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Holt E.H.,Section of Endocrinology and Metabolism
Current Opinion in Oncology | Year: 2010

Purpose of review Thyroid cancer is the fastest rising type of cancer among women in North America. Care of the pregnant patient with thyroid cancer is, therefore, of concern to obstetricians, internists and endocrine specialists. Guidelines for the care of the pregnant patient with thyroid disease were released by the Endocrine Society in late 2007, and a symposium on thyroid dysfunction and pregnancy was hosted by the American Thyroid Association in April 2009. With this increasing interest in thyroid disease and pregnancy, a variety of important studies have been published recently. Recent findings: In addition to guidelines published by the Endocrine Society, recent research has focused on detection and management of hypothyroidism in pregnancy, and consequences of hypothyroidism for the fetus and child. Impact of radioactive iodine therapy on subsequent fertility has been described. The risk of adverse outcomes due to thyroid surgery during pregnancy was evaluated in analysis of a large inpatient database. summary: Identification of hypothyroidism during pregnancy continues to be challenging due to the need for well established trimester-specific normal ranges. Physicians may reassure patients about the effects of radioactive iodine therapy on fertility, although men may wish to cryopreserve sperm prior to treatment. Thyroid surgery during pregnancy was associated with a two-fold increased risk of surgical complications. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Sancak S.,Section of Endocrinology and Metabolism | Hardt A.,University of Leipzig | Singer J.,University of Leipzig | Kloppel G.,University of Kiel | And 7 more authors.
Thyroid | Year: 2010

Background: There is a plethora of partly contradictory reports on somatostatin receptor (SSTR) expression in thyroid tumors. Therefore, our goal was to systematically determine SSTR2 expression in benign cold thyroid nodules (CNs), hot thyroid nodules (HNs), papillary carcinomas (PCs), and Graves' disease (GD) in comparison with intraindividual control tissues by means of immunohistochemistry. Methods: Tissue sections from 19 HNs, 10 CNs, 17 PCs and their surrounding tissues, and 8 GD thyroids were immunostained for SSTR2. Membranous SSTR2 staining was quantitated by evaluating 10 high-power fields (HPFs) systematically distributed along the largest diameter of the tissue section. Results: The area covered by thyroid epithelial cells in 10 HPFs expressed as median (in mm2) was 0.53 for CNs, 0.44 for HNs, 1.5 for PCs, 1.3 for GD, and 0.3 for the surrounding tissues. The SSTR2 staining density determined by dividing the area of SSTR2 positively stained thyroid epithelial cells (in mm2) by the area of all thyroid epithelial cells (in mm2) in 10 HPFs was 0.1662 for CNs, 0.0204 for HNs, 0.0369 for PCs, and 0.0386 for GD. Conclusions: SSTR2 expression is inhomogeneous in thyroid disease, with the highest density detected in CNs. It remains to be determined whether this finding could be of pathophysiologic or therapeutic relevance. The high SSTR2 density in CNs should be considered in the interpretation of SSTR scintigraphy-positive findings. © 2010 Mary Ann Liebert, Inc.

Puno-Ramos M.P.G.,Section of Endocrinology and Metabolism | Villa M.L.,Section of Endocrinology and Metabolism | Kasala R.G.,Section of Endocrinology and Metabolism | Arzadon J.,The Medical City
Phillippine Journal of Internal Medicine | Year: 2015

Introduction: Current guidelines recommend that in patients presenting with clinically palpable nodules or with an ultrasound finding of a thyroid nodule, one has to evaluate its risk for malignancy by proceeding with a fine needle aspiration biopsy (FNAB). The decision to do FNAB would depend on ultrasonographic features of the nodule, which include its size, hypoechogenicity, presence of microcalcifications, increased central vascularity, infiltrative margins, and taller than wide measures on transverse plane. Elastography, a measure of tissue stiffness, is now also being utilized as another feature that has a positive correlation with malignancy. This study hopes to determine which among the abovementioned ultrasonographic features would best correlate with a higher risk for thyroid malignancy among adult patients who had undergone ultrasound guided FNAB.  Methodology: A prospective study was done in a cohort of all Filipino patients 19 years old and above who underwent ultrasound guided FNAB of the thyroid nodule/s from July to December 2013 at the Radiology Section of The Medical City, Pasig City, Philippines. Specimen obtained from FNAB were then reviewed by a pathologist to determine its cytopathology and categorized based on the Bethesda System of Classification. The cytopathology reports were correlated with the features seen on the patient’s thyroid ultrasound to determine which characteristic would be predictive of malignancy.  Results: A total of 100 patients underwent ultrasound-guided FNAB, from which 157 nodules were biopsied. 27 nodules were excluded from the analysis due to non-diagnostic or unsatisfactory (Bethesda Category I) findings on cytopathology. Among the 100 patients, 86% of which were females with the mean age of 41 ± 11.31 in those found to have malignant cytopathologic diagnosis. Of the 130 nodules biopsied, 115 nodules were identified as benign (Bethesda Category II) while 15 were identified to be malignant or suspicious for malignancy (Bethesda Category III–VI). Each of the five sonographic features that were predictive of malignancy was compared between the two outcome groups (benign versus malignant). Among them, only the presence of microcalcifications on ultrasound showed to be significantly correlated with malignancy with an odds ratio of 11.3. Ultrasound evaluation with elastography was only performed on 24 nodules and hence results were inconclusive. A nodule possessing more than two of the ultrasound features that were predictive of malignancy was more likely to be malignant on cytopathology (p value of 0.00).  Conclusion: The presence of microcalcifications on thyroid nodules as seen on ultrasound is a significant predictor of malignancy and remains to be consistent locally as with foreign studies. Nodules that were proven to be malignant on cytopathology presented with more of the ultrasound features that are said to be predictive of malignancy. © 2015, Philippine College of Physicians. All rights reserved.

Grazia Castagna M.,Section of Endocrinology and Metabolism | Cevenini G.,University of Siena | Theodoropoulou A.,Section of Endocrinology and Metabolism | Maino F.,Section of Endocrinology and Metabolism | And 5 more authors.
European Journal of Endocrinology | Year: 2013

Background: In differentiated thyroid cancer (DTC) patients at intermediate risk of recurrences, no evidences are provided regarding the optimal radioactive iodine (RAI) activity to be administered for post-surgical thyroid ablation. Methods: This study aimed to evaluate the impact of RAI activities on the outcome of 225 DTC patients classified as intermediate risk, treated with low (1110-1850 MBq) or high RAI activities (R3700 MBq). Results: Six to 18 months after ablation, remission was observed in 60.0% of patients treated with low and in 60.0% of those treated with high RAI activities, biochemical disease was found in 18.8% of patients treated with low and in 14.3% of patients treated with high RAI activities, metastatic disease was found in 21.2% of patients treated with low and in 25.7% of patients treated with high RAI activities (PZ0.56). At the last follow-up (low activities, median 4.2 years; high activities, median 6.9 years), remission was observed in 76.5% of patients treated with low and in 72.1% of patients treated with high RAI activities, persistent disease was observed in 18.8% of patients treated with low and in 23.5% of patients treated with high RAI activities, recurrent disease was 2.4% in patients treated with low and 2.1% in patients treated with high RAI activities, deaths occurred in 2.4% of patients treated with low and in 2.1% of patients treated with high RAI activities (PZ0.87). Conclusion: Our study provides the first evidence that in DTC patients at intermediate risk, high RAI activities at ablation have no major advantage over low activities. © 2013 European Society of Endocrinology.

Kuemmerle N.B.,Dartmouth Hitchcock Medical Center | Rysman E.,Catholic University of Leuven | Lombardo P.S.,Dartmouth Hitchcock Medical Center | Flanagan A.J.,Dartmouth Hitchcock Medical Center | And 14 more authors.
Molecular Cancer Therapeutics | Year: 2011

Many types of cancer cells require a supply of fatty acids (FA) for growth and survival, and interrupting de novo FA synthesis in model systems causes potent anticancer effects. We hypothesized that, in addition to synthesis, cancer cells may obtain preformed, diet-derived FA by uptake from the bloodstream. This would require hydrolytic release of FA from triglyceride in circulating lipoprotein particles by the secreted enzyme lipoprotein lipase (LPL), and the expression of CD36, the channel for cellular FA uptake. We find that selected breast cancer and sarcoma cells express and secrete active LPL, and all express CD36. We further show that LPL, in the presence of triglyceride-rich lipoproteins, accelerates the growth of these cells. Providing LPL to prostate cancer cells, which express low levels of the enzyme, did not augment growth, but did prevent the cytotoxic effect of FA synthesis inhibition. Moreover, LPL knockdown inhibited HeLa cell growth. In contrast to the cell lines, immunohistochemical analysis confirmed the presence of LPL and CD36 in the majority of breast, liposarcoma, and prostate tumor tissues examined (n = 181). These findings suggest that, in addition to de novo lipogenesis, cancer cells can use LPL and CD36 to acquire FA from the circulation by lipolysis, and this can fuel their growth. Interfering with dietary fat intake, lipolysis, and/or FA uptake will be necessary to target the requirement of cancer cells for FA. ©2011 AACR.

Yavuz D.G.,Section of Endocrinology and Metabolism | Yoldemir T.,Marmara University | Ozaltun K.,Marmara University | Erenus M.,Marmara University
Climacteric | Year: 2012

Objective: To evaluate the frequency of the estrogen receptor (ER) gene PvuII and XbaI polymorphisms and their associations with bone mineral density (BMD) in a group of postmenopausal Turkish women. Design A total of 125 healthy postmenopausal women and 125 premenopausal healthy young women as controls were included in the study. The PvuII and XbaI polymorphisms in the ER gene were studied by the polymerase chain reaction-restriction fragment length polymorphism method. The BMD of the lumbar vertebrae and femoral neck were measured by dual-energy X-ray absorptiometry. Results: The frequencies of the ERα PVuII genotypes PP, Pp and pp were 20%, 54.4% and 25.6% in premenopausal and 24.8%, 44.8% and 30.4% in postmenopausal women, respectively. The frequencies of the ER XbaI genotypes XX, Xx, xx were 16.8%, 48.8% and 34.4% in premenopausal and 16.8%, 48% and 35.2% in postmenopausal women, respectively. There was no difference in the frequencies of ER gene polymorphisms between premenopausal and postmenopausal women. BMD measurements were not different between ER PvuII and XbaI genotypes in premenopausal and postmenopausal women. Conclusions: ER gene PvuII and XbaI polymorphisms have no major influence on bone mineral density in our group of postmenopausal women. © 2012 International Menopause Society.

Ching Sun G.E.,Section of Endocrinology and Metabolism | Ching Sun G.E.,Louisiana State University Health Sciences Center | Kashyap S.R.,Cleveland Clinic | Kashyap S.R.,Case Western Reserve University | Nasr C.,Cleveland Clinic
Cleveland Clinic Journal of Medicine | Year: 2014

The pathophysiology of type 2 diabetes mellitus conveys increased cancer risk, and any antidiabetic drug may alter that risk in a favorable or unfavorable way. This article discusses the links between diabetes and cancer, the different agents available for treating diabetes, and the cancer risk associated with these therapies.

Samaropoulos X.F.,Section of Endocrinology and Metabolism | Hairston K.G.,Section of Endocrinology and Metabolism | Haffner S.M.,University of Texas at San Antonio | Lorenzo C.,University of Texas at San Antonio | And 4 more authors.
Obesity | Year: 2013

Objective: Some obese individuals appear to be protected from developing type 2 diabetes mellitus and cardiovascular disease (CVD). This has led to characterizing body size phenotypes based on cardiometabolic risk factors specifically as obese or overweight, and as metabolically healthy (MH) or metabolically abnormal (MA) based upon blood pressure, lipids, glucose homeostasis, and inflammatory parameters. The aim of this study was to measure the prevalence of and describe fat distribution across these phenotypes in a minority population. Design and Methods: Hispanic participants (N = 1054) in the IRAS Family Study were categorized into different body size phenotypes. Computed tomography (CT) abdominal scans were evaluated for measures of nonalcoholic fatty liver disease (NAFLD) and abdominal fat distribution. Statistical models adjusting for familial relationships were estimated. Results: Seventy percent (70%) of the Hispanic cohort was overweight (32%) or obese (38%). Forty-one percent (n = 138) of overweight participants and 19% (n = 74) of obese participants met criteria for MH. Adjusted analyses showed the MH phenotype was associated with lower visceral adipose tissue (VAT) and higher liver density (indicating lower fat content) in obese participants (p = 0.0005 and p = 0.0002, respectively), and lower VAT but not liver density in overweight participants (p = 0.008 and p = 0.162, respectively) compared to their MA counterparts. Odds of NAFLD were reduced in MH obese (OR = 0.34, p = 0.0007) compared to MA obese. VAT did not differ between MH obese or overweight and normal weight groups. Conclusions: These findings suggest that lower levels of visceral and liver fat, despite overall increased total body fat, may be a defining feature of MH obesity in Hispanic Americans. Copyright © 2013 The Obesity Society.

PubMed | Washington University in St. Louis and Section of Endocrinology and Metabolism
Type: | Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists | Year: 2016

Objective The study examined whether vitamin D insufficiency is a predictor of prevalent and/or incident common chronic conditions in African American men (AAM) and Caucasian men (CAM). Methods 1,017 men were recruited at an urban VA medical center and followed prospectively for a mean of 5.4 years. Prevalent and incident chronic conditions evaluated were: obesity, type 2 diabetes (T2D), cancer, depression, dementia, and cardiovascular disease (CVD, including coronary artery disease [CAD], cerebrovascular accident [CVA], and congestive heart failure [CHF]). Univariate and multivariate regressions were performed to examine the association between 25(OH) vitamin D and these chronic illnesses. Results This analysis was limited to 955 men (65.5% AAM, 27.2% CAM, 6.4% Hispanic) who had at least 1 year follow up (range 1.0 - 7.1 years). Univariate analysis of the entire group showed that 25(OH)D correlated negatively with body mass index (BMI). There was no correlation between 25(OH)D and prevalent CVD (including separate analyses for CAD, CVA and CHF), cancer, depression, dementia, all-cause mortality or incident cancer, CAD or CVA. Independent predictors of prevalent common conditions included increasing age, BMI, smoking, alcohol and polysubstance use but not 25(OH)D levels. Conclusion The study does not support previously suggested associations of low vitamin D levels with prevalent common chronic conditions or increased risk for cancer, CAD and CVA in a population of men with high burden of chronic disease. The finding that smoking, alcohol and polysubstance use are predictors of chronic conditions is an important reminder for addressing these risks during patient encounters.

PubMed | Section of Endocrinology and Metabolism
Type: Journal Article | Journal: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme | Year: 2011

Whereas the majority of hot thyroid nodules are caused by somatic TSH-receptor mutations, the percentage of TSH-receptor mutation negative clonal hot nodules (HN) and thus the percentage of hot nodules likely caused by other somatic mutations are still debated. This is especially the case for toxic multinodular goiter (TMNG). 35 HNs [12 solitary hot nodules (SHN), 23 TMNG] were screened for somatic TSHR mutations in the exons 9 and 10 and for Gs mutations in the exons 7 and 8 using DGGE. Determination of X-chromosome inactivation was used for clonality analysis. Overall TSHR mutations were detected in 14 out of 35 (40%) HNs. A nonrandom X-chromosome inactivation pattern was detected in 18 out of 25 (72%) HNs suggesting a clonal origin. Of 15 TSHR or Gs mutation negative cases 13 (86.6%) showed nonrandom X-chromosome inactivation, indicating clonal origin. The frequency of activating TSHR and/or Gs mutations was higher in SHNs (9 of 12) than in TMNGs (6 of 23). There was no significant difference for the incidence of clonality for HNs between TMNGs or SHNs (p: 0.6396). Activating TSHR and/or Gs mutations were more frequent in SHNs than in TMNG. However, the frequency of clonality is similar for SHN and TMNG and there is no significant difference for the presence or absence of TSHR and/or Gs mutations of clonal or polyclonal HNs. The high percentage of clonal mutation-negative HNs in SHN and TMNG suggests alternative molecular aberrations leading to the development of TSHR mutation negative nodules.

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