Peter Kopp

Northwestern University, Evanston, Illinois, United States

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Publications (74)377.79 Total impact

  • 05/2015; DOI:10.1530/endoabs.37.EP796
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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.
    Journal of Clinical Endocrinology &amp Metabolism 03/2015; 100(6):jc20144507. DOI:10.1210/jc.2014-4507
  • Peter A Kopp
    Thyroid: official journal of the American Thyroid Association 12/2014; 24(12):1667-9. DOI:10.1089/thy.2014.2412
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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.
    International Journal of Pediatric Endocrinology 05/2014; 2014(1):8. DOI:10.1186/1687-9856-2014-8
  • 04/2014; DOI:10.1530/endoabs.35.OC3.2
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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
    Thyroid 03/2014; 24(3):407-409. DOI:10.1089/thy.2013.3393.nomen
  • Experimental and Clinical Endocrinology & Diabetes 03/2014; 122(03). DOI:10.1055/s-0034-1372046
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    03/2014; 3(1):7-9. DOI:10.1159/000358180
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    The Journal of Clinical Endocrinology and Metabolism 03/2014; 99(3):768-70. DOI:10.1210/jc.2013-3393
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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.
    Vascular Medicine 01/2014; 19(1). DOI:10.1177/1358863X13518364
  • Peter Kopp
    The Journal of Clinical Endocrinology and Metabolism 01/2014; 99(1):67-9. DOI:10.1210/jc.2013-4319
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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 presented at age 39 with metastatic parathyroid cancer. 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.
    The Journal of Clinical Endocrinology and Metabolism 10/2013; 99(2). DOI:10.1210/jc.2013-3031
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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 ap-proaches for patients with thyroid disease. Summary: Important clinical practices in use today for the treatment of patients with hypothy-roidism, 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 se-ries 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.
    Thyroid: official journal of the American Thyroid Association 09/2013; DOI:10.1089/thy.2013.0109
  • Peter A Kopp
    Thyroid: official journal of the American Thyroid Association 08/2013; 23(8):926. DOI:10.1089/thy.2013.2308.ed
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    ABSTRACT: Context:Postpartum, diabetes insipidus (DI) can be part of Sheehan's syndrome or lymphocytic hypophysitis in combination with anterior pituitary hormone deficiencies. In contrast, acute onset of isolated DI in the postpartum period is unusual.Case Presentation:This patient presented at 33 weeks gestation with placental abruption, prompting a cesarean delivery of twins. Immediately after delivery, she developed severe DI. The DI could be controlled with the vasopressinase-resistant 1-deamino-8-D-arginine vasopressin (DDAVP), but not with arginine vasopressin (AVP), and it resolved within a few weeks.Objective:The aim of this study was to demonstrate that the postpartum DI in this patient was caused by the release of placental vasopressinase into the maternal bloodstream.Methods and Results:Cells were transiently transfected with the AVP receptor 2 (AVPR2) and treated with either AVP or DDAVP in the presence of the patient's serum collected postpartum or 10 weeks after delivery. The response to the different treatments was evaluated by measuring the activity of a cAMP-responsive firefly luciferase reporter construct. The in vitro studies demonstrate that the patient's postpartum serum disrupts activation of the AVPR2 by AVP, but not by the vasopressinase-resistant DDAVP.Conclusions:Placental abruption can rarely be associated with acute postpartum DI caused by release of placental vasopressinase into the bloodstream. This clinical entity must be considered in patients with placental abruption and when evaluating patients presenting with DI after delivery.
    The Journal of Clinical Endocrinology and Metabolism 02/2013; 98(3). DOI:10.1210/jc.2012-3548
  • Peter Kopp
    Thyroid: official journal of the American Thyroid Association 01/2013; 23(1):5-6. DOI:10.1089/thy.2013.2301.ed
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    ABSTRACT: Diagnosing oncogenic osteomalacia is still a challenge. The disorder is characterized by osteomalacia caused by renal phosphate wasting and low serum concentration of 1,25-dihydroxyvitamin D3 occurring in the presence of a tumor that produces high levels of fibroblast growth factor 23. However, it is possible that the disease is much more misdiagnosed than rare. We present the case of a 42-year-old man with a long-term history of undiagnosed progressive muscle weakness. His laboratory results mainly showed low serum phosphate. Surgical removal of a nasal hemangiopericytoma that had been diagnosed five years earlier, brought him to a symptom-free condition. Even though knowing the underlying etiology would explain his osteomalacia, the patient sought medical help from countless physicians for five consecutive years, and only after adequate treatment a rewarding outcome was achieved. Arq Bras Endocrinol Metab. 2012;56(8):570-3.
    Arquivos brasileiros de endocrinologia e metabologia 11/2012; 56(8):570-3. DOI:10.1590/S0004-27302012000800018
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    ABSTRACT: The clinical implications of low vitamin D in peripheral artery disease (PAD) are unknown. We hypothesized that among individuals with PAD, lower levels of 25-hydroxyvitamin D would be associated with poorer functional performance, more adverse calf muscle characteristics, and poorer peripheral nerve function. Participants were 402 men and women with PAD who underwent measurement of 25-hydroxyvitamin D (DiaSorin radioimmunoassay) along with 6-minute walk testing, measurement of walking velocity at usual and fastest pace, computed tomography-measured calf muscle density, and peripheral nerve conduction velocity (NCV). Among PAD participants, 20.4% had 25-hydroxyvitamin D levels < 30 nmol/L, consistent with deficient vitamin D status. Adjusting for age, sex, and race, lower 25-hydroxyvitamin D levels were associated with poorer 6-minute walk performance (p trend = 0.002), slower usual-paced 4-meter walking velocity (p trend = 0.031), slower fast-paced 4-meter walking velocity (p trend = 0.043), and lower calf muscle density (p trend = 0.031). After additional adjustment for body mass index (BMI) and diabetes, none of these associations remained statistically significant. However, lower levels of 25-hydroxyvitamin D were associated with poorer peroneal NCV (p trend = 0.013) and poorer sural NCV (p trend = 0.039), even after adjusting for age, sex, race, BMI, comorbidities, smoking, physical activity, and other confounders. In conclusion, vitamin D deficiency is common among people with PAD encountered in clinical settings. After adjusting for BMI and diabetes mellitus, we found no significant associations of lower levels of 25-hydroxyvitamin D with poorer functional performance or calf muscle characteristics. Associations of low vitamin D levels with poorer peripheral nerve function require further study.
    Vascular Medicine 07/2012; 17(5):294-302. DOI:10.1177/1358863X12448457
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    ABSTRACT: Thyroid hormones are essential for normal development and metabolism. Their synthesis requires transport of iodide into thyroid follicles. The mechanisms involving the apical efflux of iodide into the follicular lumen are poorly elucidated. The discovery of mutations in the SLC26A4 gene in patients with Pendred syndrome (congenital deafness, goiter, and defective iodide organification) suggested a possible role for the encoded protein, pendrin, as an apical iodide transporter. We determined whether TSH regulates pendrin abundance at the plasma membrane and whether this influences iodide efflux. Results of immunoblot and immunofluorescence experiments reveal that TSH and forskolin rapidly increase pendrin abundance at the plasma membrane through the protein kinase A pathway in PCCL-3 rat thyroid cells. The increase in pendrin membrane abundance correlates with a decrease in intracellular iodide as determined by measuring intracellular (125)iodide and can be inhibited by specific blocking of pendrin. Elimination of the putative protein kinase A phosphorylation site T717A results in a diminished translocation to the membrane in response to forskolin. These results demonstrate that pendrin translocates to the membrane in response to TSH and suggest that it may have a physiological role in apical iodide transport and thyroid hormone synthesis.
    Endocrinology 11/2011; 153(1):512-21. DOI:10.1210/en.2011-1548
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    ABSTRACT: Over the past two decades, the genetic and molecular basis of familial forms of diabetes insipidus has been elucidated. Diabetes insipidus is a clinical syndrome characterized by the excretion of abnormally large volumes of diluted urine (polyuria) and increased fluid intake (polydipsia). The most common type of diabetes insipidus is caused by lack of the antidiuretic hormone arginine vasopressin (vasopressin), which is produced in the hypothalamus and secreted by the neurohypophysis. This type of diabetes insipidus is referred to here as neurohypophyseal diabetes insipidus. The syndrome can also result from resistance to the antidiuretic effects of vasopressin on the kidney, either at the level of the vasopressin 2 receptor or the aquaporin 2 water channel (which mediates the re-absorption of water from urine), and is referred to as renal or nephrogenic diabetes insipidus. Differentiation between these two types of diabetes insipidus and primary polydipsia can be difficult owing to the existence of partial as well as complete forms of vasopressin deficiency or resistance. Seven different familial forms of diabetes insipidus are known to exist. The clinical presentation, genetic basis and cellular mechanisms responsible for them vary considerably. This information has led to improved methods of differential diagnosis and could provide the basis of new forms of therapy.
    Nature Reviews Endocrinology 07/2011; 7(12):701-14. DOI:10.1038/nrendo.2011.100

Publication Stats

2k Citations
377.79 Total Impact Points

Institutions

  • 1999–2014
    • Northwestern University
      • • Division of Endocrinology, Metabolism and Molecular Medicine
      • • Division of Gastroenterology and Hepatology
      Evanston, Illinois, United States
  • 1998–2009
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 2001–2007
    • Ann & Robert H. Lurie Children's Hospital of Chicago
      Chicago, Illinois, United States
  • 1995
    • Vrije Universiteit Brussel
      Bruxelles, Brussels Capital, Belgium