Hyperthyroidism is associated with suppressed circulating ghrelin levels

Ghrelin stimulates GH secretion as well as appetite and food intake. To explore whether ghrelin is involved in the regulation of appetite and body weight in hyperthyroidism, circulating ghrelin levels were measured in nine hyperthyroid patients before and after medical treatment and compared with those in eight healthy control subjects. All participants were studied in the postabsorptive state and during a 3-h euglycemic hyperinsulinemic clamp. Before treatment the patients had 3- to 5-fold elevations of T(3), and during treatment the patients gained 5 kg of body weight. Ghrelin levels were decreased in hyperthyroidism both in the fasting state (hyperthyroid, 1080 +/- 195 pg/ml; euthyroid, 1480 +/- 215 pg/ml; P = 0.03) and during clamp (hyperthyroid, 833 +/- 150 pg/ml; euthyroid, 1210 +/- 180 pg/m; P = 0.02). After treatment, ghrelin levels did not differ from those in control subjects. In all three study groups the clamp significantly reduced ghrelin levels compared with fasting levels. In conclusion, ghrelin levels are reduced in hyperthyroidism and become normalized by medical antithyroid treatment. Hyperinsulinemia suppresses ghrelin regardless of thyroid status. Ghrelin is not a primary stimulator of appetite and food intake in hyperthyroidism, and the mechanisms underlying the suppressive effect of hyperthyroidism on ghrelin secretion remain unclear.     

Evaluation of endothelial function in subclinical hypothyroidism and subclinical hyperthyroidism.

Subclinical hypothyroidism and subclinical hyperthyroidism are two frequently occurring conditions for which exact therapeutic approaches have not yet been established. The aim of this study was to compare the endothelial function and carotid artery intimae-media thickness (IMT) of these two groups of patients to euthyroid subjects and to assess the effects of these conditions on endothelial function. Study groups comprised of 25 subclinical hypothyroid patients (mean age, 32.28 +/- 9.67 years), 13 subclinical hyperthyroid patients (mean age, 35.69 +/- 9.67 years), and 23 euthyroid subjects (mean age, 35.87 +/- 7.93 years). They were evaluated for flow-mediated dilatation (FMD), and carotid artery IMT. The groups were matched strictly for atherosclerotic risk factors. The subclinical hypothyroid group was found to have significantly lower FMD values. No significant differences were observed between the groups with respect to other vascular parameters. The only discriminative factor between the groups was the state of their thyroid function. Therefore, subclinical hypothyroidism may have adverse effects on endothelial function independent from other well-known atherosclerotic risk factors.     

Changes in endothelium-dependent arterial dilation before and after subtotal thyroidectomy in subjects with hyperthyroidism

OBJECTIVE: This case-control study was carried out to assess the alteration of endothelium-dependent arterial dilation before and after subtotal thyroidectomy in subjects with hyperthyroidism. PATIENTS AND METHODS: The study subjects included 12 patients with hyperthyroidism and 39 apparently healthy individuals. We performed a subtotal thyroidectomy on the hyperthyroid patients. The endothelium-dependent arterial dilation was determined with a high-resolution ultrasound method in each patient at the hyperthyroid stage before treatment (stage H), the euthyroid stage induced immediately before surgery (stage E), and the transient hypothyroid stage 1 or 2 months after surgery (stage L). RESULTS: The flow-mediated arterial dilation decreased significantly from H to E and from E to L (P < 0.001). As compared with H, baseline blood flow decreased markedly at stages E and L (P < 0.001). The flow-mediated arterial dilation and baseline blood flow in the control subjects were very close to those at stage E of the hyperthyroid patients. The absolute change in the flow-mediated arterial dilation showed significant negative correlation with the changes in TSH (r =-0.86, P < 0.001), lipoprotein (a) [Lp(a)] (r =-0.77, P < 0.001) and low density lipoprotein (LDL) (r =-0.79, P < 0.001), and significant positive correlation with changes in fT3 (r =+0.88, P < 0.001). The absolute change in the baseline blood flow showed significant positive correlation with the change in fT3 (r =+0.85, P < 0.001) and significant negative correlation with the change in TSH (r =-0.63, P < 0.01). CONCLUSION: The endothelium-dependent arterial dilation increases significantly in untreated hyperthyroid patients, and decreases markedly after a subtotal thyroidectomy. Therefore, we conclude that the endothelium is more responsive to reactive hyperaemia in the hyperthyroid than the euthyroid state.     

Endothelial dysfunction precedes atherosclerosis in systemic sclerosis--relevance for prevention of vascular complications

OBJECTIVES: The pathogenesis of systemic sclerosis (SSc) includes vasculopathy with endothelial dysfunction. The aim of this study was to investigate endothelium-dependent, flow-mediated dilatation (FMD), as well as endothelium-independent, nitroglycerin-mediated dilatation (NMD) of the brachial artery and to assess common carotid intimal-medial thickness (ccIMT) in SSc patients compared with healthy controls. METHODS: FMD and NMD of the brachial artery were determined using high-resolution ultrasound imaging and the values were expressed as percentage change from baseline in 29 SSc patients and 29 healthy controls. The two groups were very similar regarding sex, age and traditional cardiovascular risk factors. In addition, common carotid arteries were assessed by duplex colour ultrasound, ccIMT determined using high resolution ultrasound and expressed in mm thickness in the same patients and controls. Correlations between FMD, NMD, ccIMT, age and the SSc subtype (diffuse or limited form) were analysed. RESULTS: In the 29 SSc patients (mean age: 51.8 yrs), the FMD was significantly lower (4.82 +/- 3.76%) in comparison with the controls (8.86 +/- 3.56%) (P < 0.001). No difference was found in NMD between patients (19.13 +/- 17.68%) and controls (13.13 +/- 10.40%) (P > 0.1). There was a tendency of increased ccIMT in SSc patients (0.67 +/- 0.26 mm) compared with healthy subjects (0.57 +/- 0.09), but this difference was not significant (P = 0.067). A significant, positive correlation between ccIMT and age in SSc (r = 0.470, P = 0.013) was detected, as well as in healthy controls (r = 0.61, P = 0.003), but no correlation was found between FMD and age. In addition, ccIMT, but not FMD and NMD, displayed significant correlation with disease duration (r = 0.472, P = 0.011). NMD displayed significant inverse correlation with the age in SSc patients (r = -0.492, P = 0.012), but not in controls. We did not find any correlation between FMD, NMD, ccIMT and SSc subtype. CONCLUSIONS: There is an impairment of endothelium-dependent vasodilatation indicated by low FMD in SSc. At the same time, the endothelium-independent dilatation assessed by NMD is still preserved giving an opportunity of nitroglycerine therapy. Carotid atherosclerosis indicated by ccIMT may occur at higher ages and after longer disease duration. Thus, the assessment of FMD in the pre-atherosclerotic stage may have a beneficial diagnostic, prognostic and therapeutic relevance.     

Lipolytic and ketogenic fluxes in human hyperthyroidism

The effect of hyperthyroidism on lipolytic and ketogenic fluxes was determined by measuring simultaneously (stable isotope methodology) glycerol, nonesterified fatty acids (NEFA), and ketone body (KB) kinetics in euthyroid and hyperthyroid subjects. In the postabsorptive state hyperthyroid patients had normal concentrations of insulin and glucagon, but increased concentrations (P less than 0.01) and turnover rates (P less than 0.01) of glycerol, NEFA, and KB. The ratio of NEFA appearance rate to glycerol appearance rate was decreased in hyperthyroid subjects (2.34 +/- 0.23 vs. 3.15 +/- 0.22; P less than 0.05), indicating that intracellular cycling between triglycerides and fatty acids was increased. The percentage of NEFA flux used for KB production, calculated from NEFA disappearance rates and KB appearance rates, was increased in hyperthyroid patients (21.20 +/- 2.75% vs. 13.37 +/- 0.63%; P less than 0.05), suggesting a diversion during hyperthyroidism of hepatic fatty acid metabolism toward ketogenesis. However, when the plasma NEFA levels of control subjects were raised by the infusion of a triglyceride emulsion to levels comparable to those observed in hyperthyroid patients their percentage of NEFA flux used for ketogenesis rose to values slightly higher (26.30%) than those of hyperthyroid subjects. In conclusion, 1) hyperthyroidism results not only in increased lipolysis, but also in enhanced triglyceride-fatty acid cycling, which could contribute to the excessive energy expenditure; and 2) the increased KB production of hyperthyroid patients results more from an increase in NEFA availability than from a direct stimulation of hepatic ketogenesis.     

Altered plasma catecholamines and numbers of alpha- and beta-adrenergic receptors in platelets and leucocytes in hyperthyroid patients normalized under antithyroid treatment

We measured plasma catecholamines, alpha- and beta-adrenoreceptor numbers and the accumulation of cyclic adenosine monophosphate (cAMP) in the unstimulated state and in response to 10 mumol/l (-) isoproterenol in blood cells from 29 euthyroid controls and from 18 patients with spontaneous hyperthyroidism. In the thyrotoxic patients plasma norepinephrine (1.14 +/- 0.5 nmol/l) and epinephrine (0.3 +/- 0.14 nmol/l) were significantly decreased compared with plasma norepinephrine (1.87 +/- 0.7 nmol) and epinephrine (0.41 +/- 0.19 nmol/l) in the controls (P less than 0.01 and P less than 0.05, respectively) and the values obtained in subjects rendered euthyroid by antithyroid treatment (P less than 0.001, respectively). alpha-adrenoceptor density in platelet membranes obtained from patients in the hyperthyroid state (114 +/- 38 sites per cell) was significantly decreased when compared with controls (159 +/- 48 sites per cell, P less than 0.01) and the values from patients under effective antithyroid treatment (136 +/- 35 sites per cell, P less than 0.01). On the contrary, a significant increase in beta-adrenoceptor density in mononuclear leucocyte (MNL) membranes was found in hyperthyroid patients (1751 +/- 237 sites/cell) when compared with controls (1510 +/- 351 sites/cell, P less than 0.05) and the same patients following antithyroid treatment (1455 +/- 260 sites/cell, P less than 0.001). The equilibrium dissociation constants (KD) did not change in hyperthyroidism. Basal cAMP concentrations in MNL were higher in untreated thyrotoxicosis (45 +/- 18 pmol/10(6) cells/10 min) than in patients in the euthyroid state (35 +/- 9 pmol/10(6) cells/10 min, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

冠心病患者动脉弹性与血管舒张功能受损的关系

目的探讨冠心病患者动脉弹性和内皮与非内皮依赖性血管舒张功能的关系。方法采用高分辨率血管超声法检测30例冠心病患者(冠心病组)与健康体检非冠心病者30例(对照组)肱动脉血流介导的内皮依赖性血管舒张功能及硝酸甘油介导的非内皮依赖性血管舒张功能;动脉弹性功能检测仪测定受试者的大动脉弹性指数(C1)和小动脉弹性指数(C2)。结果冠心病组与对照组的C1差异无显著性意义,但冠心病组的C2明显低于对照组,冠心病组内皮依赖性血管舒张功能与非内皮依赖性血管舒张功能均明显低于对照组;冠心病组C2不仅与内皮依赖性血管舒张功能呈正相关,且同非内皮依赖性血管舒张功能呈正相关。结论冠心病组C2降低,C2降低不仅同血管内皮功能的受损相关,而且也受非内皮因素的影响,提示C2反映总体血管舒张功能受损的程度。     

Determinants of changes in plasma homocysteine in hyperthyroidism and hypothyroidism

OBJECTIVE: Hyperhomocysteinaemia is a risk factor for premature atherosclerotic vascular disease and venous thrombosis. The aim of the present study was to assess plasma total homocysteine (tHCys) concentrations in hypo- as well as hyperthyroid patients before and after treatment, and to evaluate the role of potential determinants of plasma tHCys levels in these patients. DESIGN: Prospective follow up study. PATIENTS: Fifty hypothyroid and 46 hyperthyroid patients were studied in the untreated state and again after restoration of euthyroidism. MEASUREMENTS: Fasting plasma levels of tHCys and its putative determinants (plasma levels of free thyroxine (fT4), folate, vitamin B(12), renal function, sex, age, smoking status and the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene were measured before and after treatment. RESULTS: Restoration of the euthyroid state decreased both tHCys (17.6 +/- 10.2-13.0 +/- 4.7 micromol/l; P < 0.005) and creatinine (83.9 +/- 22.0-69.8 +/- 14.2 micromol/l; P < 0.005) in hypothyroid patients and increased both tHCys (10.7 +/- 2.5-13.4 +/- 3.3 micromol/l; P < 0.005) and creatinine (49.0 +/- 15.4-66.5 +/- 15.0 micromol/l; P < 0.005) in hyperthyroid patients (values as mean +/- SD). Folate levels were lower in the hypothyroid group compared to the hyperthyroid group (11.7 +/- 6.4 and 15.1 +/- 7.6 nmol/l; P < 0.05). Pretreatment tHCys levels correlated with log fT(4) (r = - 0.47), folate (r = - 0.21), plasma creatinine (r = 0.45) and age (r = 0.35) but not with C677T genotype. Multivariate analysis indicated that pretreatment log(fT(4)) levels and age accounted for 28% the variability of pre-treatment tHCys (tHCys = 14.2-5.50 log(fT(4)) + 0.14 age). After treatment the logarithm of the change (Delta) in fT(4) (expressed as the post-treatment fT(4)/pre-treatment fT(4) ratio) accounted for 45% of the variability in change of tHCys ( tHCys = - 0.07-4.94 log ( fT(4))); there was no independent contribution of changes in creatinine which was, however, strongly related to changes in tHCys (r = 0.61). CONCLUSIONS: Plasma tHCys concentrations increased in hypothyroidism and decreased in hyperthyroidism. Plasma fT(4) is an independent determinant of tHCys concentrations. Lower folate levels and a lower creatinine clearance in hypo-thyroidism, and a higher creatinine clearance in hyperthyroidism only partially explain the changes in tHCys.     

Peripheral bone density in women with untreated multinodular goitre

OBJECTIVES: We wished to determine whether women with multinodular goitre and spontaneous subclinical hyperthyroidism have decreased bone density. DESIGN AND SUBJECTS: Bone density was measured at the distal and proximal forearm. Data were expressed as Z-scores relative to the mean values out of 125 control subjects matched for age and menopause. The Z-scores of 23 women with subclinical hyperthyroid goitre (TSH < 0.1 mU/l and normal values for FT4 and total T3) and of 54 women with euthyroid goitre were compared. MEASUREMENTS: Bone density was measured by single photon absorptiometry. TSH was measured by IRMA, FT4 by RIA. RESULTS: Relative to the euthyroid goitre subjects the mean +/- SEM Z-scores of both the distal and proximal forearm density were lower (-0.69 +/- 0.17 vs -0.1 +/- 0.18, P < 0.05 and -0.5 +/- 0.18 vs 0.07 +/- 0.18, P < 0.05, respectively). Median (range) FT4 in the subclinical hyperthyroid goitre subjects was significantly higher than euthyroid goitre subjects (15.6 (11-23.2) pmol/l vs 11.9 (8.3-18.3) pmol/l, P < 0.001) although still within the normal range. FT4 correlated inversely with Z-scores of both distal and proximal forearm bone density in the subjects with subclinical hyperthyroidism (r = -0.42, P < 0.05 and r = -0.43, P < 0.05, respectively), but not in the euthyroid goitre subjects. CONCLUSION: These findings indicate that women with untreated multinodular goitre and subclinical hyperthyroidism have reduced bone density in the forearm.     

Erythrocyte sorbitol levels in patients with thyrotoxicosis

Hyperglycemia and impaired glucose tolerance are frequently observed in patients with hyperthyroidism. However, little is known about whether altered polyol metabolism in hyperthyroidism is present or not. To examine changes in polyol metabolism in hyperthyroidism, we investigated changes in erythrocyte sorbitol, glyceraldehyde reductase (GAR) and sorbitol dehydrogenase (SDH) activities during hyperthyroid and euthyroid states in patients with thyrotoxicosis. Mean levels of erythrocyte sorbitol and GAR were 32.0 +/- 1.6nM/g.Hb and 147.1 +/- 0.3mU/g.Hb, respectively. In thyrotoxic patients in a hyperthyroid state, these values were significantly higher than those in euthyroid controls. Mean level of erythrocyte SDH in thyrotoxic patients was weak but was significantly increased in comparison with that of euthyroid controls. However, mean levels of erythrocyte sorbitol and GAR were remarkably reduced to 23.6 +/- 1.4nM/g.Hb and 125.3 +/- 4.6mU/g.Hb in thyrotoxic patients in a euthyroid state after treatment with anti-thyroid drugs or by subtotal thyroidectomy. Mean level of SDH, on the other hand, was increased after the treatment. In addition, positive correlations were observed between the level of erythrocyte sorbitol or GAR, and the level of free thyroxine(FT4) or free triiodothyronine(FT3). A negative correlation was observed between the level of erythrocyte SDH and the level of FT4 or FT3. These results suggest that the level of erythrocyte sorbitol may be increased through direct acceleration of erythrocyte GAR activity by increased thyroid hormone levels in patients with thyrotoxicosis.     

Endothelial dysfunction in patients with polycythaemia vera

Patients with polycythaemia vera (PV) are at increased risk of developing arterial and venous thromboembolic complications. We investigated whether endothelium-dependent, flow-mediated vasodilatation (FMD) is impaired in PV patients without clinical evidence of artery disease as observed in patients with conventional cardiovascular risk factors. FMD and endothelium-independent, nitroglycerine-induced vasodilatation (NMD) were assessed using high-resolution ultrasound in the brachial artery of 20 patients with PV and 20 sex- and age-matched control subjects (CTL). FMD was markedly impaired in PV patients compared with CTL (7.6 +/- 2.9% versus 11.6 +/- 5.7%, P = 0.009) whereas NMD was similar in both study groups. The impairment of FMD was independently related to the presence of PV (r = -0.434, P = 0.009) and vessel size (r = -0.107, P = 0.038) but was not related to haematocrit values and platelet counts. The results demonstrate that PV is associated with endothelial dysfunction in the pre-clinical phase of arterial disease. However, the precise mechanisms by which PV leads to this altered vascular reactivity remain unclear.     

Enhanced coronary calcification determined by electron beam CT is strongly related to endothelial dysfunction in patients with suspected coronary artery disease

BACKGROUND: Coronary artery calcification determined by electron beam CT (EBCT) is strongly associated with total plaque burden but is not related to systemic vascular inflammation.Aims: We sought to test the hypothesis that enhanced coronary artery calcification, a marker of atherosclerosis and plaque burden, was related to endothelial dysfunction in patients with suspected coronary artery disease (CAD). METHODS AND RESULTS: One hundred twenty-four subjects with suspected CAD were enrolled. Coronary artery calcification was detected by EBCT. A noninvasive method of brachial ultrasound was used to measure endothelium-dependent flow-mediated vasodilation (FMD) and endothelium-independent nitroglycerin-mediated vasodilation (NMD). Serum high-sensitivity C-reactive protein (hsCRP) and monocyte chemoattractant protein-1 (MCP-1) levels were also determined. Of the 124 patients, the calcium scores ranged from 0 to 4,394. All subjects were classified into three groups according to coronary calcium scores: group 1, score 0 (n = 26); group 2, scores 1 to 199 (n = 50); group 3, scores > or = 200 (n = 48). There was an inverse association between the degree of coronary artery calcification and the endothelium-dependent FMD in the three groups (6.9 +/- 0.6% vs 5.3 +/- 0.3% vs 3.7 +/- 0.3%, respectively; p < 0.001) but not the endothelium-independent NMD. Besides, no significant difference in serum levels of hsCRP and MCP-1 were found among the three groups. However, both the serum levels of hsCRP and MCP-1 were correlated significantly with endothelium-dependent FMD (r = - 0.211, p = 0.019; and r = - 0.188, p = 0.037, respectively). By multivariate analysis, enhanced coronary calcification was a strong independent predictor of endothelial dysfunction (p < 0.001). CONCLUSION: Enhanced coronary artery calcification strongly predicted endothelial dysfunction in patients with suspected CAD. Also, serum levels of hsCRP and MCP-1 were significantly correlated with endothelial function. These findings suggested that both calcium deposition and inflammation were involved in endothelial dysfunction.     

Serum paraoxonase activity before and after treatment of thyrotoxicosis

OBJECTIVE: Antioxidant effects of paraoxonase, a high density lipoprotein (HDL)-associated enzyme that inhibits low density lipoprotein cholesterol (LDL-C) oxidation in human serum, have been reported. Patients with thyroid dysfunction are more susceptible to oxidative stress, and may show enhanced LDL-C oxidation. The purpose of this study was to evaluate serum paraoxonase activity in patients with hyperthyroidism before and after treatment with methimazole (MMI). DESIGN AND PATIENTS: Twenty-four hyperthyroid patients (15 women and nine men, aged 43.0 +/- 12.9 years) and 23 age- and sex-matched healthy controls were studied. Serum paraoxonase activity, lipid, lipoprotein and apolipoprotein levels were measured in fasting samples. Patients were treated with MMI 20-30 mg daily for the first month, and 5-10 mg daily thereafter, and re-evaluated after 6-9 months of treatment. RESULTS: Significantly lower serum paraoxonase activity was present in hyperthyroid patients before treatment compared with the controls (43.4 +/- 21.9 vs. 72.6 +/- 41.2 U/ml, P < 0.005). After a mean follow-up of 7.3 months, 15 patients became euthyroid (treated) and nine were still hyperthyroid. After follow-up, serum paraoxonase activity had increased to 62.2 +/- 37.4 U/ml in those who became euthyroid (P < 0.05 compared with baseline). In patients who were still hyperthyroid serum paraoxonase was unchanged from baseline, at 43.2 +/- 23.2 U/ml. CONCLUSION: Serum paraoxonase is reduced in patients with hyperthyroidism and reverts to normal after euthyroidism is attained. Reduced serum paraoxonase activity in thyrotoxicosis might predispose lipids to oxidation.     

Work capacity and oxygen uptake abnormalities in hyperthyroidism

AIM: The aim of our study was to evaluate the haemodynamic and the respiratory response to exercise in patients with hyperthyroidism before and 30 days after normalized thyroid hormones levels. These findings were compared with those of 10 control patients. METHODS: Thirty patients (23 women, aged 34.3 +/- 12 years) with untreated hyperthyroidism were studied. Twenty-four patients were treated with methimazole, 13 of which were also treated with propranolol. Six patients underwent surgery. A symptom-limited cardiopulmonary exercise test and an echocardiography were performed in all patients. RESULTS: At rest patients with hyperthyroidism showed at echocardiography an increased cardiac index (P = 0.006 vs euthyroid, P = 0.007 vs normal) and a higher ejection fraction (P = 0.008 vs euthyroid, P = 0.007 vs normal). The duration of the exercise was lower in hyperthyroid patients (P = 0.006 vs euthyroid; P = 0.0068 vs normal). Anaerobic threshold was reached at 49.6% of peak VO2 during hyperthyroidism, at 60.8% during euthyroidism (P = 0.01) and at 62% in normal (P = 0.01). Work rate was lower in patients with hyperthyroidism at anaerobic threshold (P = 0.01 vs euthyroid, P = 0.03 vs normal) and at maximal work (P = 0.001 vs euthyroid, P = 0.01 vs normal). Patients in hyperthyroidism showed a lower increment of heart rate between rest and anaerobic threshold (P = 0.021 vs euthyroid, P < 0.0001 vs normal) and a lower VO2 at anaerobic threshold (P = 0.03 vs euthyroid; P = 0.04 vs normal). Oxygen pulse at anaerobic threshold was significantly reduced in hyperthyroidism (P = 0.04 vs euthyroid, P = 0.005 vs normal). CONCLUSIONS: The mean result is that after only 30 days of appropriate antithyroid treatment there was an appreciable improvement of exertion capacity.     

Cardiac and plasma catecholamine response to dynamic exercise in hyperthyroidism]

To investigate cardiac and sympathoadrenal responses to dynamic exercise, heart rate, systolic blood pressure, serial plasma norepinephrine (NE) and epinephrine (E) concentrations during multistage treadmill exercise were measured in 24 hyperthyroid patients (mean age; 42 +/- 16) and 24 age-sex matched control subjects. Eleven patients were re-examined in the euthyroid state after antithyroid therapy. Exercise duration was shorter in patient with hyperthyroidism. Also, the heart rates and systolic blood pressures at rest and in the early stage of exercise were significantly higher in hyperthyroidism. NE at rest (normal vs hyperthyroid: 124 +/- 10 vs 80 +/- 7 pg/ml, p < 0.01) and NE at peak exercise (475 +/- 38 vs 310 +/- 38 pg/ml, p < 0.01) were lower in hyperthyroidism. E at rest (22 +/- 2 vs 29 +/- 4 pg/ml, n.s.) did not differ, however, E during the first stage of exercise (30 +/- 3 vs 69 +/- 12 pg/ml, p < 0.01) was higher in hyperthyroidism. Re-examination for the euthyroid state revealed the decreases in the heart rates and systolic blood pressures at rest and in the early stage of exercise, and the normalization of the NE and E response. Thus, patients with hyperthyroidism was in the hyperdynamic cardiac state at rest and during dynamic exercise, which was accounted for by decreased sympathetic nervous activity and increased adrenomedullary responses. These modifications of sympathoadrenal response seemed reversible when patients were controlled by antithyroid therapy.     

老年周围动脉闭塞性疾病内皮和非内皮依赖性舒张功能的无创研究

目的　探讨老年周围动脉闭塞性疾病 (peripheralarterialocclusivedisease,PAOD)内皮依赖性舒张功能 ,即血流介导的血管扩张功能 (flow mediateddilation ,FMD)和硝酸甘油介导的非内皮依赖性舒张功能 (nitroglycerin mediateddi lation,NMD)状况及其相关因素。方法　采用超声多普勒检测 33例已确诊为PAOD的老年患者肱动脉FMD及NMD ,并分别与 40例健康老年人及 30例具有心血管危险因素的老年非PAOD患者进行对照研究。结果　老年PAOD患者FMD及NMD均显著低于对照组 ;肱动脉基础内径、收缩压、低密度脂蛋白胆固醇与FMD呈负相关 ;FMD与NMD呈正相关 ,肱动脉基础内径与NMD呈负相关。结论　老年PAOD患者FMD及NMD均受损 ;肱动脉基础内径、收缩压、低密度脂蛋白胆固醇可能是FMD独立的预测因子 ;而FMD及肱动脉基础内径与NMD密切相关。     

Recombinant human thyrotropin reduces endothelium-dependent vasodilation in patients monitored for differentiated thyroid carcinoma

AIM: We evaluated endothelial-dependent vasodilation after administration of recombinant human TSH (rhTSH) in patients monitored for differentiated thyroid carcinoma. The role of inflammation and oxidative stress was also assessed. PROTOCOL: Twenty-four patients (21 women, mean age 40.5 +/- 9.2 yr) received rhTSH (0.9 mg daily) on 2 consecutive days. At baseline and the day after the second rhTSH injection, endothelium-dependent vasodilation as flow-mediated dilation (FMD, induced by 5 min of forearm ischemia) and endothelium-independent vasodilation (glyceril trinitrate 25 microg, sublingual) were evaluated by high-resolution ultrasound in the brachial artery. At each experimental time, blood was drawn for the evaluation of thyroglobulin, TSH, free T(3), free T(4), as well as IL-6, C reactive protein, TNFalpha, lipoperoxides, and ferric reducing antioxidant power levels as markers of inflammation and oxidative stress. RESULTS: At baseline, patients' serum TSH values were below the normal range [0.12 mIU/liter (range 0.01-0.30)] in the face of normal free T(4) and free T(3) levels; FMD (8.9 +/- 3.4 vs. 9.2 +/- 3.1%, respectively) and response to glyceril trinitrate (11.0 +/- 4.3 vs. 10.8 +/- 4.7%, respectively) were similar in patients and controls. All the patients had serum thyroglobulin value less than 1 ng/ml, suggesting the absence of cancer recurrences. Besides the expected elevation of serum TSH, rhTSH induced a significant impairment of FMD (7.4 +/- 3.0 vs. 8.9 +/- 3.4%; P < 0.01) along with a significant elevation of blood IL-6 (P = 0.01), TNFalpha (P < 0.001), and lipoperoxide levels (P = 0.01), as well as a reduction of ferric reducing antioxidant power (P = 0.01). CONCLUSIONS: rhTSH administration acutely impaired endothelium-dependent vasodilation, possibly through the induction of low-grade inflammation and reduced nitric oxide availability by oxidative stress.     

Ambulatory blood pressure monitoring in patients with hyperthyroidism before and after control of thyroid function

BACKGROUND AND OBJECTIVE: Thyroid hormones have pronounced effects on the cardiovascular system. Thyrotoxicosis affects blood pressure (BP), modifying both diastolic (DBP) and systolic (SBP) pressures. There are no studies examining BP with ambulatory blood pressure monitoring (ABPM) in hyperthyroidism before and after control of thyroid function. Our aims were (1) to analyse ABPM in a group of normotensive hyperthyroid patients before and after normalizing circulating thyroid hormones and (2) to compare these results with those obtained in a group of euthyroid subjects. PATIENTS AND MEASUREMENTS: We studied 20 normotensive hyperthyroid subjects [18 women; age (mean +/- SEM) 49.0 +/- 3.0 years] and 15 healthy subjects. Patients were evaluated by ABPM over 24 h, at diagnosis and after therapy (n = 18). RESULTS: The average 24-h, daytime and night-time SBP was significantly greater in hyperthyroid patients than in controls with no significant differences in DBP. Circadian BP rhythm, estimated by the difference between mean values of SBP, DBP and mean BP during daytime and night-time, was unchanged. The average 24-h and daytime SBP significantly decreased after normalizing thyroid function in the 18 hyperthyroid evaluated patients. Daytime SBP and DBP were higher than night-time values both before and after control of thyroid function. However, no differences in circadian BP rhythm were observed. CONCLUSIONS: Normotensive hyperthyroid patients exhibit higher ambulatory SBP throughout 24 h than normotensive euthyroid subjects. Control of hyperthyroidism decreases ambulatory SBP values. Mean nocturnal fall in BP is comparable in normotensive hyperthyroid patients and control subjects.     

SERUM SOLUBLE INTERLEUKIN 2 RECEPTOR IN HYPERTHYROID Graves''DISEASE AND EFFECT OF CARBIMAZOLE THERAPY

To study the activation of T lymphocytes in hyperthyroid Graves' disease, the serum concentrations of soluble interleukin 2 receptors (sIL2R) were determined during active thyrotoxicosis and following the return to a euthyroid state with carbimazole therapy. Serum sIL2R was measured by an enzyme linked immunoassay. The mean +/- SD serum sIL2R concentration during untreated hyperthyroidism was elevated as compared with controls (919.1 +/- 523.4 vs 374.2 +/- 189.4 U/ml, P less than 0.005). However, after carbimazole therapy the serum sIL2R in euthyroid patients fell to 377.9 +/- 90.3 U/ml, which did not differ from healthy controls. Serum sIL2R correlated significantly with the serum free T3 only during hyperthyroidism (r = 0.678, P less than 0.01). Our study suggests that in vivo measurement of serum sIL2R released from activated T lymphocytes is a useful immunological indicator of disease activity.     

Chronic heart failure is associated with vascular remodeling of the brachial artery

AIMS: Endothelial dysfunction has been shown to correlate with severity of congestive heart failure (CHF) and recent data suggest morphological changes of peripheral vasculature to be associated with the syndrome. We therefore investigated the hypothesis that vascular remodeling is associated with functional changes in peripheral conduit arteries and with systemic overexpression of ET-1 in patients suffering from CHF. METHODS AND RESULTS: 57 consecutive patients referred to the Innsbruck Heart Failure and Transplantation Program (EF=23+/-7%) and 16 matched controls (EF=60+/-5%) were studied. Flow-mediated vasodilation (FMD), nitroglycerin-mediated vasodilation (NMD), wall thickness (WT), and incremental elastic modulus (Einc) were assessed by high-resolution ultrasound of the brachial artery. FMD (P=0.004) and NMD (P=0.02) were significantly higher in controls as compared to moderate and severe CHF patients. In contrast, brachial artery-wall thickness (BA-WT) was increased in severe CHF patients (P=0.038). BA-WT was significantly correlated with both FMD (r=-0.28; P=0.049) and NMD (r=-0.38; P=0.003), and with the Einc (r=0.45, P=0.001). Lumen diameter was not different among groups. In patients with BA-WT>0.31 mm, bigET-1 was higher compared to BA-WT<0.31 mm (P<0.05). CONCLUSION: CHF is associated with remodeling of the brachial artery, which is characterized by morphological, mechanical and functional changes of the vessel wall. Endothelin-1 may play a role in the vascular remodeling process.