{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:41:44Z","timestamp":1790185304304,"version":"4.1.0"},"reference-count":37,"publisher":"The Endocrine Society","issue":"3","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ZZIA DK075121"],"award-info":[{"award-number":["ZZIA DK075121"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["Z99 HD999999"],"award-info":[{"award-number":["Z99 HD999999"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>We do not fully understand how hypercortisolism causes central hypothyroidism or what factors influence recovery of the hypothalamic-pituitary-thyroid axis. We evaluated thyroid function during and after cure of Cushing syndrome (CS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a retrospective cohort study of adult patients with CS seen from 2005 to 2018 (cohort 1, c1, n = 68) or 1985 to 1994 (cohort 2, c2, n = 55) at a clinical research center. Urine (UFC) and diurnal serum cortisol (F: ~8 am and ~midnight [pm]), morning 3,5,3\u2032-triiodothyronine (T3), free thyroxine (FT4), and thyrotropin (TSH) (c1) or hourly TSH from 1500 to 1900 h (day) and 2400 to 04000 h (night) (c2), were measured before and after curative surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>While hypercortisolemic, 53% of c1 had central hypothyroidism (low\/low normal FT4\u2005+\u2005unelevated TSH). Of those followed long term, 31% and 44% had initially subnormal FT4 and T3, respectively, which normalized 6 to 12 months after cure. Hypogonadism was more frequent in hypothyroid (69%) compared to euthyroid (13%) patients. Duration of symptoms, morning and midnight F, adrenocorticotropin, and UFC were inversely related to TSH, FT4, and\/or T3 levels (r\u2005=\u2005\u20130.24 to \u20130.52, P &amp;lt; .001 to 0.02). In c2, the nocturnal surge of TSH (mIU\/L) was subnormal before (day 1.00 \u00b1 0.04 vs night 1.08 \u00b1 0.05, P = .3) and normal at a mean of 8 months after cure (day 1.30 \u00b1 0.14 vs night 2.17 \u00b1 0.27, P = .01). UFC greater than or equal to 1000 \u03bcg\/day was an independent adverse prognostic marker of time to thyroid hormone recovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Abnormal thyroid function, likely mediated by subnormal nocturnal TSH, is prevalent in Cushing syndrome and is reversible after cure.<\/jats:p><\/jats:sec>","DOI":"10.1210\/clinem\/dgaa858","type":"journal-article","created":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T08:50:38Z","timestamp":1606294238000},"page":"e1316-e1331","source":"Crossref","is-referenced-by-count":25,"title":["The Hypothalamic-Pituitary-Thyroid Axis in Cushing Syndrome Before and After Curative Surgery"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9287-6664","authenticated-orcid":false,"given":"Skand","family":"Shekhar","sequence":"first","affiliation":[{"name":"Section on Genetics and Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5817-9232","authenticated-orcid":false,"given":"Raven","family":"McGlotten","sequence":"additional","affiliation":[{"name":"Section on Translational Endocrinology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunyoung","family":"Auh","sequence":"additional","affiliation":[{"name":"Office of the Clinical Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8421-131X","authenticated-orcid":false,"given":"Kristina I","family":"Rother","sequence":"additional","affiliation":[{"name":"Section on Genetics and Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0534-8025","authenticated-orcid":false,"given":"Lynnette K","family":"Nieman","sequence":"additional","affiliation":[{"name":"Section on Translational Endocrinology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,11,24]]},"reference":[{"issue":"7","key":"2021122117333073300_CIT0001","doi-asserted-by":"crossref","first-page":"4322","DOI":"10.1210\/jc.2004-2567","article-title":"Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus","volume":"90","author":"Alkemade","year":"2005","journal-title":"J Clin Endocrinol Metab."},{"issue":"4","key":"2021122117333073300_CIT0002","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1530\/acta.0.0960480","article-title":"Regulation of TSH secretion and thyroid function in Cushing\u2019s disease","volume":"96","author":"Visser","year":"1981","journal-title":"Acta Endocrinol (Copenh)."},{"issue":"6","key":"2021122117333073300_CIT0003","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1210\/jcem-72-6-1195","article-title":"The nocturnal serum thyrotropin surge is abolished in patients with adrenocorticotropin (ACTH)-dependent or ACTH-independent Cushing\u2019s syndrome","volume":"72","author":"Bartalena","year":"1991","journal-title":"J Clin Endocrinol Metab."},{"issue":"7","key":"2021122117333073300_CIT0004","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1001\/archinte.1979.03630440033013","article-title":"Thyroid axis in patients with Cushing\u2019s syndrome","volume":"139","author":"Duick","year":"1979","journal-title":"Arch Intern Med."},{"issue":"3","key":"2021122117333073300_CIT0005","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/(SICI)1096-9861(19981123)401:3<395::AID-CNE7>3.0.CO;2-P","article-title":"Immunohistochemical localization of glucocorticoid receptors in the forebrain of the rainbow trout (Oncorhynchus mykiss)","volume":"401","author":"Teitsma","year":"1998","journal-title":"J Comp Neurol."},{"issue":"5","key":"2021122117333073300_CIT0006","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1210\/endo-115-5-1984","article-title":"Immunocytochemical localization of glucocorticoid receptor in target cells","volume":"115","author":"Antakly","year":"1984","journal-title":"Endocrinology."},{"issue":"2","key":"2021122117333073300_CIT0007","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s004410051226","article-title":"Cellular localization and distribution of glucocorticoid receptor immunoreactivity and the expression of glucocorticoid receptor messenger RNA in rat pituitary gland. 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