{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:40:06Z","timestamp":1787503206660,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,2,3]],"date-time":"2017-02-03T00:00:00Z","timestamp":1486080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Mitotane induces hepatic\n                      <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                      3A4 activity, resulting in accelerated cortisol inactivation, and also increases cortisol binding globulin (\n                      <jats:styled-content style=\"fixed-case\">CBG<\/jats:styled-content>\n                      ). Therefore, higher hydrocortisone doses are required in patients with adrenocortical cancer (\n                      <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>\n                      ) on mitotane treatment. Modified release hydrocortisone has not been used in mitotane\u2010treated\n                      <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>\n                      patients yet.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      Case series to compare serum cortisol, calculated free serum cortisol and\n                      <jats:styled-content style=\"fixed-case\">ACTH<\/jats:styled-content>\n                      levels in\n                      <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>\n                      patients on mitotane treatment with immediate and modified release hydrocortisone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>\n                      Pharmacokinetics of immediate and modified release hydrocortisone, each administered at a dose of 40\u201020\u20100 mg, in nine patients with\n                      <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>\n                      and adjuvant mitotane treatment. For comparison, ten patients with secondary adrenal insufficiency (\n                      <jats:styled-content style=\"fixed-case\">SAI<\/jats:styled-content>\n                      ) on three different hydrocortisone regimens and ten healthy males were included.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Serum cortisol and plasma\n                      <jats:styled-content style=\"fixed-case\">ACTH<\/jats:styled-content>\n                      were measured by chemiluminescent enzyme immunoassay, and\n                      <jats:styled-content style=\"fixed-case\">CBG<\/jats:styled-content>\n                      by\n                      <jats:styled-content style=\"fixed-case\">RIA<\/jats:styled-content>\n                      , followed by calculation of free cortisol.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Calculated free serum cortisol levels after 40 mg immediate release hydrocortisone in\n                      <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>\n                      patients (46 \u00b1 14 nmol\/l) were similar to those after 10 mg immediate release hydrocortisone intake in men with\n                      <jats:styled-content style=\"fixed-case\">SAI<\/jats:styled-content>\n                      (64 \u00b1 16 nmol\/l) or to the physiological morning free cortisol levels in healthy subjects (31 \u00b1 5 nmol\/l). Compared to immediate release hydrocortisone, free cortisol levels after 40 mg modified release hydrocortisone in\n                      <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>\n                      patients were significantly lower (12 \u00b1 3 nmol\/l;\n                      <jats:italic>P<\/jats:italic>\n                      = 0\u00b703) resulting in a generally lower\n                      <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>\n                      (98 \u00b1 21\n                      <jats:italic>vs<\/jats:italic>\n                      149 \u00b1 37 nmol h\/l;\n                      <jats:italic>P<\/jats:italic>\n                      = 0\u00b702).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      40\u201020\u20100 mg immediate release, but not modified release hydrocortisone, resulted in sufficient glucocorticoid coverage in patients with\n                      <jats:styled-content style=\"fixed-case\">ACC<\/jats:styled-content>\n                      receiving mitotane treatment. The use of equivalent doses of modified release hydrocortisone preparation should be avoided in patients on mitotane treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cen.13302","type":"journal-article","created":{"date-parts":[[2017,1,7]],"date-time":"2017-01-07T02:24:03Z","timestamp":1483755843000},"page":"499-505","source":"Crossref","is-referenced-by-count":6,"title":["Immediate versus modified release hydrocortisone in mitotane\u2010treated patients with adrenocortical cancer"],"prefix":"10.1111","volume":"86","author":[{"given":"Marianne","family":"Weigel","sequence":"first","affiliation":[{"name":"Clinical Endocrinology Charit\u00e9 Campus Mitte Charit\u00e9 University Medicine Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Hahner","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetes Unit Department of Internal Medicine I University Hospital of Wuerzburg 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