{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:53:50Z","timestamp":1783486430526,"version":"3.55.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,8,18]],"date-time":"2015-08-18T00:00:00Z","timestamp":1439856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2016,4]]},"abstract":"Summary<\/jats:title>Introduction<\/jats:title>Mitotane, a steroidogenesis inhibitor with adrenolytic properties used to treat adrenocortical cancer (ACC<\/jats:styled-content>), can affect thyroid function. A reduction of FT<\/jats:styled-content>4 levels with normal FT<\/jats:styled-content>3 and TSH<\/jats:styled-content> has been described in these patients. Using an in\u00a0vitro<\/jats:italic> murine model, the secretory capacity of thyrotrophic cells has been shown to be inhibited by mitotane.<\/jats:p><\/jats:sec>Objective<\/jats:title>To investigate the pathogenesis of thyroid abnormalities in mitotane\u2010treated patients with ACC<\/jats:styled-content>.<\/jats:p><\/jats:sec>Patients and Methods<\/jats:title>In five female patients with ACC<\/jats:styled-content> (median age 47; range 31\u201365) treated with mitotane (dosage 1\u00b75\u00a0g\/day; 1\u00b70\u20133\u00b70), we analysed the pattern of TSH<\/jats:styled-content> and thyroid function index (FT<\/jats:styled-content>4, FT<\/jats:styled-content>3 and FT<\/jats:styled-content>3\/FT<\/jats:styled-content>4 ratio) compared to an age\u2010 and gender\u2010matched control group. The in\u00a0vivo<\/jats:italic> secretory activity of the thyrotrophic cells was evaluated using a standard TRH<\/jats:styled-content> test (200\u00a0\u03bcg), and the response was compared to both a group of age\u2010matched female controls (n<\/jats:italic>\u00a0=\u00a010) and central hypothyroid patients (n<\/jats:italic>\u00a0=\u00a010).<\/jats:p><\/jats:sec>Results<\/jats:title>Basal TSH<\/jats:styled-content> (median 1\u00b754\u00a0mU\/l; range 1\u00b720\u20132\u00b717) was normal and scattered around our median reference value, FT<\/jats:styled-content>3 levels (median 3\u00b780\u00a0pmol\/l; 3\u00b730\u20134\u00b729) were normal but below the median reference value of 4\u00b737\u00a0pmol\/l and FT<\/jats:styled-content>4 levels were below the normal range in all patients (median 8\u00b740\u00a0pmol\/l; 7\u00b76\u20139\u00b79). FT<\/jats:styled-content>3\/FT<\/jats:styled-content>4 ratio was in the upper range in 4 patients and higher than normal in one patient. A blunted TSH<\/jats:styled-content> response to TRH<\/jats:styled-content> was observed in mitotane\u2010treated patients. \u0394TSH<\/jats:styled-content> (absolute TSH<\/jats:styled-content> response, peak TSH<\/jats:styled-content> minus basal TSH<\/jats:styled-content>) was 3\u00b765 (range 3\u00b753\u20135\u00b726), 12\u00b737 (range 7\u00b755\u201319\u00b797) and 1\u00b732\u00a0mU\/l (range 0\u00b752\u20134\u00b766) in mitotane\u2010treated patients, controls and central hypothyroid patients, respectively. PRL<\/jats:styled-content> secretion was normal.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Mitotane\u2010treated patients with ACC<\/jats:styled-content> showed low FT<\/jats:styled-content>4, normal FT<\/jats:styled-content>3 and TSH<\/jats:styled-content> and impaired TSH<\/jats:styled-content> response to TRH<\/jats:styled-content>, characteristic of central hypothyroidism. Furthermore, the elevated FT<\/jats:styled-content>3\/FT<\/jats:styled-content>4 ratio of these subjects reflects an enhanced T4 to T3 conversion rate, a compensatory mechanism characteristic of thyroid function changes observed in hypothyroid conditions. This finding thus confirms in\u00a0vitro<\/jats:italic> studies and may have a therapeutic implication for treatment with thyroid hormones, as suggested by current guidelines for this specific condition.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12868","type":"journal-article","created":{"date-parts":[[2015,7,29]],"date-time":"2015-07-29T12:20:52Z","timestamp":1438172452000},"page":"614-619","source":"Crossref","is-referenced-by-count":32,"title":["Mitotane treatment in patients with adrenocortical cancer causes central hypothyroidism"],"prefix":"10.1111","volume":"84","author":[{"given":"Marco","family":"Russo","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine Endocrinology Unit University of Catania Garibaldi\u2010Nesima Hospital Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Scollo","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine Endocrinology Unit University of Catania Garibaldi\u2010Nesima Hospital Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Pellegriti","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine Endocrinology Unit University of Catania Garibaldi\u2010Nesima Hospital Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana Ruxandra","family":"Cotta","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Endocrinology University of Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiano","family":"Squatrito","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine Endocrinology Unit University of Catania Garibaldi\u2010Nesima Hospital Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Frasca","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine Endocrinology Unit University of Catania Garibaldi\u2010Nesima Hospital Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Cannav\u00f2","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Endocrinology University of Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damiano","family":"Gullo","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine Endocrinology Unit University of Catania Garibaldi\u2010Nesima Hospital Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,8,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2013.02.034"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-005-0329-x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa063360"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-08-0103"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/acta.0.1240526"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-28-3-386"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-1404"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022552"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2006.0311"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.76.2.494"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(71)90005-5"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(90)90631-B"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.1998.8.903"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-2977(99)00040-6"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-013-0049-2"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-3020"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-13-0519"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010915)92:6<1385::AID-CNCR1461>3.0.CO;2-2"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-94-1-141"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29812"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-48-6-989"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.10.3631"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2009.08.003"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC-12-0028"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2014.0028"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcen.12868","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.12868","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T22:31:58Z","timestamp":1695508318000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.12868"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,18]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1111\/cen.12868"],"URL":"https:\/\/doi.org\/10.1111\/cen.12868","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,18]]}}}