Arterial stiffness is increased in subjects with hypothyroidism

BACKGROUND: The association between hypothyroidism and increased vascular resistance, arterial wall thickening and endothelial dysfunction is well recognized. The aim of the present study was to examine if hypothyroid subjects have increased arterial stiffness, a risk factor for cardiovascular morbidity and mortality. METHODS: Sixty-five subjects (59 females and 6 males) with normal thyroid function or hypothyroidism of varying degree were investigated by radial artery applanation tonometry and pulse wave analysis, for evaluation of arterial stiffness. RESULTS: Serum TSH values were positively correlated with central systolic blood pressure (r=0.258, p=0.037), central pulse pressure (r=0.316, p=0.010), augmentation pressure (r=0.299, p=0.015) and negatively with reflection time index (RTI), which indicates the pressure wave velocity (r=-0.311, p=0.012). Hypothyroid patients presented higher central systolic pressure and pulse pressure, higher augmentation pressure and lower RTI, indicating increased arterial stiffness in these subjects. RTI was independently related to age, central systolic pressure and TSH. Mild changes of arterial stiffness were observed even in subjects with TSH range 2.01-4.0 muU/ml suggesting that this group may have an early stage of mild thyroid failure. CONCLUSIONS: Hypothyroidism, even in the subclinical stage, is associated with changes in arterial stiffness. The observed abnormalities in arterial stiffness may have detrimental effects on left ventricular function and coronary perfusion in hypothyroid subjects.     

Na,K-ATPase expression is increased in the lungs of alcohol-fed rats

Background: Alcohol abuse independently increases the risk of developing the acute respiratory distress syndrome (ARDS), a disease characterized by diffuse alveolar epithelial damage, lung edema, and consequent severe hypoxemia. Chronic alcohol abuse increases alveolar epithelial permeability both in vitro and in vivo, in part due to altered tight junction formation. However, both alcohol‐fed animals and otherwise healthy alcoholic humans do not have pulmonary edema at baseline, even though their lungs are highly susceptible to acute edematous injury in response to inflammatory stresses. This suggests that active fluid transport by the alveolar epithelium is preserved or even augmented in the alcoholic lung. Chronic alcohol ingestion increases expression of apical sodium channels in the alveolar epithelium; however, its effects on the Na,K‐ATPase complex that drives sodium and fluid transport out of the alveolar space have not been examined. Methods: Age‐ and gender‐matched Sprague–Dawley rats were fed the Lieber–DeCarli liquid diet containing either alcohol or an isocaloric substitution (control diet) for 6 weeks. Gene and protein expression of lung Na,K‐ATPase α1, α2, and β1 subunits were quantified via real‐time PCR and immunobiological analyses, respectively. Alcohol‐induced, Na,K‐ATPase‐dependent epithelial barrier dysfunction was determined by calculating lung tissue wet:dry ratios following an ex vivo buffer‐perfused challenge for 2 hours in the presence of ouabain (10^?4 M), a Na,K‐ATPase inhibitor. Results: Chronic alcohol ingestion significantly increased gene and protein expression of each Na,K‐ATPase subunit in rat lungs. Immunohistochemical analyses of the alcoholic lung also revealed that protein expression of the Na,K‐ATPase α1 subunit was increased throughout the alveolar epithelium. Additionally, lungs isolated from alcohol‐fed rats developed more edema than comparably treated lungs from control‐fed rats, as reflected by increased lung tissue wet:dry ratios. Conclusions: These findings indicate that chronic alcohol ingestion, which is known to increase alveolar epithelial paracellular permeability, actually increases the expression of Na,K‐ATPase in the lung as a compensatory mechanism. This provides a potential explanation as to why the otherwise healthy alcoholic does not have evidence of pulmonary edema at baseline.     

Stimulation of Na,K-ATPase by hypothyroidism in the thyroid gland

Although studies have documented the regulatory effects of thyroid hormones on the Na,K-ATPase in peripheral tissues, there is little information on the regulation of this transporter in the thyroid gland itself. Accordingly, we investigated the effects of thyroid status on Na,K-ATPase specific activity and the abundance of its constituent subunits in rat thyroid. Exogenous tri-iodothyronine (T3) was administered daily to produce hyperthyroidism. 6n-propyl-2-thiouracil (PTU), an inhibitor of thyroid hormone synthesis, was used to induce hypothyroidism. There was a four-fold increase in Na,K-ATPase specific activity in the follicular membranes from PTU-treated animals after 7 days. Enzymatic activities were not changed in the T3-treated glands. Immunoblotting of membranes from T3-treated rats revealed a 75% reduction in alpha1 subunit abundance and a slight, but nonsignificant reduction in beta1 abundance. On the other hand, the membranes from PTU-treated rats displayed 136 and 567% increases in the abundance of the alpha1 and beta1 subunits respectively. These data demonstrate that thyroid hormone status regulates Na,K-ATPase in the gland, but the effects are in direct contrast to those seen in the periphery.     

Central pulse wave velocity is responsible for increased brachial-ankle pulse wave velocity in subclinical hypothyroidism

Objective Subclinical hypothyroidism affects 5–15% of the general population, and is associated with increased morbidity from cardiovascular disease. We recently reported a significant increase in brachial‐ankle pulse wave velocity (baPWV), a parameter of arterial stiffening and an independent predictor for the presence of cardiovascular disease, in subclinical hypothyroidism. The current study was performed to assess which arterial segment is responsible for enhanced baPWV in subclinical hypothyroidism. Patients and methods Central PWV (PWV in heart‐femoral segments), peripheral PWV (PWV in femoral‐ankle segments), and baPWV were measured in subclinical hypothyroid patients and normal subjects. Results Central PWV, baPWV, and peripheral PWV were significantly higher in subclinical hypothyroid patients than in normal subjects. BaPWV was significantly and positively correlated with central and peripheral PWV in both groups. However, a significant and positive correlation between central and peripheral PWV in normal subjects was not found in subclinical hypothyroid patients. Moreover, stepwise regression analysis showed that the association of central PWV with baPWV was stronger than that of peripheral PWV, whereas in normal subjects central PWV was not associated with baPWV. Conclusions Our results demonstrate that central and peripheral PWV are significantly higher in subclinical hypothyroid patients, and that the increase in baPWV depends more strongly on central PWV than on peripheral PWV in these patients. This suggests that increased elastic arterial stiffening of the aorta, rather than of peripheral muscular arteries, might be more responsible for increased general arterial stiffening in subclinical hypothyroid patients.     

Coronary flow reserve is impaired in subclinical hypothyroidism

OBJECTIVE: Although the cardiovascular system is highly sensitive to thyroid hormones, the cardiovascular effects of subtle thyroid dysfunction such as subclinical hypothyroidism (SHT) remain unclear. Therefore, we investigated coronary flow reserve (CFR) reflecting coronary microvascular function in patients with SHT. METHODS: Fifty subjects with SHT and 30 control subjects with normal serum thyroid hormones and TSH levels were included in this study. Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocity. RESULTS: Age, gender, diastolic and systolic blood pressure, body mass index (BMI), serum lipid parameters, and thyroid hormone levels were similar between the groups. Heart rate was significantly lower in the SHT group. Left ventricular diastolic filling parameters were significantly different in the SHT group while other echocardiographic parameters were similar. CFR values were significantly lower in subjects with SHT than in the control group (2.38 +/- 0.44 vs. 2.98 +/- 0.47, p < 0.0001). CONCLUSIONS: These findings suggest that CFR, which reflects coronary microvascular function, is impaired in patients with SHT.     

Iodine-induced subclinical hypothyroidism in euthyroid subjects with a previous episode of amiodarone-induced thyrotoxicosis.

Amiodarone-induced thyrotoxicosis (AIT) occurs most frequently in patients with underlying thyroid disease and is generally believed to be due to the iodine contamination of amiodarone and iodine released by the metabolism of the drug. We and others have suggested that the thyrotoxicosis may also be secondary to amiodarone-induced thyroiditis. To further determine the etiology of AIT, we administered large doses of iodides [10 drops saturated solution of potassium iodide (SSKI) daily] to 10 euthyroid patients long after an episode of AIT believed to be due at least in part to amiodarone-induced thyroiditis. Six of these 10 patients had an abnormal iodide-perchlorate discharge test before SSKI administration, indicating a subtle defect in the thyroidal organification of iodide. During SSKI administration, 6 patients developed marked iodine-induced basal and/or TRH-stimulated serum TSH elevations, 2 had suppressed basal and TRH-stimulated TSH values, and 2 had normal TSH responses compared to SSKI-treated euthyroid subjects with no history of amiodarone ingestion or thyroid disease. Serum T4 and T3 concentrations remained normal and unchanged during SSKI administration in both the AIT patients and control subjects. These results strongly suggest that excess iodine may not be the cause of the hyperthyroidism associated with amiodarone therapy, especially in those patients with probable amiodarone-induced thyroiditis. Furthermore, like patients with a previous history of subacute thyroiditis and postpartum thyroiditis, the present results suggest that some patients with a previous history of AIT may be at risk to develop hypothyroidism when given excess iodine.     

亚临床甲状腺功能减退患者的认知功能

过去20年中,对认知过程神经基础的理解已取得重大进展.认知领域包括注意力和专注力、语言、记忆、心理运动功能和执行功能.这些功能与大脑中多个区域有关,后者往往互相重叠.已有一些经验证的神经认知试验,可通过损伤性研究和功能成像测定将这些认知功能和大脑中的有关区域联系起来.     

Lymphocyte Na,K-ATPase is reduced in aged people

Na,K-ATPase-dependent 86Rb uptake, maximum velocity (Vmax), Michaelis constant (Km) of the uptake, and [3H]-ouabain binding were investigated in the lymphocytes of 10 elderly subjects (age greater than 60 years), and in 10 middle-aged (41 to 60 years) and 10 young controls (age less than or equal to 40 years). 86Rb uptake was reduced in elderly versus both middle-aged and young subjects (20.14 +/- 3.30 v 35.60 +/- 2.67, P = .002, and v 36.53 +/- 4.49 nmol, P = .012), as was the number of [3H]-ouabain binding sites per cell (32,662 +/- 2,215 v 40,420 +/- 1,184, P = .011, and v 40,596 +/- 1,349, P = .014). Vmax was reduced in elderly v young subjects (1.20 +/- 0.10 v 1.64 +/- 0.13, P = .034), but not versus the middle-age group (1.20 +/- 0.10 v 1.54 +/- 0.12 nmol.min-1, NS). Km was no different among the three groups. No differences were found between middle-aged and young subjects. Significant correlations were observed between age and Na,K-ATPase-dependent 86Rb uptake (r = -.620, P = .00009), Vmax (r = -.439, P = .024), and [3H]-ouabain binding sites (r = -.648, P = .002). Moreover, the site number was positively correlated with both uptake (r = .635, P = .002) and Vmax (r = .554, P = .011). These differences were observed both in women and men. We conclude that there is an age-dependent reduction in lymphocyte Na,K-ATPase activity, which is fully manifested over 60 years, and that this alteration is probably due to the reduced number of functional units of Na,K-ATPase in advancing age.     

Neuropsychological function and symptoms in subjects with subclinical hypothyroidism and the effect of thyroxine treatment

OBJECTIVE: Our objective was to examine the relation between neuropsychological function and subclinical hypothyroidism (SHT), defined as serum TSH of 3.5-10.0 mIU/liter and normal serum free T4 and free T3 levels, and to study the effect of T4 supplementation. SUBJECTS: A total of 89 subjects (45 males) with SHT and 154 control subjects (72 males) were recruited from a general health survey (the fifth Troms? study). Sixty-nine of those with SHT were included in a placebo-controlled, double-blind intervention study with T4 medication for 1 yr. MAIN OUTCOME MEASURES: We used fourteen tests of cognitive function, Beck Depression Inventory, General Health Questionnaire, and a questionnaire on hypothyroid symptoms. RESULTS: The mean +/- sd serum TSH in the SHT and control group were 5.57 +/- 1.68 and 1.79 +/- 0.69 mIU/liter, respectively. There were no significant differences in cognitive function and hypothyroid symptoms between the two groups, but those with SHT scored significantly better than the controls on the GHQ-30. At the end of the intervention study, serum TSH in the T4 group (n = 36) and the placebo group (n = 33) were 1.52 +/- 1.51 and 5.42 +/- 1.96 mIU/liter, respectively. T4 substitution had no effect on any of the parameters measured. CONCLUSION: In subjects with SHT where the serum TSH level is in the 3.5-10.0 mIU/liter range, there is no neuropsychological dysfunction, and compared with healthy controls, there is no difference in symptoms related to hypothyroidism.     

Cardiac troponin T is not increased in patients with hypothyroidism

Patients with hypothyroidism often have increased creatine kinase (CK) levels. It is possible that there is increased production of CK, but other mechanisms, such as an increased cell membrane permeability or decreased enzyme clearance were also proposed. Recently, troponins T and I have been extensively studied because of their cardiac specificity. Cardiac troponins are sensitive and specific markers of cardiac injury. The objective of the study was to measure cardiac troponin T (cTnT) levels in patients with hypothyroidism. Twenty-five patients with primary hypothyroidism were evaluated (thyroid-stimulating hormone (TSH) >30 mU/L and low FT₄). In all patients thyrotropin (TSH), free thyroxine (FT₄), CK, CK-MB and cTnT were measured.There were 3 men and 22 women with a mean age of 47.5 ± 12.4 years. TSH levels ranged from 31 to 75 mIU/L and mean FT₄ levels were 4.5 ± 1.9 pmol/L. CK was normal in 11 patients and increased in 14. CK levels ranged between 86 and 1221 U/L (normal levels <170 in women, <195 in men) with a mean of 322 U/L ± 279. CK-MB was increased in 4 patients (16%) and normal in 21. All 25 patients had normal cTnT levels, < 0.01 ng/mL (normal levels 0–0.1 μg/L). Increase in CK and its MB fraction are common in patients with hypothyroidism but cTnT levels are not, even in patients with increased CK-MB. Therefore, cTnT is a reliable marker of cardiac injury even in the hypothyroid patient.     

Pericardial effusion associated with subclinical hypothyroidism

Previous studies have suggested that subclinical thyroid dysfunction, as manifested by abnormalities in thyroid-stimulating hormone (TSH) levels, are associated with detrimental effects on the cardiovascular system. Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. It has been reported that subclinical hyperthyroidism is not associated with coronary heart disease or mortality from cardiovascular causes but it is sufficient to induce arrhythmias including atrial fibrillation and atrial flutter. It has also been reported that increased factor X activity in patients with subclinical hyperthyroidism represents a potential hypercoagulable state. Subclinical hypothyroidism is defined by elevated serum levels of TSH with normal levels of free thyroid hormones. Subclinical hypothyroidism is characterized by abnormal lipid metabolism, cardiac dysfunction, diastolic hypertension conferring an elevated risk of atherosclerosis, and ischemic heart disease. It has been reported that sub-clinical hypothyroidism is associated with both, a significant risk of coronary heart disease at baseline and at follow-up and that mortality from cardiovascular causes is significantly higher at follow-up. However subclinical thyroid dysfunction is currently the subject of numerous studies and remains controversial, particularly as it relates to cardiovascular morbidity and mortality and clinical applications. Pericardial effusion can be present in systemic disorders including hypothyroidism. We present a case of subclinical hypothyroidism in a 41-year-old Italian woman with an ubiquitary pericardial effusion. Also this case focuses attention on subclinical hypothyroidism.     

Erythrocyte mechanical fragility is increased in patients with type 2 diabetes

BackgroundAnemia is common among patients with type 2 diabetes. We determined whether type 2 diabetic patients significantly differed in erythrocyte mechanical fragility as compared with nondiabetic subjects.MethodsWe recruited 25 Caucasian patients with type 2 diabetes (14 men and 11 women; mean age 58 ± 8 years) and 25 age-, race- and sex-matched nondiabetic individuals. The fragility of erythrocytes was tested by inducing mechanical hemolysis by double aspiration of K₂EDTA blood through a 0.5 mL insulin syringe equipped with a very thin needle. The plasma was then separated from the blood cells by centrifugation at 2000 xg for 15 min at room temperature. A Beckman Coulter DxC 800 was used to measure the hemolysis index by direct spectrophotometry.ResultsCompared with matched nondiabetic controls, type 2 diabetic patients had a significantly increased mechanical fragility of erythrocytes (hemolysis index ratio 21 ± 13 vs. 14 ± 10, p = 0.02). Univariable linear regression analysis revealed that there was a strong positive association between percent hemolysis and fasting plasma glucose (r = 0.669, p < 0.001) and hemoglobin A1c (r = 0.549, p < 0.005) in type 2 diabetic subjects, but not in matched nondiabetic controls.ConclusionsOur data suggest that patients with type 2 diabetes have a significantly higher erythrocyte mechanical fragility than matched nondiabetic subjects, and that fasting plasma glucose is the strongest correlate of increased mechanical fragility of erythrocytes in this patients group.     

Excess urinary iodine is associated with autoimmune subclinical hypothyroidism among Egyptian women

Excessive iodine exposure was reported to be associated with thyroid dysfunctions. The aim of this study is to evaluate the link between excess urinary iodine as the prime indicator of excessive iodine intake and autoimmune subclinical hypothyroidism (SCH) among Egyptian women. Seventy three women with autoimmune SCH and 60 age- matched healthy women as controls were enrolled in this study. TSH, FT4, urinary iodine concentrations (UIC) and thyroid peroxidase antibody (TPOAb) were estimated. The levels of urinary iodine were significantly higher in patients with SCH as compared with control subjects, (326.97 112.98 vs. 274.45 98.75 microg/l, p<0.01). In patients with SCH, there was a significant correlation between UIC and TSH levels. Also, a significant correlation between UIC and TPOAb was found. We conclude that excessive iodine intake may trigger thyroid autoimmunity and eventually thyroid hypofunction among Egyptian women.