Endocrinopathies, metabolic disorders, and iron overload in major and intermedia thalassemia: serum ferritin as diagnostic and predictive marker associated with liver and cardiac T2 MRI assessment

Introduction Endocrinopathies and metabolic disorders‐characterized β thalassemic (βT) patients and the prevention and treatment of these comorbidities are important targets to be achieved. The aim of the study was to analyze the diagnostic and prognostic role of ferritin for endocrinopathies and me...

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Veröffentlicht in:European journal of haematology 2015-05, Vol.94 (5), p.404-412
Hauptverfasser: Chirico, Valeria, Rigoli, Luciana, Lacquaniti, Antonio, Salpietro, Vincenzo, Piraino, Basilia, Amorini, Maria, Salpietro, Carmelo, Arrigo, Teresa
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container_start_page 404
container_title European journal of haematology
container_volume 94
creator Chirico, Valeria
Rigoli, Luciana
Lacquaniti, Antonio
Salpietro, Vincenzo
Piraino, Basilia
Amorini, Maria
Salpietro, Carmelo
Arrigo, Teresa
description Introduction Endocrinopathies and metabolic disorders‐characterized β thalassemic (βT) patients and the prevention and treatment of these comorbidities are important targets to be achieved. The aim of the study was to analyze the diagnostic and prognostic role of ferritin for endocrinopathies and metabolic disorders in βT patients. The ability of iron chelators to treat iron overload and to prevent or reverse metabolic disorders and endocrinopathies was also evaluated. Patients and methods Seventy‐two βT patients were treated with different chelation strategies during the study. Receiver operating characteristics analysis was employed to calculate the area under the curve for serum ferritin to find the best cutoff values capable of identifying endocrine dysfunction in thalassemic patients. Kaplan–Meier curves were generated to assess the incidence of endocrinopathy. Adjusted risk estimates for endocrinopathy were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. Results High ferritin levels were observed in patients with hypothyroidism [1500 (872.5–2336.5) μg/L], hypogonadism [878 (334–2010) μg/L], and in patients with hypoparathyroidism or osteoporosis [834 (367–1857) μg/L]. A strict correlation between ferritin and T2* magnetic resonance imaging of heart (r = −0.64; P:0.0006) and liver (r = −0.40; P:0.03) values was observed. Patients with ferritin values above 1800 μg/L experienced a significantly faster evolution to hypothyroidism [log‐rank (χ2):7.7; P = 0.005], hypogonadism [log‐rank (χ2):10.7; P = 0.001], and multiple endocrinopathies [log‐rank (χ2):5.72; P = 0.02]. Ferritin predicted high risk of endocrine dysfunction independently of confounding factors (HR:1.23; P 
doi_str_mv 10.1111/ejh.12444
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The aim of the study was to analyze the diagnostic and prognostic role of ferritin for endocrinopathies and metabolic disorders in βT patients. The ability of iron chelators to treat iron overload and to prevent or reverse metabolic disorders and endocrinopathies was also evaluated. Patients and methods Seventy‐two βT patients were treated with different chelation strategies during the study. Receiver operating characteristics analysis was employed to calculate the area under the curve for serum ferritin to find the best cutoff values capable of identifying endocrine dysfunction in thalassemic patients. Kaplan–Meier curves were generated to assess the incidence of endocrinopathy. Adjusted risk estimates for endocrinopathy were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. Results High ferritin levels were observed in patients with hypothyroidism [1500 (872.5–2336.5) μg/L], hypogonadism [878 (334–2010) μg/L], and in patients with hypoparathyroidism or osteoporosis [834 (367–1857) μg/L]. A strict correlation between ferritin and T2* magnetic resonance imaging of heart (r = −0.64; P:0.0006) and liver (r = −0.40; P:0.03) values was observed. Patients with ferritin values above 1800 μg/L experienced a significantly faster evolution to hypothyroidism [log‐rank (χ2):7.7; P = 0.005], hypogonadism [log‐rank (χ2):10.7; P = 0.001], and multiple endocrinopathies [log‐rank (χ2):5.72; P = 0.02]. Ferritin predicted high risk of endocrine dysfunction independently of confounding factors (HR:1.23; P &lt; 0.0001). The intensification of chelation therapy led to an amelioration of hypothyroidism. Conclusions Ferritin represents a prognostic marker for βT patients and a predictive factor for progression to endocrine dysfunctions. Intensive chelation therapy allows the reversibility of hypothyroidism.</description><identifier>ISSN: 0902-4441</identifier><identifier>EISSN: 1600-0609</identifier><identifier>DOI: 10.1111/ejh.12444</identifier><identifier>PMID: 25200112</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; beta-Thalassemia - diagnosis ; beta-Thalassemia - epidemiology ; beta-Thalassemia - pathology ; beta-Thalassemia - therapy ; Biomarkers - blood ; Chelation Therapy ; Comorbidity ; endocrinopathies ; Female ; ferritin ; Ferritins - blood ; Humans ; Hypogonadism - diagnosis ; Hypogonadism - epidemiology ; Hypogonadism - pathology ; Hypogonadism - therapy ; hypothyroidism ; Hypothyroidism - diagnosis ; Hypothyroidism - epidemiology ; Hypothyroidism - pathology ; Hypothyroidism - therapy ; Iron - blood ; Iron Chelating Agents - therapeutic use ; iron chelation therapy ; Iron Overload - diagnosis ; Iron Overload - epidemiology ; Iron Overload - etiology ; Iron Overload - therapy ; Italy - epidemiology ; Liver - metabolism ; Liver - pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Myocardium - metabolism ; Myocardium - pathology ; Osteoporosis - diagnosis ; Osteoporosis - epidemiology ; Osteoporosis - pathology ; Osteoporosis - therapy ; Predictive Value of Tests ; Proportional Hazards Models ; ROC Curve ; thalassemia ; Transfusion Reaction</subject><ispartof>European journal of haematology, 2015-05, Vol.94 (5), p.404-412</ispartof><rights>2014 John Wiley &amp; Sons A/S. Published by John Wiley &amp; Sons Ltd</rights><rights>2014 John Wiley &amp; Sons A/S. Published by John Wiley &amp; Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2784-8b8e29bfaaea0e8516f2185652761c002dd65d90fc18de743918ad7bb9c6d4ab3</citedby><cites>FETCH-LOGICAL-c2784-8b8e29bfaaea0e8516f2185652761c002dd65d90fc18de743918ad7bb9c6d4ab3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fejh.12444$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fejh.12444$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25200112$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chirico, Valeria</creatorcontrib><creatorcontrib>Rigoli, Luciana</creatorcontrib><creatorcontrib>Lacquaniti, Antonio</creatorcontrib><creatorcontrib>Salpietro, Vincenzo</creatorcontrib><creatorcontrib>Piraino, Basilia</creatorcontrib><creatorcontrib>Amorini, Maria</creatorcontrib><creatorcontrib>Salpietro, Carmelo</creatorcontrib><creatorcontrib>Arrigo, Teresa</creatorcontrib><title>Endocrinopathies, metabolic disorders, and iron overload in major and intermedia thalassemia: serum ferritin as diagnostic and predictive marker associated with liver and cardiac T2 MRI assessment</title><title>European journal of haematology</title><addtitle>Eur J Haematol</addtitle><description>Introduction Endocrinopathies and metabolic disorders‐characterized β thalassemic (βT) patients and the prevention and treatment of these comorbidities are important targets to be achieved. The aim of the study was to analyze the diagnostic and prognostic role of ferritin for endocrinopathies and metabolic disorders in βT patients. The ability of iron chelators to treat iron overload and to prevent or reverse metabolic disorders and endocrinopathies was also evaluated. Patients and methods Seventy‐two βT patients were treated with different chelation strategies during the study. Receiver operating characteristics analysis was employed to calculate the area under the curve for serum ferritin to find the best cutoff values capable of identifying endocrine dysfunction in thalassemic patients. Kaplan–Meier curves were generated to assess the incidence of endocrinopathy. Adjusted risk estimates for endocrinopathy were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. Results High ferritin levels were observed in patients with hypothyroidism [1500 (872.5–2336.5) μg/L], hypogonadism [878 (334–2010) μg/L], and in patients with hypoparathyroidism or osteoporosis [834 (367–1857) μg/L]. A strict correlation between ferritin and T2* magnetic resonance imaging of heart (r = −0.64; P:0.0006) and liver (r = −0.40; P:0.03) values was observed. Patients with ferritin values above 1800 μg/L experienced a significantly faster evolution to hypothyroidism [log‐rank (χ2):7.7; P = 0.005], hypogonadism [log‐rank (χ2):10.7; P = 0.001], and multiple endocrinopathies [log‐rank (χ2):5.72; P = 0.02]. Ferritin predicted high risk of endocrine dysfunction independently of confounding factors (HR:1.23; P &lt; 0.0001). The intensification of chelation therapy led to an amelioration of hypothyroidism. Conclusions Ferritin represents a prognostic marker for βT patients and a predictive factor for progression to endocrine dysfunctions. Intensive chelation therapy allows the reversibility of hypothyroidism.</description><subject>Adolescent</subject><subject>Adult</subject><subject>beta-Thalassemia - diagnosis</subject><subject>beta-Thalassemia - epidemiology</subject><subject>beta-Thalassemia - pathology</subject><subject>beta-Thalassemia - therapy</subject><subject>Biomarkers - blood</subject><subject>Chelation Therapy</subject><subject>Comorbidity</subject><subject>endocrinopathies</subject><subject>Female</subject><subject>ferritin</subject><subject>Ferritins - blood</subject><subject>Humans</subject><subject>Hypogonadism - diagnosis</subject><subject>Hypogonadism - epidemiology</subject><subject>Hypogonadism - pathology</subject><subject>Hypogonadism - therapy</subject><subject>hypothyroidism</subject><subject>Hypothyroidism - diagnosis</subject><subject>Hypothyroidism - epidemiology</subject><subject>Hypothyroidism - pathology</subject><subject>Hypothyroidism - therapy</subject><subject>Iron - blood</subject><subject>Iron Chelating Agents - therapeutic use</subject><subject>iron chelation therapy</subject><subject>Iron Overload - diagnosis</subject><subject>Iron Overload - epidemiology</subject><subject>Iron Overload - etiology</subject><subject>Iron Overload - therapy</subject><subject>Italy - epidemiology</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Osteoporosis - diagnosis</subject><subject>Osteoporosis - epidemiology</subject><subject>Osteoporosis - pathology</subject><subject>Osteoporosis - therapy</subject><subject>Predictive Value of Tests</subject><subject>Proportional Hazards Models</subject><subject>ROC Curve</subject><subject>thalassemia</subject><subject>Transfusion Reaction</subject><issn>0902-4441</issn><issn>1600-0609</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1uFDEQhS0EIiGw4ALIS5DoxHb_s4uiIQkKMIJBLK1qu5rx0N0ebE9C7sfBqKGT7PDGctV7X8n1GHspxbGkc4Kb9bFURVE8YoeyEiITlWgfs0PRCpVRWR6wZzFuhBCqlfVTdqBKJYSU6pD9WUzWm-Amv4W0dhjf8hETdH5whlsXfbAYqAiT5S74iftrDIMHek18hI0Pc2tKGEa0DnhawwAx4ujgHY8YdiPvMQSXyACRmPBj8jERfm_cBjKZ5K6RaOEnEi5GbxwktPzGpTUfqDcPMRDIbfhK8Y9fLvdCjHHEKT1nT3oYIr64u4_Yt_eL1dlFdvX5_PLs9Cozqm6KrOkaVG3XAyAIbEpZ9Uo2ZVWqupKGlmNtVdpW9EY2Fusib2UDtu661lS2gC4_Yq9n7jb4XzuMSY8uGhwGmNDvopZVrUSb56Ui6ZtZaoKPMWCvt8HRD2-1FHofmqbQ9L_QSPvqDrvraIcPyvuUSHAyC27cgLf_J-nFh4t7ZDY7XEz4-8FBG9ZVndel_v7pXKvl6mveLBu9zP8Cw3C0UQ</recordid><startdate>201505</startdate><enddate>201505</enddate><creator>Chirico, Valeria</creator><creator>Rigoli, Luciana</creator><creator>Lacquaniti, Antonio</creator><creator>Salpietro, Vincenzo</creator><creator>Piraino, Basilia</creator><creator>Amorini, Maria</creator><creator>Salpietro, Carmelo</creator><creator>Arrigo, Teresa</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201505</creationdate><title>Endocrinopathies, metabolic disorders, and iron overload in major and intermedia thalassemia: serum ferritin as diagnostic and predictive marker associated with liver and cardiac T2 MRI assessment</title><author>Chirico, Valeria ; Rigoli, Luciana ; Lacquaniti, Antonio ; Salpietro, Vincenzo ; Piraino, Basilia ; Amorini, Maria ; Salpietro, Carmelo ; Arrigo, Teresa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2784-8b8e29bfaaea0e8516f2185652761c002dd65d90fc18de743918ad7bb9c6d4ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>beta-Thalassemia - diagnosis</topic><topic>beta-Thalassemia - epidemiology</topic><topic>beta-Thalassemia - pathology</topic><topic>beta-Thalassemia - therapy</topic><topic>Biomarkers - blood</topic><topic>Chelation Therapy</topic><topic>Comorbidity</topic><topic>endocrinopathies</topic><topic>Female</topic><topic>ferritin</topic><topic>Ferritins - blood</topic><topic>Humans</topic><topic>Hypogonadism - diagnosis</topic><topic>Hypogonadism - epidemiology</topic><topic>Hypogonadism - pathology</topic><topic>Hypogonadism - therapy</topic><topic>hypothyroidism</topic><topic>Hypothyroidism - diagnosis</topic><topic>Hypothyroidism - epidemiology</topic><topic>Hypothyroidism - pathology</topic><topic>Hypothyroidism - therapy</topic><topic>Iron - blood</topic><topic>Iron Chelating Agents - therapeutic use</topic><topic>iron chelation therapy</topic><topic>Iron Overload - diagnosis</topic><topic>Iron Overload - epidemiology</topic><topic>Iron Overload - etiology</topic><topic>Iron Overload - therapy</topic><topic>Italy - epidemiology</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Osteoporosis - diagnosis</topic><topic>Osteoporosis - epidemiology</topic><topic>Osteoporosis - pathology</topic><topic>Osteoporosis - therapy</topic><topic>Predictive Value of Tests</topic><topic>Proportional Hazards Models</topic><topic>ROC Curve</topic><topic>thalassemia</topic><topic>Transfusion Reaction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chirico, Valeria</creatorcontrib><creatorcontrib>Rigoli, Luciana</creatorcontrib><creatorcontrib>Lacquaniti, Antonio</creatorcontrib><creatorcontrib>Salpietro, Vincenzo</creatorcontrib><creatorcontrib>Piraino, Basilia</creatorcontrib><creatorcontrib>Amorini, Maria</creatorcontrib><creatorcontrib>Salpietro, Carmelo</creatorcontrib><creatorcontrib>Arrigo, Teresa</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chirico, Valeria</au><au>Rigoli, Luciana</au><au>Lacquaniti, Antonio</au><au>Salpietro, Vincenzo</au><au>Piraino, Basilia</au><au>Amorini, Maria</au><au>Salpietro, Carmelo</au><au>Arrigo, Teresa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endocrinopathies, metabolic disorders, and iron overload in major and intermedia thalassemia: serum ferritin as diagnostic and predictive marker associated with liver and cardiac T2 MRI assessment</atitle><jtitle>European journal of haematology</jtitle><addtitle>Eur J Haematol</addtitle><date>2015-05</date><risdate>2015</risdate><volume>94</volume><issue>5</issue><spage>404</spage><epage>412</epage><pages>404-412</pages><issn>0902-4441</issn><eissn>1600-0609</eissn><abstract>Introduction Endocrinopathies and metabolic disorders‐characterized β thalassemic (βT) patients and the prevention and treatment of these comorbidities are important targets to be achieved. The aim of the study was to analyze the diagnostic and prognostic role of ferritin for endocrinopathies and metabolic disorders in βT patients. The ability of iron chelators to treat iron overload and to prevent or reverse metabolic disorders and endocrinopathies was also evaluated. Patients and methods Seventy‐two βT patients were treated with different chelation strategies during the study. Receiver operating characteristics analysis was employed to calculate the area under the curve for serum ferritin to find the best cutoff values capable of identifying endocrine dysfunction in thalassemic patients. Kaplan–Meier curves were generated to assess the incidence of endocrinopathy. Adjusted risk estimates for endocrinopathy were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. Results High ferritin levels were observed in patients with hypothyroidism [1500 (872.5–2336.5) μg/L], hypogonadism [878 (334–2010) μg/L], and in patients with hypoparathyroidism or osteoporosis [834 (367–1857) μg/L]. A strict correlation between ferritin and T2* magnetic resonance imaging of heart (r = −0.64; P:0.0006) and liver (r = −0.40; P:0.03) values was observed. Patients with ferritin values above 1800 μg/L experienced a significantly faster evolution to hypothyroidism [log‐rank (χ2):7.7; P = 0.005], hypogonadism [log‐rank (χ2):10.7; P = 0.001], and multiple endocrinopathies [log‐rank (χ2):5.72; P = 0.02]. Ferritin predicted high risk of endocrine dysfunction independently of confounding factors (HR:1.23; P &lt; 0.0001). The intensification of chelation therapy led to an amelioration of hypothyroidism. Conclusions Ferritin represents a prognostic marker for βT patients and a predictive factor for progression to endocrine dysfunctions. Intensive chelation therapy allows the reversibility of hypothyroidism.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>25200112</pmid><doi>10.1111/ejh.12444</doi><tpages>9</tpages></addata></record>
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subjects Adolescent
Adult
beta-Thalassemia - diagnosis
beta-Thalassemia - epidemiology
beta-Thalassemia - pathology
beta-Thalassemia - therapy
Biomarkers - blood
Chelation Therapy
Comorbidity
endocrinopathies
Female
ferritin
Ferritins - blood
Humans
Hypogonadism - diagnosis
Hypogonadism - epidemiology
Hypogonadism - pathology
Hypogonadism - therapy
hypothyroidism
Hypothyroidism - diagnosis
Hypothyroidism - epidemiology
Hypothyroidism - pathology
Hypothyroidism - therapy
Iron - blood
Iron Chelating Agents - therapeutic use
iron chelation therapy
Iron Overload - diagnosis
Iron Overload - epidemiology
Iron Overload - etiology
Iron Overload - therapy
Italy - epidemiology
Liver - metabolism
Liver - pathology
Magnetic Resonance Imaging
Male
Middle Aged
Myocardium - metabolism
Myocardium - pathology
Osteoporosis - diagnosis
Osteoporosis - epidemiology
Osteoporosis - pathology
Osteoporosis - therapy
Predictive Value of Tests
Proportional Hazards Models
ROC Curve
thalassemia
Transfusion Reaction
title Endocrinopathies, metabolic disorders, and iron overload in major and intermedia thalassemia: serum ferritin as diagnostic and predictive marker associated with liver and cardiac T2 MRI assessment
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