Thyroid blood flow in inferior thyroid artery as predictor for increase in levothyroxine dosage during pregnancy in women with Hashimoto's thyroiditis - a retrospective study.

BACKGROUND: We examined whether inferior thyroid artery peak systolic velocity (ITA-PSV) predicts an increase in levothyroxine (LT4) dosage in pregnant women with Hashimoto's thyroiditis. METHODS: Twenty-two women with Hashimoto's thyroiditis who were planning and later achieved pregnancy or confirmed as pregnant were enrolled in this retrospective longitudinal observational study. ITA-PSV and thyroid volume were measured using ultrasonography. Serum concentrations of free thyroxine (F-T4), free triiodothyronine (F-T3), and thyroid stimulating hormone (TSH) were simultaneously determined. We adjusted LT4 dosage to maintain serum TSH at < 2.5 µIU/mL (1st trimester) and later at < 3 µIU/mL (2nd, 3rd trimester). RESULTS: Eighteen patients (81.8%) required an increase in LT4 dosage during pregnancy, of whom 7 (31.8%) required an increase ≥50 µg. Multivariable regression analysis showed that TSH (ß = 0.507, p = 0.008) and ITA-PSV (ß = - 0.362, p = 0.047), but not thyroid volume, F-T4, or F-T3, were independently associated with increased LT4 dosage. Receiver-operating characteristic analysis for predicting an increase in LT4 ≥ 50 µg/day showed that the area under the curve (0.905) for ITA-PSV with TSH was not significantly increased (p = 0.123) as compared to that (0.743) for TSH alone, whereas integrated discrimination improvement was significantly increased (27.9%, p = 0.009). CONCLUSIONS: In pregnant patients with Hashimoto's thyroiditis, ITA-PSV was a significant predictor of increase in LT4 dosage independent of TSH level, while ITA-PSV plus TSH showed significantly improved predictability as compared to TSH alone. These results suggest that ITA-PSV reflects residual thyroid function and is useful for evaluating the need for increased thyroid hormone production in pregnant patients with Hashimoto's thyroiditis.

Electronic and Thermoelectric Properties of Layered Oxychalcogenides (BiO)Cu Ch ( Ch = S, Se, Te).

We study the new details of electronic and thermoelectric properties of polycrystalline layered oxychalcogenide systems of (BiO)Cu Ch ( Ch = Se, Te) prepared by using a solid-state reaction. The systems were characterized by using photoemission (PE) spectroscopy and four-probe temperature-dependent electrical resistivity ρ( T). PE spectra are explained by calculating the electronic properties using the generalized-gradient approximation method. PE spectra and ρ( T) show that (BiO)CuSe system is a semiconductor, while (BiO)CuTe system exhibits the metallic behavior that induces the high thermoelectric performance. The calculation of electronic properties of (BiO)Cu Ch ( Ch = S, Se, Te) confirms that the metallic behavior of (BiO)CuTe system is mainly induced by Te 5p states at Fermi energy level, while the indirect bandgaps of 0.68 and 0.40 eV are obtained for (BiO)CuS and (BiO)CuSe systems, respectively. It is also shown that the local symmetry distortion at Cu site strongly stimulates Cu 3d-t2g to be partially hybridized with Ch p orbitals. This study presents the essential properties of the inorganic systems for novel functional device applications.

Association of heterogeneity of the thyroid gland with matrix metalloproteinase-3 in rheumatoid arthritis patients with Hashimoto's thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is highly prevalent in patients with rheumatoid arthritis (RA). The aim is to determine their relation, focusing on matrix metalloproteinase-3 (MMP-3), a marker predicting joint destruction and RA activity. METHODS: Fifty-three consecutive RA patients were prospectively separated into two groups based on the presence or absence of HT; those with and without TPO-Ab or Tg-Ab (34.0% and 66.0%, respectively). To estimate the extent of inflammation and destruction of the thyroid gland, Heterogeneity Index (HI) was determined ultrasonographically. RESULTS: While the male/female ratio, TSH and HI were significantly higher in those with HT than in those without (5/13 vs. 7/28, P=0.047, mean±SE; 7.25±0.69 vs.2.52±0.30 mIU/L, P<0.001; 3.8±0.2 vs.3.2±0.2%, P=0.042, respectively), no differences existed in MMP-3. In those with HT, MMP-3 correlated negatively with FT3 (rho=-0.545, P=0.048) and positively with TPO-Ab and HI (rho=0.735, P=0.02; rho=0.769, P=0.01, respectively). Among them, HI was a significant factor associated positively with MMP-3 (r=0.883, F=31.91). CONCLUSIONS: The present study demonstrated significant increases of HI and an association between HI and MMP-3 in RA patients with HT. These findings suggest that the inflammation and destruction of the thyroid gland might be closely related to the current activity and terminal joint destruction of RA.

Changes in brachial-ankle pulse wave velocity in subclinical hypothyroidism during normalization of thyroid function.

OBJECTIVE: Subclinical hypothyroidism affects 5-15% of the population and is associated with increased cardiovascular morbidity, although this is controversial. We recently reported a significant increase in brachial-ankle pulse wave velocity (baPWV), a parameter of arterial stiffening and an independent predictor for cardiovascular events, in subclinical hypothyroidism. The current study was performed to assess changes in enhanced baPWV in subclinical hypothyroidism during normalization of thyroid function. METHODS: Forty-two subclinical hypothyroid patients (male/female ratio 8/34) were monitored for changes in baPWV before and after levothyroxine (L-T(4)) replacement therapy. RESULTS: After attaining euthyroidism, 59.5% and 40.5% of the patients showed reduction and increase of baPWV, respectively. Baseline baPWV and pulse pressure were significantly higher in patients with reduced baPWV (1940.3+/-126.4 vs. 1726.4+/-110.4 cm/s, P=0.046; 62.1+/-3.1 vs. 50.7+/-3.7 mmHg, P=0.026, respectively). Baseline baPWV was significantly correlated with baseline pulse pressure in both groups, but the change in baPWV was significantly correlated with baseline pulse pressure only in patients with reduced baPWV (rho=-0.522, P=0.046). The male/female ratio was significantly lower in patients with reduced baPWV (4/21 vs. 7/10), and systolic, diastolic and pulse pressures and pulse rate decreased significantly only in patients with reduced baPWV. CONCLUSIONS: Our results suggest that L-T(4) replacement therapy may be especially beneficial in female subclinical hypothyroid patients with high baseline baPWV and pulse pressure. The beneficial effects of L-T(4) replacement therapy in decreasing arterial stiffening and thus preventing cardiovascular disease might be limited to this sub-population.

Significance of thyroid blood flow as a predictor of methimazole sensitivity in untreated hyperthyroid patients with Graves' disease.

OBJECTIVE: The peak systolic velocity (PSV) of the inferior thyroid artery (ITA) is increased in untreated hyperthyroid patients with Graves' disease (GD). We investigated the clinical significance of the ITA-PSV and its determinants in hyperthyroid GD patients. PATIENTS AND METHODS: ITA-PSV, together with thyroid volume, was measured by ultrasonography in untreated hyperthyroid GD patients (n=49) and healthy subjects (n=22). Established markers of GD activity such as TSH receptor antibody (TRAb), thyroid stimulating antibody (TSAb), vascular endothelial growth factor (VEGF) and immunoglobulin E (IgE) were simultaneously determined. RESULTS: ITA-PSV, thyroid volume, VEGF and IgE were significantly higher in hyperthyroid GD patients than in normal subjects. ITA-PSV in hyperthyroid GD patients was correlated positively with serum levels of FT(3), FT(4) and IgE, smoking index and thyroid volume, and negatively with total, HDL- and LDL-cholesterols, but did not correlate significantly with age, triglyceride, TRAb, TSAb or VEGF. In stepwise regression analysis, ITA-PSV showed significant positive and negative associations with IgE and LDL-cholesterol, respectively, in hyperthyroid GD patients. In the pre-treatment hyperthyroid state, FT(4) and ITA-PSV, but not IgE, were found to be significantly and positively associated with the maintenance dose of methimazole (MMI) required to keep serum TSH within normal range for at least 12 months. CONCLUSION: These results suggest that ITA-PSV in untreated hyperthyroid GD patients may reflect GD activity and thus MMI sensitivity.

Increased levels of C-reactive protein in hypothyroid patients and its correlation with arterial stiffness in the common carotid artery.

OBJECTIVE: Hypothyroidism is associated with increased morbidity from cardiovascular disease. The arterial stiffness index beta (stiffness beta) in the common carotid artery (CCA), which is a parameter of arterial stiffening, is known to increase in hypothyroid patients, while normalization of thyroid function for 1 year by levothyroxine (L-T(4)) replacement therapy significantly decreases CCA stiffness beta. Since serum C-reactive protein (CRP) has recently emerged as an independent factor for cardiovascular risk, the present study was designed to examine whether hypothyroidism causes an increase in CRP and whether the serum CRP level is correlated with CCA stiffness beta in hypothyroid patients. PATIENTS AND METHODS: Serum CRP levels and CCA stiffness beta were determined in 46 patients with hypothyroidism and in 46 age- and sex-matched normal control subjects. Thirty-five patients were further monitored for change in CCA stiffness beta during 1 year in the euthyroid state induced by L-T(4) therapy. RESULTS: Baseline CRP and CCA stiffness beta were both significantly higher in hypothyroid patients than in normal controls [1064.6+/-224.3 vs. 602.1+/-43.3 ng/ml (mean+/-SE), p<0.0001; and 9.25+/-0.84 vs. 8.21+/-0.85, p<0.05, respectively]. Baseline CRP was significantly correlated in a positive manner with baseline values of CCA stiffness beta (r=0.683, p<0.0001). In multivariate analysis, baseline CCA stiffness beta was significantly associated with baseline levels of serum CRP (r=0.740, p<0.0001). During 1 year of L-T(4) replacement therapy, significant decrease in stiffness beta (from 9.25+/-0.84 to 8.57+/-0.58, p<0.0001) to the normal levels was found. Moreover, the change in CCA stiffness beta during L-T(4) replacement therapy was significantly and independently associated in a negative fashion with baseline levels of serum CRP (r=-0.696, p=0.0002). CONCLUSIONS: This study suggests that increased serum CRP might have an important independent role in increased arterial stiffening and the measurement of serum CRP is a useful predictor for the degree of improvement of arterial stiffening in hypothyroid patients.

Increased 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. Brachial-ankle pulse wave velocity (baPWV) is a parameter of arterial stiffening and a good independent predictor for the presence of coronary artery disease. This study was performed to assess whether subclinical hypothyroidism might cause enhanced baPWV. PATIENTS AND METHODS: baPWV was examined in subclinical hypothyroid patients (n = 50) and normal control subjects (n = 50). RESULTS: Diastolic blood pressure (DBP), a main risk factor for cardiovascular disease, and baPWV were both significantly higher in subclinical hypothyroid patients than normal subjects. baPWV was significantly positively correlated with age and systolic, diastolic, and pulse pressure and significantly negatively correlated with pulse rate in both subclinical hypothyroid patients and normal subjects. In contrast, there was no significant correlation of baPWV with free T3, free T4, TSH, total, high-density lipoprotein- and low-density lipoprotein-cholesterol, and the preejection time to ejection time ratio. A comparison of individual values of baPWV and DBP and regression slopes in two groups revealed that baPWV values increase to a larger extent than the increase in DBP in subclinical hypothyroid patients. In both groups, stepwise regression analysis showed a significant and independent association of DBP with baPWV. CONCLUSIONS: The present study demonstrated significant increases of baPWV and DBP in subclinical hypothyroid patients. Furthermore, the results suggest that increased DBP might be one of the main factors responsible for increased arterial stiffening in subclinical hypothyroid patients.

Increased levels of serum osteoprotegerin in hypothyroid patients and its normalization with restoration of normal thyroid function.

Hypothyroidism is associated with increased morbidity from cardiovascular disease, and an increase in serum osteoprotegerin (OPG) has recently been reported to be associated with the severity of coronary heart disease and cardiovascular mortality. The present study was designed to examine whether hypothyroidism causes an increase in serum OPG, and to determine whether levothyroxine (L-T4) replacement therapy might suppress serum OPG levels in hypothyroid patients. Fifty-three hypothyroid patients with chronic thyroiditis and age- and sex-matched normal control subjects were examined for the levels of serum OPG and plasma von Willebrand factor (vWF), a vascular injury marker. Thirty-seven of the hypothyroid patients were further monitored for changes in these markers during 1 year in a euthyroid state induced by L-T4 replacement therapy. Baseline OPG was significantly higher in hypothyroid patients than in normal controls (4.51 +/- 0.50 vs 3.72 +/- 0.23 pmol/l (mean +/- S.E.); P = 0.0182). In multivariate analysis, baseline OPG was significantly associated with baseline levels of TSH (r = 0.280, P = 0.0162) and vWF (r = 0.626, P < 0.0001). During one year of L-T4 replacement therapy, hypothyroid patients showed a significant decrease in OPG levels from 4.35 +/- 0.51 to 3.48 +/- 0.26 pmol/l (P = 0.0166), a level comparable to normal controls. The change in serum OPG levels during L-T4 replacement therapy was significantly and independently associated in a negative fashion with baseline vWF (r = -0.503, P = 0.0014). This study suggested that the severity of hypothyroidism and vascular injury might have important independent roles in increasing the serum OPG level in hypothyroid patients. Furthermore, it was demonstrated that a sustained euthyroid state might have the potential to decrease the serum OPG level in hypothyroid patients and that the degree of vascular injury in the hypothyroid state is independently associated with a decrease in serum OPG during a 1-year normalization of thyroid function.

Plasma levels of adiponectin and soluble thrombomodulin in hypothyroid patients with normal thyroid function following levothyroxine replacement therapy.

Hypothyroidism is associated with increased morbidity from cardiovascular disease, and adiponectin (ApN) is a newly-identified adipocytokine, which is expressed in human adipose cells and may have a protective effect against the development of coronary artery disease. The aim of the study was to evaluate the involvement of ApN secretion in hypothyroid patients with normal thyroid function following levothyroxine (L-T(4)) replacement therapy, and to associate plasma ApN levels with intima-media thickness (IMT) in the common carotid artery (CCA), an indicator of early atherosclerosis, and cardiovascular parameters including soluble thrombomodulin (sTM), a plasma endothelial injury marker. The CCA IMT and plasma levels of ApN and sTM were measured in 52 hypothyroid patients and in age-, sex- and body mass index (BMI)-matched normal control subjects. Thirty-six of the hypothyroid patients were further monitored for changes in these markers during 1 year in a euthyroid state induced by L-T(4) replacement therapy. Although the basal CCA IMT was significantly higher in hypothyroid patients [0.633 +/- 0.018 mm (mean +/- S.E.)] than in control subjects (0.552 +/- 0.022 mm, P < 0.005), both groups had similar baseline ApN and sTM levels [10.23 +/- 0.76 vs. 10.10 +/- 0.93 microg/ml: NS; and 2.58 +/- 0.14 vs. 2.68 +/- 0.20 ng/ml: NS, respectively]. Simple regression analysis revealed that plasma ApN was significantly correlated in a positive manner with age (r = 0.339, P = 0.015), HDL-cholesterol (r = 0.295, P = 0.048), and sTM (r = 0.490, P = 0.0005), but not with CCA IMT (r = 0.059, P = 0.742). In multivariate analysis, the plasma ApN level was significantly associated with that of sTM (r = 0.546, P = 0.0001) and with serum high-density lipoprotein (HDL)-cholesterol levels (r = 0.291, P = 0.029) in hypothyroid patients. During 1 year of L-T(4) replacement therapy, hypothyroid patients showed a significant decrease in CCA IMT, to 0.553 +/- 0.016 mm (P < 0.0001), a level comparable to normal controls, but no significant change in ApN (from 10.79 +/- 1.07 to 10.6 9+/- 1.14 microg/ml, NS) or sTM (from 2.59 +/- 0.15 to 2.74 +/- 0.18 ng/ml, NS). Hence, we provide evidence that ApN and sTM might not contribute to enhanced atherosclerosis, as reflected by increased CCA IMT in hypothyroid patients. However, this is the first report to demonstrate a positive and significant association of sTM with ApN. These data support the hypothesis that sTM is one of the determinant of ApN and thus suggest the presence of an sTM-associated regulatory mechanism for ApN secretion in hypothyroid patients.

Decrease of arterial stiffness at common carotid artery in hypothyroid patients by normalization of thyroid function.

This study examined the effect of hypothyroidism on arterial stiffening and the effect of levothyroxine (l-T(4)) replacement. The arterial stiffness index beta (stiffness beta) and intima-media thickness (IMT), a parameter of arterial stiffening and thickening, respectively, were determined in common carotid artery (CCA) by ultrasonography in 30 hypothyroid patients before and after 1 year of normalization of thyroid function by l-T(4) replacement. Baseline CCA stiffness beta and IMT was significantly higher in the hypothyroid patients than in age- and sex-matched normal controls [9.46 +/- 0.93 vs. 8.02 +/- 0.91 (mean +/- SE); P < 0.05, 0.635 +/- 0.018 mm vs. 0.541 +/- 0.019 mm; P < 0.005, respectively]. In multivariate analysis, baseline stiffness beta was significantly associated with baseline levels of IMT (r = 0.457, P = 0.0311), FT(4) (r = -0.413, P = 0.0169), and a plasma vascular injury marker, von Willebrand factor (vWF) (r = 0.412, P = 0.0261). During 1 year of euthyroidism, 22 and 29 out of 30 patients showed significant decreases of stiffness beta and IMT to normal respective level, from 9.46 +/- 0.93 to 7.58 +/- 0.34 and from 0.635 +/- 0.018 to 0.552 +/- 0.015 mm, respectively. Change in stiffness beta during l-T(4) therapy correlated significantly in a negative manner with baseline levels of age (r = -0.465, P = 0.011) and IMT (r = -0.406, P = 0.029). Stiffness beta after but not before l-T(4) therapy showed a tendency towards a positive correlation with age. This study suggested that increases of arterial thickening, and plasma vWF, and a reduction in serum FT(4) might have an important role independently in the increased arterial stiffening in hypothyroid patients. Furthermore, it was demonstrated that sustained euthyroidism might have the potential to reverse arterial stiffening in addition to thickening in hypothyroid patients.

Change in von Willebrand factor and carotid intima-media thickness in hypothyroid patients with normal thyroid function after levothyroxine replacement therapy.

OBJECTIVE: This study examined whether levothyroxine (L-T4) replacement might affect serum markers of endothelium injury, including von Willebrand factor (vWF), factor VIII activity and thrombomodulin (TM), during normalization of increased intima-media thickness (IMT) in the common carotid artery (CCA) in hypothyroid patients after L-T4 replacement therapy. PATIENTS AND METHODS: Thirty-three hypothyroid patients were examined for vWF, factor VIII, TM and CCA IMT before and after 1 year of normalization of thyroid function by L-T4 replacement. CCA IMT was measured from digitized still images taken during scanning by high-resolution ultrasonography as an indicator of early atherosclerosis. RESULTS: Serum factor VIII and vWF increased significantly during 1 year of normalization of thyroid function (from 122.7+/-9.4 to 151.3+/-18.8% (P<0.05) and from 109.9+/-9.6 to 135.2+/-12.4% (P<0.005) respectively), although these values all fell within the respective normal range. Serum TM, in contrast, did not change appreciably in response to L-T4 treatment, moving from 2.57+/-0.15 to 2.74+/-0.18 ng/ml (P=0.086). During 1 year of a euthyroid state, all patients showed a significant decrease in CCA IMT (P<0.0001). Change in serum vWF, but not in factor VIII or TM, showed a positive correlation with that of CCA IMT during L-T4 replacement therapy. Furthermore, the change in serum vWF was significantly and independently associated with change in CCA IMT (r=0.490, P=0.0038). CONCLUSIONS: The present study demonstrated that the improvement of CCA IMT during L-T4 treatment might have the potential to attenuate an elevation of vWF and to attenuate vascular injury by the cardiovascular effects of thyroid hormone in hypothyroid patients.

Thyroid heterogeneity, as indicated by the CV of ultrasonographic intensities, correlates with anti-thyroid peroxidase antibodies in euthyroid Hashimoto's thyroiditis.

OBJECTIVE: To prospectively evaluate the heterogeneous appearance of the thyroid gland, reflecting inflammation and destruction in euthyroid Hashimoto's thyroiditis (HT), we investigated the clinical utilities of the heterogeneity index (HI) [the coefficient of variance (CV) of the ultrasonographic (US) intensities], focusing on anti-thyroid peroxidase antibodies (TPO-Ab), which represent not only disease activity but also subsequent thyroid destruction of HT. METHODS: Forty-four consecutive patients with euthyroid HT [60.5 ± 2.7 years old (mean ± SE)] and 30 age-matched normal controls were studied. HI was calculated as the CV (SD/mean) of US intensities of either four points per lobe of the thyroid gland along a horizontal line at the depth of the right common carotid artery. Evaluation included serum levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH), anti-thyroid peroxidase antibodies (TPO-Ab), anti-thyroglobulin antibodies (Tg-Ab), thyroglobulin and thyroid volume. RESULTS: While no differences were observed for TSH, FT4 and FT3, thyroglobulin and thyroid volume between the two groups, HI exhibited a tendency towards a significant difference (3.59 ± 0.20% in HT patients vs 3.23 ± 0.19% in normal group, p = 0.089). In HT patients, there was a significant and positive correlation of HI with TPO-Ab (r = 0.396, p = 0.034), whereas such a correlation was absent in normal controls. In both groups, there were no significant correlations of HI with Tg-Ab, FT3, FT4 or TSH. CONCLUSIONS: This is the first report of the close relation between heterogeneity of US of the thyroid gland and TPO-Ab in euthyroid HT patients before the heterogeneity becomes distinguishable from normal thyroid glands. Furthermore, at this stage, subsequent thyroid destruction in HT might be already be predicted through the heterogeniety of the thyroid tissue.

Thyroid blood flow as a useful predictor of relapse of Graves' disease after normal delivery in patients with Graves' disease.

OBJECTIVE: Measurement of the peak systolic velocity (PSV) in the inferior thyroid artery (ITA) before withdrawal of an anti-thyroid drug (ATD) is useful for predicting relapse of Graves' disease (GD). We further investigated whether the ITA-PSV can be used for prediction of GD relapse after delivery in euthyroid women with GD who stopped ATD administration during mid- to late pregnancy. PATIENTS AND METHODS: ITA-PSV was monitored monthly for three months after delivery in 42 women with GD aged from 24 to 45 years old (mean+/-SE: 34.7+/-0.92 years old) who met the above criteria. To confirm the stability of the measurement, ITA-PSV was also measured monthly in 32 age-matched non-pregnant normal women and for three months after delivery in 10 age-matched women. RESULTS: ITA-PSV and thyroid volume were higher in women with GD immediately after delivery compared to normal women, but the levels of TSH receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb) did not differ significantly between the two groups. Of the 42 patients, 23 had relapse of GD and the smoker/non-smoker ratio and thyroid volume in these patients immediately after delivery were significantly higher than those in the 19 patients who did not undergo relapse (10/23 vs. 0/19, p<0.0001; 24280.3+/-2280.9 vs. 19670.0+/-2103.7mm(3), p=0.046), while ITA-PSV, TRAb and TSAb did not differ between the two groups of patients. The ITA-PSV ratio was calculated by dividing each value in the follow-up period by that obtained immediately after delivery. A significant increase in the mean ITA-PSV ratio occurred at least one month before the time of relapse (1.00+/-0.00 at -3 months before relapse vs. 1.46+/-0.12 at -1 month, p=0.010; 1.00+/-0.00 at -3 months vs. 1.77+/-0.13 at the time of relapse, p=0.0048). In contrast, there were no significant changes in this ratio during the follow-up period in non-relapse patients. CONCLUSION: Monthly measurement of ITA-PSV after delivery in remitted euthyroid women with GD may assist in early prediction of GD relapse.

Decrease of brachial-ankle pulse wave velocity in female subclinical hypothyroid patients during normalization of thyroid function: a double-blind, placebo-controlled study.

OBJECTIVE: Subclinical hypothyroidism affects 5-15% of the general population, is especially prevalent in females, and may be associated with increased morbidity from cardiovascular disease, although it remains controversial. We recently reported a significant increase in the brachial-ankle pulse wave velocity (baPWV), a parameter of arterial stiffening and an independent predictor of cardiovascular events, in subclinical hypothyroidism without thyroiditis. The current study was performed to assess changes in baPWV in female subclinical hypothyroidism with autoimmune chronic thyroiditis (Hashimoto's disease) after restoration of normal thyroid function. METHODS: In a randomized placebo-controlled study, 95 female subclinical hypothyroid patients were monitored for changes in baPWV before and after levothyroxine (l-T(4)) replacement therapy. Changes in baPWV were also measured in 42 age-matched normal female subjects. RESULTS: The baseline baPWV values in patients with subclinical hypothyroidism were significantly higher than in normal subjects. With attainment of euthyroidism, baPWV showed a significant decrease from 1776.7+/-86.0 to 1674.3+/-79.2 cm/s (P=0.006) in patients treated with l-T(4), but the changes in baPWV and TSH were not correlated. The change in baPWV was significantly and negatively correlated with age and baseline pulse pressure, but multiple regression analysis revealed that these parameters failed to be associated with the change in baPWV. CONCLUSIONS: Sustained normalization of thyroid function during l-T(4) replacement therapy significantly decreases baPWV in female subclinical hypothyroid patients with autoimmune chronic thyroiditis, suggesting the improvement of arterial stiffening and, consequently, possible prevention of cardiovascular disease.

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.

The significance of thyroid blood flow at the inferior thyroid artery as a predictor for early Graves' disease relapse.

OBJECTIVE: We investigated the clinical usefulness of thyroid blood-flow measurement in predicting relapse of Graves' disease (GD) in comparison with known risk factors for GD relapse. MEASUREMENT: Thyroid blood flow was measured in pulsed Doppler mode at the inferior thyroid artery (ITA), and the peak systolic velocity (PSV) calculated. PATIENTS: ITA-PSV was measured in euthyroid GD patients (n = 79) immediately before withdrawal of anti-thyroid drug (ATD) and in healthy subjects (n = 17). RESULTS: In the 79 euthyroid GD patients, the values of free triiodothyronine (FT3), TSH receptor autoantibody (TRAb), ITA-PSV and thyroid volume were significantly higher in the relapse group (n = 40) than in the nonrelapse group (n = 39) and the Youden index of ITA-PSV was significantly higher than that of FT3, TSH, TRAb and vascular endothelial growth factor (VEGF). CONCLUSION: ITA-PSV may assist in the prediction of early GD relapse after ATD withdrawal.

Decrease in carotid intima-media thickness in hypothyroid patients after normalization of thyroid function.

OBJECTIVE: This case-control study was carried out to assess whether levothyroxine (L-T4) replacement might cause regression of the enhanced atherosclerosis seen in hypothyroid patients. PATIENTS AND METHODS: Intima-media thickness (IMT) in the common carotid artery (CCA) was measured from digitalized still images taken during scanning by high-resolution ultrasonography as an indicator of early atherosclerosis. Thirty-five hypothyroid patients were examined for their CCA IMT before and 1 year after normalization of thyroid function by L-T4 replacement. As control, 35 healthy subjects were enrolled from among the participants in a local health-check programme conducted at the Osaka City University Hospital. RESULTS: Basal CCA IMT was significantly higher in hypothyroid patients [0.635 +/- 0.018 (mean +/- SE) mm] than in control subjects (0.559 +/- 0.021 mm, P < 0.005). After 1 year of euthyroidism, 34 out of 35 patients showed a significant decrease of CCA IMT, to 0.552 +/- 0.015 mm (P < 0.0001), a level comparable to normal controls. CCA IMT change was closely associated with basal levels of total cholesterol (r = -0.472, P= 0.0031), low-density lipoprotein (LDL) cholesterol (r = -0.441, P= 0.0076) and the total/HDL cholesterol ratio (r =-0.435, P= 0.0057), but not with any of the other variables measured except for age (r = -0.353, P= 0.0296). CONCLUSIONS: This study demonstrated that L-T4 treatment might have the potential to reverse the progression of atherosclerosis in hypothyroid patients. Furthermore, it suggests that increased levels of LDL cholesterol and the total/HDL cholesterol ratio have an important role in the increased common carotid intima-media thickness in hypothyroid patients.