Peter Kopp

Northwestern University, Evanston, Illinois, United States

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Publications (98)472.14 Total impact

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    ABSTRACT: Objectives: Whether endogenous sex hormones play a role in cardiovascular disease (CVD) risk in men is unclear. Few studies have examined associations of sex hormones with atherosclerosis measured by coronary artery calcium score (CACS) and carotid intima-media thickness (cIMT).We evaluated the association of testosterone (T) and other sex hormones with CACS and cIMT. Methods: Using the large multi-ethnic cohort of 3164 men without known CVD in the Multi-Ethnic Study of Atherosclerosis (MESA), cross-sectional associations of tertiles of endogenous sex hormones with CACS and cIMT were analyzed. Results: In regards to CAC, there was a significant negative trend (P-trend=0.02) for CACS>0 over tertiles of free T (FT) with RRs (95% CI) for the lowest to highest tertiles. There was also a marginally significant positive trend (P-trend=0.06) for CACS>0 over tertiles of sex hormone binding globulin (SHBG) with RRs for the lowest to highest tertiles. There were no significant associations with CACS > 0 for tertiles of TT (Total T), bioavailable T (BT), estradiol (E2), and dehydroepiandrosterone (DHEA).There was significantly higher log CACS after adjustment for CVD risk factors for lower TT levels, compared to higher levels, using 9.54 and 10.4 nmol/l as cutoff points. In regards to cIMT, there was a significant positive trend (P=0.003) in mean cIMT over the tertiles of BT, but not for TT, FT, E2, DHEA and SHBG. There was significantly lower cIMT after adjustment for CVD risk factors for lower TT levels compared to higher levels. Conclusion: In a population of male subjects with no known CVD, lower FT is associated with higher RR of CACS>0 and lower TT is associated with higher log CACS. Lower BT and TT are associated with lower cIMT. While these findings support the positive correlation between low T and coronary atherosclerosis, the opposite findings on cIMT warrant further evaluation. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · Clinical Endocrinology
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    ABSTRACT: Background: The molecular basis underlying the development of thyroid dysgenesis remains largely unknown. The objective of this study was to analyze the PAX8 gene in 32 children with congenital hypothyroidism due to thyroid dysgenesis for mutations, and to characterize the functional consequences of the mutations. Methods: The 5'-untranslated region and the entire coding region of the PAX8 gene were analyzed in 32 children. Functional analyses with a reporter gene assay were performed in transfected PCCL3 and TSA cells. Results: Thirty children did not have any sequence alterations. Two individuals had a previously identified monoallelic cytosine to thymine transition at position -983 in the promoter (-983C>T; mutant P. A of the ATG of the initiator codon is designated as +1), and a novel guanine to cytosine transversion in the non-coding exon 1 (-465G>C; mutant E). Functional analysis revealed that the basal transcriptional activity of the mutants is decreased compared to the wild type. Gel mobility shift assays indicated that mutant P does not interact with a transacting factor whose nature remains to be elucidated. The DNA binding property of mutant E were similar compared to the wild type. Conclusions: These results suggest that mutations in PAX8 are most likely a very rare cause of thyroid dysgenesis. The observed sequence alterations result in diminished transcriptional activity and, in conjunction with other genetic and non-genetic modifiers, they may contribute to the pathogenesis of thyroid hypoplasia and hypothyroidism.
    No preview · Article · Oct 2015
  • Jamile C Silveira · Peter A Kopp
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    ABSTRACT: Thyroid hormones are essential for normal development, growth, and metabolism. Their synthesis occurs in thyroid follicles and requires an adequate iodide supply and a sequence of regulated biochemical steps. The uptake of iodide into thyrocytes is well characterized, but its efflux at the apical membrane is poorly understood. This review discusses potential mechanisms underlying iodide efflux with emphasis on recent developments and controversies. The functional characterization of pendrin (PDS/SLC26A4), a multifunctional anion exchanger, suggested that it could be involved in mediating iodide efflux. This is supported by the phenotype of patients with Pendred syndrome (deafness, goiter, partial iodide organification defect), which is caused by biallelic mutations in the SLC26A4 gene, as well as functional studies. However, apical iodide efflux is also possible in the absence of pendrin, implicating the presence of at least another channel. Recently, Anoctamin 1 (TMEM16A), a calcium-activated anion channel has been identified at the apical membrane of thyrocytes and functional studies suggest that it may play a predominant role in mediating iodide efflux. Anoctamin and pendrin are two plausible candidates as mediators of apical iodide efflux. Their relative affinity for iodide and their exact physiological role await, however, further characterization.
    No preview · Article · Oct 2015 · Current opinion in endocrinology, diabetes, and obesity
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    ABSTRACT: This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Thyroid Carcinoma focuses on anaplastic carcinoma because substantial changes were made to the systemic therapy recommendations for the 2015 update. Dosages and frequency of administration are now provided, docetaxel/doxorubicin regimens were added, and single-agent cisplatin was deleted because it is not recommended for patients with advanced or metastatic anaplastic thyroid cancer.
    No preview · Article · Sep 2015 · Journal of the National Comprehensive Cancer Network: JNCCN
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    ABSTRACT: Congenital hyperthyroidism can be a cause of failure to thrive (FTT), hyperactivity, developmental delay, and craniosynostosis during infancy. Most commonly, the condition occurs in the setting of maternal autoimmune thyroid disease. Rarely, congenital hyperthyroidism can also occur secondary to activating mutations within the TSH receptor. This Hispanic male infant presented at age 6 months with severe thyrotoxicosis. At the time of presentation he was being evaluated for squamosal suture synostosis and he was noted to have significant developmental delays. This patient's thyrotoxicosis was initially treated with antithyroid medication, and he subsequently underwent craniosynostosis repair leading to neurodevelopmental improvement. DNA from the patient and his parents was submitted for mutational analysis of exons 9 and 10 of the TSH receptor. He was found to carry a monoallelic transition 1895C>T in exon 10 that results in the substitution of threonine at position 632 by isoleucine (T32I). This mutation results in constitutive activation of the TSH receptor. Neither parent carried this mutation indicating that the child has acquired a de novo germline mutation. We report the first case of squamosal suture craniosynostosis in a patient with non-autoimmune hyperthyroidism. Squamosal suture craniosynotosis is rare, often has a subtle presentation, and should be considered in all patients with this condition as prompt treatment of hyperthyroidism and craniosynotosis repair can lead to normalization of neurodevelopment.
    No preview · Article · Jun 2015 · Thyroid: official journal of the American Thyroid Association
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    ABSTRACT: Differentiated thyroid cancer is the most common endocrine malignancy, and its incidence has been rising rapidly over the past 10years. Although most patients with this disease have an excellent prognosis, a subset develops a more aggressive disease phenotype refractory to conventional therapies. Until recently, there was no effective therapy for these patients. With increasing knowledge of the molecular pathogenesis of thyroid cancer, novel targeted therapies are being developed for this group of patients. Sorafenib and lenvatinib, small-molecule multikinase inhibitors, were approved for the treatment of progressive, symptomatic, radioactive iodine refractory, advanced differentiated thyroid cancer in 2013 and 2015, respectively. This represents a major innovation in the therapy of patients with advanced thyroid cancer. However, these therapies still have many limitations and further research needs to be pursued with the ultimate goal of providing safe and effective personalized therapy for patients with advanced thyroid cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Jun 2015 · Cancer Treatment Reviews
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    Full-text · Article · May 2015
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    ABSTRACT: The polyuria-polydipsia syndrome comprises primary polydipsia (PP) and central and nephrogenic diabetes insipidus (DI). Correctly discriminating these entities is mandatory, since inadequate treatment causes serious complications. The diagnostic "gold standard" is the water deprivation test with assessment of arginine vasopressin (AVP) activity. However, test interpretation and AVP measurement are challenging. Evaluate accuracy of copeptin, a stable peptide stoichiometrically co-secreted with AVP, in the differential diagnosis of polyuria-polydipsia syndrome. Prospective multicenter observational cohort study. Four Swiss or German tertiary referral centers. Adults >18 years old with history of polyuria and polydipsia. Standardized combined water deprivation/3% saline infusion test, terminated when serum sodium exceeded 147 mmol/L; circulating copeptin and AVP levels; final diagnosis based on water deprivation/saline infusion test results, clinical information, and treatment response. Fifty-five patients were enrolled (11 complete central DI, 16 partial central DI, 18 PP, 10 nephrogenic DI). Without prior thirsting, a single baseline copeptin level >21.4 pmol/L differentiated nephrogenic DI from other etiologies with 100% sensitivity and specificity, rendering water deprivation testing unnecessary in such cases. Stimulated copeptin >4.9 pmol/L (at sodium levels >147 mmol/L) differentiated between patients with PP and patients with partial central DI with 94.0% specificity and 94.4% sensitivity; stimulated AVP >1.8 pg/ml differentiated between these same categories with 93.0% specificity and 83.0% sensitivity. Incorporation bias from including AVP levels as a diagnostic criterion. Copeptin is a promising new tool in the differential diagnosis of the polyuria-polydipsia syndrome, and a valid surrogate marker for AVP. Primary funding sources: Swiss National Science Foundation, University of Basel.
    Full-text · Article · Mar 2015 · Journal of Clinical Endocrinology & Metabolism
  • Peter A Kopp

    No preview · Article · Dec 2014 · Thyroid: official journal of the American Thyroid Association
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    ABSTRACT: These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on "Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer" was added to the NCCN Guidelines to assist with using these novel targeted agents. Copyright © 2014 by the National Comprehensive Cancer Network.
    No preview · Article · Dec 2014 · Journal of the National Comprehensive Cancer Network: JNCCN
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    Liuska Pesce · Peter Kopp
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    ABSTRACT: Disorders of the thyroid gland are among the most common conditions diagnosed and managed by pediatric endocrinologists. Thyroid hormone synthesis depends on normal iodide transport and knowledge of its regulation is fundamental to understand the etiology and management of congenital and acquired thyroid conditions such as hypothyroidism and hyperthyroidism. The ability of the thyroid to concentrate iodine is also widely used as a tool for the diagnosis of thyroid diseases and in the management and follow up of the most common type of endocrine cancers: papillary and follicular thyroid cancer. More recently, the regulation of iodide transport has also been the center of attention to improve the management of poorly differentiated thyroid cancer. Iodine deficiency disorders (goiter, impaired mental development) due to insufficient nutritional intake remain a universal public health problem. Thyroid function can also be influenced by medications that contain iodide or interfere with iodide metabolism such as iodinated contrast agents, povidone, lithium and amiodarone. In addition, some environmental pollutants such as perchlorate, thiocyanate and nitrates may affect iodide transport. Furthermore, nuclear accidents increase the risk of developing thyroid cancer and the therapy used to prevent exposure to these isotopes relies on the ability of the thyroid to concentrate iodine. The array of disorders involving iodide transport affect individuals during the whole life span and, if undiagnosed or improperly managed, they can have a profound impact on growth, metabolism, cognitive development and quality of life.
    Full-text · Article · May 2014 · International Journal of Pediatric Endocrinology

  • No preview · Article · Apr 2014
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    ABSTRACT: 17 R esistance to thyroid hormone (RTH) was first de-scribed in 1967 (1), and the first mutations in the THRB gene were identified in 1989 (2,3), only three years after the cloning of the THR genes (4,5). The cardinal features of this syndrome of reduced sensitivity to thyroid hormone are el-evated serum levels of free thyroid hormone with non-suppressed thyrotropin (TSH), often with goiter and no clear symptoms and signs of thyrotoxicosis (6). In fact, signs of decreased and increased thyroid hormone action in different tissues may coexist. During the First International Workshop on Resistance to Thyroid Hormone in Cambridge, United Kingdom, in 1993, a consensus statement was issued to establish a unified no-menclature of THRB gene mutations in RTH (7), as defined above. In the ensuing years more than 3000 cases have been identified, 80% of which harbored mutations in the THRB gene. More recently, two syndromes with reduced cellular access of the biologically active thyroid hormone, triiodo-thyronine (T 3), were identified. These are caused by defects of thyroid hormone cell membrane transport (8,9) and a de-fect reducing the intracellular metabolism generating T 3 from thyroxine (T 4) (10). To accommodate these new findings, it was proposed to broaden the definition of hormone resis-tance. Thus, the Fifth International Workshop on Resistance to Thyroid Hormone, which took place in Lyon, France, in 2005, saw the introduction of the term ''reduced sensitivity to thyroid hormone (RSTH) to encompass all defects that can interfere with the biological activity of a chemically intact thyroid hormone secreted in normal or excessive amounts.'' Following the 10th International Workshop on Resistance to Thyroid Hormone and Action that took place in Quebec City, Canada, in 2012, a number of investigators took on the task to develop a nomenclature for inherited forms of im-paired sensitivity to thyroid hormone (Table 1). The term ''impaired'' was to substitute for ''reduced'' because nascent data indicate that syndromes of increased sensitivity may also exist. We are cognizant that no nomenclature can fit perfectly all aspects of the described syndromes because variability exists. Several aspects were taken into consideration: the already existing nomenclature, new findings, and anticipated putative discoveries. For example, in over 2000 publications ''RTH'' is used to define a phenotype of congenitally in-creased free T 4 with nonsuppressed TSH, irrespective of the presence or absence of a THRB gene mutation (see non-TR-RTH). In view of the identification of THRA gene mu-tations that present a distinct phenotype (11,12), we propose using the term ''RTH a,'' and in new publications to use ''RTH b'' when a THRB gene mutation is present in Citation of this publication should include the three journals in which it has been simultaneously published: Journal of Clinical Endocrinology and Metabolism, Thyroid, and European Thyroid Journal. Departments of
    Full-text · Article · Mar 2014 · Thyroid

  • No preview · Article · Mar 2014 · Experimental and Clinical Endocrinology & Diabetes
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    Full-text · Article · Mar 2014 · European Thyroid Journal
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    Full-text · Article · Mar 2014 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Associations of vitamin D levels with prospectively measured functional decline and mortality in people with lower extremity peripheral artery disease (PAD) are unknown. We determined whether lower baseline vitamin D levels are associated with a faster decline in functional performance and higher mortality among people with and without PAD. A total of 658 participants (395 with PAD) underwent baseline measurement of 25-hydroxyvitamin D (DiaSorin radioimmunoassay), a 6-minute walk test, 4-meter walking velocity and the Short Physical Performance Battery (SPPB), and were followed annually for up to 4 years. Analyses were adjusted for age, sex, race, body mass index, comorbidities, the ankle-brachial index, and other confounders. Among participants with PAD, lower baseline vitamin D levels were associated with a faster decline in the 6-minute walk (vitamin D < 30 nmol/L: -70.0 feet/year; vitamin D 30 to < 50 nmol/L: -72.3 feet/year; vitamin D 50 to < 75 nmol/L: -35.5 feet/year; vitamin D 75 to < 120 nmol/L: -35.9 feet/year; p trend=0.012). PAD participants with vitamin D < 30 nmol/L had a faster decline in the SPPB and 6-minute walk compared to those with levels of 50 to < 75 (p=0.034 and p=0.04, respectively). Among participants without PAD, lower vitamin D was associated with a faster decline in the fast 4-meter walking velocity (p trend=0.003). There were no significant associations of baseline vitamin D levels with all-cause or cardiovascular disease mortality in PAD or non-PAD participants. In conclusion, among individuals with and without PAD, low vitamin D status was associated with a faster decline in some measures of functional performance but was not related to mortality.
    Full-text · Article · Jan 2014 · Vascular Medicine
  • Peter Kopp

    No preview · Article · Jan 2014 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Context: Most of the morbidity and mortality from parathyroid cancer is due to PTH-mediated hypercalcemia. Classically, management mainly consists of surgical resection, chemotherapy, and alleviation of hypercalcemia using bisphosphonates and calcium receptor agonists. The use of denosumab in the treatment of parathyroid cancer-mediated hypercalcemia has not been reported. Objective: The aim of this report is to describe the effect of denosumab on parathyroid cancer-induced hypercalcemia. SUBJECT, MEASURES, AND RESULT: The patient is a 39-year-old man with metastatic parathyroid cancer who presented at age 35. His calcium levels initially responded to surgery, bisphosphonates, calcium receptor agonist, and chemotherapy (dacarbazine). However, his disease progressed, and his hypercalcemia became refractory to these measures in the setting of rising PTH levels. The addition of denosumab, a humanized monoclonal antibody inhibiting receptor activator of nuclear factor κB ligand resulted in successful management of his hypercalcemia for an additional 16 months. Conclusions: Denosumab can be effective in the treatment of refractory hypercalcemia in parathyroid cancer. It may also be of potential use in settings of benign hyperparathyroid-related hypercalcemia such as parathyromatosis, where hypercalcemia is not amenable to surgery or medical therapy with bisphosphonates and calcium receptor agonists.
    No preview · Article · Oct 2013 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Background: An in-depth understanding of the fundamental principles that regulate thyroid hormone homeostasis is critical for the development of new diagnostic and treatment approaches for patients with thyroid disease. Summary: Important clinical practices in use today for the treatment of patients with hypothyroidism, hyperthyroidism, or thyroid cancer are the result of laboratory discoveries made by scientists investigating the most basic aspects of thyroid structure and molecular biology. In this document, a panel of experts commissioned by the American Thyroid Association makes a series of recommendations related to the study of thyroid hormone economy and action. These recommendations are intended to promote standardization of study design, which should in turn increase the comparability and reproducibility of experimental findings. Conclusions: It is expected that adherence to these recommendations by investigators in the field will facilitate progress towards a better understanding of the thyroid gland and thyroid hormone dependent processes.
    Full-text · Article · Sep 2013 · Thyroid: official journal of the American Thyroid Association

Publication Stats

2k Citations
472.14 Total Impact Points

Institutions

  • 1995-2015
    • Northwestern University
      • • Division of Endocrinology, Metabolism and Molecular Medicine
      • • Division of Gastroenterology and Hepatology
      • • Division of Endocrinology
      Evanston, Illinois, United States
  • 1998-2009
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 2007
    • The University of Manchester
      Manchester, England, United Kingdom
  • 2001-2007
    • Ann & Robert H. Lurie Children's Hospital of Chicago
      Chicago, Illinois, United States
  • 2000
    • The University of Chicago Medical Center
      Chicago, Illinois, United States