甲亢、甲低患者血清生长抑素含量及分析

目的 :探讨甲亢、甲低患者血清SS与正常人含量的关系及临床意义。方法 :应用放射免疫分析检测39例甲亢 ,39例甲低及 4 2例正常人血清SS含量。结果 :甲亢患者血清SS含量明显高于正常对照组 ,甲低患者SS含量明显低于正常对照组。经统计学分析 ,甲亢、甲低组与正常组对比具有显著性差异 (P <0 0 5 )。结论 :甲亢患者SS含量高于对照组 ,甲低患者SS含量低于对照组。血清中SS与甲状腺激素水平有一致性改变。     

Effects of thyroid hormone on the action potential and membrane currents of guinea pig ventricular myocytes

We studied the effects of thyroid hormone on the action potential and membrane currents recorded from enzymatically dissociated guinea pig ventricular myocytes, by means of the whole-cell recording technique. Hypothyroidism was associated with an increase in action potential duration, whereas hyperthyroidism was associated with a decrease in duration. These effects are similar to those reported in multicellular preparations. Hypo-and hyperthyroidism were also associated with a decrease and an increase, respectively, in the slope of the action potential plateau. Resting potential and action potential amplitude were unaffected by the alterations in the thyroid state. The voltage-clamp experiments revealed that as compared with euthyroid myocytes, the peak calcium current, was bigger in hyperthyroid myocytes and smaller in hypothyroid myocytes. The potassium outward current (at a membrane potential =50 mV) was of similar amplitude in hypo- and euthyroid myocytes and bigger in hyperthyroid myocytes. Our major conclusion is that thyroid hormones regulate the amplitude of the calcium current and that this effect may be responsible in part for the modulation of myocardial contractility by thyroid hormones.     

Myocardial ultrastructure in cardiac hypertrophy induced by thyroid hormone—an acute study in rats

The early responses of the myocardium ultrastructure under thyroid dysfunction conditions, hemodynamic parameters, cardiac hypertrophy and ultrastructural evaluations were performed in hypothyroid and hyperthyroid rats submitted to different doses [T4–25 and T4–100; 0.025 mg and 0.1 mg kg^–1 body weight (BW) ·per day, respectively)]. All groups were treated for 7 days. The animals were sacrificed, the hearts were excised and weighed and the left ventricle tissue samples were processed for transmission election microscopy. Systolic blood pressure (SBP) was not altered by administration of T4. An increased heart rate and ratio of heart weight to body weight (HW/BW) were found in the hyperthyroid rats. However, the SBP and HW/BW decreased significantly in hypothyroid rats. No significant ultrastructural alterations were detected when the hypothyroid and T4–25 groups were compared with the control group. Alterations of cardiomyocytes nuclei of these groups were also not detected. Notably, disorganization of intercellular junctions was observed in many cardiomyocytes of T4–100 group. The present results indicate that in the early stages of hyperthyroidism, the cardiac hypertrophy development was mainly due to direct effects of thyroid hormone. Despite cardiac hypertrophy development, there is no ultrastructural evidence of myocardial degeneration.     

Chronic thyroiditis: thyroid function and histologic correlations in 601 cases.

Six hundred one patients with histologically proven "chronic thyroiditis" were assessed for the correlation of thyroid function to histologic findings. The histology of chronic thyroiditis was classified into four groups (oxyphilic, mixed, focal, and hyperplastic), and the thyroid function of patients was divided into hyperthyroid, euthyroid, latent hypothyroid, and overt hypothyroid, based on the laboratory data of serum triiodothyronine (T3), thyroxine (T4), and thyrotropin (TSH) levels, as well as thyrotropin-releasing hormone (TRH) tests. In the oxyphilic group (137 cases), 116 (85%) of the patients were classified as hypothyroid: 52 (38%) as latent hypothyroid and 64 (47%) as overt hypothyroid. In the mixed group (161 cases), the thyroid function of the patients varied. Thirty-seven (23%) of the patients were classified as hyperthyroid, 61 (39%) as euthyroid, 54 (33%) as latent hypothyroid, and nine (5%) as overt hypothyroid. In this group thyroid function was intimately related to the ratio of replacement by hyperplastic-changed follicles and oxyphilic-changed follicles. In the focal group (149 cases), 123 (83%) of the patients were classified as euthyroid, while 22 (14%) were classified as latent hypothyroid. The frequency of latent hypothyroid patients increased in parallel with the severity of cell infiltration. In the hyperplastic group (154 cases), 130 (85%) of the patients were classified as hyperthyroid. In this series 19 patients under 10 years of age were included, and no difference in the distribution of histologic varieties was observed between juvenile and adult patients. Thyroid needle biopsy is a useful and safe tool, not only for the histologic diagnosis of chronic thyroiditis, but also for the evaluation of thyroid function and the identification of causes for hyperthyroidism or hypothyroidism.     

Increased serum beta 2-microglobulin concentrations in hyperthyroid states.

Serum beta 2-microglobulin concentrations were determined in 21 untreated hyperthyroid patients (12 with Graves' disease, and nine with toxic nodular adenoma) and in 20 healthy controls. All subjects had normal serum creatinine concentrations and urine analysis. Both total and free thyroid hormones were significantly higher in the hyperthyroid groups than in controls. Beta 2-microglobulin concentrations were significantly increased in both groups of hyperthyroid patients compared with controls. No difference was found in the thyroid hormone and beta 2-microglobulin concentrations between both sets of patients. The beta 2-microglobulin and thyroid hormone concentrations were not correlated. These data show that hyperthyroidism is another cause of increased beta 2-microglobulin production along with viral infections, immunologically mediated diseases, and malignant neoplasms. The increased serum beta 2-microglobulin concentration in thyroid hyperfunction is probably related to metabolic rate, even if autoimmunity might contribute to its overproduction.     

甲亢和甲减患者血清PTH、CT水平的变化

目的：探讨了甲亢和甲减患者血清甲状旁腺素（PTH）和降钙素（CT）水平的变化。方法：应用放射免疫分析法测定了62例甲亢患者和32例原发性甲减患者血清中PTH、CT含量,并以35名健康人作对照。结果：甲亢组血清PTH水平低于正常人组（P＜0．05）、甲减组高于正常人组（P＜0．01）,CT水平两组均低于正常人组（P＜0．01）。结论：测定甲亢和甲减病人血清中PTH、CT水平的变化对了解病情,指导临床实践均有重要的临床意义 。     

血浆NT-ProBNP在~(131)碘治疗甲亢及甲亢性心脏病中的应用

目的:探讨血浆N末端脑钠肽前体(NT-ProBNP)在131碘治疗甲亢及甲亢性心脏病(甲亢心)中的应用价值。方法:亚临床甲亢组30例,平均年龄39.4±14.2岁,甲亢组45例,平均年龄42.9±16.7岁,甲亢心组21例,平均年龄46.4±13.9岁,正常对照组37例,平均年龄41.5±11.4岁,采用门控心肌显像法评价心脏功能,血浆NT-ProBNP、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)水平用罗氏电化学发光分析仪(Cobase601)测定。结果:甲状腺激素FT3、FT4与NT-ProBNP水平之间呈显著正相关,相关系数分别为0.505(P<0.01)和0.535(P<0.01);治疗前后的NT-ProBNP水平比较差异有显著性统计学意义(P<0.01)。结论:131碘治疗甲亢及甲亢心时,NT-ProBNP是评价疗效的有用指标。     

Increased serum PIVKA-II levels in hyperthyroidism]

PIVKA-II has been practically used as a tumor marker of hepatocellular carcinoma. On the other hand, increased serum PIVKA-II concentration was reported in a Japanese patient who had hyperthyroidism without liver diseases. To evaluate whether thyroid hormone is related with serum PIVKA-II, we examined serum PIVKA-II concentrations in patients with various thyroid diseases. Eight patients with Hashimoto disease, 24 patients with Graves' disease, and 8 healthy subjects were studied. There was no significant difference of serum PIVKA-II levels among the three groups. However, serum PIVKA-II concentrations(mean +/- SD mAU/ml) in hyperthyroidism(37 +/- 27) were significantly higher than those in hypothyroidism(16 +/- 9) and normal controls(12 +/- 4) (p < 0.05 and p < 0.01, respectively). When hyperthyroid patients were treated by antithyroid drug or isotope, serum PIVKA-II concentrations decreased in accordance with the decrease of serum FT4 concentrations. Our data indicate that serum PIVKA-II concentration was increased in patients with hyperthyroidism, but further in vivo studies are necessary to clarify the mechanism related to increased serum PIVKA-II by thyroid hormone.     

Radial partition fluorescent immunoassay of thyrotropin. Analytic evaluation and clinical correlation

The authors evaluated the analytic and clinical performance of a sensitive radial partition fluorescent enzyme immunoassay for thyrotropin (TSH) performed on Stratus and compared it with a nonsensitive radioimmunoassay (RIA) method. Sensitivity of 0.15 mIU/L was obtained, and precision, specificity, and linearity were acceptable. A good correlation was observed between the two assays in samples from 311 hospitalized patients (r = 0.976). Stratus TSH results were outside the reference range for 20% of clinically euthyroid patients (n = 126), and 2.4% had undetectable levels. The clinically hyperthyroid group (n = 11) with the exception of one patient had TSH values below 0.2 mIU/L. Only 39% of hypothyroid patients on thyroid hormone replacement (n = 74) had TSH values in the reference range, with 38% and 23% exhibiting low and high values, respectively. All untreated primary hypothyroid patients (n = 8) had elevated TSH concentrations. The authors conclude that this sensitive TSH assay is useful for diagnosing hyperthyroidism when there is a clinical suspicion but cannot be recommended for thyroid screening in hospitalized patients.     

甲状腺功能与血浆BNP的临床相关性研究

目的：B型脑钠肽（BNP）由心室心肌细胞分泌,并对血容量和压力负荷增加做出反应。在充血性心力衰竭时血浆BNP水平升高。本文旨在评估甲状腺的功能状态对血浆BNP水平的影响。方法：选择32例甲状腺功能亢进（甲亢）患者和36例甲状腺功能减退（甲减）患者,采用化学发光免疫分析测定其血浆FT3、FT4、TSH和BNP水平,并与33例正常对照作比较。结果：甲亢患者血浆BNP水平显著高于甲减组以及正常对照组,平均值分别为（203.03±48.61）pg/ml,（48.27±12.53）pg/ml,（57.96±13.59）pg/ml（P〈0.01）。血浆BNP水平与甲状腺的功能状态有显著的相关性（与FT4比较：r=0.625,P〈0.01,n=32）。多重线性回归分析提示FT3、FT4的值与BNP的水平具有独立相关性。结论：血浆BNP的水平受甲状腺的功能状态影响,这一点可能源于甲状腺激素是BNP的直接刺激物。     

Evaluation of brain natriuretic peptide levels in hyperthyroidism and hypothyroidism

BACKGROUND: Brain natriuretic peptide (BNP) is secreted from the ventricular myocardium in response to volume expansion and pressure overload. Serum BNP levels are also affected by thyroid function status, which was mostly related to a direct stimulatory effect of thyroid hormones on the secretion of BNP. Although the diagnostic value of BNP in heart failure is undisputed, its value in the presence of the thyroid dysfunction has been recently questioned. The aim of this study was to evaluate the influence of thyroid dysfunction on BNP levels. METHODS: Evaluation of 18 overt and 47 subclinical hyperthyroid patients together with 39 subclinical and 13 overt hypothyroid patients was carried out in a cross-sectional study. Thirty-three age-, sex- and body mass index (BMI)-matched control subjects were also included. RESULTS: BNP levels were more than five times higher in hyperthyroid than euthyroid control subjects (P < 0.001). BNP levels were also higher in subclinical hyperthyroidism than euthyroid control subjects (P = 0.09). Correlation analysis revealed that free T4 and free T3 concentrations were associated with high serum BNP levels. The BNP level in patients with subclinical or overt hypothyroidism was similar to that of the controls. CONCLUSION: The current study provides additional insight into the diagnostic value of BNP in the presence of coexistent thyroid dysfunction and demonstrates important independent effects of thyroid hormones upon BNP plasma concentrations.     

Cross-bridge and calcium behavior in ferret papillary muscle in different thyroid states

X-ray diffraction studies were made using synchrotron radiation on ferret right ventricular papillary muscle under three different thyroid states: euthyroidism, hyperthyroidism, and hypothyroidism. The latter two states were induced by treatment with L-thyroxine and methimazole, respectively. The X-ray equatorial reflections were recorded at a time resolution of 10 ms to study the mass movement of myosin cross-bridges from thick to thin filaments. The myosin isomer content was measured by gel electrophoresis which showed that V3 isomer was predominant in euthyroid muscle and 27% of myosin was V1 isomer in hyperthyroid muscle. The intracellular free Ca concentration was measured by using the aequorin method. The peak Ca concentration was similar in all three states, but in the hypothyroid state the time-to-peak was longer and the decay was slower. The time-to-peak of twitch tension was shorter in hyperthyroidism and longer in hypothyroidism than in euthyroidism. The different time courses of twitch tension in different thyroid states accompanied a cross-bridge movement which closely followed the tension development. In hyperthyroidism, the cross-bridge movement significantly preceded tension development, suggesting that hyperthyroid myosin (V1) has a longer latency period between the shift to the vicinity of the thin filament and force development.     

甲亢和甲减患者血浆心钠素和内皮素的检测及其临床意义

采用放免法检测58例甲亢和47例甲减患者血浆心钠素(ANF)和内皮素(ET)水平.甲亢未治组ANF和ET水平显著高于甲亢缓解组、 甲减未治组、甲减治疗组及对照组(P＜0.01), ANF和ET水平与血清FT3、FT4存在正相关.甲亢缓解组、 甲减未治组和治疗组ANF浓度与对照组比较无显著性差异(P＞0.05),但甲减未治组ANF明显低于治疗组(P＜0.05).甲亢缓解组、 甲减治疗组ET与对照组比较无显著性差异(P＞0.05),但甲减未治疗组ET均明显低于其它组(P＜0.01,P＜0.05).测定ANF和ET对甲亢和甲减的辅助诊断和疗效观察具有一定临床价值.     

Thyroid hormone regulates excitability in central neurons from postnatal rats

A lack of thyroid hormone in the postnatal period causes an irreversible mental retardation, characterized by a slowing of thoughts and movements accompanied by prolonged latencies of several evoked potentials and slowed electroencephalographic rhythms. Here we show that in cultured hippocampal and cortical neurons from postnatal rats treatment with thyroid hormone not only up-regulates Na(+)-current densities but also increases rates of rise, amplitudes and firing frequencies of action potentials. Furthermore, we show that the regulation of the Na(+)-current density by thyroid hormones also occurs in vivo: recordings from acutely isolated cortical neurons obtained from hypothyroid, euthyroid and hyperthyroid postnatal rats showed that hypothyroidism decreases the ratio of Na(+) inward- to K(+) outward-currents while hyperthyroidism upregulates Na(+)-currents with respect to K(+)-currents. Our observation of a regulation of neuronal excitability by thyroid hormone offers a direct explanation for the origin of various neurological symptoms related to thyroid dysfunction.     

成人原发性甲减患者血浆SS、SP含量的变化

目的:观察成人原发性甲状腺机能减退(甲减)患者甲状腺素(TH)治疗前后脑神经肽变化,以探索甲减致脑中枢神经系统损害的机制。方法:采用放射免疫分析,对比分析了45例成人原发性甲减患者TH治疗前后血浆中生长抑素(SS)、P物质(SP)变化。结果:甲减组血浆中SP水平明显低于正常对照组(P<0.01),SS水平与正常对照组比较无显著性差异(P>0.05),其中FT3≥2.5pmol/L组病人血浆中SS水平与正常对照组比较无显著性差异(P>0.05),FT3<2.5pmol/L组血浆中SS含量低于正常对照组(P<0.05),经过TH治疗后SS、SP水平提高(P<0.05,P<0.01)。结论:成人原发性甲减患者血浆存在不同程度的SS、SP减低,这与其引起的神经精神症状可能密切相关,早期、积极、正规的TH治疗对脑功能的恢复有很重要的意义。     

The ultrasensitive determination of TSH permits the prediction of the response to TSH in the TRH test

A new ultrasensitive TSH immunoradiometric assay (IRMA) using two monoclonal antibodies is now able to distinguish between euthyroid and hyperthyroid patients. The aim of this study was to compare data given by ultrasensitive basal TSH (IRMA) and by the response of TSH to TRH test considered until now as the more reliable test in case of mild or atypical hyperthyroidism. Basal plasma TSH levels were determined in euthyroid (n = 80), hyperthyroid (n = 30), hypothyroid (n = 14) and pituitary deficient patients (n = 8) before and 30 minutes after a TRH test (250 micrograms i.v.). A close linear correlation was found between basal and post-stimulative TSH levels. Normal TSH response ranged from 2 to 22 uU/ml. The sensibility and the specificity of these two parameters appeared comparable in the case of primary dysthyroidism; on the contrary basal TSH levels were not sufficient for the diagnosis of central hypothyroidism. In conclusion, excepted for pituitary deficiency, basal plasma TSH (IRMA) levels are accurate and sufficient in the evaluation of the thyroid function and make the TRH-test useless.     

Peripheral effects of thyroid hormones: Alteration of intracellular Na-concentration,ouabain-sensitive Na-transport,and Na-Li countertransport in human red blood cells

Summary To investigate the effect of thyroid hormones on erythrocyte cation transport systems and intracellular electrolyte content we have measured the activity of Na-K ATPase, Na-Li countertransport, as well as red cell sodium and potassium contents in patients with hyperthyroidism and in euthyroid controls. Intracellular Na- and K-concentrations were determined in erythrocytes washed three times in isotonic MgCl₂ solution. Ouabain-sensitive Na-transport was estimated as the increase of Na before and after addition of ouabain in an erythrocyte suspension in isotonic Na-free medium. Na-Li countertransport was measured according to the method described by Canessa et al. [2]. The patients with hyperthyroidism exhibited a significantly elevated intracellular sodium content as well as a highly increased Na-K ATPase activity. Intracellular potassium content was not altered in the hyperthyroid subjects, but Na-Li countertransport was markedly decreased as compared to the controls.The results indicate that different ion transport systems of the erythrocyte membrane are influenced by thyroid hormones. We suggest that the elevation of Na-K ATPase activity might be due to the increased intracellular sodium concentration which is caused by the diminished countertransport pathway. Furthermore, the activity of Na-K ATPase, Na-Li countertransport, and intracellular sodium content in erythrocytes might be a useful peripheral indicator of thyroid hormone excess.Supported by the Bundesministerium für Forschung und Technologie (MMT 27)     

Iron supplementation in experimental hyperthyroidism: effects on oxidative stress in skeletal muscle tissue

This study was designed to investigate the effects of iron supplementation on the parameters of oxidative stress in the skeletal muscle tissue of hyperthyroidism induced rats. Hyperthyroidism was found to cause an increase in thiobarbituric acid-reactive substances (TBARS) and copper zinc superoxide dismutase (Cu, Zn SOD) activity, but decreases in the glutathione-peroxidase (GSH Px) activity and glutathione (GSH). Iron supplementation caused an increase in TBARS and a decrease in GSH. Iron supplementation in hyperthyroid rats attenuated the hyperthyroid state, but lowered the plasma ferritin level, which is considered an indicator of thyroid hormone action. Iron supplementation caused no additional increase in the TBARS in hyperthyroid rats, ameliorated the decrease in GSH content and abolished the induction of Cu, Zn SOD. Our findings suggested no increase, but a decrease, in the risk of oxidative stress in iron supplemented hyperthyroid rats. Whether supplementation of iron would have similar effects in humans should be further investigated in clinical studies.     

Influence of thyroid dysfunction on liver lipid peroxidation and antioxidant status in experimental rats

The purpose of this study was to evaluate the effects of dysthyroidism on lipid peroxidation, antioxidants status, liver, and serum dysfunction parameters in the hypo-/hyperthyroidism-induced rats. Hypothyroidism and hyperthyroidism conditions were induced for 5 weeks by administration of 0.05% benzythiouracile (BTU) and l-thyroxine sodium salt (0.0012%), in drinking water, respectively. The enzymatic activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and the lipid peroxidation product; thiobarbituric acid reacting substances (TBARS) were measured in liver as indicators of oxidative damage. However, liver dysfunction parameters represented by the activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma glutamyl transferase (GGT), were measured in serum. In hyperthyroidism rats, the TBARS contents of liver have significantly increased compared to those in hypothyroid rats and the controls (p<0.001), associated with a fall of the total antioxidant status (TAS) in the serum of the hyperthyroid rats. The SOD, CAT, and GPx activities in liver of hyperthyroid rats have significantly increased compared to hypothyroid rats and the controls (p<0.001). The AST, ALT, LDH, GGT, and ALP activities increased in the hyperthyroidism rats (p<0.05).We conclude that thyroid dysfunction induces oxidative stress and modifies some biochemical parameters of liver. Our results show the occurrence of a state of oxidizing stress in relation to hyperthyroidism.     

The effect of altered thyroid state on atrial intracellular potentials

1. A group of rabbits was made hypothyroid by thyroidectomy, and another group was injected daily with L-thyroxine. After an appropriate interval respective alterations in thyroid state were confirmed by measurement of heart weight and of plasma iodine, and the animals' atria were isolated for recording.2. Measurements were made of atrial contractions, conduction velocity, spontaneous heart rate and maximum driven frequency, and action potentials were recorded with intracellular micro-electrodes.3. The resting potential and action potential heights were not affected by differences of thyroid state.4. Atrial arrhythmias are common in hyperthyroidism, rare in myxoedema. The possibility that hypothyroidism might reduce the rate of rise of the action potential, as do anti-arrhythmic drugs, and hyperthyroidism increase it, was investigated. Although the rate of rise was slower in hypothyroid atria at some driving frequencies, this could not alone account for an anti-arrhythmic effect, because at frequencies near the spontaneous heart rate the rate of rise of the action potential was not reduced.5. The duration of the repolarization phase of the action potential was greatly prolonged in atria from thyroidectomized rabbits, and was shortened in hyperthyroid atria. These changes could account for a reduced probability of arrhythmias in hypothyroidism, and the converse in hyperthyroidism.