ 0.05).No significant difference in TSH level was found among the three types.There were no significantly differences in FT3 and FT4 between type Ⅰ and type Ⅱ,but the higher incidences of shock and MODS were found in type Ⅰ (P ＞ 0.05).Conclusions Most septic patients have thyroid function disorder.Serum thyroid hormone levels in early stage of sepsis have certain role in predicting changes in left ventricular structure and function in the late stage of disease.

Impact of iodine deficiency on expression of thyroid stimulating hormone β splice variant in BALB/c mice / 中国地方病学杂志

ObjectiveTo find out if the immune system derived thyroid stimulating hormone(TSH) β splice variant(TSHβ-Ⅴ) would be regulated by circulating thyroid hormone levels to get a further understanding of the function and mechanism of this TSHβ-Ⅴ in thyroid homeostasis.MethodsA total of 20 weaning Balb/c mice (half male and half female) were selected and randomly divided into two groups according to their body mass and gender(n =10).Mice of control group were fed with common diet and deionized water.Mice of the low-iodine(LI) group were fed with low-iodine diet(containing iodine 20 - 40 μg/kg,iodine-intake about 0.25 μg/d) and deionized water.The experimental period was 3 months.At the end of the experiment,mice were executed and the blood was collected to observe the levels of TSH and thyroid hormone by chemiluminescence immunoassay (CIA) ; bone marrow (BM),peripheral blood(PBL),thyroid gland and pituitary were collected to assay the TSHβ-Ⅴ mRNA expression by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR).ResultsThe serum free thyroxine(FT4) and total thyroxine(TT4) levels in LI group of mice[(0.47 ± 0.70)nmol/L,(2.41 ± 0.28)pmol/L] were significantly lower than that of the control group of mice [(55.2 ± 3.68) nmol/L, (32.72 ± 1.02) pmol/L,t =43.81,86.04 、all P ＜ 0.01 ] and the serum total triiodothyronine(TT3) and free triiodothyronine(FT3) reduction in LI group of mice[ (0.76 ± 0.08)nmol/L,(4.01 ± 0.40)pmol/L] were significantly lower than that of the control group of mice [ (1.10 ± 0.06)nmol/L,(5.40 ± 0.38)pmol/L,t =9.81,7.5 1,P ＜ 0.01 ].Iodine insufficiency strongly elevated the serum TSH in LI group of mice[ (35.67 ± 17.39)mU/L] than that in control group of mice[ (0.24 ± 0.10)mU/L,t =- 6.11,P ＜ 0.01 ].The mRNA levels of TSH β-Ⅴ in BM (9.62 ± 0.60) and in PBL( 9.25 ± 0.83 ) of LI group of mice were lower than those in control group of mice (7.69 ± 0.36,7.11 ± 0.41,t =6.77,5.64,P ＜ 0.01),while the mRNA level of TSH β-Ⅴ in pituitary of LI group of mice (1.99 ± 0.61) was increased compared with that in control group of mice (5.75 ± 0.98,t =- 8.02,P＜ 0.01).Compared with control group of mice(9.12 ± 0.62),the level of thyroid TSH β-Ⅴ mRNA in LI group of mice (9.32 ± 0.91 ) was not significantly changed (t =0.45,P ＞ 0.05).There was no detectable native TSHβ in BM,PBL and thyroid.The mRNA level of native TSHβ in pituitary in LI group of mice( - 7.17 ± 1.78) was dramatically elevated compared to that in control group of mice( - 1.43 ± 0.51,t =- 7.60,P ＜ 0.01 ).ConclusionsThe mRNA levels of TSHβ-Ⅴ are suppressed in BM and PBL in low iodinediet induced hypothyroidism mice,which suggest that immune system derived TSHβ-Ⅴ may be more important thannative TSHβ in immune-thyroid regulation.

Electrical heterogeneity of transient outward current in thyroxine induced ventricular myocytes of cardiomyopathy rat / 中国病理生理杂志

AIM: To study the electrical heterogeneity of transient outward potassium current (I_(to)) in left and right ventricular myocytes of cardiomyopathy rat. METHODS: The rats were peritoneally injected with L-thyroxine 0.5 mg/kg for 10 d to establish the model of ventricular hypertrophy. The right and left ventricular parts of the heart were separated and the ventricular myocytes were prepared by step digestion using enzyme solution. I_(to) was recorded by using whole cell patch clamp technique. The change of the electrical heterogeneity was determined. RESULTS: The electrical heterogeneity of I_(to) existed in the normal myocytes of left and right ventricles. In the myocytes of left and right ventricles isolated from the cardiomyopathy rats, the electrical heterogeneity was enhanced obviously and showed statistical difference. At +40 mV depolarizing test potential, the current density of I_(to) in the myocytes of right ventricle was increased from (9.23±0.84) pA/pF to (11.19±1.73) pA/pF, while the current density of I_(to) in the myocytes of left ventricle was decreased from (6.99±1.14) pA/pF to (4.95 ±1.84) pA/pF and the dispersion was increased. The V_(1/2) of right ventricle steady inactivation was increased significantly [from (-68.85±1.37) mV to (-49.86±0.69) mV]. The time constant τ of de-inactivation changed significantly [τ left=(79.16±7.04) ms, τ right=(53.19±3.72) ms]. CONCLUSION: Enhanced electrical heterogeneity of I_(to) in the left and right ventricular myocytes of cardiomyopathy rat may represent one of the important ionic mechanisms for some arrhythmia caused by myocardial hypertrophy.

Programa de triagem neonatal para hipotireoidismo congênito no nordeste do Brasil: critérios diagnósticos e resultados / Neonatal screening program for congenital hypothyroidism in northeast of Brazil: criteria, diagnosis and results

Avaliamos as concentrações do TSH em papel-filtro colhido no calcanhar (TSHneo) de 48.039 crianças triadas do programa de triagem neonatal (PTN) para o hipotireoidismo congênito (HC) de Sergipe, as concentrações de TSH, T4 total e T4 livre colhidas em sangue periférico nas crianças convocadas suspeitas de HC, a idade nas diversas fases do programa, a cobertura e a freqüência do PTN de janeiro de 2005 a agosto de 2006, comparando-as com dados da literatura. Utilizamos para análise os seguintes parâmetros: média, mediana, coeficiente de variação e distribuição de freqüência. A idade da criança por ocasião da coleta em papel filtro no calcanhar foi 10 ± 9 dias (média ± desvio-padrão) e a idade na reali-zação do ensaio do TSHneo foi de 31 ± 13 dias. Em 2005, a cobertura do PTN, para o interior e para a capital de Sergipe, foi de 77 por cento e 73 por cento, respectivamente. Verificamos que em 99,484 por cento das crianças triadas as concentrações do TSH coletado em papel-filtro encontravam-se entre 0,01 e 5,20 µU/mL. As concentrações do TSH decrescem com o aumento da idade até estabilizar entre 11 e 15 dias de vida. Foram convocadas 248 crianças a partir do TSH coletado em papel-filtro (1/194). Na convocação, as concentrações do TSH, T4 e T4 livre coletado por punção venosa estavam normais em 119 crianças (1/404). A freqüência de HC suspeito foi de 1/485 (99 casos), de HC foi de 1/6.005 (8 casos) e de hipotiroxinemia foi de 1/16.013 (3 casos). A terapia para o HC foi iniciada com 51 ± 12 dias.

It was evaluated the concentration of TSH in blood spot (TSHneo) of 48.039 children included in the Neonatal Screening Program (NSP) for Congenital Hypothyroidism (CH) of Sergipe (SE), a state in the northeast of Brazil. It was also evaluated the concentration of serum TSH, total T4 and free T4 in the recalled children suspicious of having CH, their age in several phases of the program, the covering and frequency of the NSP in the cases from January 2005 to August 2006, comparing them with literature data. The following parameters were used or the analysis: mean, standard deviation, median, coefficient of variation and frequency distribution. The children's age at the collection in filter-paper specimen was 10 ± 9 days (Mean±SD) and the TSHneo execution assay was done in the period of 31 ± 13 days. In 2005 the covering by the NSP was about 77 percent in the countryside and 73 percent in Aracaju, the capital of Sergipe. It was verified that in 99,484 percent of the children included in the screening, the TSHneo varied from 0,01 to 5,20µU/ml, decreasing according to the age and stabilizing when they were between 11 and 15 days. 248 children were recalled from the TSHneo (1/194).The concentrations of TSH, T4 and free T4 collected by venous puncture were normal in 119 children (1/404). The frequency of suspected CH was 1/485 (99 cases), of CH was 1/6005 (8 cases) and of hypothyroxinemia was 1/16013 (3 cases). Therapy for CH began within 51 ± 12 days.

Model of induction of thyroid dysfunctions in adult female mice

It is described the elaboration of a protocol to induce hyperthyroidism and hypothyroidism in mice by administrating thyroxin and propylthiouracil, respectively, in the drinking water. The drugs were administered to adult female mice of the Swiss strain for 30 days in order to obtain a systemic status of thyroid dysfunction. The induction of hyperthyroidism and hypothyroidism in the animals was confirmed by the histomorphological analysis of the thyroid in the end of the experiment, when the state of gland dysfunction in the animals submitted to the treatment was observed

Descreve-se a elaboração de um novo protocolo de indução ao hipertireoidismo e hipotireoidismo em camundongos, por meio da administração de tiroxina e propiltiouracil, respectivamente, na água de beber. As drogas foram administradas a camundongos fêmeas adultas Swiss por 30 dias para obtenção das disfunções tireoidianas sistêmicas. A indução de hipertireoidismo e hipotireoidismo nos animais foi confirmada pela análise histomorfológica e histomorfométrica da glândula tireoidiana ao final do experimento, quando observou-se o estado de disfunção glandular nos animais submetidos ao tratamento

CPU86017 and its enantiomers inhibit abnormal gene expression of calcineurin and NFκB in rat cardiomyopathy induced by L-thyroxin / 中国临床药理学与治疗学

AIM: To investigate the CPU86017 and its enantiomers inhibit abnormal gene expression of calcineurin and NFκB in rat cardiomyopathy induced by L-thyroxin and compare the effect of CPU86017 (racemate) with its 4 enantiomers: (7S, 13R), (7S, 13S), (7R,13S), and (7R,13R)-CPU86017 in this model. METHODS: The animals were randomly divided into 7 groups. The rat hypertrophied model was produced by treatment with L-thyroxin 0.2 mg·kg-1·d-1, sc for 10 d and treated with CPU86017 or its enantiomers 4 mg·kg-1·d-1, sc from d 6 to d 10. The changes in left ventricular (LV) weight index, redox system, and the NO and iNOS activity in the myocardium were investigated. The expression of mRNA of calcineurin、NF-κB in the left ventricle was measured. RESULTS: There were significant cardiac hypertrophy and oxidative stress in rats treated by L-thyroxin. The expression of calcineurin, NFκB mRNA were upregulated (P<0.05, compared with that of control). After treatment with CPU86017 (racemate and enantiomers), LV remodeling and the redox system were improved. CPU86017 and (7S,13R)-CPU86017 showed a better improvement on LV remodeling and the redox than the other isomers and restored the normal expression of calcineurin, NF-κB (P<0.05, P<0.01), respectively. CONCLUSION: It suggested that an up-regulation of calcineurin and NFκB possibly related to the altered intracellular calcium handling system plays a role in the progression of L-thyroxin induced cardiomyopathy and CPU-86017 and its 7S,13R-CPU86017 enantiomer effectively inhibit the abnormal expression of calcineurin and NFκB genes, the NOS enzyme and oxidant stress in the cardiomyopathy.

Influence of a new endothelin receptor antagonist CPU-0213 on expression of MMPs mRNA and TIMPs mRNA in rats with hypertrophic myocardium induced by L-thyroxin / 中国临床药理学与治疗学

AIM: To observe the alterations of matrix metalloproteinases (MMPs) and TIMPs (the inhibitor of MMPs) and to study the influence of a new endothelin receptor antagonist CPU 0213 on MMPs mRNA and TIMPs mRNA in rats with hypertrophic myocardium induced by L thyroxin (L thy). METHODS: Male Sprague Dawley rats were randomly divided into three groups and sc administrated suspension of L thy ( 0.4 mg?kg -1 ?d -1 ) for consecutive 10 d except for normal group. On the 7th day, the rats treated with L thy were given CPU 0213(ig, 100 mg ? kg -1 ?d -1 ) for 3 d . The whole collagen content in myocardium was measured. Relative LV myocardial mRNA levels of MMPs (MMP 2, MMP 9) and tissue inhibitor (TIMP 1, TIMP 2) were detected with semi quantitative RT PCR. RESUITS: The whole collagen content in myocardium induced by L thy decreased but it increased in the group CPU 0213. The expression of MMPs (MMP 2, MMP 9) mRNA was downregulated in L thy group and the expression of TIMPs mRNA was upregulated in L thy group markedly. Treated with CPU 0213, the expressions of MMP 9 and TIMP 1 mRNA were downregulated, whereas the expression of MMP 2 mRNA coming from CPU 0213 group tended to upregulate. But there was no statistical significance among these groups. CONCLUSION: CPU 0213 can inhibit the expression of MMPs and increase collagen content, which can improve heart function.

A sandwich method of enzyme immunoassay for serum FT_4 / 中华内分泌代谢杂志

T_4 was coupled to human serum albumin(HSA)to make the conjugate T_4-HSA,a polyvalent T_4 analogue rather than monovalent T_4 per se alone.A new strategy for sandwich enzyme immunoassay model system of small molecular hapten hormones FT_4 was developed,such as intra-assay CV,inter-assay CV,average recovery, normal and abnormal values were fit for clinical application.The sensitivity was as much as 10 times higher than conventional competitive enzyme immunoassay.

INTRAUTERINE GROWTH RETARDATION AT FULL TERM PREGNANCIES WITH ENDOCRINE FACTORS / 药物分析学报

Objective To investigate the relationship between intrauterine growth retardation (IUGR) and en docrine parameters so as to assess the effects of the main endocrine factors on IUGR. The concentrations of growth hormone (GH), insulin, T3, T4 and TSH were measured in umbilical cord blood, amniotic fluid and maternal serum. Methods The samples were collected from 23 pregnant women who were diagnosed as the full term IUGR, 42 normal full term pregnant women with normal infants' weight were taken as control. Growth hormone and insulin were mea sured by radioimmunoassay. T3, T4 and TSH were investigated by micro-radioimmunoassay. Results The concentra tions of growth hormone, insulin and T4 in umbilical cord blood were lower in IUGR than that in control group(GH 4. 63μg/L vs 7.01μg/L, insulin 10. 68μIU/ml vs 31.44μIU/ml, T4 87. 39nmol/L vs 138. 10nmol/L. P ＜0. 05, 0. 05 and 0. 05, respectively). The TSH concentration in umbilical cord blood was higher in IUGR than in control group (10. 84μmIU/L vs 5. 75μmIU/L, P ＜0. 01). The concentration of growth hormone in maternal serum and the concen tration of insulin in amniotic fluid were also lower in IUGR group than in control group(GH 1.77μg/L vs 2.74μg/L, P ＜0. 01, insulin 5. 84μIU/mi vs 15. 64μIU/ml, P ＜0. 01). Conclusion This study confirms that full term neonates with IUGR are abnormal in endocrine factors. The inadequacy of growth hormone may be one of the causes of IUGR. The relative scarcity of growth hormone and insulin seems to be a factor to compromise the fetus' metabolism. Be sides, the early hypothyrosis of infants with IUGR might protect them from unfavorable environment in the uterine.

Effect of hemihepatectomy on the level of serum thyroxin and insulin / 中国普通外科杂志

Objective To study the mechanism of serum thyroxin and insulin change after hemihepatectomy. Methods The hemihepatectomy was performed in rabbits, the fasting peripheral blood samples were drawn on the day prior to surgery, and 24 hour, 48 hour, the first week, one month after operation respectively for monitoring the serum thyroxin and insulin.Results The level of TT 3 was (1.93?0.47) nmol/L, TT 4 (53.56?8.4) nmol/L preoperatively. The levels of TT 3 and TT 4 significantly decreased at 24 hour postoperatively, and gradually rose at 48 hour and up to normal levels in the first month postoperatively. The level of insulin rapidly rose immediately after operation, and began to decrease in the first week, and returned to the preoperative level in one month after operation. Conclusions The syndrome of normal thyroid disease and the syndrome of non thyroid disease can occur after hemihepatectomy; and hyperinsulinemia also can occur after hemihepatectomy.

Effects of Huangqi Sijun Decoction on Thyroxin and Cyclic Nucleotide Levels in Rat Models with Spleen Deficiency Syndrome / 中药新药与临床药理

Objective To investigate the effects of Huangqi Sijun Decoction on the levels of thyroxin and cAMP and cGMP in model rats with spleen deficiency syndrome and to explore its therapeutic mechanism.Methods Male SD rats aged three months were randomly divided into 3 groups:normal control group,spleen deficiency model group and Huangqi Sijun Decoction group.The rat models of spleen deficiency syndrome were established by gavage with the decoction of Rhubarb.The serum levels of thyroxin(T4),3,5,3'-triiodothyronine(T3),thyrotropin(TSH)and plasma levels of cAMP,cGMP were determined.Results T3 and T4 were significantly lower but the levels of cAMP and cAMP/cGMP were significantly higher in the spleen deficiency models than those in the normal control group(P