Quantitative measurement of thyroid blood flow for differentiation of painless thyroiditis from Graves' disease

OBJECTIVE: Differentiation between destruction-induced thyrotoxicosis and Graves' thyrotoxicosis is important for selection of proper therapy. It is, however, often difficult to make this distinction without measurement of radioactive iodine uptake. We investigated the possibility that assessment of thyroid blood flow would allow differentiation between the two entities. PATIENTS AND MEASUREMENTS: One hundred and fourteen untreated patients with thyrotoxicosis (56 Graves' disease, 28 painless thyroiditis, 30 subacute thyroiditis) and 25 normal controls were examined. Serum levels of freeT4 (FT4), freeT3 (FT3) and TSH were measured by chemiluminescent immunoassay, and anti-TSH receptor antibodies (TSH-binding inhibitory immunoglobulin, TBII) were measured by enzyme-linked immunosorbent assay. Thyroid volume and blood flow (TBF) were measured quantitatively by ultrasonography. RESULTS: TBF was significantly higher in Graves' disease (mean +/- 1SD: 14.9 +/- 6.4%, P < 0.0001) than in painless thyroiditis (0.8 +/- 0.5%), subacute thyroiditis (0.9 +/- 0.7%) and in normal controls (0.8 +/- 0.5%). All patients with Graves' disease had TBF values of more than 4% and all patients with painless thyroiditis and subacute thyroiditis had TBF values less than 4%. TBF values significantly correlated with values of radioactive iodine uptake (RAIU) either at 3 h (r = 0.492, P < 0.01) or 24 h (r = 0.762, P < 0.001) within the Graves' disease and painless thyroiditis groups. There was no relationship between TBF values and thyroid volumes or values of TBII in the Graves' disease group. All patients with Graves' disease had positive TBII of 15% or more. Three of 28 patients with painless thyroiditis and one of 30 patients with subacute thyroiditis had positive TBII. CONCLUSION: TBF was quantitatively measured by power Doppler ultrasonography and was more effective than TBII for differentiation between destruction-induced thyrotoxicosis (painless or subacute thyroiditis) and Graves' thyrotoxicosis. TBF values of less than 4% in untreated thyrotoxic patients are laboratory signals of destruction-induced thyrotoxicosis and if these are determined, the radioactive iodine uptake test can be omitted for differential diagnosis of these two types of thyrotoxicosis.     

Prediction of relapse in drug-treated Graves' disease using thyroid stimulation indices.

Thyroid stimulation indices such as high thyroidal radioactive iodine uptake, increased estimated thyroid weight, presence of TSH-binding inhibitor immunoglobulin or thyroid-stimulating antibody, and elevated serum thyroglobulin level, were evaluated in 148 patients with Graves' disease who had been treated with antithyroid drugs for two years or more before the drugs were withdrawn. In all 19 patients in whom three or more indices were positive, early relapse, within 12 months, occurred after reducing the dosage of antithyroid drugs. Other 129 patients were followed after the drug was withdrawn and in 77 patients with one or two positive indices, early relapse occurred in 65-71% and late relapse, after 12 months or later, occurred in 2-11%. In 52 patients in whom none of the indices were positive, 86% remained in remission, but 10% developed an early relapse, and 4% a late relapse. We conclude that a combined analysis of thyroid stimulation indices is useful in predicting relapse in Graves' disease whereas it remains difficult to predict permanent remission.     

Increased retinal blood flow in patients with Graves' disease: influence of thyroid function and ophthalmopathy

OBJECTIVE: Graves' ophthalmopathy (GO), resulting from the inflammation of retro-orbital tissue, is one of the major complications of Graves' disease (GD). We investigated the clinical usefulness of the measurement of retinal blood flow (RBF) in the evaluation of GO and its activity. MEASUREMENT: RBF was quantitated by pulsed Doppler mode at just below the branch of central retinal artery, from which the resistance index (RI) was calculated. PATIENTS: Forty-seven euthyroid GD patients and 70 gender- and age-matched normal controls were measured for RI to investigate the effect of GO on RBF. To investigate the effect of hyperthyroidism, 20 GD patients were measured for RI changes during antithyroid drug (ATD) therapy. Furthermore, 17 GD patients with clinically overt GO were measured for RI changes during treatment with glucocorticoid plus retro-orbital radiation. RESULTS: RI and exophthalmos showed a significant positive correlation in 47 treated euthyroid GD patients without clinically overt GO (r=0.307, P<0.05), but not in 70 age- and sex-matched normal subjects (r=0.185, P=0.161). Furthermore, RI, but not exophthalmos, significantly correlated with serum TSH receptor antibodies, an indicator for the disease activity of GO. ATD therapy significantly reduced RI in GD patients from 0.719+/-0.041 in the hyperthyroid state to 0.661+/-0.051 in the euthyroid state, but not to the levels observed in normal subjects having the similar exophthalmos (0.640+/-0.049). The fractional reduction of RI during ATD therapy significantly correlated with those of pulse pressure and ultrasonographic distensibility in carotid artery, but not with those of serum vascular injury markers. In 17 GD patients with clinically overt GO, all four patients having adipose tissue enlargement but not extraocular muscle hypertrophy (inactive GO) showed RI within the mean +/- 1 s.d. for treated GD patients without GO. In the other 13 GD patients having extraocular muscle hypertrophy (active GO), four and eight patients showed RI outside mean +/- 2 s.d. and mean +/- 1 s.d. respectively. Treatment with glucocorticoid plus radiation moved RI in 8 out of 10 patients toward the mean values of GD patients without GO, in spite of little improvement of exophthalmos. CONCLUSIONS: It was suggested that GD patients showed altered retinal hemodynamics, possibly resulting either from the cardiovascular effect of hyperthyroidism or from retro-orbital inflammation, particularly in extraocular muscle.     

Effect of lugol solution on thyroid gland blood flow and microvessel density in the patients with Graves' disease

CONTEXT: Although some endocrine surgeons administer Lugol solution to decrease thyroid gland vascularity, there is still not an agreement on its effectiveness. OBJECTIVE: The aims of this clinical trial are to evaluate thyroid blood flow and microvessel density in patients with Graves' disease who received Lugol solution treatment preoperatively. DESIGN: This was a prospective clinical trial. SETTING: This clinical trial took place at a tertiary referral center. METHOD: Thirty-six patients were randomly assigned to receive either preoperative treatment with Lugol solution (group 1, n = 17) or no preoperative treatment with Lugol solution (group 2, n = 19). MAIN OUTCOME MEASURES: Blood flow through the thyroid arteries of patients with Graves' disease was measured by color flow Doppler ultrasonography. The microvessel density (MVD) was assessed by immunohistochemical and Western blot analysis of the level of expression of CD-34 in thyroid tissue. The weight and blood loss of the thyroid gland were measured in all patients. RESULTS: The mean blood flow, MVD, CD-34 expression, and blood loss in group 1 patients were significantly lower than those in group 2 patients. There was a negative correlation between Lugol solution treatment and blood flow (r(s) = -0.629; P = 0.0001), blood loss (r(s) = -0.621; P = 0.0001), MVD (r(s) = -0.865; P = 0.0001), and CD-34 expression (r(s) = -0.865; P = 0.0001). According to logistic regression analysis, Lugol solution treatment resulted in a 9.33-fold decreased rate of intraoperative blood loss. CONCLUSION: Preoperative Lugol solution treatment decreased the rate of blood flow, thyroid vascularity, and intraoperative blood loss during thyroidectomy.     

Atrial stunning as predictor of early relapse into atrial fibrillation after cardioversion

Although the high rate of success after cardioversion, less than 50% of patients maintain sinus rhythm for the first year. In view for the high percentage of relapse into atrial fibrillation, it is interesting to analyze the relationship between atrial stunning after cardioversion and relapse into atrial fibrillation. Thus, we evaluated 101 patients with atrial fibrillation and successful cardioversion. Atrial mechanical function was assessed by measures of transmitral peak A wave velocity, determined before and weekly after cardioversion during 1 month. Fifty-five percent of patient relapse into atrial fibrillation during follow-up. No significant differences were found in clinical and echocardiographic variables between the group with and without relapse. However, the group of patients who relapsed into atrial fibrillation showed a lower peak A wave velocity immediately after cardioversion than patients who maintain in sinus rhythm at month (0.44 ± 0.27 vs. 0.60 ± 0.38 m/s p < 0.01). Impaired atrial function improves during the first 14 days after cardioversion.     

Retrospective reevaluation of the significance of thyroid microsomal antibody in the treatment of Graves' disease

The results of treatment were analyzed in relation to serum microsomal antibody (MCAb) titre before treatment in 1185 patients with Graves' disease. The percentage of patients who had ablative therapy because of poor response to antithyroid drug treatment was significantly greater in those with MCAb haemagglutination test (MCHA) titres greater than 1:25,000. With 131I treatment, the patients with MCHA titres greater than 1:6400 responded significantly less to therapy, although the analysis was done in 146 selected patients with certain defined radiation doses and small goitres. With surgical treatment, the percentage of the patients entering into remission was significantly smaller for patients with MCHA titres greater than 1:25,000, because of an increase in both hypothyroidism and relapses. The incidence of hypothyroidism was significantly higher in patients with marked lymphocyte infiltration and/or lymphoid follicles. The degree of these histological findings in Graves' disease was not marked in spite of high MCAb titre and it was significantly different from that in Hashimoto's disease when analyzed in relation to the MCHA titre. These data indicate that in Graves' patients with high MCAb titre, remission is difficult to obtain by treatment, and suggest that the significance of MCAb is different in Graves' disease and Hashimoto's disease. The titre in Graves' disease may be one expression of the activity of this disease.     

The usefulness of exercise-induced QRS axis shift as a predictor of coronary artery disease

The QRS axis of 101 patients with coronary artery disease (CAD) and 57 normal subjects without CAD who underwent coronary arteriograms were measured before and after exercise testing. There was no improvement in the sensitivity of positive axis shifts (15 degrees or greater) for CAD (18%) when compared to the value of positive ST depression (61%). However, the specificity of positive axis shifts for CAD was significantly increased (98%) when compared to the value of positive ST depression (77%). In addition, 39% of those patients with CAD (39 of 101) showed false negative ST depression, but 18% of these patients (7 of 39) showed a positive axis shift. In normal subjects 21% (12 of 57) showed false positive ST depression, but all of the 21% (12 of 12) showed negative axis shift. There was no significant difference in the increments of heart rate between positive ST depression, positive axis shift, and negative ST depression, negative axis shift. No statistical differences in the sensitivity of ST depression and an axis shift for one-, two- and three-vessel diseases were noted. The specificity of left-axis shift for the left anterior descending artery lesion was 98% and the specificity of right-axis shift for the right coronary artery and/or left circumflex artery lesion was 91%. Therefore, the axis shift response is no more sensitive for the detection of CAD than ST depression. However, when a positive axis shift is observed, one can predict two things: the CAD and the localization of the coronary stenosis.     

Clinical significance of a sensitive assay for thyroid-stimulating antibodies in Graves' disease using polyethylene glycol at high concentrations and porcine thyroid cells.

The Inui and Ochi group recently reported that cAMP production by porcine thyroid cells (PTC) was augmented more by polyethylene glycol (PEG) 22.5% precipitated fractions from almost all Graves' sera than those of PEG 12.5%. In the present study, thyroid stimulating immunoglobulin (TSI) activity was determined with PTC and prepared crude Ig fractions precipitated by two different concentrations of PEG (final concentrations 13.5% and 22.5%) from sera obtained from 117 Graves' patients. The activity of TSI determined by the PEG 13.5% assay and activity determined by the PEG 22.5% assay were designated as thyroid-stimulating antibody (TSAb) and sTSAb, respectively. At first we studied 55 TSAb-positive patients with untreated hyperthyroid Graves' disease and classified them according to the TSAb activity-below 500% (group 1) and above 500% (group 2). The positive stimulatory effect, arbitrarily defined as the ratio of sTSAb to TSAb, being more than 1.2, was observed in 85% of patients, and group 1 had a significantly (P<0.025) greater stimulatory effect (34/35, 97.1%) than group 2 (13/20, 65%). Subsequently, in 29 TSAb-negative patients, sTSAb was measured and detected in 26 (89.7%). Finally, sTSAb, TSAb and TBII were compared between patients presenting with recurrent Graves' disease and those with silent thyroiditis after withdrawal of antithyroid drug treatment for Graves' disease. sTSAb was detected in all 14 relapsed patients, but none of the 9 patients with silent thyroiditis had detectable sTSAb. In contrast, TSAb and TBII activities were found in only 7 (50.0%) of the 14 relapsed cases. The present paper demonstrated that the assay with a higher PEG concentration was found to be sensitive, specific and useful for the diagnosis and follow-up of Graves' disease after drug withdrawal, although the underlying mechanism remains unclear.     

The significance of hypertensive response to exercise as a predictor of hypertension and cardiovascular disease

Several studies have shown that exaggerated blood pressure (BP) response to exercise can predict the development of hypertension and target organ damage, but others did not. The aim of this study was to evaluate the relationship between exaggerated BP response to exercise (ExBPR) and the development of hypertension or cardiovascular disease. We reviewed the charts of male subjects who, during the years 1991-1994, had a routine check up that included an exercise stress-test. For each subject, the following parameters were noted: age; body mass index (BMI); history of diabetes; cigarette smoking; family history of ischaemic heart disease and lipid profile. BP and heart rate at rest and during exercise were recorded as well. ExBPR was defined whenever peak exercise systolic BP or diastolic BP was over 200 mm Hg or 100 mm Hg respectively. We identified 73 males who exhibited ExBPR and matched them with a control group of 117 subjects with similar age who had a normal BP response. The mean age of the studied group was 42.6 years and the average follow-up was 5.7 years. Baseline characteristics were similar in both groups. During the follow-up we observed hypertension among 22% in those with ExBPR in contrast to 2.6% in the control group (P < 0.0001). In addition, more subjects of the ExBPR group required cardiovascular medications than of those in the control group (19.2% vs 4.3%, P = 0.0008). Thus, it seems that ExBPR predicts the development of hypertension and cardiovascular diseases. We therefore suggest that subjects with ExBPR should be followed more closely and be instructed for lifestyle modifications which may delay the development of such diseases.     

Sinus bradycardia as a predictor of right coronary artery occlusion in patients with inferior myocardial infarction

Differentiation of right coronary artery (RCA) from left circumflex artery (LCxA) occlusion may be difficult since both can present an electrocardiographic pattern of inferior myocardial infarction (IMI). We studied 133 patients with IMI, 92 patients with RCA occlusion and 41 patients with LCxA occlusion. Risk factors such as previous MI, arterial hypertension, diabetes, smoking, and dislipemia, were similar for RCA and LCxA occlusions. Patients with RCA occlusion had a higher incidence of isolated IMI than patients with LCxA occlusion, 50% vs. 17%, respectively (P<0.001). Arterial hypotension was more prevalent (P<0.05) among patients with RCA (18%) rather than those with LCxA occlusion (2%). RCA occlusion presented an association with sinus bradycardia, an association not observed with LCxA occlusion (15% vs. 0%, respectively; P<0.01). Total atrioventricular block was only present among patients with RCA (18%). Proximal occlusions of the RCA presented lower heart rates (sinus bradycardia) than medial and distal occlusions (13% vs. 1% and 1%, respectively; P<0.0001 and P<0.001). Therefore, regarding patients with IMI: (1) sinus bradycardia is more frequent when the infarct-related artery is the RCA; (2) proximal occlusions of the right coronary predispose low heart rates; and (3) occlusion of the LCxA rarely induces sinus bradycardia.     

Circulating Chlamydia pneumoniae DNA as a predictor of coronary artery disease.

OBJECTIVE: To determine whether current vascular Chlamydia pneumoniae (CPn) infection as diagnosed by circulating CPn DNA is more common in subjects with coronary artery disease (CAD). BACKGROUND: Serological, pathological and animal studies have associated CPn with CAD and preliminary trials suggest antibiotics may prevent adverse coronary events. C. pneumoniae is thought to disseminate systemically within macrophages. We therefore detected CPn DNA in blood to determine whether its presence was a predictor of CAD. METHODS: One thousand, two hundred and five subjects attending for diagnostic and interventional coronary arteriography were recruited. The mononuclear cell layer and platelets were separated from collected blood and the polymerase chain reaction (PCR) was used to detect CPn DNA. RESULTS: Circulating CPn DNA was found in 8.8% of 669 men with CAD compared with 2.9% of 135 men with normal coronary arteries (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.1-8.9). In men with CAD, those with CPn DNA had higher mean platelet counts than those without CPn DNA. Monocyte counts and indirect fibrinogen levels were also raised but not significantly so. By contrast, no association of circulating CPn DNA and CAD was seen in women. CONCLUSIONS: Circulating CPn DNA is a predictor of CAD in men. Unlike serology, it is a specific indicator of current infection and is a means of identifying subjects who may potentially benefit from antichlamydial therapy.     

Rectilinear thyroid scanning as a predictor of malignancy

Rectilinear scan findings were correlated with the surgically documented size, location, and histology of thyroid carcinoma in 67 patients. At the site of the carcinoma, 36 (54%) had hypofunction, associated with a palpable abnormality in all but one patient; 16 (24%) had an abnormality on palpation but not on scanning; 11 (16%) had both a normal clinical examination and a normal scan, associated with a benign abnormality in another part of the thyroid; and four (6%) had a patchy uptake. A literature review established that use of the gamma camera with pinhole collimator does not increase the specificity of carcinoma predictability, despite the enhanced sensitivity. The scan may still be used in evaluating the clinically solitary module that is not obviously malignant. However, unless that module is hyperfunctioning, clinical criteria rather than appearance of the scan should contribute most to the decision of whether to treat surgically.     

Left atrial deformation analysis as a predictor of severity of coronary artery disease

Background

Two-dimensional (2D) speckle-tracking strain imaging is a novel method for assessment of regional myocardial deformation that uses tracking of acoustic speckles or kernels rather than Doppler myocardial velocities. It has been suggested that Left atrial (LA) strain as measured by 2D speckle tracking can be used to evaluate dynamic LA function.

Circulating IL-17 levels during the peri-transplant period as a predictor for early leukemia relapse after myeloablative allogeneic stem cell transplantation

IL-17 is involved in inducing and mediating pro-inflammatory responses. The association of IL-17 with tumor growth or graft-versus-host disease (GVHD) has become a subject of controversy. We hypothesized that serum IL-17 (sIL-17) levels during the peri-transplant period may affect alloreactive responses after allogeneic stem cell transplantation (SCT). sIL-17 levels of 95 patients with leukemia who had undergone myeloablative allogeneic SCT were measured using ELISA before conditioning and on day?0, +7, and +14 after transplantation. With a median follow-up of 17?months, the overall survival, disease-free survival, non-relapse mortality, and relapse incidence were 70.9%, 66.3%, 10.3%, and 23.4%, respectively. Ten patients relapsed within 180?days (early relapse, 10.5%) post-transplant. The cumulative incidence of acute GVHD over grade II and chronic GVHD was 55.8% and 69.0%, respectively. Analyses using repeated measures of ANOVA and mean values of sIL-17 revealed that patients relapsed within 180?days had higher sIL-17 levels, whereas no association existed between sIL-17 levels and other clinical outcomes, including acute GVHD. Receiver operating characteristic curve analyses also revealed that sIL-17 levels were available for the prediction of early relapse and that patients with higher sIL-17 levels at each time point had a significantly higher early relapse. Multivariate analyses and subgroup analyses with only standard disease status suggest the association of sIL-17 levels with subsequent early relapse independent of disease status at transplantation. This study is the first one demonstrating the early change in sIL-17 during the peri-transplant period and the association with early relapse in humans.     

Epicardial adipose tissue as a predictor of coronary artery disease in asymptomatic subjects

This study sought to elucidate the relation between epicardial adipose tissue (EAT) thickness measured by multidetector computed tomography and presence of coronary artery atherosclerosis. Recent studies have suggested that fat disposition in visceral organs and epicardial tissue could serve as a predictor of coronary artery disease (CAD). The sample included 190 asymptomatic subjects with ≥ 1 cardiovascular risk factor who were referred for cardiac computed tomographic angiography. Body mass index, blood pressure, fasting glucose level, and lipid profile were measured. Multidetector computed tomographic results were analyzed for atherosclerosis burden, calcium Agatston score, and EAT thickness: mean EAT values were 3.54 ± 1.59 mm in patients with atherosclerosis and 1.85 ± 1.28 mm in patients without atherosclerosis (p <0.001). On receiver operating characteristic analysis, an EAT value ≥ 2.4 mm predicted the presence of significant (>50% diameter) coronary artery stenosis. There was a significant difference in EAT values between patients with and without metabolic syndrome (2.58 ± 1.63 vs 2.04 ± 1.46 mm, p <0.05) and between patients with a calcium score >400 and <400 (3.38 ± 1.58 vs 2.02 ± 1.42 mm, p <0.0001). In conclusion, asymptomatic patients with CAD have significantly more EAT than patients without CAD. An EAT thickness of 2.4 mm is the optimal cutoff for prediction of presence of significant CAD.