A case-control study of the effects of hydroxyurea on circulating cortisol levels in patients with acute myelogenous leukemia and chronic myeloproliferative disorders
We have shown previously that the antitumor drug, hydroxyurea (HU) is able to induce dose-dependent increases in plasma corticosterone levels in the rat. The drug was administered early in the morning, when the levels of circulating glucocorticoids are low in this species. Normally, in humans under...
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Veröffentlicht in: | Pharmacological research 2000-10, Vol.42 (4), p.389-392 |
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description | We have shown previously that the antitumor drug, hydroxyurea (HU) is able to induce dose-dependent increases in plasma corticosterone levels in the rat. The drug was administered early in the morning, when the levels of circulating glucocorticoids are low in this species. Normally, in humans under physiological conditions, cortisol levels are elevated early in the morning, to which a sharp decrease follows between 09:00 and 11:00 hours. In a group of healthy volunteers, HU significantly attenuated the decrease in cortisol levels occurring between 09:00 and 11:00 hours with respect to the same subjects receiving placebo. Given the different circadian rhythms of the two species, such an effect of HU in man appeared to be the counterpart of the increase in serum corticosterone occurring in the rat. In the present study, we have attempted to ascertain whether HU is also able to influence adrenocortical function in patients with acute and chronic myeloproliferative disorders undergoing treatments with high doses of the drug. We found that the rate of decline in circulating cortisol observed in patients during the time interval 09:00–11:00 hours was overlapping to that previously found in healthy volunteers treated with HU. In patients, serum cortisol was still elevated at 15:00 hours, since average hormone levels were near to the upper normal limit of the assay. However, in the absence of a control group treated with placebo, we could not draw any clear-cut conclusion as to whether HU was able to modify significantly the pattern of cortisol release in the study population. |
doi_str_mv | 10.1006/phrs.2000.0709 |
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The drug was administered early in the morning, when the levels of circulating glucocorticoids are low in this species. Normally, in humans under physiological conditions, cortisol levels are elevated early in the morning, to which a sharp decrease follows between 09:00 and 11:00 hours. In a group of healthy volunteers, HU significantly attenuated the decrease in cortisol levels occurring between 09:00 and 11:00 hours with respect to the same subjects receiving placebo. Given the different circadian rhythms of the two species, such an effect of HU in man appeared to be the counterpart of the increase in serum corticosterone occurring in the rat. In the present study, we have attempted to ascertain whether HU is also able to influence adrenocortical function in patients with acute and chronic myeloproliferative disorders undergoing treatments with high doses of the drug. We found that the rate of decline in circulating cortisol observed in patients during the time interval 09:00–11:00 hours was overlapping to that previously found in healthy volunteers treated with HU. In patients, serum cortisol was still elevated at 15:00 hours, since average hormone levels were near to the upper normal limit of the assay. However, in the absence of a control group treated with placebo, we could not draw any clear-cut conclusion as to whether HU was able to modify significantly the pattern of cortisol release in the study population.</description><identifier>ISSN: 1043-6618</identifier><identifier>EISSN: 1096-1186</identifier><identifier>DOI: 10.1006/phrs.2000.0709</identifier><identifier>PMID: 10988000</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Adult ; Aged ; Antineoplastic Agents - pharmacology ; Case-Control Studies ; Chronic Disease ; Drug Interactions ; Female ; Humans ; Hydrocortisone - blood ; Hydroxyurea - pharmacology ; hydroxyurea, cortisol, myeloproliferative disorders, hypothalamo–pituitary–adrenal axis ; Leukemia, Myeloid, Acute - blood ; Leukemia, Myeloid, Acute - drug therapy ; Male ; Middle Aged ; Myeloproliferative Disorders - blood ; Myeloproliferative Disorders - drug therapy</subject><ispartof>Pharmacological research, 2000-10, Vol.42 (4), p.389-392</ispartof><rights>2000 Academic Press</rights><rights>Copyright 2000 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c340t-a3ba8aea0059fe37ee9dd8f16473b60ce2925d1940543b3deea8b83b574528613</citedby><cites>FETCH-LOGICAL-c340t-a3ba8aea0059fe37ee9dd8f16473b60ce2925d1940543b3deea8b83b574528613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/phrs.2000.0709$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10988000$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Navarra, P.</creatorcontrib><creatorcontrib>Aloe-Spiriti, M.A.</creatorcontrib><creatorcontrib>Boccarini, F.</creatorcontrib><creatorcontrib>Montefusco, E.</creatorcontrib><creatorcontrib>Latagliata, R.</creatorcontrib><creatorcontrib>Preziosi, P.</creatorcontrib><creatorcontrib>Petti, M.C.</creatorcontrib><title>A case-control study of the effects of hydroxyurea on circulating cortisol levels in patients with acute myelogenous leukemia and chronic myeloproliferative disorders</title><title>Pharmacological research</title><addtitle>Pharmacol Res</addtitle><description>We have shown previously that the antitumor drug, hydroxyurea (HU) is able to induce dose-dependent increases in plasma corticosterone levels in the rat. The drug was administered early in the morning, when the levels of circulating glucocorticoids are low in this species. Normally, in humans under physiological conditions, cortisol levels are elevated early in the morning, to which a sharp decrease follows between 09:00 and 11:00 hours. In a group of healthy volunteers, HU significantly attenuated the decrease in cortisol levels occurring between 09:00 and 11:00 hours with respect to the same subjects receiving placebo. Given the different circadian rhythms of the two species, such an effect of HU in man appeared to be the counterpart of the increase in serum corticosterone occurring in the rat. In the present study, we have attempted to ascertain whether HU is also able to influence adrenocortical function in patients with acute and chronic myeloproliferative disorders undergoing treatments with high doses of the drug. We found that the rate of decline in circulating cortisol observed in patients during the time interval 09:00–11:00 hours was overlapping to that previously found in healthy volunteers treated with HU. In patients, serum cortisol was still elevated at 15:00 hours, since average hormone levels were near to the upper normal limit of the assay. However, in the absence of a control group treated with placebo, we could not draw any clear-cut conclusion as to whether HU was able to modify significantly the pattern of cortisol release in the study population.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Case-Control Studies</subject><subject>Chronic Disease</subject><subject>Drug Interactions</subject><subject>Female</subject><subject>Humans</subject><subject>Hydrocortisone - blood</subject><subject>Hydroxyurea - pharmacology</subject><subject>hydroxyurea, cortisol, myeloproliferative disorders, hypothalamo–pituitary–adrenal axis</subject><subject>Leukemia, Myeloid, Acute - blood</subject><subject>Leukemia, Myeloid, Acute - drug therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myeloproliferative Disorders - blood</subject><subject>Myeloproliferative Disorders - drug therapy</subject><issn>1043-6618</issn><issn>1096-1186</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtOxCAUhonRODq6dWl4gVYovdDlZOItmcSNrhsKp1O0Uxqgo30hn1OaunDj6pwTvv8P-RC6oSSmhOR3Q2tdnBBCYlKQ8gRdUFLmEaU8P533lEV5TvkKXTr3HqgypeQcrQLEeTgv0PcGS-Egkqb31nTY-VFN2DTYt4ChaUB6N5_tpKz5mkYLApseS23l2Amv-z2WxnrtQraDI3QO6x4P4QX6kPzUvsVCjh7wYYLO7KE3owvk-AEHLbDoFZatNb2WCzCET-gGbCg4Alah1yqw7gqdNaJzcP071-jt4f51-xTtXh6ft5tdJFlKfCRYLbgAQUhWNsAKgFIp3tA8LVidEwlJmWSKlinJUlYzBSB4zVmdFWmW8JyyNYqXXmmNcxaaarD6IOxUUVLNwqtZeDULr2bhIXC7BIaxPoD6gy-GA8AXIKiBowZbORncSFDaBrmVMvq_7h_djJUu</recordid><startdate>20001001</startdate><enddate>20001001</enddate><creator>Navarra, P.</creator><creator>Aloe-Spiriti, M.A.</creator><creator>Boccarini, F.</creator><creator>Montefusco, E.</creator><creator>Latagliata, R.</creator><creator>Preziosi, P.</creator><creator>Petti, M.C.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20001001</creationdate><title>A case-control study of the effects of hydroxyurea on circulating cortisol levels in patients with acute myelogenous leukemia and chronic myeloproliferative disorders</title><author>Navarra, P. ; Aloe-Spiriti, M.A. ; Boccarini, F. ; Montefusco, E. ; Latagliata, R. ; Preziosi, P. ; Petti, M.C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c340t-a3ba8aea0059fe37ee9dd8f16473b60ce2925d1940543b3deea8b83b574528613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Case-Control Studies</topic><topic>Chronic Disease</topic><topic>Drug Interactions</topic><topic>Female</topic><topic>Humans</topic><topic>Hydrocortisone - blood</topic><topic>Hydroxyurea - pharmacology</topic><topic>hydroxyurea, cortisol, myeloproliferative disorders, hypothalamo–pituitary–adrenal axis</topic><topic>Leukemia, Myeloid, Acute - blood</topic><topic>Leukemia, Myeloid, Acute - drug therapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myeloproliferative Disorders - blood</topic><topic>Myeloproliferative Disorders - drug therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Navarra, P.</creatorcontrib><creatorcontrib>Aloe-Spiriti, M.A.</creatorcontrib><creatorcontrib>Boccarini, F.</creatorcontrib><creatorcontrib>Montefusco, E.</creatorcontrib><creatorcontrib>Latagliata, R.</creatorcontrib><creatorcontrib>Preziosi, P.</creatorcontrib><creatorcontrib>Petti, M.C.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Pharmacological research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Navarra, P.</au><au>Aloe-Spiriti, M.A.</au><au>Boccarini, F.</au><au>Montefusco, E.</au><au>Latagliata, R.</au><au>Preziosi, P.</au><au>Petti, M.C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A case-control study of the effects of hydroxyurea on circulating cortisol levels in patients with acute myelogenous leukemia and chronic myeloproliferative disorders</atitle><jtitle>Pharmacological research</jtitle><addtitle>Pharmacol Res</addtitle><date>2000-10-01</date><risdate>2000</risdate><volume>42</volume><issue>4</issue><spage>389</spage><epage>392</epage><pages>389-392</pages><issn>1043-6618</issn><eissn>1096-1186</eissn><abstract>We have shown previously that the antitumor drug, hydroxyurea (HU) is able to induce dose-dependent increases in plasma corticosterone levels in the rat. The drug was administered early in the morning, when the levels of circulating glucocorticoids are low in this species. Normally, in humans under physiological conditions, cortisol levels are elevated early in the morning, to which a sharp decrease follows between 09:00 and 11:00 hours. In a group of healthy volunteers, HU significantly attenuated the decrease in cortisol levels occurring between 09:00 and 11:00 hours with respect to the same subjects receiving placebo. Given the different circadian rhythms of the two species, such an effect of HU in man appeared to be the counterpart of the increase in serum corticosterone occurring in the rat. In the present study, we have attempted to ascertain whether HU is also able to influence adrenocortical function in patients with acute and chronic myeloproliferative disorders undergoing treatments with high doses of the drug. We found that the rate of decline in circulating cortisol observed in patients during the time interval 09:00–11:00 hours was overlapping to that previously found in healthy volunteers treated with HU. In patients, serum cortisol was still elevated at 15:00 hours, since average hormone levels were near to the upper normal limit of the assay. However, in the absence of a control group treated with placebo, we could not draw any clear-cut conclusion as to whether HU was able to modify significantly the pattern of cortisol release in the study population.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>10988000</pmid><doi>10.1006/phrs.2000.0709</doi><tpages>4</tpages></addata></record> |
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subjects | Adult Aged Antineoplastic Agents - pharmacology Case-Control Studies Chronic Disease Drug Interactions Female Humans Hydrocortisone - blood Hydroxyurea - pharmacology hydroxyurea, cortisol, myeloproliferative disorders, hypothalamo–pituitary–adrenal axis Leukemia, Myeloid, Acute - blood Leukemia, Myeloid, Acute - drug therapy Male Middle Aged Myeloproliferative Disorders - blood Myeloproliferative Disorders - drug therapy |
title | A case-control study of the effects of hydroxyurea on circulating cortisol levels in patients with acute myelogenous leukemia and chronic myeloproliferative disorders |
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