Thyroid Nodules Are More Prevalent in Subjects with Colon Polyps, Independent of Insulin Resistance.

OBJECTIVE: Colorectal polyps and thyroid nodules are common disorders linked to hyperinsulinemia and metabolic syndrome (Mets). The direct association between these two diseases is not clear. We aimed to analyze the prevalence of thyroid nodules in subjects with and without colorectal polyps. The secondary aim was to establish the prevalence of Mets and its parameters in both disorders and to determine if insulin resistance and hyperinsulinemia are common underlying pathophysiological mechanisms. SUBJECTS AND METHODS: One hundred and five subjects with colorectal polyps (71 males, 34 females) and 68 controls (28 males, 40 females) were enrolled. The parameters of Mets together with TSH, insulin, low-density lipoprotein cholesterol, and homeostasis model for assessment of insulin resistance levels were calculated. We performed thyroid ultrasonography in all participants. RESULTS: The prevalence of Mets was similar in the colorectal polyp and control groups (37.1 vs. 37.3%, p = 0.982). The prevalence of Mets was nonsignificantly higher in subjects with a documented thyroid nodule compared to subjects without a thyroid nodule (43.0 vs. 32.6%, p = 0.205). The prevalence of thyroid nodules in subjects with colorectal polyps was significantly higher than in subjects without polyps (52.9 vs. 35.3%, p = 0.017). Compared to subjects with no colorectal polyps, we established a significant increase in the odds of having thyroid nodules (OR 2.05; 95% CI: 1.097-3.860, p = 0.017). The presence of colorectal polyps and age in the adjusted model were established to be independent risk factors for having thyroid nodules (p = 0.025 and p = 0.007, respectively). CONCLUSION: These results may support the presence of other common mechanisms in the development of these two pathologies other than insulin resistance and hyperinsulinemia.

Metformin Decreases Thyroid Volume and Nodule Size in Subjects with Insulin Resistance: A Preliminary Study.

OBJECTIVE: The aim of this study was to investigate the effects of metformin on thyroid volume and nodule size. SUBJECTS AND METHODS: Prospective data were gathered on 100 newly diagnosed subjects with insulin resistance (68 female, 32 male) between August 2008 and May 2010. Each subject followed a standard diet and exercise program, and received 1,700 mg/day of metformin therapy for 6 months. The height, weight, waist circumference (WC) and thyroid hormone levels of each subject were measured. Additionally, the dimensions of the thyroid lobes and maximum diameter of each thyroid nodule were determined by ultrasonography. BMI and thyroid volumes were also calculated. Insulin resistance was estimated by homeostasis model assessment. All these parameters were measured at the beginning and at the end of the treatment period. RESULTS: BMI and WC decreased significantly after metformin therapy (34.5 ± 5.1 vs. 32.7 ± 4.8, p < 0.0001, and 106.3 ± 11.8 vs. 101.8 ± 19.0 cm, p = 0.008, respectively). Insulin resistance also decreased after metformin therapy (4.5 ± 1.9 vs. 2.9 ± 1.7, p < 0.0001). The mean thyroid volume (22.5 ± 11.2 vs. 20.3 ± 10.4 ml, p < 0.0001) and mean thyroid nodule size (12.9 ± 7.6 vs. 11.7 ± 7.2 mm, p < 0.0001) also decreased after treatment. CONCLUSION: In subjects with insulin resistance, metformin therapy significantly decreased thyroid volume and nodule size.

Sonographic Features of Atypical and Initially Missed Parathyroid Adenomas: Lessons Learned From a Single-Center Cohort.

CONTEXT: Awareness of typical and atypical ultrasonographic (US) features of parathyroid adenomas (PAs) is crucial since US is the most widely used first-line imaging modality. OBJECTIVE: The purpose of this study was to describe the atypical features of PAs on US and other possible factors leading to a false negative examination in a large single-center cohort. MATERIALS AND METHODS: The US records of 457 PAs in 445 patients with biochemically proven primary hyperparathyroidism (PHPT) were evaluated in a prospectively maintained database. Atypical size, composition, shape, echogenicity, location, and vascular pattern on US were noted. For patients who previously had at least one negative US examination in referring centers, the main possible reason was defined accordingly. RESULTS: The study group included 359 female and 86 male patients with PHPT. Typical sonographic features were observed in 231 PAs (51%), whereas 226 (49%) had at least one atypical US feature. The most common atypical features were atypical size (29%), followed by atypical echogenicity (19%), shape (8%), location (7%), and composition (7%), respectively. There were 122 initially missed PAs in all groups. The most frequent main atypical US features leading to false negative examinations were atypical size (22.1%) and atypical location (18.8%). Inexperience was third most common reason (16.3%) for false negative US examinations. CONCLUSIONS: Almost half of PAs have at least one atypical feature on US. Awareness of the high prevalence of atypical US features could increase the accuracy of US examination and potentially decrease demand for more expensive second-line imaging modalities.

The relationship between glucose metabolism disorders and malignant thyroid disease.

BACKGROUND: Previous studies have shown a positive relationship between insulin resistance and several common adult cancers. The present retrospective study aimed to investigate the association between glucose metabolism disorders (GMDs) and the prevalence of thyroid cancer. METHODS: We investigated the data of 4272 patients who had undergone fine-needle aspiration biopsy (FNAB) of thyroid nodules. The biopsy results were evaluated as diagnostic or non-diagnostic and the diagnostic results were classified as benign, malignant, and indeterminate. In this study, we included 2234 of the above patients who had undergone FNAB at our hospital and whose biopsy results were evaluated as diagnostic and were classified as either benign or malignant. We obtained the cytologic data and the glucose metabolism status of these patients retrospectively. RESULTS: Of the 2234 patients, 629 (28.1 %) had GMD (impaired fasting glucose, impaired glucose tolerance). Malignant cytology was determined in 106 (4.7 %) patients overall. Of the 629 patients with GMD, 582 (92.5 %) patients had benign cytology and 47 (7.5 %) patients had malignant cytology. Fifty-nine (3.7 %) of the 1605 normoglycemic patients had malignant cytology. Malignant cytology was determined more frequently in the patients who had GMDs (p < 0.001). CONCLUSION: The results demonstrated that thyroid cancer prevalence was higher in patients with GMD. According to our results, GMD should be considered as a risk factor for malignancy in the evaluation of thyroid nodules.

The sonographer's and pathologist's perspective of echogenic microfoci in papillary thyroid carcinoma.

Objective: Punctate echogenic foci (PEF)/microcalcifications are thought to represent psammoma bodies (PB) in histopathology. However, there are few and contradictory data on this. Different types of sonographic echogenic microfoci (EMF) are seen in papillary thyroid carcinoma (PTC), and their histopathological equivalents are not clearly known. There is also conflicting data on the interobserver agreement between the sonographers on EMF. Methods: We prospectively collected US video records of PTC nodules with and without EMF in two large thyroid centers. All video recordings were independently interpreted by three blinded, experienced sonographers. EMF were classified as true microcalcifications (punctate echogenic foci (PEF) ≤1 mm long), linear microechogenities (>1 mm long, posterior acoustic enhancement of the back wall of a microcystic area), comet-tail artifacts/reverberations or linear microechogenities with comet-tail artifacts/reverberations, non-shadowing coarse echogenic foci (>1 mm nonlinear areas) and unclassifiable. Histopathological evaluation was performed by two blinded, qualified pathologists. Results: A total of 114 malignant nodules were included. The average Cohen's kappa (κ) of three sonographers for the EMF presence was 0.775, indicating substantial agreement. A substantial agreement for PEF with 0.658 κ, only fair agreement for other types of EMF with 0.052 to 0.296 κ were detected. EMF were significantly associated with PB and papillae. PEF had an evident relationship with PB in multivariate analysis. There was a strong positive correlation between the amount of PEF and PB (r = 0.634, P < 0.001). Conclusions: PEF in PTC mainly correspond to PB on histopathology. Although observation of EMF varies among sonographers, this inconsistency can be reduced by classifying EMF into subgroups and keeping the term 'PEF' only for true microcalcifications.

Radioguided occult lesion localization for minimally-invasive parathyroidectomy without quick PTH monitoring and frozen section: impact of the learning curve.

OBJECTIVES: Minimally-invasive parathyroidectomy (MIP) is a surgical procedure that reduces the duration of operation, hospital costs, and hypocalcemia, and shortens the length of hospital stay. This study addressed the important procedural details of the radioguided occult lesion localization (ROLL)-MIP technique and evaluated the consequences of the learning curve from a series of patients. PATIENTS AND METHODS: A total of 80 patients who underwent ROLL-MIP for a single parathyroid adenoma were included into this retrospective study. In order to analyze the effect of the learning curve, these subjects were then divided into 2 groups per time period and the operative times were compared. Group A consisted of 22 previously reported patients who served as the control group. Group B consisted of 58 consecutive patients. RESULTS: Serum calcium and parathyroid hormone (PTH) levels were normalized in all of the patients within 2 days and remained normal during the follow-up period (31 ± 18.5 months). None of the patients who underwent ROLL-guided parathyroidectomy suffered temporary or permanent recurrent laryngeal nerve injuries. Mean operation time (time from incision to excision of the adenoma) was 23 ± 6 min in Group A and 18 ± 7 min in Group B. Mean operative times were significantly shorter in group B. CONCLUSION: The success of MIP administered with the ROLL technique in a single adenomatous patient was quite high. This method seems especially valuable in patients with atypically located or small adenomas.

Clinicopathological characteristics of thyroid cancer in patients on dialysis for end-stage renal disease.

BACKGROUND: The prevalence rate of thyroid cancers in patients with renal failure is variable in different studies. Our aim was to determine the prevalence and clinicopathological characteristics of thyroid cancers in the dialysis population and to evaluate the potential risk factors. METHODS: We performed a retrospective analysis on end-stage renal disease (ESRD) patients on dialysis and thyroidectomized patients without ESRD (2000-2006). Then we compared the data of thyroid cancer patients on dialysis (n = 9) with the data of patients who had histopathologically verified benign thyroid disease on dialysis (n = 23) and with the histopathological data of thyroid cancer patients without ESRD. RESULTS: Papillary thyroid cancer (PTC) was the only histotype that was found in 9 of 420 (2.1%) ESRD patients on dialysis. Multifocal PTC was found in eight of nine patients; of them, four had follicular variant of PTC (FVPTC). Two patients had lymphatic metastasis at diagnosis. Eight PTCs were classified as tumor-node-metastasis (TNM) stage I and one as stage II. Among the analyzed factors, age (r = 0.374, p = 0.01) and duration of dialysis (r = 0.436, p = 0.007) showed a significant positive correlation with the occurrence of thyroid cancer. CONCLUSIONS: We conclude that the prevalence of thyroid cancer in patients undergoing dialysis was not higher than that in the background population. Age and duration of dialysis showed a significant positive correlation with the occurrence of thyroid cancer in patients on dialysis. Among the histotypes, there may be higher percentage of PTC, FVPTC, and multifocality in dialysis patients. The effect of these characteristics on prognosis of thyroid cancer in dialysis patients is needed to be further evaluated.

Vitamin D receptor gene polymorphism and osteoporosis in the Turkish population.

Osteoporosis is one of the most important medical problems facing the aging population. It is defined as a decrease in the bone mass leading to an unacceptably high risk of fractures. Osteoporosis is a multifactorial disease. It is well established that genetic factors are involved in the pathogenesis of osteoporosis. Polymorphism of the vitamin D receptor (VDR) gene has been reported to play a major role in variations for genetic regulation of bone mass. Its role within various ethnic populations is not clear. The purpose of this project was to determine the frequencies of VDR genotypes in Turkey. Three polymorphisms of the VDR gene were analyzed using the polymerase chain reaction-restriction fragment length polymorphism technique. The sample for our study was comprised of postmenopausal women in Turkey, 100 of whom were diagnosed with osteoporosis. They were compared with 146 healthy controls. BsmI genotype frequencies in Turks resemble Caucasians rather than Asians, and Taq genotype frequencies in Turks neither resemble Caucasians nor Asians. The genotype frequencies of VDR were not statistically different between patients with osteoporosis and the control group. Among VDR haplotypes, bbAATT and bbTtAa are more frequent in the osteoporosis group than the control group.

Radioactive iodine in the treatment of type-2 amiodarone-induced thyrotoxicosis.

OBJECTIVE: Amiodarone-induced thyrotoxicosis (AIT) is usually classified into two types: type 1, in which a high iodine content triggers the autonomous production of thyroid hormone; and type 2, in which destructive thyroiditis causes the release of preformed thyroid hormone. AIT is a difficult management problem that sometimes requires ablative thyroid therapy. The use of radioactive iodine (RAI) therapy in patients with type-1 AIT who had a 24-hour radioactive iodine uptake (RAIU) value of >10% has been previously reported. Despite its documented efficacy at usual doses (10-30 mCi) in patients with type-1 AIT, the efficacy of RAI in those with type-2 AIT has never been questioned, because type-2 patients usually have low RAIU. We thought that high adjusted-dose RAI might be an attractive alternative to thyroid gland ablation in patients with type-2 AIT. PATIENTS AND METHODS: Four patients with type-2 AIT who required thyroid ablation were included in the study. These individuals were either poor candidates for surgery or had refused surgery. The size of the thyroid gland in all subjects was within normal limits, and each thyroid was characterized by a homogenous echotexture on ultrasonography, the absence of vascularity on Doppler sonography, a low (<4%) 24-hour RAIU value and the absence of thyroid autoantibodies-all of which are characteristic of type-2 AIT. RESULTS: The patients were initially treated with thionamides and glucocorticoids. All patients except one achieved euthyroidism before RAI therapy. All four patients received one dose of RAI (range 29-80 mCi) and followed up for 12 months. No exacerbation of thyrotoxicosis was noted after RAI therapy. Hypothyroidism (in three patients) or euthyroidism (in one patient) was achieved in first six months. CONCLUSIONS: In patients with type-2 AIT, RAI treatment may be the therapy of choice for thyroid gland ablation.

Evaluation of brain natriuretic peptide levels in hyperthyroidism and hypothyroidism.

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

Rosiglitazone decreases serum bone-specific alkaline phosphatase activity in postmenopausal diabetic women.

OBJECTIVES: Our objectives were to evaluate the effect of rosiglitazone on bone metabolism and to assess the association between changes in bone turnover parameters and plasma cytokine levels in postmenopausal diabetic women. DESIGN: This was a 12-wk open-label randomized-controlled trial. PATIENTS OR OTHER PARTICIPANTS: A total of 56 obese postmenopausal women with newly diagnosed diabetes and 26 nondiabetic healthy controls matched for age and body mass index were included in the study. INTERVENTIONS: The subjects were instructed to follow a weight-maintenance diet. Half were randomly assigned to receive rosiglitazone 4 mg/d, and the other half remained on diet alone. MAIN OUTCOME MEASURES: Before and after the interventions, metabolic bone markers and serum cytokine levels were assessed. RESULTS: Serum total alkaline phosphatase (ALP) and bone-specific ALP levels were statistically significantly lower 12 wk after initiation of rosiglitazone treatment. There were no statistically significant changes in osteocalcin levels among the three groups or in deoxypyridinoline levels in the rosiglitazone group. At the end of 12 wk, all patients had statistically significantly decreased IL-1beta and TNF-alpha levels compared with baseline. Changes in bone-specific ALP levels showed a moderate negative correlation with the changes in the TNF-alpha levels after rosiglitazone treatment and after diet in the diabetic control group. CONCLUSIONS: Rosiglitazone use is associated with reduced bone formation at earlier stages in postmenopausal diabetic women. The cytokine-lowering effects of rosiglitazone and lifestyle changes could reverse the early inhibitory effect of rosiglitazone therapy on bone formation. Further studies will clarify the long-term effects of rosiglitazone therapy on bone loss and fracture.

Needle-free delivery of lidocaine for reducing the pain associated with the fine-needle aspiration biopsy of thyroid nodules: time-saving and efficacious procedure.

OBJECTIVE: Fine-needle aspiration biopsy (FNAB) is a mandatory procedure in evaluation of thyroid nodules. However, it is sometimes perceived as a painful procedure by the patients. Efficacy of the needle-free injection of local anesthesia for reducing the pain associated with other cutaneous procedures that involve needle insertion was previously reported. In this double-blind, placebo-controlled clinical trial, we evaluated the effectiveness of a needle-free injection of lidocaine in achieving satisfactory pain control in patients undergoing FNAB of thyroid nodules. DESIGN: Patients were allocated to receive either lidocaine administered by needle-free injection system (n = 55) or placebo (isotonic saline) (n = 52) 2-3 minutes before FNAB. A series of four aspirations of each nodule was performed. The patients rated pain associated with the procedure according to a 100-mm visual analog scale (VAS), an 11-point numeric rating scale (NRS), and a four-category verbal rating scale (VRS). MAIN OUTCOME MEASURE: The two groups studied were similar with respect to age, sex, thyroid volume, nodule size, and nodule site. When the effectiveness of lidocaine was compared with that of placebo, the mean VAS score was 11.4 +/- 13.6 mm versus 38.2 +/- 35.5 mm (p < 0.0001) and the mean NRS score was 1.4 +/- 1.5 points versus 3.9 +/- 2.6 points (p < 0.0001), respectively. The absolute numbers according to VRS score in each group was also significantly different (p < 0.0001). The percentage of patients with "no pain" or "mild pain" in the lidocaine group (90.9%) was significantly higher than that in the placebo group (44.2%) (p < 0.0001). Less than 10% of the patients in lidocaine group experienced moderate pain and none experienced severe pain. No adverse treatment-related effects were observed. CONCLUSIONS: To our knowledge, this is the first study demonstrating that the needle-free delivery of lidocaine is an effective, useful, and noninvasive method of providing local anesthesia for the FNAB of thyroid nodules.

A comparison of glycemic effects of glimepiride, repaglinide, and insulin glargine in type 2 diabetes mellitus during Ramadan fasting.

Although diabetics may be exempted from Ramadan fasting, many patients still insist on this worship. Aim of the present study is to compare the effects of glimepiride, repaglinide, and insulin glargine in type 2 diabetics during Ramadan fasting on the glucose metabolism. Patients, who were willing to fast, were treated with glimepiride (n=21), repaglinide (n=18), and insulin glargine (n=10). Sixteen non-fasting control type 2 diabetics matched for age, sex, and body mass index were also included. Fasting blood glucose (FBG), post-prandial blood glucose (PBG), HbA1c, and fructosamine as well as lipid metabolism were evaluated in pre-Ramadan, post-Ramadan, and 1-month post-Ramadan time points. There was no significant change from pre-Ramadan in FBG, PBG, and HbA1c variables in fasting diabetics at post-Ramadan and 1-month post-Ramadan. However, PBG was found higher in non-fasting control diabetics at post-Ramadan and 1-month post-Ramadan (p<0.05 and p<0.001, respectively). In fructosamine levels, a significant increase was noted both in fasting group and non-fasting group at 1-month post-Ramadan (p<0.01 for all). However, no significant difference was found in the comparison of the changes in fructosamine levels between fasting group and non-fasting group. Risk of hypoglycemia did not significantly differ between fasting and non-fasting diabetics. There was no significant difference between three drug therapies regarding glucose metabolism and rate of hypoglycemia. No adverse effects on plasma lipids were noted in fasting diabetics. In this fasting sample of patients with type 2 diabetes, glimepiride, repaglinide, and insulin glargine did not produce significant changes in glucose and lipid parameters.

Comparison of insulin monotherapy and combination therapy with insulin and metformin or insulin and rosiglitazone or insulin and acarbose in type 2 diabetes.

The aim of this study was to compare the efficacy of treatment with insulin alone, insulin plus acarbose, insulin plus metformin, or insulin plus rosiglitazone in type 2 diabetic subjects who were previously on insulin monotherapy, and to evaluate the effects of these treatments on cardiovascular risk factors including lipid profile, C-reactive protein (CRP) and fibrinogen. Sixty-six poorly controlled type 2 diabetic patients on insulin monotherapy were involved. They were randomized to insulin alone, insulin plus acarbose, insulin plus metformin, or insulin plus rosiglitazone groups for 6 months period. Mean fasting and postprandial glucose values as well as HbA1c levels significantly decreased in all groups. The greatest improvement in HbA1c was observed in insulin plus rosiglitazone (2.4%) and in insulin plus metformin (2%) groups. Daily total insulin dose was increased to 12.7 units/day in insulin alone group, decreased to 4.7 units/day in insulin plus rosiglitazone group, to 4.2 units/day in insulin plus metformin group, and to 2.7 units/day in insulin plus acarbose group. Least weight gain occurred in insulin plus metformin group (1.4 kg) and greatest weight gain occurred in insulin plus rosiglitazone group (4.6 kg). No significant change in lipid levels--except serum triglycerides--was observed in any groups. CRP and fibrinogen levels decreased in all groups, but the decrease in fibrinogen level was significantly greater in insulin plus rosiglitazone group. All groups were comparable in hypoglycemic episodes. No serious adverse event was noted in any group.

Changes in insulin sensitivity and glucose and bone metabolism over time in patients with asymptomatic primary hyperparathyroidism.

OBJECTIVE: The clinical profile of asymptomatic primary hyperparathyroidism (PHPT) has shifted from a symptomatic disorder toward a more subtle, asymptomatic state. The lack of knowledge about the natural course of asymptomatic PHPT contributes to the controversy regarding the optimal management of these patients. The aim of this study is to evaluate the natural course of calcium and glucose metabolism abnormalities, insulin sensitivity, and bone mineral density (BMD) in subjects with asymptomatic PHPT over 18 months. DESIGN: The study was designed as a prospective observational examination of asymptomatic PHPT patients at baseline and at 6-month intervals for 18 months. METHODS: Our study examined 61 patients with asymptomatic PHPT and 80 healthy control subjects matched for age, sex, and body mass index. We evaluated calcium metabolism, glucose metabolism by oral glucose tolerance test, insulin sensitivity by homeostasis model assessment index, and BMD by dual-energy x-ray absorptiometry at distal radius, lumbar spine, and femur. RESULTS: Although in asymptomatic PHPT patients, homeostasis model assessment index at baseline was slightly higher than in controls (3.0 +/- 2.2 vs. 2.2 +/- 1.3; P = 0.035), the prevalence of preexisting diabetes mellitus (13.1 vs. 11.3%), undiagnosed impaired fasting glucose (34.4 vs. 30%), impaired glucose tolerance (13.1 vs. 18.8%), and newly diagnosed diabetes mellitus (4.9% vs. 2.5%) was similar. Baseline BMDs (g/cm2) at all three sites were not different between two groups. Six-month interval measurements showed no change in calcium metabolism parameters including serum calcium, phosphorus, 25-hydroxyvitamin D, and 24-h calcium excretion. No significant longitudinal adverse changes were noted in glucose metabolism, insulin sensitivity, or BMD at any site over the 18-month observation period. CONCLUSIONS: Our follow-up of patients with asymptomatic PHPT revealed no progression of calcium and glucose metabolism abnormalities, insulin sensitivity, and loss of BMD during the 18-month study period.

Effects of thyroxine therapy on right ventricular systolic and diastolic function in patients with subclinical hypothyroidism: a study by pulsed wave tissue Doppler imaging.

INTRODUCTION: The effects of l-thyroxine (l-T(4)) replacement for subclinical hypothyroidism (SH) on right ventricle (RV) functions has not been previously studied by means of pulsed wave tissue Doppler imaging (PWTDI). We investigated the effects of l-T(4) therapy on RV function in patients with SH using PWTDI. PATIENTS AND METHODS: Fifty-three patients with newly diagnosed SH and 25 controls were evaluated by standard echocardiography and PWTDI. After euthyroidism was restored by l-T(4), measurements were repeated. Myocardial systolic wave (S(m)) velocity, isovolumic acceleration (IVA), myocardial precontraction time (PCT(m)), and PCT(m) to contraction time (CT(m)) ratio were calculated as systolic indices. Early (E(m)) velocity, late (A(m)) velocity, E(m) to A(m) ratio, and myocardial relaxation time (RT(m)) were determined as diastolic measurements. RESULTS: S(m) was similar in patients and controls, whereas IVA was significantly lower in patients with SH (P < 0.001). SH patients had significantly decreased E(m) velocity, whereas A(m) velocity and E(m) to A(m) ratio did not differ. PCT(m) and RT(m) were significantly longer, and PCT(m) to CT(m) ratio was significantly higher in patients (P = 0.002, P = 0.002, P < 0.001, respectively). S(m) velocities were similar before and after l-T(4) replacement, whereas IVA significantly increased after therapy (P < 0.001). E(m) tended to increase (P = 0.05), whereas A(m) and E(m) to A(m) ratio were not changed. PCT(m), PCT(m) to CT(m) ratio, and RT(m) decreased significantly (P < 0.001 for all). CONCLUSIONS: SH is associated with RV systolic and diastolic dysfunction, and l-T(4) treatment improves these abnormalities. PWTDI, especially IVA, may be a suitable tool for the early detection of RV systolic dysfunction.

Evidence from autoimmune thyroiditis of skewed X-chromosome inactivation in female predisposition to autoimmunity.

The etiologic factors in the development of autoimmune thyroid diseases (AITDs) are not fully understood. We investigated the role of skewed X-chromosome inactivation (XCI) mosaicism in female predisposition to AITDs. One hundred and ten female AITDs patients (81 Hashimoto's thyroiditis (HT), 29 Graves' disease (GD)), and 160 female controls were analyzed for the androgen receptor locus by the HpaII/polymerase chain reaction assay to assess XCI patterns in DNA extracted from peripheral blood cells. In addition, thyroid biopsy, buccal mucosa, and hair follicle specimens were obtained from five patients whose blood revealed an extremely skewed pattern of XCI, and the analysis was repeated. Skewed XCI was observed in DNA from peripheral blood cells in 28 of 83 informative patients (34%) as compared with 10 of 124 informative controls (8%, P<0.0001). Extreme skewing was present in 16 patients (19%), but only in three controls (2.4%, P<0.0001). The buccal mucosa, and although less marked, the thyroid specimens also showed skewing. Analysis of two familial cases showed that only the affected individuals demonstrate skewed XCI patterns. Based on these results, skewed XCI mosaicism may play a significant role in the pathogenesis of AITDs.

Comparison of palpation-guided fine-needle aspiration biopsy to ultrasound-guided fine-needle aspiration biopsy in the evaluation of thyroid nodules.

OBJECTIVE: Although fine-needle aspiration biopsy (FNAB) of thyroid nodules is a reliable and simple method, the diagnostic value may be limited by inadequate and false-negative results. In this prospective study, we compared palpation-guided FNAB (PGFNAB) with ultrasound-guided FNAB (UGFNAB) to establish the rates of inadequate material and cost-effectiveness. DESIGN: A total of 285 thyroid nodules in 215 patients were included in the study. Palpable nodules with the greatest diameter between 1 and 2.5 cm were included in the study. PGFNAB and UGFNAB techniques were applied to the same nodule by the same operator. Cytologic evaluations were performed by the same cytologist in a blinded fashion. To provide cost analysis, the prices obtained from different hospitals were evaluated. MAIN OUTCOME: The rates of inadequate material for PGFNAB and UGFNAB were significantly different as 32.3% and 21.4%, respectively (p = 0.004). There was significantly higher inadequate material rate in PGFNAB group for small-sized nodules (greatest nodule diameter between 10 and 15 mm) (p = 0.009), despite inadequate material rate was not significant for both procedures for larger sized nodules. False-negative results were 15.8% for PGFNAB and 5.6% for UGFNAB. Regarding cost analysis, the difference between the two methods was 20 dollars on average for each patient. CONCLUSIONS: We consider UGFNAB to be superior to PGFNAB for obtaining adequate material especially for small-sized nodules, as well as providing more accurate cytologic evaluation. Indeed, the difference between the costs of two procedures might be acceptable.

Radioactive iodine treatment in medullary thyroid carcinoma.

BACKGROUND: Elevated levels of basal and stimulated calcitonin are commonly seen in hereditary and sporadic medullary thyroid cancer (MTC) following total thyroidectomy. The cause of these high levels can be residual thyroid tissue, possibly with C-cell hyperplasia, and/or residual micro-MTC foci. MTC does not have the ability to concentrate radioactive iodine. However, radioactive iodine trapped by thyroid follicular cells may affect the neighbouring parafollicular cells. AIM: To investigate the effect of radioactive iodine treatment as adjuvant therapy to surgery in seven patients with persistent elevation of basal and stimulated calcitonin levels. METHODS: Pentagastrin testing was performed in each case immediately before surgery and at intervals of 6 months over a maximum period of 5 years (range, 44-60 months) after surgery. RESULTS: A significant decrease in basal and stimulated calcitonin levels was observed in three patients whose disease was localized to the thyroid gland at the final visit. In the remaining four patients, who initially had lymph node involvement at surgery, basal and stimulated calcitonin levels were decreased significantly in only one. At follow-up, of the three patients who showed no decrease in basal and stimulated calcitonin levels, two developed further regional lymph node and distant metastases. CONCLUSIONS: In patients with persistently elevated basal and stimulated calcitonin levels, radioactive iodine treatment may be the therapy of choice for C-cell hyperplasia and/or micro-MTC after optimal thyroid surgery, especially if the disease has not spread beyond the thyroid gland.

Isolated office hypertension: association with target organ damage and cardiovascular risk indices.

BACKGROUND: Isolated office hypertension (IOH) has been accepted as a benign condition by some researchers, whereas others believe that it is associated with cardiovascular abnormalities and increased cardiovascular risk. The aim of this present study was to evaluate the effects of IOH on target organ damage and cardiovascular risk indices. METHODS: Arterial blood pressure (BP) measured in the office and by 24-hour ambulatory blood pressure measurement (ABMP), carotid intima-media thickness (CIMT), left ventricular mass index (LVMI), cardiothoracic index (CTI), duration of QTc, 24-hour microalbuminuria, fibrinogen, C-reactive protein (CRP), total cholesterol, low-density-lipoprotein (LDL) cholesterol, high-density-lipoprotein (HDL) cholesterol and triglyceride levels were evaluated. Thirty-three subjects with IOH (office BP > or = 140/90 mmHg and daytime ambulatory BP <135/85 mmHg), 17 patients with sustained hypertension (office BP > or = 140/90 mmHg and daytime ambulatory BP > or = 135/85 mmHg), and 17 normotensive control subjects were recruited in the study. The three groups were matched for age, sex and body mass index. RESULTS: CIMT was greater in patients with IOH than in normotensive subjects, and it was significantly lower than that of sustained hypertension patients. Significantly higher LVMI was determined in subjects with IOH compared to normotensive subjects. CTI, QTc, microalbuminuria, fibrinogen, CRP, total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels did not differ significantly among the three groups. CONCLUSIONS: IOH causes significant target organ damage and should not be regarded as a benign condition.